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Sample records for characterize polysorbate-containing igg

  1. A Rapid Method to Characterize Mouse IgG Antibodies and Isolate Native Antigen Binding IgG B Cell Hybridomas.

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    Haolin Liu

    Full Text Available B cell hybridomas are an important source of monoclonal antibodies. In this paper, we developed a high-throughput method to characterize mouse IgG antibodies using surface plasmon resonance technology. This assay rapidly determines their sub-isotypes, whether they bind native antigen and their approximate affinities for the antigen using only 50 μl of hybridoma cell culture supernatant. Moreover, we found that mouse hybridomas secreting IgG antibodies also have membrane form IgG expression without Igα. Based on this surface IgG, we used flow cytometry to isolate rare γ2a isotype switched variants from a γ2b antibody secreting hybridoma cell line. Also, we used fluorescent antigen to single cell sort antigen binding hybridoma cells from bulk mixture of fused hybridoma cells instead of the traditional multi-microwell plate screening and limiting dilution sub-cloning thus saving time and labor. The IgG monoclonal antibodies specific for the native antigen identified with these methods are suitable for in vivo therapeutic uses, but also for sandwich ELISA assays, histology, flow cytometry, immune precipitation and x-ray crystallography.

  2. Characterization of IgG1 Conformation and Conformational Dynamics by Hydrogen/Deuterium Exchange Mass Spectrometry

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    Houde, Damian; Arndt, Joseph; Domeier, Wayne; Berkowitz, Steven; Engen, John R.; (NEU); (Biogen)

    2009-04-22

    Protein function is dictated by protein conformation. For the protein biopharmaceutical industry, therefore, it is important to have analytical tools that can detect changes in protein conformation rapidly, accurately, and with high sensitivity. In this paper we show that hydrogen/deuterium exchange mass spectrometry (H/DX-MS) can play an important role in fulfilling this need within the industry. H/DX-MS was used to assess both global and local conformational behavior of a recombinant monoclonal IgG1 antibody, a major class of biopharmaceuticals. Analysis of exchange into the intact, glycosylated IgG1 (and the Fab and Fc regions thereof) showed that the molecule was folded, highly stable, and highly amenable to analysis by this method using less than a nanomole of material. With improved chromatographic methods, peptide identification algorithms and data-processing steps, the analysis of deuterium levels in peptic peptides produced after labeling was accomplished in 1--2 days. On the basis of peptic peptide data, exchange was localized to specific regions of the antibody. Changes to IgG1 conformation as a result of deglycosylation were determined by comparing exchange into the glycosylated and deglycosylated forms of the antibody. Two regions of the IgG1 (residues 236-253 and 292-308) were found to have altered exchange properties upon deglycosylation. These results are consistent with previous findings concerning the role of glycosylation in the interaction of IgG1 with Fc receptors. Moreover, the data clearly illustrate how H/DX-MS can provide important characterization information on the higher order structure of antibodies and conformational changes that these molecules may experience upon modification.

  3. Characterizing IgG4-related disease with {sup 18}F-FDG PET/CT: a prospective cohort study

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    Zhang, Jingjing; Ma, Yanru; Niu, Na; Wang, Xinwei; Li, Fang; Zhu, Zhaohui [Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Nuclear Medicine, Peking Union Medical College Hospital, Beijing (China); Chen, Hua; Lin, Wei; Zhang, Fengchun; Zhang, Wen [Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Rheumatology, Peking Union Medical College Hospital, Beijing (China); Xiao, Yu; Liang, Zhiyong [Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Pathology, Peking Union Medical College Hospital, Beijing (China)

    2014-08-15

    IgG4-related disease (IgG4-RD) is an increasingly recognized clinicopathological disorder with immune-mediated inflammatory lesions mimicking malignancies. A cohort study was prospectively designed to investigate the value of {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in characterizing IgG4-RD. Thirty-five patients diagnosed with IgG4-RD according to the consensus criteria were enrolled with informed consent. All patients underwent baseline {sup 18}F-FDG PET/CT evaluation. Among them, 29 patients underwent a second {sup 18}F-FDG PET/CT scan after 2 to 4 weeks of steroid-based therapy. All 35 patients were found with {sup 18}F-FDG-avid hypermetabolic lesion(s); 97.1 % (34/35) of these patients showed multi-organ involvement. Among the 35 patients, 71.4 % (25/35) patients were found with more organ involvement on {sup 18}F-FDG PET/CT than conventional evaluations including physical examination, ultrasonography, and computed tomography (CT). {sup 18}F-FDG PET/CT demonstrated specific image characteristics and pattern of IgG4-RD, including diffusely elevated {sup 18}F-FDG uptake in the pancreas and salivary glands, patchy lesions in the retroperitoneal region and vascular wall, and multi-organ involvement that cannot be interpreted as metastasis. Comprehensive understanding of all involvement aided the biopsy-site selection in seven patients and the recanalization of ureteral obstruction in five patients. After 2 to 4 weeks of steroid-based therapy at 40 mg to 50 mg prednisone per day, 72.4 % (21/29) of the patients showed complete remission, whereas the others exhibited > 81.8 % decrease in {sup 18}F-FDG uptake. F-FDG PET/CT is a useful tool for assessing organ involvement, monitoring therapeutic response, and guiding interventional treatment of IgG4-RD. The image pattern is suggested to be updated into the consensus diagnostic criteria for IgG4-RD. (orig.)

  4. Production, Characterization, and Biological Evaluation of Well-Defined IgG1 Fc Glycoforms as a Model System for Biosimilarity Analysis.

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    Okbazghi, Solomon Z; More, Apurva S; White, Derek R; Duan, Shaofeng; Shah, Ishan S; Joshi, Sangeeta B; Middaugh, C Russell; Volkin, David B; Tolbert, Thomas J

    2016-02-01

    Four different well-defined IgG1 Fc glycoforms are proposed as a model system to examine important biological and physicochemical features for protein drug biosimilar analyses. The IgG1 Fc glycoforms were produced by yeast expression combined with in vitro enzymatic synthesis as a series of sequentially truncated high-mannose IgG1 Fc glycoforms with an anticipated range of biological activity and structural stability. Initial characterization with mass spectrometry, SDS-PAGE, size exclusion HPLC, and capillary isoelectric focusing confirmed that the glycoproteins are overall highly similar with the only major difference being glycosylation state. Binding to the activating Fc receptor, FcγRIIIa was used to evaluate the potential biological activity of the IgG1 Fc glycoproteins. Two complementary methods using biolayer interferometry, 1 with protein G-immobilized IgG1 Fc and the other with streptavidin-immobilized FcγRIIIa, were developed to assess FcγRIIIa affinity in kinetic binding studies. The high-mannose IgG1 Fc and Man5-IgG1 Fc glycoforms were highly similar to one another with high affinity for FcγRIIIa, whereas GlcNAc-Fc had weak affinity, and the nonglycosylated N297Q-Fc had no measurable affinity for FcγRIIIa. These 4 IgG1 Fc glycoforms were also evaluated in terms of physical and chemical stability profiles and then used as a model system to mathematically assess overall biosimilarity, as described in a series of companion articles. PMID:26869419

  5. Generation and characterization of antibodies against Asian elephant (Elephas maximus IgG, IgM, and IgA.

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    Alan F Humphreys

    Full Text Available Asian elephant (Elephas maximus immunity is poorly characterized and understood. This gap in knowledge is particularly concerning as Asian elephants are an endangered species threatened by a newly discovered herpesvirus known as elephant endotheliotropic herpesvirus (EEHV, which is the leading cause of death for captive Asian elephants born after 1980 in North America. While reliable diagnostic assays have been developed to detect EEHV DNA, serological assays to evaluate elephant anti-EEHV antibody responses are lacking and will be needed for surveillance and epidemiological studies and also for evaluating potential treatments or vaccines against lethal EEHV infection. Previous studies have shown that Asian elephants produce IgG in serum, but they failed to detect IgM and IgA, further hampering development of informative serological assays for this species. To begin to address this issue, we determined the constant region genomic sequence of Asian elephant IgM and obtained some limited protein sequence information for putative serum IgA. The information was used to generate or identify specific commercial antisera reactive against IgM and IgA isotypes. In addition, we generated a monoclonal antibody against Asian elephant IgG. These three reagents were used to demonstrate that all three immunoglobulin isotypes are found in Asian elephant serum and milk and to detect antibody responses following tetanus toxoid booster vaccination or antibodies against a putative EEHV structural protein. The results indicate that these new reagents will be useful for developing sensitive and specific assays to detect and characterize elephant antibody responses for any pathogen or vaccine, including EEHV.

  6. Generation and characterization of antibodies against Asian elephant (Elephas maximus) IgG, IgM, and IgA.

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    Humphreys, Alan F; Tan, Jie; Peng, RongSheng; Benton, Susan M; Qin, Xiang; Worley, Kim C; Mikulski, Rose L; Chow, Dar-Chone; Palzkill, Timothy G; Ling, Paul D

    2015-01-01

    Asian elephant (Elephas maximus) immunity is poorly characterized and understood. This gap in knowledge is particularly concerning as Asian elephants are an endangered species threatened by a newly discovered herpesvirus known as elephant endotheliotropic herpesvirus (EEHV), which is the leading cause of death for captive Asian elephants born after 1980 in North America. While reliable diagnostic assays have been developed to detect EEHV DNA, serological assays to evaluate elephant anti-EEHV antibody responses are lacking and will be needed for surveillance and epidemiological studies and also for evaluating potential treatments or vaccines against lethal EEHV infection. Previous studies have shown that Asian elephants produce IgG in serum, but they failed to detect IgM and IgA, further hampering development of informative serological assays for this species. To begin to address this issue, we determined the constant region genomic sequence of Asian elephant IgM and obtained some limited protein sequence information for putative serum IgA. The information was used to generate or identify specific commercial antisera reactive against IgM and IgA isotypes. In addition, we generated a monoclonal antibody against Asian elephant IgG. These three reagents were used to demonstrate that all three immunoglobulin isotypes are found in Asian elephant serum and milk and to detect antibody responses following tetanus toxoid booster vaccination or antibodies against a putative EEHV structural protein. The results indicate that these new reagents will be useful for developing sensitive and specific assays to detect and characterize elephant antibody responses for any pathogen or vaccine, including EEHV. PMID:25658336

  7. Immunophenotyping and characterization of BNP colostra revealed pathogenic alloantibodies of IgG1 subclass with specifity to platelets, granulocytes and monocytes of all maturation stages.

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    Assad, Aryan; Amann, Barbara; Friedrich, Annette; Deeg, Cornelia Annette

    2012-06-15

    Bovine neonatal pancytopenia (BNP) is mainly characterized by multiple haemorrhages, thrombocytopenia and leukocytopenia as a result of bone marrow depletion. BNP can be induced in healthy calves through application of colostrum from BNP donors, proofing that BNP is mediated to maternal alloantibodies. Alloantibody binding to bovine blood cells is present in sera and colostra of BNP donors and is probably initialized by vaccination with a certain BVD vaccine. To understand etiology and pathomechanisms of BNP, we closely characterized disease inducing antibodies regarding immunoglobulin subclass and binding specificities to peripheral blood derived leukocytes and platelets. By exact phenotyping the targeted blood cell subsets, including platelets for the first time, we investigated that BNP alloantibodies are exclusively of IgG1 subclass. Interestingly, IgG1 of BNP colostra bound to 70% leukocytes and 100% platelets irrespective of different bovine breeds and cellular maturity of all specimens tested. Furthermore, staining pattern on platelets as well as leukocyte subsets by BNP-IgG1 alloantibody exposed 100% reactivity to platelets, granulocytes and monocytes. Interestingly, the main part of T-helper cells was not bound by colostral alloantibodies. Our results point to a crucial role of IgG1 antibodies in BNP and to a target antigen that is expressed by all cells of myeloid lineage, but only partially by the lymphoid lineage. PMID:22554492

  8. Isolation and characterization of a monoclonal anti CK-2 alpha subunit antibody of the IgG1 subclass

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    Schmidt-Spaniol, I; Boldyreff, B; Issinger, O G

    1992-01-01

    A monoclonal antibody was produced against the recombinant human alpha subunit of CK-2. The antibody was of the IgG1 subclass and it was isolated from serum-free cell culture media and purified by affinity chromatography on Protein G Sepharose. The antibody can be used to detect specifically the ...

  9. IgG4-related skin disease.

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    Tokura, Y; Yagi, H; Yanaguchi, H; Majima, Y; Kasuya, A; Ito, T; Maekawa, M; Hashizume, H

    2014-11-01

    IgG4-related disease (IgG4-RD) is a recently established clinical entity characterized by high levels of circulating IgG4, and tissue infiltration of IgG4(+) plasma cells. IgG4-RD exhibits a distinctive fibroinflammatory change involving multiple organs, such as the pancreas and salivary and lacrimal glands. The skin lesions of IgG4-RD have been poorly characterized and may stem not only from direct infiltration of plasma cells but also from IgG4-mediated inflammation. Based on the documented cases together with ours, we categorized the skin lesions into seven subtypes: (1) cutaneous plasmacytosis (multiple papulonodules or indurations on the trunk and proximal part of the limbs), (2) pseudolymphoma and angiolymphoid hyperplasia with eosinophilia (plaques and papulonodules mainly on the periauricular, cheek and mandible regions), (3) Mikulicz disease (palpebral swelling, sicca syndrome and exophthalmos), (4) psoriasis-like eruption (strikingly mimicking psoriasis vulgaris), (5) unspecified maculopapular or erythematous eruptions, (6) hypergammaglobulinaemic purpura (bilateral asymmetrical palpable purpuric lesions on the lower extremities) and urticarial vasculitis (prolonged urticarial lesions occasionally with purpura) and (7) ischaemic digit (Raynaud phenomenon and digital gangrene). It is considered that subtypes 1-3 are induced by direct infiltration of IgG4(+) plasma cells, while the other types (4-7) are caused by secondary mechanisms. IgG4-related skin disease is defined as IgG4(+) plasma-cell-infiltrating skin lesions that form plaques, nodules or tumours (types 1-3), but may manifest secondary lesions caused by IgG4(+) plasma cells and/or IgG4 (types 4-7). PMID:25065694

  10. Expression and Characterization of a Potent Long-Acting GLP-1 Receptor Agonist, GLP-1-IgG2σ-Fc.

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    Yang, Yi; Chen, Fang; Wan, Deyou; Liu, Yunhui; Yang, Li; Feng, Hongru; Cui, Xinling; Gao, Xin; Song, Haifeng

    2016-01-01

    Human GLP-1 (glucagon-like peptide-1) can produce a remarkable improvement in glycemic control in patients with type 2 diabetes. However, its clinical benefits are limited by its short half-life, which is less than 2 min because of its small size and rapid enzymatic inactivation by dipeptidyl peptidase IV. We engineered GLP-1-IgG2σ-Fc, a 68-kDa fusion protein linking a variant human GLP-1 (A8G/G26E/R36G) to a human IgG2σ constant heavy-chain. A stably transfected Chinese hamster ovary cell line was obtained using electroporation. Western blotting showed that the expressed protein was immunoreactive to both GLP-1 and IgG antibodies. GLP-1-IgG2σ-Fc stimulated insulin secretion from INS-1 cells in a dose- and glucose-dependent manner and increased insulin mRNA expression. The half-life of GLP-1-IgG2σ-Fc in cynomolgus monkeys was approximately 57.1 ± 4.5 h. In the KKAy mouse model of diabetes, one intraperitoneal injection of GLP-1-IgG2σ-Fc (1 mg/kg) reduced blood glucose levels for 5 days. A 4-week repeat-administration study identified sustained effects on blood glucose levels. Oral glucose tolerance tests conducted at the beginning and end of this 4-week period showed that GLP-1-IgG2σ-Fc produced a stable glucose lowering effect. In addition, KKAy mice treated with GLP-1-IgG2σ-Fc showed statistically significant weight loss from day 23. In conclusion, these properties of GLP-1-IgG2σ-Fc demonstrated that it represented a potential long-acting GLP-1 receptor agonist for the treatment of type 2 diabetes. PMID:27232339

  11. Expression and Characterization of a Potent Long-Acting GLP-1 Receptor Agonist, GLP-1-IgG2σ-Fc.

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    Yi Yang

    Full Text Available Human GLP-1 (glucagon-like peptide-1 can produce a remarkable improvement in glycemic control in patients with type 2 diabetes. However, its clinical benefits are limited by its short half-life, which is less than 2 min because of its small size and rapid enzymatic inactivation by dipeptidyl peptidase IV. We engineered GLP-1-IgG2σ-Fc, a 68-kDa fusion protein linking a variant human GLP-1 (A8G/G26E/R36G to a human IgG2σ constant heavy-chain. A stably transfected Chinese hamster ovary cell line was obtained using electroporation. Western blotting showed that the expressed protein was immunoreactive to both GLP-1 and IgG antibodies. GLP-1-IgG2σ-Fc stimulated insulin secretion from INS-1 cells in a dose- and glucose-dependent manner and increased insulin mRNA expression. The half-life of GLP-1-IgG2σ-Fc in cynomolgus monkeys was approximately 57.1 ± 4.5 h. In the KKAy mouse model of diabetes, one intraperitoneal injection of GLP-1-IgG2σ-Fc (1 mg/kg reduced blood glucose levels for 5 days. A 4-week repeat-administration study identified sustained effects on blood glucose levels. Oral glucose tolerance tests conducted at the beginning and end of this 4-week period showed that GLP-1-IgG2σ-Fc produced a stable glucose lowering effect. In addition, KKAy mice treated with GLP-1-IgG2σ-Fc showed statistically significant weight loss from day 23. In conclusion, these properties of GLP-1-IgG2σ-Fc demonstrated that it represented a potential long-acting GLP-1 receptor agonist for the treatment of type 2 diabetes.

  12. Preparation and Characterization of Covalently Binding of Rat Anti-human IgG Monolayer on Thiol-Modified Gold Surface

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    Lv Zhengjian

    2009-01-01

    Full Text Available Abstract The 16-mercaptohexadecanoic acid (MHA film and rat anti-human IgG protein monolayer were fabricated on gold substrates using self-assembled monolayer (SAM method. The surface properties of the bare gold substrate, the MHA film and the protein monolayer were characterized by contact angle measurements, atomic force microscopy (AFM, grazing incidence X-ray diffraction (GIXRD method and X-ray photoelectron spectroscopy, respectively. The contact angles of the MHA film and the protein monolayer were 18° and 12°, respectively, all being hydrophilic. AFM images show dissimilar topographic nanostructures between different surfaces, and the thickness of the MHA film and the protein monolayer was estimated to be 1.51 and 5.53 nm, respectively. The GIXRD 2θ degrees of the MHA film and the protein monolayer ranged from 0° to 15°, significantly smaller than that of the bare gold surface, but the MHA film and the protein monolayer displayed very different profiles and distributions of their diffraction peaks. Moreover, the spectra of binding energy measured from these different surfaces could be well fitted with either Au4f, S2p or N1s, respectively. Taken together, these results indicate that MHA film and protein monolayer were successfully formed with homogeneous surfaces, and thus demonstrate that the SAM method is a reliable technique for fabricating protein monolayer.

  13. IgG4-related sclerosing disease

    Institute of Scientific and Technical Information of China (English)

    Terumi Kamisawa; Atsutake Okamoto

    2008-01-01

    Based on histological and immunohistochemical examination of various organs of patients with autoimmune pancreatitis (AIP), a novel clinicopathological entity of IgG4-related sclerosing disease has been proposed. This is a systemic disease that is characterized by extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs. Clinical manifestations are apparent in the pancreas, bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung, and prostate, in which tissue fibrosis with obliterative phlebitis is pathologically induced. AIP is not simply pancreatitis but, in fact, is a pancreatic disease indicative of IgG4-related sclerosing diseases. This disease includes AIP, sclerosing cholangitis, cholecystitis, sialadenitis, retroperitoneal fibrosis, tubulointerstitial nephritis, interstitial pneumonia, prostatitis, inflammatory pseudotumor and lymphadenopathy, all IgG4-related. Most IgG4-related sclerosing diseases have been found to be associated with AIP, but also those without pancreatic involvement have been reported. In some cases, only one or two organs are clinically involved, while in others, three or four organs are affected. The disease occurs predominantly in older men and responds well to steroid therapy. Serum IgG4 levels and immunostaining with anti-IgG4 antibody are useful in making the diagnosis. Since malignant tumors are frequently suspected on initial presentation, IgG4-related sclerosing disease should be considered in the differential diagnosis to avoid unnecessary surgery.

  14. IgG4-associated cholangitis.

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    Nath, Vikas; Lewin, Jack; Subramony, Charu; Shenoy, Veena

    2014-12-01

    We report a young female patient with IgG4-associated cholangitis (IAC) who presented with common bile duct (CBD) stricture and review the features that distinguish IAC from both primary sclerosing cholangitis (PSC) and other types of secondary sclerosing cholangitis (SSC). IAC is a biliary manifestation of IgG4-related sclerosing disease, an autoimmune condition characterized by elevated serum IgG4 and infiltrates containing lymphocytes and IgG4-positive plasma cells, accompanied by sclerosis. On endoscopic retrograde cholangiopancreatography, IAC consists of segmental biliary strictures with a predilection for the distal CBD, whereas in PSC the strictures are more band-like; other types of SSC often demonstrate unifocal ductal obstructions, sometimes associated with choleliths. On histologic examination, the bile duct wall in IAC contains a denser lymphocytic infiltrate and sparser sclerosis than in PSC; other types of SSC can be distinguished histologically by the types of inflammatory cells present. Unlike those of PSC, IAC-related strictures are reversible with corticosteroids.

  15. IgG4-Related Disease: A Multispecialty Condition

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    Iuri Usêda Santana

    2014-01-01

    Full Text Available IgG4-related disease (IgG4-RD is a recently recognized group of conditions, characterized by tumor-like swelling of involved organs, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, variable degrees of fibrosis, and elevated serum IgG4 concentrations. Currently IgG4-RD is recognized as a systemic condition that can affect several organs and tissues. Herein we report the case of a 34-year-old male patient who was admitted to our hospital with diffuse abdominal pain, weight loss, and painful stiffness in his neck. He had a history of tumoral mass of the left maxillary region, right palpebral ptosis with protrusion of the eyeball, and chronic dry cough for about 6 years. Laboratory tests revealed polyclonal hypergammaglobulinemia and increased serum IgG4 levels. Immunohistochemical staining of the maxillary biopsy was compatible with IgG4-RD. He had an excellent response to corticosteroid therapy. This case highlights that IgG4-RD should be included in the differential diagnosis with multisystem diseases.

  16. IgG4-Related Disease in a Urachal Tumor

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    Travis W. Dum

    2014-01-01

    Full Text Available IgG4-related disease is a newly recognized fibroinflammatory disorder that has the ability to affect nearly every organ system. It is characterized by tumefactive lesions and fibrosis and closely mimics neoplasms. Only one case of IgG4-related bladder mass has been reported in the literature, but there are no reports of IgG4-related disease in a urachal mass. Herein, we report a 26-year-old male who initially presented with symptoms of recurrent UTI. Work-up revealed a 6 cm urachal tumor, a 1.4 cm pulmonary lesion, and mediastinal lymphadenopathy; all metabolically active on PET scan and suspicious for urachal adenocarcinoma. Lung lesion fine needle aspiration and TURBT pathology revealed inflammation but no evidence of malignancy. The patient underwent a partial cystectomy and umbilectomy with pathology demonstrating dense plasmacytic cells, a high rate of immunohistochemistry staining positive for IgG4 plasma cells, a storiform pattern of fibrosis, and an obliterative phlebitis. Furthermore, the patient had an elevated serum IgG4 level of 227 mg/dL (range 2.4–121 mg/dL. IgG4-related disease is a newly recognized fibroinflammatory disorder that can mimic neoplastic processes and a high index of suspicion and accurate tissue pathology is necessary for an accurate diagnosis.

  17. IgG4-Related Disease in a Urachal Tumor.

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    Dum, Travis W; Zhang, Da; Lee, Eugene K

    2014-01-01

    IgG4-related disease is a newly recognized fibroinflammatory disorder that has the ability to affect nearly every organ system. It is characterized by tumefactive lesions and fibrosis and closely mimics neoplasms. Only one case of IgG4-related bladder mass has been reported in the literature, but there are no reports of IgG4-related disease in a urachal mass. Herein, we report a 26-year-old male who initially presented with symptoms of recurrent UTI. Work-up revealed a 6 cm urachal tumor, a 1.4 cm pulmonary lesion, and mediastinal lymphadenopathy; all metabolically active on PET scan and suspicious for urachal adenocarcinoma. Lung lesion fine needle aspiration and TURBT pathology revealed inflammation but no evidence of malignancy. The patient underwent a partial cystectomy and umbilectomy with pathology demonstrating dense plasmacytic cells, a high rate of immunohistochemistry staining positive for IgG4 plasma cells, a storiform pattern of fibrosis, and an obliterative phlebitis. Furthermore, the patient had an elevated serum IgG4 level of 227 mg/dL (range 2.4-121 mg/dL). IgG4-related disease is a newly recognized fibroinflammatory disorder that can mimic neoplastic processes and a high index of suspicion and accurate tissue pathology is necessary for an accurate diagnosis. PMID:25202466

  18. Erdheim-Chester Disease as a Mimic of IgG4-Related Disease

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    Gianfreda, Davide; Musetti, Claudio; Nicastro, Maria; Maritati, Federica; Cobelli, Rocco; Corradi, Domenico; Vaglio, Augusto

    2016-01-01

    Abstract Immunoglobulin-G4 (IgG4)-related disease (IgG4RD) is a fibro-inflammatory disorder characterized by tissue-infiltrating IgG4+ plasma cells, and, often, high serum IgG4. Several autoimmune, infectious, or proliferative conditions mimic IgG4RD. Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterized by foamy histiocytic infiltration, fibrosis, and chronic inflammation. ECD and IgG4RD manifestations may overlap. A patient presented with huge fibrous retroperitoneal masses causing compression on neighboring structures; the case posed the challenge of the differential diagnosis between IgG4RD and ECD mainly because of a prominent serum and tissue IgG4 response. Retroperitoneal biopsy led to the diagnosis of ECD; the V600E BRAF mutation was found. Treatment with the BRAF inhibitor vemurafenib was started. Treatment failed to induce mass regression and the patient died after 3 months of therapy. Prompted by this case, we examined serum and tissue IgG4 in a series of 15 ECD patients evaluated at our center, and found that approximately one-fourth of the cases have increased IgG4 in the serum and often in the tissue. The differential diagnosis between IgG4RD and ECD can be challenging, as some ECD patients have prominent IgG4 responses. This suggests the possibility of common pathogenic mechanisms between ECD and IgG4RD. PMID:27227923

  19. [Review of ear and nose and throat involvement in IgG4-RD].

    Science.gov (United States)

    Tao, Xiaofeng; Liu, Chang; Song, Bo

    2015-11-01

    IgG4-related disease (IgG4-RD) is a newly recognized disease entity. IgG4-RD is characterized by a single or multiple masses in one or more organs; a lymphoplasmacytic infiltrate with a high percentage of plasma cells within the lesion staining for IgG4; a peculiar pattern of fibrosis known as "storiform" fibrosis; and elevated serum IgG4 concentrations. IgG4-RD can occur in various organs, including pancreas, kidneys, lungs, retroperitoneum, and prostate gland. The head and neck involvements of IgG4-RD have been chiefly described in Mikulicz disease (MD), Küttner's tumor, orbital? inflammatory pseudotumor, and idiopathic hypertrophic pachymeningitis (IHP) previously. Recent studies reported that IgG4-RD could also involve ear, nose and throat. Here we reviewed the literatures about ear, nose and throat involvement by IgG4-RD, in order to provide some theoretical bases for the diagnosis and treatment of IgG4-RD.

  20. Clinical and imaging diagnosis of IgG4-related disease in the head and neck

    International Nuclear Information System (INIS)

    IgG4-related disease in the head and neck is a newly recognized multi-organ system disease characterized by elevated serum IgG4, infiltration of numerous IgG4-positive plasma cells, tissue fibrosis, and dramatic response to corticosteroid treatment. IgG4-related disease of the head and neck has some relative characteristics on CT and MRI, which can provide valuable information for the diagnosis and differential diagnosis, and are helpful for the clinical treatment, evaluation of therapeutic effects and prediction of prognosis. (authors)

  1. Are Classification Criteria for IgG4-RD Now Possible? The Concept of IgG4-Related Disease and Proposal of Comprehensive Diagnostic Criteria in Japan

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    Kazuichi Okazaki

    2012-01-01

    Full Text Available Recent studies suggest simultaneous or metachronous lesions in multiorgans characterized by elevated serum levels of IgG4 and abundant infiltration of IgG4-positive plasma cells with various degrees of fibrosis. Two Japanese research committees for IgG4-RD, one from fibrosclerosis (Okazaki team and the other from lymph proliferation (Umehara team supported by the “Research Program for Intractable Disease” of the Ministry of Health, Labor, and Welfare of Japan, have agreed with the unified nomenclature as “IgG4-RD” and proposed the comprehensive diagnostic criteria (CDC for IgG4-RD. Validation of the CDC demonstrated satisfactory sensitivity for the practical use of general physicians and nonspecialists but low sensitivity in the organs to be difficult in taking biopsy specimens such as type1 autoimmune pancreatitis (IgG4-related AIP, compared with IgG4-related sialadenitis/dacryoadenitis (Mikulicz's disease and IgG4-related kidney disease. Although the diagnostic criteria covering all IgG4-RD are hard to be established, combination with the CDC and organ-specific diagnostic criteria should improve sensitivity.

  2. Characterization of cytological changes, IgA, IgG and IL-8 levels and pH value in the vagina of prepubertal and sexually mature Ellegaard Göttingen minipigs during an estrous cycle

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    Lorenzen, Emma; Agerholm, Jørgen Steen; Grossi, Anette Blak;

    2016-01-01

    minipigs ( n = 10). In sexually mature minipigs ( n = 10), evaluated through an estrous cycle, there was an increase in number of mucosal neutrophils and other leukocytes during estrus. The level of total IgA on the vaginal mucosa increased during diestrus. The level of total IgG showed no significant...... changes through the cycle. The vaginal IgA level in the prepubertal minipigs was similar to the low estrus level in sexually mature minipigs, and the IgG level in prepubertal was similar to the stable level in the sexually mature minipigs....

  3. IgG4 Related Sclerosing Cholangitis

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    D. Joshi

    2014-01-01

    Full Text Available IgG4 related disease (IgG4-RD is a multisystemic disorder which has only recently been recognized. IgG4 related sclerosing cholangitis (IgG4-SC is the biliary manifestation of the disease, often in association with autoimmune pancreatitis (AIP. In this review, we provide an overview of IgG4-RD, with a focus on the biliary manifestations. In particular, we describe the important differential diagnoses of IgG4-SC that need to be considered, namely, primary sclerosing cholangitis (PSC and cholangiocarcinoma, and provide a management algorithm. Finally, we highlight future directions and unanswered questions which will provide new insights into this exciting and evolving disease entity.

  4. Cutoff Values of Serum IgG4 and Histopathological IgG4+ Plasma Cells for Diagnosis of Patients with IgG4-Related Disease

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    Yasufumi Masaki

    2012-01-01

    Full Text Available IgG4-related disease is a new disease classification established in Japan in the 21st century. Patients with IgG4-related disease display hyper-IgG4-gammaglobulinemia, massive infiltration of IgG4+ plasma cells into tissue, and good response to glucocorticoids. Since IgG4 overexpression is also observed in other disorders, it is necessary to diagnose IgG4-related disease carefully and correctly. We therefore sought to determine cutoff values for serum IgG4 and IgG4/IgG and for IgG4+/IgG+ plasma cells in tissue diagnostic of IgG4-related disease. Patients and Methods. We retrospectively analyzed serum IgG4 concentrations and IgG4/IgG ratio and IgG4+/IgG+ plasma cell ratio in tissues of 132 patients with IgG4-related disease and 48 patients with other disorders. Result. Serum IgG4 >135  mg/dl demonstrated a sensitivity of 97.0% and a specificity of 79.6% in diagnosing IgG4-related disease, and serum IgG4/IgG ratios >8% had a sensitivity and specificity of 95.5% and 87.5%, respectively. IgG4+cell/IgG+ cell ratio in tissues >40% had a sensitivity and specificity of 94.4% and 85.7%, respectively. However, the number of IgG4+ cells was reduced in severely fibrotic parts of tissues. Conclusion. Although a recent unanimous consensus of all relevant researchers in Japan recently established the diagnostic criteria for IgG4-related disease, findings such as ours indicate that further discussion is needed.

  5. Contactin-1 IgG4 antibodies cause paranode dismantling and conduction defects.

    Science.gov (United States)

    Manso, Constance; Querol, Luis; Mekaouche, Mourad; Illa, Isabel; Devaux, Jérôme J

    2016-06-01

    Paranodal axoglial junctions formed by the association of contactin-1, contactin-associated protein 1, and neurofascin-155, play important functions in nerve impulse propagation along myelinated axons. Autoantibodies to contactin-1 and neurofascin-155 define chronic inflammatory demyelinating polyradiculoneuropathy subsets of patients with specific clinical features. These autoantibodies are mostly of the IgG4 isotype, but their pathogenicity has not been proven. Here, we investigated the mechanisms how IgG subclasses to contactin-1 affect conduction. We show that purified anti-contactin-1 IgG1 and IgG4 bind to paranodes. To determine whether these isotypes can pass the paranodal barrier, we incubated isolated sciatic nerves with the purified antibody or performed intraneural injections. We found that IgG4 diffused into the paranodal regions in vitro or after intraneural injections. IgG4 infiltration was slow and progressive. In 24 h, IgG4 accessed the paranode borders near the nodal lumen, and completely fill the paranodal segments by 3 days. By contrast, control IgG, anti-contactin-1 IgG1, or even anti-contactin-associated-protein-2 IgG4 did not pass the paranodal barrier. To determine whether chronic exposure to these antibodies is pathogenic, we passively transferred anti-contactin-1 IgG1 and IgG4 into Lewis rats immunized with P2 peptide. IgG4 to contactin-1, but not IgG1, induced progressive clinical deteriorations combined with gait ataxia. No demyelination, axonal degeneration, or immune infiltration were observed. Instead, these animals presented a selective loss of the paranodal specialization in motor neurons characterized by the disappearance of the contactin-associated protein 1/contactin-1/neurofascin-155 complex at paranodes. Paranode destruction did not affect nodal specialization, but resulted in a moderate node lengthening. The sensory nerves and dorsal root ganglion were not affected in these animals. Electrophysiological examination further

  6. IgG4-related disease simulating Hodgkin lymphoma in a child

    Directory of Open Access Journals (Sweden)

    D. Eric Ewing, MD

    2016-06-01

    Full Text Available Immunoglobulin (Ig G4-related disease is a recently described syndrome characterized by mass forming lymphoplasmacytic tissue infiltration and elevated serum IgG4 concentrations usually affecting middle-aged or older individuals. Lymphadenopathy is frequently observed and is sometimes the first or only manifestation of the disease. We report a case of IgG4-related disease mimicking Hodgkin lymphoma in a 13-year-old girl. The patient presented with progressive unilateral cervical lymphadenopathy of several months duration. Biopsy showed follicular hyperplasia with progressive transformation of germinal centers. Interfollicular areas were expanded by small lymphocytes, histiocytes, eosinophils and fibrosis with occasional CD30 positive cells initially concerning for interfollicular Hodgkin lymphoma. Immunohistochemical analysis revealed an intrafollicular plasmacytosis with an IgG4-positive/IgG-positive plasma cell ratio of 50% supporting a diagnosis of IgG4-related lymphadenopathy, progressively transformed germinal centers type. Laboratory studies were supportive with elevated serum IgG4 (178 mg/dL and IgE (30.40 kU/L levels along with an elevated serum IgG4/IgG ratio (0.16. Very few cases of IgG4-related disease have been described in children. Within this age group, there is considerable clinical overlap between IgG4-related disease associated lymphadenopathy and Hodgkin lymphoma. In addition, lymphadenopathy secondary to IgG4-related disease demonstrates substantial histologic diversity with the potential to simulate the inflammatory background and fibrosis of Hodgkin lymphoma. The importance of accurate diagnosis is underscored by the prognostic implications considering the marked response of the syndrome to steroid therapy. In addition, appropriate follow up is critical to monitor for relapse and additional organ involvement.

  7. Adverse effects of IgG therapy.

    Science.gov (United States)

    Berger, Melvin

    2013-01-01

    IgG is widely used for patients with immune deficiencies and in a broad range of autoimmune and inflammatory disorders. Up to 40% of intravenous infusions of IgG may be associated with adverse effects (AEs), which are mostly uncomfortable or unpleasant but often are not serious. The most common infusion-related AE is headache. More serious reactions, including true anaphylaxis and anaphylactoid reactions, occur less frequently. Most reactions are related to the rate of infusion and can be prevented or treated just by slowing the infusion rate. Medications such as nonsteroidal anti-inflammatory drugs, antihistamines, or corticosteroids also may be helpful in preventing or treating these common AEs. IgA deficiency with the potential of IgG or IgE antibodies against IgA increases the risk of some AEs but should not be viewed as a contraindication if IgG therapy is needed. Potentially serious AEs include renal dysfunction and/or failure, thromboembolic events, and acute hemolysis. These events usually are multifactorial, related to combinations of constituents in the IgG product as well as risk factors for the recipient. Awareness of these factors should allow minimization of the risks and consequences of these AEs. Subcutaneous IgG is absorbed more slowly into the circulation and has a lower incidence of AEs, but awareness and diligence are necessary whenever IgG is administered. PMID:24565701

  8. A case of tubulointerstitial nephritis in IgG4-related systemic disease with markedly enlarged kidneys.

    Science.gov (United States)

    Mise, Naobumi; Tomizawa, Yutaka; Fujii, Akiko; Yamaguchi, Yutaka; Sugimoto, Tokuichiro

    2009-06-01

    IgG4-related systemic disease, including autoimmune pancreatitis, is a multi-organ disorder characterized by elevated serum immunoglobulin G4 (IgG4) concentration and IgG4-positive plasma cell infiltration. We report the case of a 67-year-old man with IgG4-related tubulointerstitial nephritis, presenting with markedly enlarged kidneys and renal dysfunction. The serum IgG4 level was elevated with 4200 mg/dl and pathological examination revealed patchy, clearly fringed areas of IgG4-positive plasma cell infiltration and advanced fibrosis in the renal parenchyma, perirenal tissue and lymph nodes. With oral prednisolone at a dose of 60 mg daily, a contraction of the kidneys and an improvement of renal function were observed. No recurrence of the disease was observed during the reduction of prednisolone to 2 mg daily over 4 years.

  9. IgG4-Related Disease Is Not Associated with Antibody to the Phospholipase A2 Receptor

    Directory of Open Access Journals (Sweden)

    Arezou Khosroshahi

    2012-01-01

    Full Text Available Patients with IgG4-related disease (IgG4-RD share histopathological characteristics that are similar across affected organs. The finding of infiltration with IgG4+ plasma cells in the proper clinical and histopathological contexts connects a large number of clinical entities that were viewed previously as separate conditions. The renal involvement in IgG4-RD is usually characterized by tubulointerstitial nephritis, but membranous nephropathy has also been reported to be one of the renal complications of IgG4-RD. The recent discovery that a high proportion of patients with idiopathic membranous nephropathy (IMN have IgG4 autoantibodies to the M-type phospholipase A2 receptor (PLA2R in the circulation and glomerular immune deposits, together with the profound IgG4 hypergammaglobulinemia and occasional reports of membranous nephropathy in IgG4-RD, raised the question of a common antigen. To assess the presence of anti-PLA2R antibody in patients with IgG4-RD, we screened sera from 28 IgG4-RD patients by immunoblot. None of the patients in this cohort had detectable circulating anti-PLA2R antibodies. This study suggests that despite some clinical and serological overlaps between IgG4-RD and IMN,anti-PLA2R antibodies do not play a role in the pathogenesis of IgG4-RD. Additional studies of IgG4-RD with evidence of membranous nephropathy are important to exclude any definite relationship.

  10. A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis.

    Science.gov (United States)

    Miyatani, Kozo; Saito, Hiroaki; Murakami, Yuki; Watanabe, Joji; Kuroda, Hirohiko; Matsunaga, Tomoyuki; Fukumoto, Yoji; Osaki, Tomohiro; Nakayama, Yuji; Umekita, Yoshihisa; Ikeguchi, Masahide

    2016-05-01

    IgG4-related disease is a newly defined disease characterized by elevated serum IgG4 levels and infiltration of affected organs by IgG4-positive plasma cells. Recently, increased IgG4 levels were reported to be closely related with malignancy. To assess the relationship between IgG4 and the progression of gastric cancer, we immunohistochemically stained in this study gastric cancer tissue samples for IgG4-positive cells using an anti-IgG4 antibody. In addition, pre- and postoperative serum concentrations of IgG4 were measured, using an enzyme-linked immunosorbent assay. In gastric cancer samples, the number of CD138-positive plasma cells was significantly lower and the number of IgG4-positive cells significantly higher than in non-cancerous gastric mucosa. The number of IgG4-positive cells was significantly correlated with gross tumor appearance, tumor depth, lymph node metastasis, venous invasion, and lymphatic invasion. Prognosis was significantly poorer in patients with a high number of IgG4-positive cells than in those with a low number. Multivariate analysis indicated that both the number of IgG4-positive cells and the depth of tumor invasion were independently prognostic of survival. In conclusion, in gastric cancer, the number of IgG4-positive cells is increased and this is closely associated with gastric cancer progression.

  11. [An IgG4-related pancreatitis mimicking an adenocarcinoma: A case report].

    Science.gov (United States)

    Courcet, Emilie; Beltjens, Françoise; Charon-Barra, Céline; Guy, France; Orry, David; Ghiringhelli, François; Arnould, Laurent

    2015-12-01

    Type 1 auto-immune pancreatitis (type 1 AIP) is the pancreatic manifestation of IgG4-related systemic disease (IgG4-RD). This disease has recently been individualized and is characterized by elevated serum IgG4 levels and extrapancreatic lesions with common histologic characteristic: dense infiltration of lymphocytes, IgG4-positive plasma cells and storiforme fibrosis. Obliterative phlebitis is frequently detected. The pancreas is frequently involved in this disease. As approach to the pancreas for histological examination is generally difficult, AIP is diagnosed using a combination of clinical, serological, morphological and histopathological features. In pseudotumoral cases, AIP can be misdiagnosed as pancreatic cancer. Since AIP responds dramatically to steroid therapy, accurate diagnosis of AIP can avoid unnecessary laparotomy or pancreatic resection. We report here a case of a patient who underwent surgery for presumed pancreatic cancer. The final diagnosis was type 1 AIP.

  12. IgG4 related sclerosing mastitis: expanding the morphological spectrum of IgG4 related diseases.

    Science.gov (United States)

    Chougule, Abhijit; Bal, Amanjit; Das, Ashim; Singh, Gurpreet

    2015-01-01

    IgG4 related disease (IgG4RD) is a recently recognised condition characterised by mass forming lesions associated with storiform fibrosis, obliterative phlebitis, lymphoplasmacytic infiltrate rich in IgG4 positive plasma cells and elevated serum IgG4 levels. Although rare, mammary involvement has been reported as IgG4 related sclerosing mastitis, the morphological counterpart of a growing family of IgG4 related diseases. A total of 17 cases belonging to mass forming benign inflammatory breast lesions such as plasma cell mastitis, granulomatous lobular mastitis, non-specific mastitis and inflammatory pseudotumour were investigated as a possible member of IgG4 related sclerosing mastitis. Clinical, radiological, histopathological and immunohistochemistry findings were noted in all cases. Cases diagnosed as inflammatory pseudotumour showed all the histopathological features of IgG4RD along with increased number of IgG4 positive plasma cells and IgG4/IgG ratio >40%. However, only a few IgG4 positive cells were seen in plasma cell mastitis, granulomatous lobular mastitis and non-specific mastitis cases. These cases also did not fulfill the morphological criteria for the diagnosis of IgG4 related diseases. IgG4RD should be excluded in plasma cell rich lesions diagnosed on core biopsies by IgG4 immunostaining. This can avoid unnecessary surgery as IgG4 related diseases respond to simple and effective steroid treatment.

  13. Heat sensitivity of porcine IgG.

    Science.gov (United States)

    Metzger, J J; Bourdieu, C; Rouze, P; Houdayer, M

    1975-09-01

    The sensitivity to heat of porcine IgG was studied. The serum from immunized pigs was heated at 56 degrees C for 30 min as for decomplementation. The elution pattern of the serum proteins on an agarose gel column showed a dramatic change with the appearance of a large peak of the gel-excluded material. This peak contained mainly IgG molecules which still retained its antibody activity. This fact points to misinterpretations which can easily occur in 7S and 19S antibody recognition during the porcine immune response. Correlation is suggested of this property with the large number of interheavy chain disulfide bridges present in porcine IgG.

  14. Histopathology of IgG4-Related Autoimmune Hepatitis and IgG4-Related Hepatopathy in IgG4-Related Disease.

    Science.gov (United States)

    Nakanuma, Yasuni; Ishizu, Yoji; Zen, Yoh; Harada, Kenichi; Umemura, Takeji

    2016-08-01

    Immunoglobulin G4-related disease (IgG4-RD) is a systemic disease involving many organs; it includes IgG4-related sclerosing cholangitis and inflammatory pseudotumor in the hepatobiliary system. Two types of hepatic parenchymal involvement have been reported in IgG4-RD: IgG4-related autoimmune hepatitis (AIH) and IgG4-hepatopathy. Moreover, only three cases of IgG4-related AIH have been reported. Immunoglobulin G4-related AIH is clinicopathologically similar to AIH, except for an elevated serum IgG4 level and heavy infiltration of IgG4-positive plasma cells in the liver tissue. Interestingly, IgG4-related AIH can be complicated by well-known IgG4-RD(s). Immunoglobulin G4-hepatopathy, which includes various histopathological lesions encountered in the liver of patients with type I autoimmune pancreatitis, is classified into five histological categories: portal inflammation, large bile duct damage, portal sclerosis, lobular hepatitis, and cholestasis. Immunoglobulin G4-hepatopathy is currently a collective term covering hepatic lesions primarily or secondarily related to IgG4-related sclerosing cholangitis and type 1 autoimmune pancreatitis. In conclusion, the liver is not immune to IgG4-RD, and at least two types of hepatic involvement in IgG4-RD have been reported: IgG4-related AIH and IgG4-hepatopathy. Additional studies are required to clarify their precise clinical significance with respect to IgG4-RD and inherent liver diseases. PMID:27466793

  15. Neuromyelitis optica IgG stimulates an immunological response in rat astrocyte cultures

    Institute of Scientific and Technical Information of China (English)

    Howe CL; Kaptzan T; Magaa SM; Ayers-Ringler JR; LaFrance-Corey RG; Lucchinetti CF

    2014-01-01

    Neuromyelitis optica (NMO) is a primary astrocyte disease associated with central nervous system inflammation, demyelination, and tissue injury. Brain lesions are frequently observed in regions enriched in expression of the aquaporin-4 (AQP4) water channel, an antigenic target of the NMO IgG serologic marker. Based on observations of disease reversibility and careful characterization of NMO lesion development, we propose that the NMO IgG may induce a dynamic immunological response in astrocytes. Using primary rat astrocyte-enriched cultures and treatment with NMO patient-derived serum or purified IgG, we observed a robust pattern of gene expression changes consistent with the induction of a reactive and inflammatory phenotype in astrocytes. The reactive astrocyte factor lipocalin-2 and a broad spectrum of chemokines, cytokines, and stress response factors were induced by either NMO patient serum or purified IgG. Treatment with IgG from healthy controls had no effect. The effect is disease-specific, as serum from patients with relapsing-remitting multiple sclerosis, Sj gren's, or systemic lupus erythematosus did not induce a response in the cultures. We hypothesize that binding of the NMO IgG to AQP4 induces a cellular response that results in transcriptional and translational events within the astrocyte that are consistent with a reactive and inflammatory phenotype. Strategies aimed at reducing the inflammatory response of astrocytes may short circuit an amplification loop associated with NMO lesion development.

  16. The Pathology of IgG4-Related Disease in the Bile Duct and Pancreas.

    Science.gov (United States)

    Zen, Yoh

    2016-08-01

    Immunoglobulin G4-related disease (IgG4-RD) in the pancreatobiliary system manifests as sclerosing cholangitis (SC), hepatic inflammatory pseudotumors, and type 1 autoimmune pancreatitis (AIP). The pathology of IgG4-RD involves an inflammatory process and fibrogenic pathway, the combination of which damages the affected organs. Fibroinflammatory injury is characterized by three microscopic findings: a diffuse lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, obliterative phlebitis, and storiform fibrosis. Although the diagnosis of IgG4-related pancreatocholangitis is relatively straightforward in surgical specimens, the current clinical requirement is to diagnose patients using biopsy samples, which remains challenging. Histological differential diagnoses include primary SC, follicular cholangitis/pancreatitis, SC with granulocytic epithelial lesions, and type 2 AIP. Although the massive infiltration of IgG4-positive plasma cells is a histological hallmark of IgG4-RD, many other immune cells (e.g., Th2 lymphocytes, regulatory T cells, and M2 macrophages) appear to be strongly involved in orchestral immune reactions. PMID:27466794

  17. Increased in vivo effector function of human IgG4 isotype antibodies through afucosylation.

    Science.gov (United States)

    Gong, Qian; Hazen, Meredith; Marshall, Brett; Crowell, Susan R; Ou, Qinglin; Wong, Athena W; Phung, Wilson; Vernes, Jean-Michel; Meng, Y Gloria; Tejada, Max; Andersen, Dana; Kelley, Robert F

    2016-01-01

    For some antibodies intended for use as human therapeutics, reduced effector function is desired to avoid toxicities that might be associated with depletion of target cells. Since effector function(s), including antibody-dependent cell-mediated cytotoxicity (ADCC), require the Fc portion to be glycosylated, reduced ADCC activity antibodies can be obtained through aglycosylation of the human IgG1 isotype. An alternative is to switch to an IgG4 isotype in which the glycosylated antibody is known to have reduced effector function relative to glycosylated IgG1 antibody. ADCC activity of glycosylated IgG1 antibodies is sensitive to the fucosylation status of the Fc glycan, with both in vitro and in vivo ADCC activity increased upon fucose removal ("afucosylation"). The effect of afucosylation on activity of IgG4 antibodies is less well characterized, but it has been shown to increase the in vitro ADCC activity of an anti-CD20 antibody. Here, we show that both in vitro and in vivo activity of anti-CD20 IgG4 isotype antibodies is increased via afucosylation. Using blends of material made in Chinese hamster ovary (CHO) and Fut8KO-CHO cells, we show that ADCC activity of an IgG4 version of an anti-human CD20 antibody is directly proportional to the fucose content. In mice transgenic for human FcγRIIIa, afucosylation of an IgG4 anti-mouse CD20 antibody increases the B cell depletion activity to a level approaching that of the mIgG2a antibody. PMID:27216702

  18. Neonatal Fc Receptor-Mediated IgG Transport Across Porcine Intestinal Epithelial Cells: Potentially Provide the Mucosal Protection.

    Science.gov (United States)

    Guo, Jinyue; Li, Fei; He, Qigai; Jin, Hui; Liu, Mei; Li, Shaowen; Hu, Sishun; Xiao, Yuncai; Bi, Dingren; Li, Zili

    2016-06-01

    It has been well characterized that piglets can absorb colostrum IgG across the intestine to neonatal bloodstream and a certain level of IgG has been found in the mucosal secretions of the porcine intestinal tract. However, little is known about how the maternal IgG transport across the intestinal barrier and how IgG enter the lumen of intestinal tract. In this study, we demonstrated that the porcine neonatal Fc receptor (pFcRn) was expressed in a model of normal porcine intestinal epithelial cells (IPEC-J2) as well as in kidney cells (PK-15), and pFcRn was mainly distributed in the apical side of the polarized IPEC-J2 cells. Analyzing the phylogenetic relatedness of this gene we found that swine and human neonatal Fc receptor (FcRn) amino acid sequence are closer than rodents. We also showed that pFcRn mediated bidirectional IgG transport across polarized IPEC-J2 cells and bound to IgG in a pH-dependent manner. Furthermore, pFcRn-transcytosed viral-specific IgG reduced the transmissible gastroenteritis virus (TGEV) yield from the luminal direction by a 50% tissue culture infective dose (TCID50) assay. Our results indicate that pFcRn-dependent bidirectional IgG transport across the intestinal epithelium plays critical role in the acquisition of humoral immunity in early life and in host defense at mucosal surfaces. PMID:26982157

  19. Erdheim-Chester Disease as a Mimic of IgG4-Related Disease: A Case Report and a Review of a Single-Center Cohort.

    Science.gov (United States)

    Gianfreda, Davide; Musetti, Claudio; Nicastro, Maria; Maritati, Federica; Cobelli, Rocco; Corradi, Domenico; Vaglio, Augusto

    2016-05-01

    Immunoglobulin-G4 (IgG4)-related disease (IgG4RD) is a fibro-inflammatory disorder characterized by tissue-infiltrating IgG4 plasma cells, and, often, high serum IgG4. Several autoimmune, infectious, or proliferative conditions mimic IgG4RD. Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterized by foamy histiocytic infiltration, fibrosis, and chronic inflammation. ECD and IgG4RD manifestations may overlap.A patient presented with huge fibrous retroperitoneal masses causing compression on neighboring structures; the case posed the challenge of the differential diagnosis between IgG4RD and ECD mainly because of a prominent serum and tissue IgG4 response.Retroperitoneal biopsy led to the diagnosis of ECD; the V600E BRAF mutation was found. Treatment with the BRAF inhibitor vemurafenib was started.Treatment failed to induce mass regression and the patient died after 3 months of therapy. Prompted by this case, we examined serum and tissue IgG4 in a series of 15 ECD patients evaluated at our center, and found that approximately one-fourth of the cases have increased IgG4 in the serum and often in the tissue.The differential diagnosis between IgG4RD and ECD can be challenging, as some ECD patients have prominent IgG4 responses. This suggests the possibility of common pathogenic mechanisms between ECD and IgG4RD. PMID:27227923

  20. Autoimmune pancreatitis metachronously associated with retroperitoneal fibrosis with IgG4-positive plasma cell infiltration

    Institute of Scientific and Technical Information of China (English)

    Terumi Kamisawa; Pong Yui Chen; Yuyang Tu; Hitoshi Nakajima; Naoto Egawa

    2006-01-01

    Retroperitoneal fibrosis is an uncommon disorder characterized by the formation of a dense plaque of fibrous tissue in the retroperitoneum, and its etiology remains unknown. Autoimmune pancreatitis is a rare type of chronic pancreatitis characterized by fibrosis with abundant infiltration of IgG4-positive plasma cells and lymphocytes and obliterative phlebitis in the pancreas. We present a case of autoimmune pancreatitis that developed 10 mo after the occurrence of retroperitoneal fibrosis. Histological findings of the resected retroperitoneal mass were marked periureteral fibrosis with abundant infiltration of IgG4-positive plasma cells and lymphocytes and obliterative phlebitis.These findings suggest a common pathophysiological mechanism for retroperitoneal fibrosis and autoimmune pancreatitis in this case. Some cases of retroperitoneal fibrosis might be a retroperitoneal lesion of IgG4-related sclerosing disease.

  1. Glycosylation of plasma IgG in colorectal cancer prognosis

    OpenAIRE

    Evropi Theodoratou; Kujtim Thaçi; Felix Agakov; Timofeeva, Maria N.; Jerko Štambuk; Maja Pučić-Baković; Frano Vučković; Peter Orchard; Anna Agakova; DIN, FARHAT V. N.; Ewan Brown; Rudd, Pauline M; Susan M. Farrington; Dunlop, Malcolm G; Harry Campbell

    2016-01-01

    In this study we demonstrate the potential value of Immunoglobulin G (IgG) glycosylation as a novel prognostic biomarker of colorectal cancer (CRC). We analysed plasma IgG glycans in 1229 CRC patients and correlated with survival outcomes. We assessed the predictive value of clinical algorithms and compared this to algorithms that also included glycan predictors. Decreased galactosylation, decreased sialylation (of fucosylated IgG glycan structures) and increased bisecting GlcNAc in IgG glyca...

  2. Diagnostic performance of serum IgG4 level for IgG4-related disease: a meta-analysis.

    Science.gov (United States)

    Xu, Wen-Long; Ling, Ying-Chun; Wang, Zhi-Kai; Deng, Fang

    2016-01-01

    An elevated serum IgG4 level is one of the most useful factors in the diagnosis of IgG4-related disease (IgG4-RD). In this study, we performed a meta-analysis of the published articles assessing the diagnostic accuracy of serum IgG4 concentrations for IgG4-RD. The databases of MEDLINE/PubMed, EMBASE and Web of Science were systematically searched for relevant studies. Sensitivities and specificities of serum IgG4 in each study were calculated, and the hierarchical summary receiver operating characteristic (HSROC) model with a random effects model were employed to obtain the individual and pooled estimates of sensitivities and specificities. In total, twenty-three studies comprising 6048 patients with IgG4-RD were included in the meta-analysis. The pooled sensitivity was 85% with a 95% confidence interval (CI) of 78-90%; the pooled specificity was 93% with a 95% CI of 90-95%. The HSROC curve for quantitative serum IgG4 lies closer to the upper left corner of the plot, and the area under the curve (AUC) was 0.95 (95% CI 0.93, 0.97), which suggested a high diagnostic accuracy of serum IgG4 for the entity of IgG4-RD. Our study suggests that serum IgG4 has high sensitivity and specificity in the diagnosis of IgG4-RD. PMID:27558881

  3. Unusual IgG4-related hypophysitis: one case report and analysis of clinicopathological characteristics

    Directory of Open Access Journals (Sweden)

    Zhen-qi LI

    2014-10-01

    Full Text Available Background Immunoglobulin G4 (IgG4-related disease is a recently characterized autoimmune disease entity marked by elevated serum IgG4 levels and tissue infiltration by IgG4-positive plasma cells in multiple involved organs. Hypophysitis is a rare inflammatory disorder and IgG4-related sclerosing disease involving the ituitary alone is especially rare. Imaging studies may reveal a mass lesion in the sellar area or a thickening of pituitary stalk, mimicking a pituitary tumor. Due to its rarity and non-specific appearance in radiological examination, it is a diagnostic challenge for clinicians and histopathologists to differentiate solitary IgG4-related hypophysitis from other pituitary lesions. The aim of this study is to summarize the clinicopathological features of unusual IgG4-related hypophysitis and discuss the differential diagnosis of histologically similar inflammatory lesions in pituitary. Methods The clinical manifestation of a patient with solitary IgG4-related hypophysitis was presented retrospectively. Resected mass was routinely paraffin-embedded and stained with Hematoxylin and Eosin. Dako EnVision immunohistochemical staining system was used to detect the tumor antigen expressions, including vimentin (Vim, S-100 protein (S-100, pan cytokeratin (PCK, epithelial membrane antigen (EMA, CD3, CD20, CD68, CD1a, κ-light chain, λ-light chain and progestrone receptor (PR.  Results A 47-year-old male patient presented with 1-year history of mild limb weakness and hyposexuality. Laboratory examination revealed hypopituitarism with low levels of serum testosterone, cortisol, luteinizing hormone (LH and follicle stimulating hormone (FSH, although his serum IgG4 level was high. MRI of the pituitary gland revealed a mass lesion in the sellar area with T1WI mild hyperintense and homogeneous enhancement after gadolinium administration. The patient underwent a transsphenoidal mass resection of the pituitary gland. Histological examination

  4. Use of IgG avidity ELISA to differentiate acute from persistent infection with Salmonella Dublin in cattle

    DEFF Research Database (Denmark)

    Hansen, K.R.; Nielsen, L.R.; Lind, Peter

    2006-01-01

    Aims: To investigate whether an immunoglobulin (Ig)G avidity ELISA can be used to differentiate between acute and persistent infection with Salmonella (S.) Dublin in cattle. To determine whether the IgG isotype, IgG(1) and IgG(2) responses in acute and persistent infections differ. Methods...... of persistent infection with S. Dublin in cattle, it can be concluded that the IgG-AI can aid in differentiating between acute and long-term infection on herd level. However, for the test to be useful as an alternative tool to repeated sampling over time for detection of persistently infected carriers during...... control strategies in cattle herds, the test needs to be optimized and studied further in a larger sample of well-characterized infections in cattle. The affinity of IgG(2) is higher than IgG(1) early in the S. Dublin infection. There appears to be no difference in the IgG(2)-AI between the acute...

  5. Simultaneous Quantification of Anticardiolipin IgG and IgM by Time Resolved Fluoroimmunoassay

    Science.gov (United States)

    Liu, Jie; Li, Mei; Ye, Yan; Chen, Yu

    2016-01-01

    The autoimmune disease antiphospholipid syndrome (APS) is characterized by the presence of anticardiolipin antibodies (aCL), along with anti-β2-glycoprotein I (β2GPI) antibodies and lupus anticoagulant (LA). In this study, we developed a time-resolved fluoroimmunoassay (TRFIA) system for simultaneous quantification of aCL IgG and IgM. A 96-well microtiter plate precoated with the complex of cardiolipin from bovine heart and bovine β2GPI was incubated with the anticardiolipin IgG and IgM standard substance or serum, and the conjugate of Eu3+-labeled anti-human IgG and Sm3+-labeled anti-human IgM was pipetted to the wells to form a tipical double-antibody-sandwich immunoreactions; finally the fluorescent intensity of Eu3+ and Sm3+ was detected to reflect the quantity of anticardiolipin IgG and IgM. This assay showed a good relationship between fluorescence intensities and the concentration of anticardiolipin antibody(aCL) IgG and IgM, with a low-end sensitivity of 0.1 U/ml for IgG and 0.1 U/ml for IgM, respectively. The intra- and inter-assay coefficients of variation (CV) of the calibrators was 3.0% and 4.51% for IgG, and 2.76% and 4.45% for IgM. The average recovery was 100.38% for aCL IgG and 100.45% for aCL IgM. For serum samples, the results of our method showed a good correlation with those obtained with ELISA kit. Simultaneous detection of aCL-IgG and aCL-IgM in the same reaction well can optimize assay performance by avoiding potential influence of different reaction conditions-timing, and well-to-well difference in concentration and characteristics of cardiolipin antigen. The results of a combo aCL-IgG and aCL-IgM assay for the same sample are more consistent and more reliable. This dual-label time-resolved fluoroimmunoassay is sensitive for detecting aCL IgG and IgM across a wide concentration range with stable reagents and may assist in the clinical diagnosis of antiphospholipid syndrome. PMID:27661084

  6. The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies.

    Science.gov (United States)

    Lewis, Melanie J; Wagner, Bettina; Woof, Jenny M

    2008-02-01

    Recombinant versions of the seven equine IgG subclasses were expressed in CHO cells. All assembled into intact immunoglobulins stabilised by disulphide bridges, although, reminiscent of human IgG4, a small proportion of equine IgG4 and IgG7 were held together by non-covalent bonds alone. All seven IgGs were N-glycosylated. In addition IgG3 appeared to be O-glycosylated and could bind the lectin jacalin. Staphylococcal protein A displayed weak binding for the equine IgGs in the order: IgG1>IgG3>IgG4>IgG7>IgG2=IgG5>IgG6. Streptococcal protein G bound strongly to IgG1, IgG4 and IgG7, moderately to IgG3, weakly to IgG2 and IgG6, and not at all to IgG5. Analysis of antibody effector functions revealed that IgG1, IgG3, IgG4, IgG5 and IgG7, but not IgG2 and IgG6, were able to elicit a strong respiratory burst from equine peripheral blood leukocytes, predicting that the former five IgG subclasses are able to interact with Fc receptors on effector cells. IgG1, IgG3, IgG4 and IgG7, but not IgG2, IgG5 and IgG6, were able to bind complement C1q and activate complement via the classical pathway. The differential effector function capabilities of the subclasses suggest that, for maximum efficacy, equine vaccine strategies should seek to elicit antibody responses of the IgG1, IgG3, IgG4, and IgG7 subclasses. PMID:17669496

  7. Pseudotumors due to IgG4 immune-complex tubulointerstitial nephritis associated with autoimmune pancreatocentric disease.

    Science.gov (United States)

    Cornell, Lynn D; Chicano, Sonia L; Deshpande, Vikram; Collins, A Bernard; Selig, Martin K; Lauwers, Gregory Y; Barisoni, Laura; Colvin, Robert B

    2007-10-01

    Autoimmune pancreatitis (AIP) is a mass-forming chronic fibroinflammatory condition centered on the pancreatobiliary system and characterized by predominant immunoglobulin G4 (IgG4)-positive plasma cells. Recent reports have brought to light the multiorgan involvement of this disease. We describe a series of 5 cases of tubulointerstitial nephritis (TIN) associated with AIP and characterize the clinical, pathologic, ultrastructural, and immunopathologic features of TIN. The specimens consisted of 4 biopsies and 1 nephrectomy. The average patient age was 64 years (range 45 to 78) and the male to female ratio was 4:1. All had histologic and/or clinical and radiographic evidence of AIP, mass-forming sclerosing cholangitis, or both. The clinical impression in 4 patients was a renal mass or vasculitis. Two patients had renal insufficiency. Histologic preparations revealed a dense tubulointerstitial lymphoplasmacytic infiltrate. Eosinophils were often numerous. Tubulitis and tubular injury were present, along with tubular atrophy with focally thickened tubular basement membranes (TBMs). The histologic appearance ranged from a cellular, inflammatory pattern without tubular atrophy to a striking expansive interstitial fibrosis with tubular destruction. The nephrectomy specimen demonstrated a masslike nodular pattern of inflammation with normal renal tissue elsewhere. Glomeruli were uninvolved. By immunohistochemistry or immunofluorescence, numerous plasma cells in the infiltrate were positive for IgG4. TBM granular IgG deposits, predominantly of the IgG4 subclass, were detected in 4 of 5 cases by either immunofluorescence or immunohistochemistry. By electron microscopy, corresponding amorphous electron-dense deposits were present in the TBM in these cases. This type of TIN, typically characterized by a masslike lesion consisting of a lymphoplasmacytic infiltrate with eosinophils and prominent IgG4-positive plasma cells and immune-complex deposits in the TBM, may be part of

  8. Pseudotumors due to IgG4 immune-complex tubulointerstitial nephritis associated with autoimmune pancreatocentric disease.

    Science.gov (United States)

    Cornell, Lynn D; Chicano, Sonia L; Deshpande, Vikram; Collins, A Bernard; Selig, Martin K; Lauwers, Gregory Y; Barisoni, Laura; Colvin, Robert B

    2007-10-01

    Autoimmune pancreatitis (AIP) is a mass-forming chronic fibroinflammatory condition centered on the pancreatobiliary system and characterized by predominant immunoglobulin G4 (IgG4)-positive plasma cells. Recent reports have brought to light the multiorgan involvement of this disease. We describe a series of 5 cases of tubulointerstitial nephritis (TIN) associated with AIP and characterize the clinical, pathologic, ultrastructural, and immunopathologic features of TIN. The specimens consisted of 4 biopsies and 1 nephrectomy. The average patient age was 64 years (range 45 to 78) and the male to female ratio was 4:1. All had histologic and/or clinical and radiographic evidence of AIP, mass-forming sclerosing cholangitis, or both. The clinical impression in 4 patients was a renal mass or vasculitis. Two patients had renal insufficiency. Histologic preparations revealed a dense tubulointerstitial lymphoplasmacytic infiltrate. Eosinophils were often numerous. Tubulitis and tubular injury were present, along with tubular atrophy with focally thickened tubular basement membranes (TBMs). The histologic appearance ranged from a cellular, inflammatory pattern without tubular atrophy to a striking expansive interstitial fibrosis with tubular destruction. The nephrectomy specimen demonstrated a masslike nodular pattern of inflammation with normal renal tissue elsewhere. Glomeruli were uninvolved. By immunohistochemistry or immunofluorescence, numerous plasma cells in the infiltrate were positive for IgG4. TBM granular IgG deposits, predominantly of the IgG4 subclass, were detected in 4 of 5 cases by either immunofluorescence or immunohistochemistry. By electron microscopy, corresponding amorphous electron-dense deposits were present in the TBM in these cases. This type of TIN, typically characterized by a masslike lesion consisting of a lymphoplasmacytic infiltrate with eosinophils and prominent IgG4-positive plasma cells and immune-complex deposits in the TBM, may be part of

  9. In-depth analysis of subclass-specific conformational preferences of IgG antibodies

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    Xinsheng Tian

    2015-01-01

    Full Text Available IgG subclass-specific differences in biological function and in vitro stability are often referred to variations in the conformational flexibility, while this flexibility has rarely been characterized. Here, small-angle X-ray scattering data from IgG1, IgG2 and IgG4 antibodies, which were designed with identical variable regions, were thoroughly analysed by the ensemble optimization method. The extended analysis of the optimized ensembles through shape clustering reveals distinct subclass-specific conformational preferences, which provide new insights for understanding the variations in physical/chemical stability and biological function of therapeutic antibodies. Importantly, the way that specific differences in the linker region correlate with the solution structure of intact antibodies is revealed, thereby visualizing future potential for the rational design of antibodies with designated physicochemical properties and tailored effector functions. In addition, this advanced computational approach is applicable to other flexible multi-domain systems and extends the potential for investigating flexibility in solutions of macromolecules by small-angle X-ray scattering.

  10. IgG glycosylation changes and MBL2 polymorphisms

    DEFF Research Database (Denmark)

    Troelsen, Lone N; Jacobsen, Søren; Abrahams, Jodie L;

    2012-01-01

    To examine whether IgG glycosylation changes and MBL2 genotypes are associated with systemic inflammation and joint destruction in rheumatoid arthritis (RA).......To examine whether IgG glycosylation changes and MBL2 genotypes are associated with systemic inflammation and joint destruction in rheumatoid arthritis (RA)....

  11. Clinical study on IgG4-related autoimmune pancreatitis

    Institute of Scientific and Technical Information of China (English)

    吴庆军

    2013-01-01

    Objective To investigate the clinical features of IgG4-related autoimmune pancreatitis(IgG4-related AIP). Methods A prospective cohort study on IgG4 related disease(IgG4-RD) was carried out in Peking Union Medical College Hospital during December 2010 to June

  12. IgG4-Seronegative Autoimmune Pancreatitis and Sclerosing Cholangitis

    Directory of Open Access Journals (Sweden)

    Allon Kahn

    2015-01-01

    Full Text Available IgG4-related disease is a relatively novel clinical entity whose gastrointestinal manifestations include type 1 autoimmune pancreatitis (AIP and IgG4-associated sclerosing cholangitis. The presence of elevated serum IgG4 is suggestive but not essential for the diagnosis of type 1 AIP and is a pervasive feature of the proposed diagnostic criteria. The differential diagnosis of type 1 AIP includes malignant conditions, emphasizing the importance of a deliberate, comprehensive evaluation. Management of patients with a suggestive clinical presentation, but without serum IgG4 elevation, is difficult. Here we present three cases of IgG4-seronegative AIP and sclerosing cholangitis that responded to empiric steroid therapy and discuss approach considerations. These cases demonstrate the value of meticulous application of existing diagnostic algorithms to achieve a clinical diagnosis and avoid surgical intervention.

  13. IgG transport across mucosal barriers by neonatal Fc receptor for IgG and mucosal immunity.

    Science.gov (United States)

    Yoshida, Masaru; Masuda, Atsuhiro; Kuo, Timothy T; Kobayashi, Kanna; Claypool, Steven M; Takagawa, Tetsuya; Kutsumi, Hiromu; Azuma, Takeshi; Lencer, Wayne I; Blumberg, Richard S

    2006-12-01

    Mucosal secretions of the human gastrointestinal, respiratory, and genital tracts contain significant quantities of IgG. The neonatal Fc receptor for IgG (FcRn) plays a major role in regulating host IgG levels and transporting IgG and associated antigens across polarized epithelial barriers. The FcRn can then recycle the IgG/antigen complex back across the intestinal barrier into the lamina propria for processing by dendritic cells and presentation to CD4(+) T cells in regional organized lymphoid structures. FcRn, through its ability to secrete and absorb IgG, thus integrates luminal antigen encounters with systemic immune compartments and, as such, provides essential host defense and immunoregulatory functions at the mucosal surfaces. PMID:17051393

  14. [IgG4-related kidney disease. Diagnosis and treatment].

    Science.gov (United States)

    Kawano, Mitsuhiro; Mizushima, Ichiro; Yamada, Kazunori; Taniguchi, Yoshinori; Saeki, Takako

    2015-01-01

    IgG4-related disease (IgG4-RD) is a systemic inflammatory disorder that can affect most organs/tissues like sarcoidosis. The kidney is one of the most frequently affected organs. While tubulointerstitial nephritis (TIN) with characteristic imaging findings is the representative lesion of IgG4-related kidney disease (IgG4-RKD), a variety of glomerular lesions, particularly membranous nephropathy, sometimes overlap on TIN. Clinically, either decreased renal function and/or characteristic imaging findings such as multiple low-density lesions on contrast-enhanced computed tomography are typical presenting features. Histologically, plasma cell (PC)-rich TIN accompanied by characteristic fibrosis called storiform fibrosis with dense IgG4-positive PC infiltration is a typical finding. Although a swift response to corticosteroid is a very important feature of IgG4-RKD, in cases with moderately to severely decreased renal function before therapy, only partial recovery of renal function is obtained. This review provides a comprehensive overview of IgG4-RKD from the clinical, laboratory, imaging, and histological aspects and also addresses some of the therapeutic issues concerning it.

  15. Production of biologically active IgG hinge-tag soluble epidermal growth factor receptors (ErbB).

    Science.gov (United States)

    Otani, Takayuki; Hashizume, Toshihiro; Nagaoka, Tadahiro; Fukuda, Tomoko; Tang, Careen K; Salomon, David S; Seno, Masaharu

    2010-03-01

    The extracellular domains (ECD) of epidermal growth factor receptors, ErbB1, 2, 3 and 4, were designed as soluble dimeric forms. Each ECD was fused to a short hinge region derived from IgG, such that the stable dimer could be formed with disulfide bridges. This hinge-tagged design minimized the molecular weight to approximately 50% of the conventional Fc-fusion design without an Fc domain of IgG. The refolded dimers could be easily analyzed and characterized by SDS-PAGE. Hinge-tagged soluble ErbBs demonstrated significant affinity for betacellulin and heregulin. The IgG hinge-tag should be a simple method to design soluble dimers that would be useful for high throughput screening of ligands, antagonists or derivatives.

  16. Indel Group in Genomes (IGG) Molecular Genetic Markers.

    Science.gov (United States)

    Toal, Ted W; Burkart-Waco, Diana; Howell, Tyson; Ron, Mily; Kuppu, Sundaram; Britt, Anne; Chetelat, Roger; Brady, Siobhan M

    2016-09-01

    Genetic markers are essential when developing or working with genetically variable populations. Indel Group in Genomes (IGG) markers are primer pairs that amplify single-locus sequences that differ in size for two or more alleles. They are attractive for their ease of use for rapid genotyping and their codominant nature. Here, we describe a heuristic algorithm that uses a k-mer-based approach to search two or more genome sequences to locate polymorphic regions suitable for designing candidate IGG marker primers. As input to the IGG pipeline software, the user provides genome sequences and the desired amplicon sizes and size differences. Primer sequences flanking polymorphic insertions/deletions are produced as output. IGG marker files for three sets of genomes, Solanum lycopersicum/Solanum pennellii, Arabidopsis (Arabidopsis thaliana) Columbia-0/Landsberg erecta-0 accessions, and S. lycopersicum/S. pennellii/Solanum tuberosum (three-way polymorphic) are included. PMID:27436831

  17. Indel Group in Genomes (IGG) Molecular Genetic Markers1[OPEN

    Science.gov (United States)

    Burkart-Waco, Diana; Kuppu, Sundaram; Britt, Anne; Chetelat, Roger

    2016-01-01

    Genetic markers are essential when developing or working with genetically variable populations. Indel Group in Genomes (IGG) markers are primer pairs that amplify single-locus sequences that differ in size for two or more alleles. They are attractive for their ease of use for rapid genotyping and their codominant nature. Here, we describe a heuristic algorithm that uses a k-mer-based approach to search two or more genome sequences to locate polymorphic regions suitable for designing candidate IGG marker primers. As input to the IGG pipeline software, the user provides genome sequences and the desired amplicon sizes and size differences. Primer sequences flanking polymorphic insertions/deletions are produced as output. IGG marker files for three sets of genomes, Solanum lycopersicum/Solanum pennellii, Arabidopsis (Arabidopsis thaliana) Columbia-0/Landsberg erecta-0 accessions, and S. lycopersicum/S. pennellii/Solanum tuberosum (three-way polymorphic) are included. PMID:27436831

  18. Large vessel involvement by IgG4-related disease

    Science.gov (United States)

    Perugino, Cory A.; Wallace, Zachary S.; Meyersohn, Nandini; Oliveira, George; Stone, James R.; Stone, John H.

    2016-01-01

    Abstract Objectives: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect multiple organs and lead to tumefactive, tissue-destructive lesions. Reports have described inflammatory aortitis and periaortitis, the latter in the setting of retroperitoneal fibrosis (RPF), but have not distinguished adequately between these 2 manifestations. The frequency, radiologic features, and response of vascular complications to B cell depletion remain poorly defined. We describe the clinical features, radiology findings, and treatment response in a cohort of 36 patients with IgG4-RD affecting large blood vessels. Methods: Clinical records of all patients diagnosed with IgG4-RD in our center were reviewed. All radiologic studies were reviewed. We distinguished between primary large blood vessel inflammation and secondary vascular involvement. Primary involvement was defined as inflammation in the blood vessel wall as a principal focus of disease. Secondary vascular involvement was defined as disease caused by the effects of adjacent inflammation on the blood vessel wall. Results: Of the 160 IgG4-RD patients in this cohort, 36 (22.5%) had large-vessel involvement. The mean age at disease onset of the patients with large-vessel IgG4-RD was 54.6 years. Twenty-eight patients (78%) were male and 8 (22%) were female. Thirteen patients (36%) had primary IgG4-related vasculitis and aortitis with aneurysm formation comprised the most common manifestation. This affected 5.6% of the entire IgG4-RD cohort and was observed in the thoracic aorta in 8 patients, the abdominal aorta in 4, and both the thoracic and abdominal aorta in 3. Three of these aneurysms were complicated by aortic dissection or contained perforation. Periaortitis secondary to RPF accounted for 27 of 29 patients (93%) of secondary vascular involvement by IgG4-RD. Only 5 patients demonstrated evidence of both primary and secondary blood vessel involvement. Of those treated with

  19. IgG Placental Transfer in Healthy and Pathological Pregnancies

    Directory of Open Access Journals (Sweden)

    Patricia Palmeira

    2012-01-01

    Full Text Available Placental transfer of maternal IgG antibodies to the fetus is an important mechanism that provides protection to the infant while his/her humoral response is inefficient. IgG is the only antibody class that significantly crosses the human placenta. This crossing is mediated by FcRn expressed on syncytiotrophoblast cells. There is evidence that IgG transfer depends on the following: (i maternal levels of total IgG and specific antibodies, (ii gestational age, (iii placental integrity, (iv IgG subclass, and (v nature of antigen, being more intense for thymus-dependent ones. These features represent the basis for maternal immunization strategies aimed at protecting newborns against neonatal and infantile infectious diseases. In some situations, such as mothers with primary immunodeficiencies, exogenous IgG acquired by intravenous immunoglobulin therapy crosses the placenta in similar patterns to endogenous immunoglobulins and may also protect the offspring from infections in early life. Inversely, harmful autoantibodies may cross the placenta and cause transitory autoimmune disease in the neonate.

  20. Estimation of anti-D IgG in red blood cell eluates using the specific radioactivity of 125I-labeled IgG: effect of unlabeled, cytophilic IgG

    Energy Technology Data Exchange (ETDEWEB)

    Masouredis, S.P.; Mahan, L.C.; Sudora, E.J.; Langley, J.W.; Victoria, E.J.

    1981-01-01

    The specific radioactivity of conventionally prepared 125I IgG anti-D eluates is significantly less (from 1/5 to 1/20) than that of the 125I IgG fraction used to prepare the eluate. This discrepancy is due to the release of unlabeled, cytophilic IgG from normal red blood cells during eluate preparation and does not represent an underestimation of the eluate anti-D IgG content. Cytophilic IgG content of eluates plays an important role in reducing the nonimmunologic binding of labeled antibody IgG. The results justify the assumption used in numerous studies that the specific radioactivity of 125I IgG fractions can be used to provide a valid estimate of the anti-D IgG content of eluates.

  1. Results from an inter-laboratory comparison of pneumococcal serotype-specific IgG measurement and critical parameters that affect assay performance.

    Science.gov (United States)

    Balloch, A; Licciardi, P V; Leach, A; Nurkka, A; Tang, M L K

    2010-02-01

    Quantitation of specific IgG to polysaccharides (serotypes) of Streptococcus pneumoniae provides the basis for evaluating vaccine efficacy. Different enzyme-linked immunosorbent assay (ELISA) methods are used internationally, making comparisons between laboratories difficult. We undertook an inter-laboratory comparison between two international laboratories performing serotype-specific IgG ELISAs using a panel of well-characterized serum samples: the Murdoch Childrens Research Institute Pneumococcal Laboratory (Melbourne, Australia) and the Vaccine Immunology Laboratory, National Public Health Institute (Helsinki, Finland). While good agreement was found for the inter-laboratory comparison for most serotypes, differences in ELISA methodology influenced specific IgG measurement. Therefore, use of the World Health Organization (WHO)-based ELISA methods for measurement of serotype-specific IgG is reliable, accurate and provides consistent results between international laboratories.

  2. Does the Maternal Serum IgG Level during Pregnancy in Primary Antibody Deficiency Influence the IgG Level in the Newborn?

    Directory of Open Access Journals (Sweden)

    Vasantha Nagendran

    2015-01-01

    Full Text Available Purpose. To find out if the serum IgG level in the newborn baby was affected by low maternal serum IgG during pregnancy in two newly diagnosed primary antibody deficient patients. Method. Infant cord blood IgG level was compared with maternal IgG level in 2 mothers with newly diagnosed primary antibody deficiency, who declined replacement IgG treatment during pregnancy. Results. Both mothers delivered healthy babies with normal IgG levels at birth. Conclusions. The normal IgG levels and sound health in these 2 babies in spite of low maternal IgG throughout pregnancy raise interesting discussion points about maternofoetal immunoglobulin transport mechanisms in primary antibody deficiency.

  3. In a SLE mouse model the production of IgG autoantibody requires expression of activation-induced deaminase in early developing B cells

    Science.gov (United States)

    Umiker, Benjamin R.; McDonald, Gabrielle; Larbi, Amma; Medina, Carlos O.; Reth, Michael; Imanishi-Kari, Thereza

    2014-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the presence of pathogenic IgG anti-nuclear antibodies. Pathogenic IgG autoantibody production requires B-cell activation, leading to the production of activation-induced deaminase (AID) and class switching of IgM genes to IgG. To understand how and when B cells are activated to produce these IgG autoantibodies, we studied cells from 564Igi, a mouse model of SLE. 564Igi mice develop a disease profile closely resembling that found in human SLE patients, including the presence of IgG anti-nucleic acid antibodies. We have generated 564Igi mice that conditionally express an activation-induced cytidine deaminase transgene (Aicdatg), either in all B cells or only in mature B cells. Here we show that class-switched pathogenic IgG autoantibodies were produced only in 564Igi mice in which AID was functional in early developing B cells, resulting in loss of tolerance. Furthermore, we show that the absence of AID in early developing B cells also results in increased production of self-reactive IgM, indicating that AID, through somatic hypermutation (SHM), contributes to tolerance. Our results suggest that the pathophysiology of clinical SLE might also be dependent on AID expression in early developing B cells. PMID:25044405

  4. 418 Frequency of Food Hypersensitivity Mediated by IGG in Patients Received in a Venezuelan Laboratory During 2011

    OpenAIRE

    Lic, Cristina Najm; Benarroch, Lorena; Camacho, Natacha; Figueroa, Daniela; Guzmán, Jhonarly; Perdomo, Angel; García, Nirsen; Silva, Noel A.

    2012-01-01

    Background Foods could cause adverse reactions, which manifested with similar symptoms that could complicate the diagnosis, that is, gastrointestinal disease, rashes, edema, eczema, asthma, anaphylaxis, others; these reactions may be mediated or not by immunological processes. In the past years there were many research studies related with different types of immunological reactions, like for example those mediated by IgG, which are characterized with delayed and insidious manifestations. Thes...

  5. On the perplexingly low rate of transport of IgG2 across the human placenta.

    Directory of Open Access Journals (Sweden)

    Helga K Einarsdottir

    Full Text Available The neonatal receptor, FcRn, mediates both serum half-life extension as well as active transport of maternal IgG to the fetus during pregnancy. Therefore, transport efficiency and half-life go hand-in-hand. However, while the half-life of the human IgG2 subclass is comparable to IgG1, the placental transport of IgG2 is not, with the neonatal IgG1 levels generally exceeding maternal levels at birth, but not for IgG2. We hypothesized that the unique short-hinged structure of IgG2, which enables its κ-, but not λ-isotype to form at least three different structural isoforms, might be a contributing factor to these differences. To investigate whether there was any preference for either light chain, we measured placental transport of IgG subclasses as well as κ/λ-light chain isotypes of IgG1 and IgG2 in 27 matched mother-child pairs. We also studied the half-life of IgG1 and IgG2 light chain isotypes in mice, as well as that of synthesized IgG2 structural isotypes κA and κB. In order to investigate serum clearance of IgG1 and IgG2 light-chain isotypes in humans, we quantified the relative proportions of IgG1 and IgG2 light chains in hypogammaglobulinemia patients four weeks after IVIg infusion and compared to the original IVIg isotype composition. None of our results indicate any light chain preference in either of the FcRn mediated mechanisms; half-life extension or maternal transport.

  6. Recurrent Mastoiditis Mimics IgG4 Related Disease: A Potential Diagnostic Pitfall.

    Science.gov (United States)

    Deshpande, Vikram; Zane, Nicolas A; Kraft, Stefan; Stone, John H; Faquin, William C

    2016-09-01

    IgG4-related disease (IgG4-RD) is a recently recognized entity that causes progressive fibrosis and formation of mass lesions. IgG4-RD can be diagnosed histologically by its hallmarks of storiform fibrosis, prominent lymphoplasmacytic infiltrate, and obliterative phlebitis, accompanied by the infiltration of excessive numbers of IgG4-positive plasma cells as well as elevations in serum IgG4 concentrations. A recent publication reported a case of IgG4-RD in the mastoid sinus, representing a new anatomic location for this disease. We report two additional cases of IgG4-RD occurring in the mastoid and causing clinical mastoiditis. The presenting symptoms were varied-tinnitus, hearing loss, and cranial nerve palsies. All three cases showed a dense lymphoplasmacytic infiltrate, storiform type fibrosis as well as elevated numbers of IgG4 positive plasma cells. The three patients responded to immunosuppressive therapy that included steroids and Rituximab. We further investigated 162 consecutive mastoiditis cases at our institution in order to determine the frequency of IgG4-RD as a previously unrecognized cause of mastoiditis. Within this latter cohort we identified nine cases of mastoiditis that had two of the histologic features of IgG4-RD, specifically storiform fibrosis and a dense lymphoplasmacytic infiltrate. Two of these cases showed >50 IgG4-positive plasma cells per high-power field with IgG4-IgG ratio of >40 %, thus fulfilling histological criteria for IgG4-RD. However, both were due to severe acute or chronic infection. In conclusion, we reaffirm IgG4 related mastoiditis as a distinct but uncommon cause of recurrent mastoiditis. The diagnosis of IgG4-related mastoiditis should be rendered with caution, and only after the exclusion of potential mimickers, particularly infection. PMID:27091207

  7. Molecular recognition of antibody (IgG) by cellular Fc receptor (FcRI).

    Science.gov (United States)

    Burton, D R; Jefferis, R; Partridge, L J; Woof, J M

    1988-11-01

    Earlier studies from this and other laboratories have provided indirect evidence for the involvement of the C gamma 2 domain of human IgG in the binding of IgG to the high affinity monocyte Fc receptor (FcRI). Two approaches have been used to extend these studies and to further localize the site of interaction on human IgG. Firstly, monoclonal antibodies (MAbs) directed against different epitopes on IgG were assayed for their capacity to inhibit the binding of radiolabelled IgG to human monocytes or U937 cells. The capacity of the MAbs to interact with their respective epitopes on FcR-bound IgG was also studied using indirect radiobinding and immunofluorescence assays. Secondly, a number of IgGs from several different species and fragments of human IgGs were assayed for their ability to inhibit the binding of radiolabelled IgG to human monocytes. The amino acid sequences of those IgGs exhibiting relatively tight, intermediate or weak binding to monocyte FcRs were compared. On the basis of these studies a possible monocyte FcR-binding site on human IgG is postulated, involving the lower hinge region of IgG (residues Leu 234-Ser 239) with possible involvement of the nearby N-proximal bend and two beta-strands (Gly 316-Lys 338). PMID:2975762

  8. Anaplasma marginale infection with persistent high-load bacteremia induces a dysfunctional memory CD4+ T lymphocyte response but sustained high IgG titers

    Science.gov (United States)

    Control of blood-borne infections is dependent on antigen-specific effector and memory T cells and high-affinity IgG responses. In chronic infections characterized by a high antigen load, it has been shown that antigen-specific T and B cells are vulnerable to downregulation and apoptosis. Anaplasma ...

  9. The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity

    Science.gov (United States)

    Abdiche, Yasmina Noubia; Yeung, Yik Andy; Chaparro-Riggers, Javier; Barman, Ishita; Strop, Pavel; Chin, Sherman Michael; Pham, Amber; Bolton, Gary; McDonough, Dan; Lindquist, Kevin; Pons, Jaume; Rajpal, Arvind

    2015-01-01

    The neonatal Fc receptor (FcRn) is expressed by cells of epithelial, endothelial and myeloid lineages and performs multiple roles in adaptive immunity. Characterizing the FcRn/IgG interaction is fundamental to designing therapeutic antibodies because IgGs with moderately increased binding affinities for FcRn exhibit superior serum half-lives and efficacy. It has been hypothesized that 2 FcRn molecules bind an IgG homodimer with disparate affinities, yet their affinity constants are inconsistent across the literature. Using surface plasmon resonance biosensor assays that eliminated confounding experimental artifacts, we present data supporting an alternate hypothesis: 2 FcRn molecules saturate an IgG homodimer with identical affinities at independent sites, consistent with the symmetrical arrangement of the FcRn/Fc complex observed in the crystal structure published by Burmeister et al. in 1994. We find that human FcRn binds human IgG1 with an equilibrium dissociation constant (KD) of 760 ± 60 nM (N = 14) at 25°C and pH 5.8, and shows less than 25% variation across the other human subtypes. Human IgG1 binds cynomolgus monkey FcRn with a 2-fold higher affinity than human FcRn, and binds both mouse and rat FcRn with a 10-fold higher affinity than human FcRn. FcRn/IgG interactions from multiple species show less than a 2-fold weaker affinity at 37°C than at 25°C and appear independent of an IgG's variable region. Our in vivo data in mouse and rat models demonstrate that both affinity and avidity influence an IgG's serum half-life, which should be considered when choosing animals, especially transgenic systems, as surrogates. PMID:25658443

  10. Performance Evaluation of the VIDAS(®) Measles IgG Assay and Its Diagnostic Value for Measuring IgG Antibody Avidity in Measles Virus Infection.

    Science.gov (United States)

    Dina, Julia; Creveuil, Christian; Gouarin, Stephanie; Viron, Florent; Hebert, Amelie; Freymuth, Francois; Vabret, Astrid

    2016-01-01

    The objective of this study is primarily to compare the performance of the VIDAS(®) Measles immunoglobulin (Ig)G assay to that of two other serological assays using an immunoassay technique, Enzygnost(®) Anti-measles Virus/IgG (Siemens) and Measles IgG CAPTURE EIA(®) (Microimmune). The sensitivity and the agreement of the VIDAS(®) Measles IgG assay compared to the Enzygnost(®) Anti-measles Virus/IgG assay and the Measles IgG CAPTURE EIA(®) assay are 100%, 97.2% and 99.0%, 98.4%, respectively. The very low number of negative sera for IgG antibodies does not allow calculation of specificity. As a secondary objective, we have evaluated the ability of the VIDAS(®) Measles IgG assay to measure anti-measles virus IgG antibody avidity with the help of the VIDAS(®) CMV IgG Avidity reagent, using 76 sera from subjects with measles and 238 other sera. Different groups of populations were analyzed. In the primary infection measles group, the mean IgG avidity index was 0.16 (range of 0.07 to 0.93) compared to 0.79 (range of 0.25 to 1) in the serum group positive for IgG antibodies and negative for IgM. These data allow to define a weak anti-measles virus IgG antibody avidity as an avidity index (AI) AI > 0.6. The VIDAS(®) Measles IgG assay has a performance equivalent to that of other available products. Its use, individual and quick, is well adapted to testing for anti-measles immunity in exposed subjects. PMID:27556477

  11. Performance Evaluation of the VIDAS® Measles IgG Assay and Its Diagnostic Value for Measuring IgG Antibody Avidity in Measles Virus Infection

    Science.gov (United States)

    Dina, Julia; Creveuil, Christian; Gouarin, Stephanie; Viron, Florent; Hebert, Amelie; Freymuth, Francois; Vabret, Astrid

    2016-01-01

    The objective of this study is primarily to compare the performance of the VIDAS® Measles immunoglobulin (Ig)G assay to that of two other serological assays using an immunoassay technique, Enzygnost® Anti-measles Virus/IgG (Siemens) and Measles IgG CAPTURE EIA® (Microimmune). The sensitivity and the agreement of the VIDAS® Measles IgG assay compared to the Enzygnost® Anti-measles Virus/IgG assay and the Measles IgG CAPTURE EIA® assay are 100%, 97.2% and 99.0%, 98.4%, respectively. The very low number of negative sera for IgG antibodies does not allow calculation of specificity. As a secondary objective, we have evaluated the ability of the VIDAS® Measles IgG assay to measure anti-measles virus IgG antibody avidity with the help of the VIDAS® CMV IgG Avidity reagent, using 76 sera from subjects with measles and 238 other sera. Different groups of populations were analyzed. In the primary infection measles group, the mean IgG avidity index was 0.16 (range of 0.07 to 0.93) compared to 0.79 (range of 0.25 to 1) in the serum group positive for IgG antibodies and negative for IgM. These data allow to define a weak anti-measles virus IgG antibody avidity as an avidity index (AI) AI > 0.6. The VIDAS® Measles IgG assay has a performance equivalent to that of other available products. Its use, individual and quick, is well adapted to testing for anti-measles immunity in exposed subjects. PMID:27556477

  12. Genetic and infectious profiles influence cerebrospinal fluid IgG abnormality in Japanese multiple sclerosis patients.

    Directory of Open Access Journals (Sweden)

    Satoshi Yoshimura

    Full Text Available BACKGROUND: Abnormal intrathecal synthesis of IgG, reflected by cerebrospinal fluid (CSF oligoclonal IgG bands (OBs and increased IgG index, is much less frequently observed in Japanese multiple sclerosis (MS cohorts compared with Western cohorts. We aimed to clarify whether genetic and common infectious backgrounds influence CSF IgG abnormality in Japanese MS patients. METHODOLOGY: We analyzed HLA-DRB1 alleles, and IgG antibodies against Chlamydia pneumoniae, Helicobacter pylori, Epstein-Barr virus nuclear antigen (EBNA, and varicella zoster virus (VZV in 94 patients with MS and 367 unrelated healthy controls (HCs. We defined CSF IgG abnormality as the presence of CSF OBs and/or increased IgG index (>0.658. PRINCIPAL FINDINGS: CSF IgG abnormality was found in 59 of 94 (62.8% MS patients. CSF IgG abnormality-positive patients had a significantly higher frequency of brain MRI lesions meeting the Barkhof criteria compared with abnormality-negative patients. Compared with HCs, CSF IgG abnormality-positive MS patients showed a significantly higher frequency of DRB1 1501, whereas CSF IgG abnormality-negative patients had a significantly higher frequency of DRB1 0405. CSF IgG abnormality-positive MS patients had a significantly higher frequency of anti-C. pneumoniae IgG antibodies compared with CSF IgG abnormality-negative MS patients, although there was no difference in the frequency of anti-C. pneumoniae IgG antibodies between HCs and total MS patients. Compared with HCs, anti-H. pylori IgG antibodies were detected significantly less frequently in the total MS patients, especially in CSF IgG abnormality-negative MS patients. The frequencies of antibodies against EBNA and VZV did not differ significantly among the groups. CONCLUSIONS: CSF IgG abnormality is associated with Western MS-like brain MRI features. DRB1 1501 and C. pneumoniae infection confer CSF IgG abnormality, while DRB1 0405 and H. pylori infection are positively and negatively

  13. Serological IgG avidity test for ocular toxoplasmosis

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    Suresh S

    2012-01-01

    Full Text Available Subramaniam Suresh1, Saidin Nor-Masniwati1, Muhd Nor Nor-Idahriani1, Wan-Hitam Wan-Hazabbah1, Mohamed Zeehaida2, Embong Zunaina11Department of Ophthalmology, 2Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, MalaysiaBackground: The purpose of this study was to evaluate the immunoglobulin (Ig G avidity of serological toxoplasmosis testing in patients with ocular inflammation and to determine the clinical manifestations of ocular toxoplasmosis.Methods: A retrospective review of all patients presenting with ocular inflammation to the Hospital Universiti Sains Malaysia, Kelantan, Malaysia between 2005 and 2009 was undertaken. Visual acuity, clinical manifestations at presentation, toxoplasmosis antibody testing, and treatment records were analyzed.Results: A total of 130 patients with ocular inflammation were reviewed retrospectively. The patients had a mean age of 38.41 (standard deviation 19.24, range 6–83 years. Seventy-one patients (54.6% were found to be seropositive, of whom five (3.8% were both IgG and IgM positive (suggestive of recently acquired ocular toxoplasmosis while one (0.8% showed IgG avidity ≤40% (suggestive of recently acquired ocular toxoplasmosis and 65 patients (50.0% showed IgG avidity >40% (suggestive of reactivation of toxoplasmosis infection. Chorioretinal scarring as an ocular manifestation was significantly more common in patients with seropositive toxoplasmosis (P = 0.036. Eighteen patients (13.8% were diagnosed as having recent and/or active ocular toxoplasmosis based on clinical manifestations and serological testing.Conclusion: Ocular toxoplasmosis is a clinical diagnosis, but specific toxoplasmosis antibody testing helps to support the diagnosis and to differentiate between reactivation of infection and recently acquired ocular toxoplasmosis.Keywords: ocular toxoplasmosis, chorioretinal scar, toxoplasmosis antibody, IgG avidity test

  14. Recombinant Human IgG antibodies against Human Cytomegalovirus

    Institute of Scientific and Technical Information of China (English)

    TAO DUAN; XIAO-FANG WANG; SHU-YUAN XIAO; SHU-YAN GU; MI-FANG LIANG

    2008-01-01

    Objective To study the passive immunization with human monoclonal antibodies as for prophylaxis of human eytomegalovirus (HCMV) infection. Methods Fab monochinal antibodies to HCMV were recovered by repertoire cloning of mRNA from a HCMV infected individual. Antigen binding specificity, CDR sequence of Vhand Vland neutralizing activity on HCMV AD169 stain were analyzed in vitro. The light and heavy chain Fd fragment genes of Fab antibodies were further cloned into a recombinant baculovirus expression vector pAC-κ-Fc to express intact IgG. Secreted products were purified with affinity chromatography using protein G. Results SDS-PAGE and Western blot confirmed the expression of the intact IgG. Immuno-blotting and -precipitation were used to identify HCMV proteins. One Fab monoclonal antibodyrecognized a conformational HCMV protein. Conclusion IgG antibodies can neutralize the HCMV AD169 strain efficiently at a titer of 2.5 μg/mL and may prove valuable for passive immunoprophylaxis against HCMV infection in humans.

  15. Evaluation of IgG4 and total IgG antibodies against cysticerci and peptide antigens for the diagnosis of human neurocysticercosis by ELISA.

    Science.gov (United States)

    Intapan, Pewpan M; Khotsri, Piyarat; Kanpittaya, Jaturat; Chotmongkol, Verajit; Maleewong, Wanchai; Morakote, Nimit

    2008-12-01

    To support the clinical diagnosis of human neurocysticercosis (NCC), we evaluated two peptides, HP6-3 and Ts45W-1, as well as crude saline extract (SE) of Tenia solium cysticerci as antigens for the detection of specific IgG4 subclass and total IgG antibodies by an enzyme-linked immunosorbent assay (ELISA). The sera of definitive diagnosed NCC patients, patients infected with other parasitoses and healthy controls were examined. The diagnostic sensitivity for IgG4 and total IgG detection of the ELISA against SE antigen was 100% and 64.3% with a high amount of cross-reactions to taeniasis saginata at 88.9% (8/9) and 100% (9/9), respectively. The SE-based IgG4-ELISA showed the highest specificity (80.9%). Both peptide-based IgG4-ELISAs provided a superior sensitivity (78.6%) to the total IgG tests whereas their specificity was 66.7% for HP6-3 and 69.8% for Ts45W-1 only. The SE-based ELISA for the detection of specific IgG4 antibody can be used for the diagnosis of neurocysticercosis as well as for serological surveys of NCC endemic areas. The peptide-based IgG4 ELISAs potentially provide a reliable and cost effective alternative method independent from live parasite supply.

  16. CONTENTS OF SERUM MYELIN BASIC PROTEIN-IGG ANTIBODIES COMPLEXES IN NORMAL PREGNANCY AND GESTOSIS

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    V. G. Levchenko

    2010-01-01

    Full Text Available Serum levels of myelin basic protein (MBP-bound immune complexes were studied in blood sera from women with gestosis, as compared with those in normal pregnancy and non-pregnant woman. The amounts of IgG-MBP complex in blood serum were determined by enzyme immunoassay using isolated anti-МBP-antibodies. The study has shown that about 0.05 mcg of IgG ml of blood serum are associated with myelin basic protein in unpregnant women or in normal pregnancy. Mild gestosis is accompanied by a 2-3-fold increase in MBP immunocomplex concentrations in blood serum. More severe stages of gestosis are characterized by its further rise, thus achieving maximal values of such MBP immune complexes (0.8 mcg/ml in patients with pre-eclampsia and eclampsia. Their amounts were reduced twice after the periods of eclampsia. Serum levels of MBP-bound IgGs may be used to determine severity of gestosis and to predict a risk of eclampsia in pregnant women.

  17. In vitro Fab display: a cell-free system for IgG discovery.

    Science.gov (United States)

    Stafford, Ryan L; Matsumoto, Marissa L; Yin, Gang; Cai, Qi; Fung, Juan Jose; Stephenson, Heather; Gill, Avinash; You, Monica; Lin, Shwu-Hwa; Wang, Willie D; Masikat, Mary Rose; Li, Xiaofan; Penta, Kalyani; Steiner, Alex R; Baliga, Ramesh; Murray, Christopher J; Thanos, Christopher D; Hallam, Trevor J; Sato, Aaron K

    2014-04-01

    Selection technologies such as ribosome display enable the rapid discovery of novel antibody fragments entirely in vitro. It has been assumed that the open nature of the cell-free reactions used in these technologies limits selections to single-chain protein fragments. We present a simple approach for the selection of multi-chain proteins, such as antibody Fab fragments, using ribosome display. Specifically, we show that a two-chain trastuzumab (Herceptin) Fab domain can be displayed in a format which tethers either the heavy or light chain to the ribosome while retaining functional antigen binding. Then, we constructed synthetic Fab HC and LC libraries and performed test selections against carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF). The Fab selection output was reformatted into full-length immunoglobulin Gs (IgGs) and directly expressed at high levels in an optimized cell-free system for immediate screening, purification and characterization. Several novel IgGs were identified using this cell-free platform that bind to purified CEA, CEA positive cells and VEGF.

  18. Association between IgG4 Autoantibody and Complement Abnormalities in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Pan, Qingjun; Guo, Linjie; Wu, Jing; Cai, Jun; Liao, Huanjin; Lan, Qiaofen; Peng, Yanxia; He, Yiming; Liu, Hua-Feng

    2016-01-01

    In order to investigate the association between IgG4 autoantibody and complement abnormalities in systemic lupus erythematosus (SLE), 72 newly diagnosed SLE patients, 67 rheumatoid arthritis (RA) patients, and 41 healthy normals were employed. Serum levels of antinuclear IgG4 and IgG4-specific IgM-rheumatoid factor (RF) were measured, and the correlations between serum levels of antinuclear IgG4 and several clinical parameters were analyzed. Also, the levels of IgG subclasses, C1q, and C3 deposition in lupus nephritis (LN) were detected. The results showed that serum levels of antinuclear IgG4 were higher in SLE patients relative to healthy normals (P < 0.01). Serum levels of antinuclear IgG4 in SLE patients were positively correlated with serum levels of total IgG4, albumin, and C3 (r = 0.61, P < 0.05; r = 0.40, P < 0.05; and r = 0.54, P < 0.05, resp.) and negatively correlated with 24-hour urinary protein (r = 0.49, P < 0.05). Serum levels of IgG4-specific IgM-RF were higher in RA patients than in SLE patients (P < 0.001). Also, the ratio of the deposition score for IgG4/(IgG1 + IgG2 + IgG3 + IgG4) was negatively correlated with the score for C1q and C3 deposition in LN (r = 0.34, P < 0.05; r = 0.51, P < 0.01, resp.). In summary, the IgG4 autoantibody may dampen the inflammatory response in SLE, thus maybe providing a novel therapeutic target for SLE. PMID:27597802

  19. Neuron-derived IgG protects neurons from complement-dependent cytotoxicity.

    Science.gov (United States)

    Zhang, Jie; Niu, Na; Li, Bingjie; McNutt, Michael A

    2013-12-01

    Passive immunity of the nervous system has traditionally been thought to be predominantly due to the blood-brain barrier. This concept must now be revisited based on the existence of neuron-derived IgG. The conventional concept is that IgG is produced solely by mature B lymphocytes, but it has now been found to be synthesized by murine and human neurons. However, the function of this endogenous IgG is poorly understood. In this study, we confirm IgG production by rat cortical neurons at the protein and mRNA levels, with 69.0 ± 5.8% of cortical neurons IgG-positive. Injury to primary-culture neurons was induced by complement leading to increases in IgG production. Blockage of neuron-derived IgG resulted in more neuronal death and early apoptosis in the presence of complement. In addition, FcγRI was found in microglia and astrocytes. Expression of FcγR I in microglia was increased by exposure to neuron-derived IgG. Release of NO from microglia triggered by complement was attenuated by neuron-derived IgG, and this attenuation could be reversed by IgG neutralization. These data demonstrate that neuron-derived IgG is protective of neurons against injury induced by complement and microglial activation. IgG appears to play an important role in maintaining the stability of the nervous system.

  20. IgG Suppresses Antibody Responses in Mice Lacking C1q, C3, Complement Receptors 1 and 2, or IgG Fc-Receptors.

    Science.gov (United States)

    Bergström, Joakim J E; Heyman, Birgitta

    2015-01-01

    Antigen-specific IgG antibodies, passively administered to mice or humans together with large particulate antigens like erythrocytes, can completely suppress the antibody response against the antigen. This is used clinically in Rhesus prophylaxis, where administration of IgG anti-RhD prevents RhD-negative women from becoming immunized against RhD-positive fetal erythrocytes aquired transplacentally. The mechanisms by which IgG suppresses antibody responses are poorly understood. We have here addressed whether complement or Fc-receptors for IgG (FcγRs) are required for IgG-mediated suppression. IgG, specific for sheep red blood cells (SRBC), was administered to mice together with SRBC and the antibody responses analyzed. IgG was able to suppress early IgM- as well as longterm IgG-responses in wildtype mice equally well as in mice lacking FcγRIIB (FcγRIIB knockout mice) or FcγRI, III, and IV (FcRγ knockout mice). Moreover, IgG was able to suppress early IgM responses equally well in mice lacking C1q (C1qA knockout mice), C3 (C3 knockout mice), or complement receptors 1 and 2 (Cr2 knockout mice) as in wildtype mice. Owing to the previously described severely impaired IgG responses in the complement deficient mice, it was difficult to assess whether passively administered IgG further decreased their IgG response. In conclusion, Fc-receptor binding or complement-activation by IgG does not seem to be required for its ability to suppress antibody responses to xenogeneic erythrocytes. PMID:26619292

  1. IgG Suppresses Antibody Responses in Mice Lacking C1q, C3, Complement Receptors 1 and 2, or IgG Fc-Receptors.

    Directory of Open Access Journals (Sweden)

    Joakim J E Bergström

    Full Text Available Antigen-specific IgG antibodies, passively administered to mice or humans together with large particulate antigens like erythrocytes, can completely suppress the antibody response against the antigen. This is used clinically in Rhesus prophylaxis, where administration of IgG anti-RhD prevents RhD-negative women from becoming immunized against RhD-positive fetal erythrocytes aquired transplacentally. The mechanisms by which IgG suppresses antibody responses are poorly understood. We have here addressed whether complement or Fc-receptors for IgG (FcγRs are required for IgG-mediated suppression. IgG, specific for sheep red blood cells (SRBC, was administered to mice together with SRBC and the antibody responses analyzed. IgG was able to suppress early IgM- as well as longterm IgG-responses in wildtype mice equally well as in mice lacking FcγRIIB (FcγRIIB knockout mice or FcγRI, III, and IV (FcRγ knockout mice. Moreover, IgG was able to suppress early IgM responses equally well in mice lacking C1q (C1qA knockout mice, C3 (C3 knockout mice, or complement receptors 1 and 2 (Cr2 knockout mice as in wildtype mice. Owing to the previously described severely impaired IgG responses in the complement deficient mice, it was difficult to assess whether passively administered IgG further decreased their IgG response. In conclusion, Fc-receptor binding or complement-activation by IgG does not seem to be required for its ability to suppress antibody responses to xenogeneic erythrocytes.

  2. A Case of IgG4-Related Lung Disease Presenting as Interstitial Lung Disease.

    Science.gov (United States)

    Ahn, Jee Hwan; Hong, Sun In; Cho, Dong Hui; Chae, Eun Jin; Song, Joon Seon; Song, Jin Woo

    2014-08-01

    Intrathoracic involvement of immunoglobulin G4 (IgG4)-related disease has recently been reported. However, a subset of the disease presenting as interstitial lung disease is rare. Here, we report a case of a 35-year-old man with IgG4-related lung disease with manifestations similar to those of interstitial lung disease. Chest computed tomography showed diffuse ground glass opacities and rapidly progressive pleural and subpleural fibrosis in both upper lobes. Histological findings showed diffuse interstitial lymphoplasmacytic infiltration with an increased number of IgG4-positive plasma cells. Serum levels of IgG and IgG4 were also increased. The patient was diagnosed with IgG4-related lung disease, treated with anti-inflammatory agents, and showed improvement. Lung involvement of IgG4-related disease can present as interstitial lung disease and, therefore, should be differentiated when evaluating interstitial lung disease.

  3. Covariance structures of fat and protein influence the estimation of IgG in bovine colostrum.

    Science.gov (United States)

    Løkke, Mette Marie; Engelbrecht, Rikke; Wiking, Lars

    2016-02-01

    On-farm instruments for assessing colostrum quality are needed in order to ensure that the calf is supplied with enough IgG to avoid failure of passive transfer. The aim of this study was to evaluate methods for estimating the IgG concentration in cows' colostrum. This research included 126 colostrum samples from 21 Danish farms with different breeds, ensuring a broad variation pattern in IgG, total protein and fat concentration. Approximately one third of the samples did not fulfil the recommendation of >50 g IgG/l colostrum, and the IgG concentration decreased with time from calving to milking. The ratio of IgG to total protein varied from 6 to 61%, however IgG and total protein were correlated with r2 = 0.70. The variation in fat was independent of variations in protein and IgG. The IgG concentration was measured by ELISA and compared to fast measurements by specific gravity by colostrometer, Brix by refractometer and prediction from infrared spectroscopy. The three fast methods were all correlated to the total protein concentration of colostrum; however specific gravity was also influenced by the fat concentration. Furthermore, specific gravity generally overestimated the IgG concentration, and the cut-off level should be raised to 1050 in order to ensure adequate IgG in colostrum. None of the methods estimated IgG concentration better than the correlation of total protein and IgG, meaning that they all depended on the indirect correlation between total protein and IgG. The results suggest that using a refractometer for quality control of colostrum is an easy and feasible method, and a cut-off level of Brix 22 seems sufficient to assure adequate IgG concentration in colostrum fed to the calf. PMID:26869112

  4. Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo

    NARCIS (Netherlands)

    A.F. Labrijn; A.O. Buijsse; E.T.J. van den Bremer; A.Y.W. Verwilligen; W.K. Bleeker; S.J. Thorpe; J. Killestein; C.H. Polman; R.C. Aalberse; J. Schuurman; J.G.J. van de Winkel; P.W.H.I. Parren

    2009-01-01

    Two humanized IgG4 antibodies, natalizumab and gemtuzumab, are approved for human use, and several others, like TGN1412, are or have been in clinical development. Although IgG4 antibodies can dynamically exchange half-molecules(1), Fab-arm exchange with therapeutic antibodies has not been demonstrat

  5. IgG Conformer's Binding to Amyloidogenic Aggregates.

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    Monichan Phay

    Full Text Available Amyloid-reactive IgGs isolated from pooled blood of normal individuals (pAbs have demonstrated clinical utility for amyloid diseases by in vivo targeting and clearing amyloidogenic proteins and peptides. We now report the following three novel findings on pAb conformer's binding to amyloidogenic aggregates: 1 pAb aggregates have greater activity than monomers (HMW species > dimers > monomers, 2 pAbs interactions with amyloidogenic aggregates at least partially involves unconventional (non-CDR interactions of F(ab regions, and 3 pAb's activity can be easily modulated by trace aggregates generated during sample processing. Specifically, we show that HMW aggregates and dimeric pAbs present in commercial preparations of pAbs, intravenous immunoglobulin (IVIg, had up to ~200- and ~7-fold stronger binding to aggregates of Aβ and transthyretin (TTR than the monomeric antibody. Notably, HMW aggregates were primarily responsible for the enhanced anti-amyloid activities of Aβ- and Cibacron blue-isolated IVIg IgGs. Human pAb conformer's binding to amyloidogenic aggregates was retained in normal human sera, and mimicked by murine pAbs isolated from normal pooled plasmas. An unconventional (non-CDR component to pAb's activity was indicated from control human mAbs, generated against non-amyloid targets, binding to aggregated Aβ and TTR. Similar to pAbs, HMW and dimeric mAb conformers bound stronger than their monomeric forms to amyloidogenic aggregates. However, mAbs had lower maximum binding signals, indicating that pAbs were required to saturate a diverse collection of binding sites. Taken together, our findings strongly support further investigations on the physiological function and clinical utility of the inherent anti-amyloid activities of monomeric but not aggregated IgGs.

  6. Factor XIa-specific IgG and a reversal agent to probe factor XI function in thrombosis and hemostasis.

    Science.gov (United States)

    David, Tovo; Kim, Yun Cheol; Ely, Lauren K; Rondon, Isaac; Gao, Huilan; O'Brien, Peter; Bolt, Michael W; Coyle, Anthony J; Garcia, Jorge L; Flounders, Eric A; Mikita, Thomas; Coughlin, Shaun R

    2016-08-24

    Thrombosis is a major cause of morbidity and mortality. Current antithrombotic drugs are not ideal in that they must balance prevention of thrombosis against bleeding risk. Inhibition of coagulation factor XI (FXI) may offer an improvement over existing antithrombotic strategies by preventing some forms of thrombosis with lower bleeding risk. To permit exploration of this hypothesis in humans, we generated and characterized a series of human immunoglobulin Gs (IgGs) that blocked FXIa active-site function but did not bind FXI zymogen or other coagulation proteases. The most potent of these IgGs, C24 and DEF, inhibited clotting in whole human blood and prevented FeCl3-induced carotid artery occlusion in FXI-deficient mice reconstituted with human FXI and in thread-induced venous thrombosis in rabbits at clinically relevant doses. At doses substantially higher than those required for inhibition of intravascular thrombus formation in these models, DEF did not increase cuticle bleeding in rabbits or cause spontaneous bleeding in macaques over a 2-week study. Anticipating the desirability of a reversal agent, we also generated a human IgG that rapidly reversed DEF activity ex vivo in human plasma and in vivo in rabbits. Thus, an active site-directed FXIa-specific antibody can block thrombosis in animal models and, together with the reversal agent, may facilitate exploration of the roles of FXIa in human disease. PMID:27559095

  7. RARE DIAGNOSIS OF IGG4-RELATED SYSTEMIC DISEASE BY LIP BIOPSY IN AN INTERNATIONAL SJÖGREN SYNDROME REGISTRY

    Science.gov (United States)

    Baer, Alan N.; Gourin, Christine; Westra, William H.; Cox, Darren; Greenspan, John; Daniels, Troy E.

    2012-01-01

    IgG4-related disease has been recently defined as a distinct clinic-pathologic entity, characterized by dense IgG-4 plasmacytic infiltration of diverse organs, fibrosis, and tumefactive lesions. Salivary and lacrimal glands are a target of this disease and, when affected, may clinically resemble Küttner tumor, Mikulicz disease, or orbital inflammatory pseudotumor. In some patients, the disease is systemic, with metachronous involvement of multiple organs, including the pancreas, aorta, kidneys, and biliary tract. We report a 66-year old man who presented with salivary gland enlargement and severe salivary hypofunction and was diagnosed with IgG4-related disease on the basis of a labial salivary gland biopsy. Additional features of his illness included a marked peripheral eosinophilia, obstructive pulmonary disease, and lymphoplasmacytic aortitis. He was evaluated in the context of a research registry for Sjögren syndrome and was the only one of 2594 registrants with minor salivary gland histopathologic findings supportive of this diagnosis. PMID:23146570

  8. Pancreatic cancer with a high serum IgG4 concentration

    Institute of Scientific and Technical Information of China (English)

    Terumi Kamisawa; Pong Yui Chen; Yuyang Tu; Hitoshi Nakajima; Naoto Egawa; Kouji Tsuruta; Atsutake Okamoto; Tsunekazu Hishima

    2006-01-01

    Differentiation between autoimmune pancreatitis and pancreatic cancer is sometimes difficult. It has been reported that serum IgG4 concentrations are significantly elevated and particularly high (>135 mg/dL) in autoimmune pancreatitis. Measurement of serum IgG4 has become a useful tool for differentiating between autoimmune pancreatitis and pancreatic cancer. However,we present a 74-year-old female with a markedly elevated serum IgG4 (433 mg/dL) who underwentpancreaticoduodenectomy for pancreatic cancer. Elevated serum IgG4 levels continued after the resection. On histology, adenocarcinoma of the pancreas accompanied with moderate lymphoplasmacytic infiltration infiltrated the lower bile duct and duodenum, but there were no findings of autoimmune pancreatitis. Although a small metastasis was detected in one parapancreatic lymph node, regional lymph nodes were swollen. Abundant IgG4-positive plasma cells infiltrated the cancerous areas of the pancreas, but only a few IgG4-positive plasma cells were detected in the noncancerous areas.Pancreatic cancer cells were not immunoreactive for IgG4. An abundant infiltration of IgG4-positive plasma cells was detected in the swollen regional lymph nodes and in the duodenal mucosa. We believe that the serum IgG4 level was elevated in this patient with pancreatic cancer as the result of an IgG4-related systemic disease that had no clinical manifestations other than lymphadenopathy.

  9. IgG4 immunostaining and its implications in orbital inflammatory disease.

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    Amanda J Wong

    Full Text Available OBJECTIVE: IgG4-related disease is an emerging clinical entity which frequently involves tissue within the orbit. In order to appreciate the implications of IgG4 immunostaining, we analyzed gene expression and the prevalence of IgG4- immunostaining among subjects with orbital inflammatory diseases. METHODS: We organized an international consortium to collect orbital biopsies from 108 subjects including 22 with no known orbital disease, 42 with nonspecific orbital inflammatory disease (NSOI, 26 with thyroid eye disease (TED, 12 with sarcoidosis, and 6 with granulomatosis with polyangiitis (GPA. Lacrimal gland and orbital adipose tissue biopsies were immunostained for IgG4 or IgG secreting plasma cells. RNA transcripts were quantified by Affymetrix arrays. RESULTS: None of the healthy controls or subjects with TED had substantial IgG4 staining. Among the 63 others, the prevalence of significant IgG4-immunostaining ranged from 11 to 39% depending on the definition for significant. IgG4 staining was detectable in the majority of tissues from subjects with GPA and less commonly in tissue from subjects with sarcoidosis or NSOI. The detection of IgG4+ cells correlated with inflammation in the lacrimal gland based on histology. IgG4 staining tissue expressed an increase in transcripts associated with inflammation, especially B cell-related genes. Functional annotation analysis confirmed this. CONCLUSION: IgG4+ plasma cells are common in orbital tissue from patients with sarcoidosis, GPA, or NSOI. Even using the low threshold of 10 IgG4+ cells/high powered field, IgG4 staining correlates with increased inflammation in the lacrimal gland based on histology and gene expression.

  10. A New Nanogold-Labeled Immunoresonance Scattering Spectral Probe for Determination of Trace IgG

    Institute of Scientific and Technical Information of China (English)

    JIANG,Zhi-Liang; LI,Yan; SUN,Shuang-Jiao; CHEN,Bing

    2007-01-01

    A kind of 9 nm gold nanoparticles was prepared with the trisodium citrate and used to label goat anti-human IgG to obtain an IgG immunoresonance scattering spectral probe. In pH 5.8 buffer solution and in the presence of polyethylene glycol (PEG), the immune reaction between gold-labeled goat anti-human IgG and IgG took place,and the resonance scattering intensity at 580 nm (I580nm) was enhanced greatly. The enhanced intensity △IRS is proportional to the IgG concentration from 1.3 to 1.5 × 103 ng·mL 1, with a detection limit of 0.78 ng·mL-1. This assay showed high sensitivity and good selectivity for quantitative determination of IgG in human serum, with satisfactory results.

  11. Elevated serum IgG4 levels in two cases of paragonimiasis

    Science.gov (United States)

    Saeki, Sho; Horio, Yuko; Hirosako, Susumu; Ichiyasu, Hidenori; Fujii, Kazuhiko; Kohrogi, Hirotsugu

    2015-01-01

    Paragonimiasis is a parasitic pleuropulmonary infection caused by eating raw crustaceans and wild boar meat and this infection is endemic in Asia. We herein report two cases of pulmonary Paragonimus westermani infection associated with elevated levels of serum immunoglobulin (Ig) G4 and dense infiltration of IgG4-positive plasma cells in the lung lesions. Treatment with praziquantel resolved the pulmonary lesions and decreased the serum levels of IgG4. IgG4-related disease is a systemic disease occasionally involving the lungs and leads to increased serum levels of IgG4. Our findings suggest that P. westermani infection requires a differential diagnosis from IgG4-related diseases and the serum IgG4 level may be a potentially useful marker of P. westermani infection. PMID:26392854

  12. Nontuberculous mycobacterial infection with concurrent IgG4-related lymphadenopathy.

    Science.gov (United States)

    Liu, Ting-Ting; Weng, Shao-Wen; Wang, Ming-Chung; Huang, Wan-Ting

    2016-03-01

    Disseminated nontuberculous mycobacteria (NTM) infection with concurrent IgG4-related lymphadenopathy has not been reported. We described a patient with neutralizing autoantibodies to interferon-gamma (IFN-γ) and elevated levels of serum IgG4 presenting with generalized lymphadenopathy and reactive dermatosis. Histologically, lymph nodes (LNs) showed effaced nodal architecture with polymorphic infiltrates, mimicking angioimmunoblastic T-cell lymphoma. Both the absolute number and the ratio of IgG4+ plasma cells to IgG+ plasma cells were increased. Mycobacterium abscessus was isolated from cultures of LNs, and demonstrated by polymerase chain reaction-restriction fragment length polymorphism. The skin biopsy showed neutrophilic dermatosis, consistent with Sweet syndrome. The patient met the criteria of both adult-onset immunodeficiency syndrome and IgG4-related lymphadenopathy. This case provides evidence of disseminated NTM infection with concurrent type III IgG4-related lymphadenopathy in the patient with anti-IFN-γ autoantibodies. PMID:26660641

  13. Isolated Mass-Forming IgG4-Related Cholangitis as an Initial Clinical Presentation of Systemic IgG4-Related Disease.

    Science.gov (United States)

    Kim, Seokhwi; Bae, Hyunsik; Choi, Misun; Kim, Binnari; Heo, Jin Seok; Kim, Ho Seong; Choi, Seung Hee; Jang, Kee-Taek

    2016-07-01

    IgG4-related disease (IgG4-RD) may involve multiple organs. Although it usually presents as diffuse organ involvement, localized mass-forming lesions have been occasionally encountered in pancreas. However, the same pattern has been seldom reported in biliary tract. A 61-year-old male showed a hilar bile duct mass with multiple enlarged lymph nodes in imaging studies and he underwent trisectionectomy under impression of cholangiocarcinoma. Gross examination revealed a mass-like lesion around hilar bile duct. Histopathologically, dense lymphoplasmacytic infiltration and storiform fibrosis were identified without evidence of malignancy. Immunohistochemical stain demonstrated rich IgG4-positive plasma cell infiltration. Follow-up imaging studies disclosed multiple enlarged lymph nodes with involvement of pancreas and perisplenic soft tissue. The lesions have been significantly reduced after steroid treatment, which suggests multi-organ involvement of systemic IgG4-RD. Here, we report an unusual localized mass-forming IgG4-related cholangitis as an initial presentation of IgG4-RD, which was biliary manifestation of systemic IgG4-related autoimmune disease.

  14. Isolated Mass-Forming IgG4-Related Cholangitis as an Initial Clinical Presentation of Systemic IgG4-Related Disease.

    Science.gov (United States)

    Kim, Seokhwi; Bae, Hyunsik; Choi, Misun; Kim, Binnari; Heo, Jin Seok; Kim, Ho Seong; Choi, Seung Hee; Jang, Kee-Taek

    2016-07-01

    IgG4-related disease (IgG4-RD) may involve multiple organs. Although it usually presents as diffuse organ involvement, localized mass-forming lesions have been occasionally encountered in pancreas. However, the same pattern has been seldom reported in biliary tract. A 61-year-old male showed a hilar bile duct mass with multiple enlarged lymph nodes in imaging studies and he underwent trisectionectomy under impression of cholangiocarcinoma. Gross examination revealed a mass-like lesion around hilar bile duct. Histopathologically, dense lymphoplasmacytic infiltration and storiform fibrosis were identified without evidence of malignancy. Immunohistochemical stain demonstrated rich IgG4-positive plasma cell infiltration. Follow-up imaging studies disclosed multiple enlarged lymph nodes with involvement of pancreas and perisplenic soft tissue. The lesions have been significantly reduced after steroid treatment, which suggests multi-organ involvement of systemic IgG4-RD. Here, we report an unusual localized mass-forming IgG4-related cholangitis as an initial presentation of IgG4-RD, which was biliary manifestation of systemic IgG4-related autoimmune disease. PMID:26755360

  15. IgG4-related tubulointerstitial nephritis accompanied with cystic formation

    OpenAIRE

    Fukuhara, Hideo; Taniguchi, Yoshinori; Matsumoto, Manabu; Kuroda, Naoto; Fukata, Satoshi; Inoue, Keiji; Fujimoto, Shimpei; Terada, Yoshio; Shuin, Taro

    2014-01-01

    Background An immunoglobulin G4 (IgG4)-related disease is important disease in differential diagnosis of tumors in kidney, pancreas, lung and other organs. The imaging findings of IgG4-related kidney diseases are usually expressed as defect contrast region, while cystic formation in kidney is extremely rare. Here, we report a case of IgG4-related tubulointerstitial nephritis with renal cystic change caused by the narrowing or obstruction of collecting duct in renal medulla. Case presentation ...

  16. Refractory gastric ulcer with abundant IgG4-positive plasma cell infiltration: A case report

    Institute of Scientific and Technical Information of China (English)

    Takayoshi; Fujita; Takafumi; Ando; Masatoshi; Sakakibara; Waki; Hosoda; Hidemi; Goto

    2010-01-01

    We describe a 77-year-old man with refractory gastric ulcer that worsened after Helicobacter pylori eradication therapy.Pathology showed marked infiltration of IgG4-positive plasma cells in the gastric lesions,which led us to suspect IgG4-related sclerosing disease.To the best of our knowledge,this is the first report of IgG4-related gastric ulcer without the main manifestation of autoimmune pancreatitis.

  17. Snake venomics of monocled cobra (Naja kaouthia) and investigation of human IgG response against venom toxins

    DEFF Research Database (Denmark)

    Laustsen, Andreas Hougaard; Gutiérrez, José María; Lohse, Brian;

    2015-01-01

    The venom proteome of the monocled cobra, Naja kaouthia, from Thailand, was characterized by RP-HPLC, SDS-PAGE, and MALDI-TOF-TOF analyses, yielding 38 different proteins that were either identified or assigned to families. Estimation of relative protein abundances revealed that venom is dominate...... against N. kaouthia venom was therefore detected. Combined, our results display a high level of venom complexity, unveil the most relevant toxins to be neutralized, and provide prospects of discovering human IgGs with toxin neutralizing abilities through use of phage display screening....

  18. An IgG4-Related Salivary Gland Disorder: A Case Series Presenting with a Different Clinical Setting

    Directory of Open Access Journals (Sweden)

    Masayuki Ishida

    2011-01-01

    Full Text Available Küttner tumor is a chronic inflammatory disease that presents with a firm swelling of the submandibular gland and often mimics a neoplasm. Recently evidence suggests that Küttner tumor may be a type of disorder characterized by IgG4-related inflammations. Herein, we report 3 cases of submandibular gland swellings with severe fibrosis, inflammation with marked lymphoplasmacytic infiltration; this pathology mimics clinical manifestation of a malignant tumor in 18-fluorodeoxyglucose positron emission tomography (FDG-PET findings.

  19. Granuloma faciale: a cutaneous lesion sharing features with IgG4-associated sclerosing diseases.

    Science.gov (United States)

    Cesinaro, Anna Maria; Lonardi, Silvia; Facchetti, Fabio

    2013-01-01

    The pathogenesis of granuloma faciale (GF), framed in the group of cutaneous vasculopathic dermatitis, is poorly understood. The present study investigated whether GF might be part of the spectrum of IgG4-related sclerosing diseases (IgG4-RD). Erythema elevatum diutinum (EED), believed to belong to the same group of disorders as GF, was also studied for comparison. Thirty-one biopsies of GF obtained from 25 patients (18 men, 7 women) and 5 cases of EED (4 women and 1 man) were analyzed morphologically and for the expression of IgG and IgG4 by immunohistochemistry. The distribution of Th1, T regulatory and Th2 T-cell subsets, respectively, identified by anti-T-bet, anti-FoxP3, and anti-GATA-3 antibodies, was also evaluated. The dermal inflammatory infiltrate in GF contained eosinophils and plasma cells in variable proportions. Obliterative venulitis was found in 16 cases, and storiform fibrosis, a typical feature of IgG4-RD, was observed in 8 cases and was prominent in 3 of them. On immunohistochemical analysis 7 of 31 biopsies (22.6%) from 6 GF patients fulfilled the criteria for IgG4-RD (IgG4/IgG ratio >40%, and absolute number of IgG4 per high-power field >50). Interestingly, the 6 patients were male, and 4 showed recurrent and/or multiple lesions. In an additional 5 cases, only the IgG4/IgG ratio was abnormal. None of the 5 EED cases fulfilled the criteria for IgG4-RD. The T-cell subsets in GF were quite variable in number, GATA-3 lymphocytes were generally more abundant, but no relationship with the number of IgG4 plasma cells was found. The study indicates that a significant number of GF cases are associated with an abnormal content of IgG4 plasma cells; this association was particularly obvious in male patients and in cases presenting with multiple or recurrent lesions. As morphologic changes typically found in IgG4-RD, such as obliterative vascular inflammation and storiform sclerosis, are found in GF, we suggest that GF might represent a localized form of

  20. IgG1 Fc N-glycan galactosylation as a biomarker for immune activation.

    Science.gov (United States)

    de Jong, Sanne E; Selman, Maurice H J; Adegnika, Ayola A; Amoah, Abena S; van Riet, Elly; Kruize, Yvonne C M; Raynes, John G; Rodriguez, Alejandro; Boakye, Daniel; von Mutius, Erika; Knulst, André C; Genuneit, Jon; Cooper, Philip J; Hokke, Cornelis H; Wuhrer, Manfred; Yazdanbakhsh, Maria

    2016-01-01

    Immunoglobulin G (IgG) Fc N-glycosylation affects antibody-mediated effector functions and varies with inflammation rooted in both communicable and non-communicable diseases. Worldwide, communicable and non-communicable diseases tend to segregate geographically. Therefore, we studied whether IgG Fc N-glycosylation varies in populations with different environmental exposures in different parts of the world. IgG Fc N-glycosylation was analysed in serum/plasma of 700 school-age children from different communities of Gabon, Ghana, Ecuador, the Netherlands and Germany. IgG1 galactosylation levels were generally higher in more affluent countries and in more urban communities. High IgG1 galactosylation levels correlated with low total IgE levels, low C-reactive protein levels and low prevalence of parasitic infections. Linear mixed modelling showed that only positivity for parasitic infections was a significant predictor of reduced IgG1 galactosylation levels. That IgG1 galactosylation is a predictor of immune activation is supported by the observation that asthmatic children seemed to have reduced IgG1 galactosylation levels as well. This indicates that IgG1 galactosylation levels could be used as a biomarker for immune activation of populations, providing a valuable tool for studies examining the epidemiological transition from communicable to non-communicable diseases. PMID:27306703

  1. [Two cases of IgG4-related disease with pleural effusion].

    Science.gov (United States)

    Suzuki, Nobuaki; Saeki, Takako; Shimaoka, Yuichi; Kuriyama, Hideyuki; Nishibori, Takeaki; Ebe, Yusuke; Sato, Kazuhiro

    2011-02-01

    We describe 2 cases of IgG4-related disease with pleural effusion in elderly men. Both patients had elevated serum IgG4 levels, and the characteristics of their pleural effusion were similar. Patient 1 had pericardial effusion and retroperitoneal fibrosis, and a biopsy specimen from the pericardium showed infiltration of abundant IgG4-positive plasma cells with fibrosis. Because his pleurisy, pericarditis and retroperitoneal fibrosis responded to steroid therapy, we diagnosed pleurisy associated with IgG4-related disease. Patient 2 had been treated with steroids because of IgG4-related sialadenitis and interstitial pneumonitis, but pleural effusion developed. Although histopathological examination of the pleura showed infiltration of abundant IgG4-positive plasma cells with fibrosis, Mycobacterium tuberculosis was cultured from the pleural effusion, and histologic examination also showed epithelioid granuloma. Chemotherapy for tuberculosis was effective for the pleurisy, and we diagnosed tuberculous pleurisy as a complication of IgG4-related disease. In cases of IgG4-related disease associated with pleural effusion, the clinical course should be considered together with the serum IgG4 levels and pleural histology.

  2. IgG1 Fc N-glycan galactosylation as a biomarker for immune activation

    Science.gov (United States)

    de Jong, Sanne E.; Selman, Maurice H. J.; Adegnika, Ayola A.; Amoah, Abena S.; van Riet, Elly; Kruize, Yvonne C. M.; Raynes, John G.; Rodriguez, Alejandro; Boakye, Daniel; von Mutius, Erika; Knulst, André C.; Genuneit, Jon; Cooper, Philip J.; Hokke, Cornelis H.; Wuhrer, Manfred; Yazdanbakhsh, Maria

    2016-01-01

    Immunoglobulin G (IgG) Fc N-glycosylation affects antibody-mediated effector functions and varies with inflammation rooted in both communicable and non-communicable diseases. Worldwide, communicable and non-communicable diseases tend to segregate geographically. Therefore, we studied whether IgG Fc N-glycosylation varies in populations with different environmental exposures in different parts of the world. IgG Fc N-glycosylation was analysed in serum/plasma of 700 school-age children from different communities of Gabon, Ghana, Ecuador, the Netherlands and Germany. IgG1 galactosylation levels were generally higher in more affluent countries and in more urban communities. High IgG1 galactosylation levels correlated with low total IgE levels, low C-reactive protein levels and low prevalence of parasitic infections. Linear mixed modelling showed that only positivity for parasitic infections was a significant predictor of reduced IgG1 galactosylation levels. That IgG1 galactosylation is a predictor of immune activation is supported by the observation that asthmatic children seemed to have reduced IgG1 galactosylation levels as well. This indicates that IgG1 galactosylation levels could be used as a biomarker for immune activation of populations, providing a valuable tool for studies examining the epidemiological transition from communicable to non-communicable diseases. PMID:27306703

  3. IgG2 antibodies against a clinical grade Plasmodium falciparum CSP vaccine antigen associate with protection against transgenic sporozoite challenge in mice.

    Directory of Open Access Journals (Sweden)

    Robert Schwenk

    Full Text Available The availability of a highly purified and well characterized circumsporozoite protein (CSP is essential to improve upon the partial success of recombinant CSP-based malaria vaccine candidates. Soluble, near full-length, Plasmodium falciparum CSP vaccine antigen (CS/D was produced in E. coli under bio-production conditions that comply with current Good Manufacturing Practices (cGMP. A mouse immunogenicity study was conducted using a stable oil-in-water emulsion (SE of CS/D in combination with the Toll-Like Receptor 4 (TLR4 agonist Glucopyranosyl Lipid A (GLA/SE, or one of two TLR7/8 agonists: R848 (un-conjugated or 3M-051 (covalently conjugated. Compared to Alum and SE, GLA/SE induced higher CS/D specific antibody response in Balb/c mice. Subclass analysis showed higher IgG2:IgG1 ratio of GLA/SE induced antibodies as compared to Alum and SE. TLR synergy was not observed when soluble R848 was mixed with GLA/SE. Antibody response of 3M051 formulations in Balb/c was similar to GLA/SE, except for the higher IgG2:IgG1 ratio and a trend towards higher T cell responses in 3M051 containing groups. However, no synergistic enhancement of antibody and T cell response was evident when 3M051 conjugate was mixed with GLA/SE. In C57Bl/6 mice, CS/D adjuvanted with 3M051/SE or GLA/SE induced higher CSP repeat specific titers compared to SE. While, 3M051 induced antibodies had high IgG2c:IgG1 ratio, GLA/SE promoted high levels of both IgG1 and IgG2c. GLA/SE also induced more potent T-cell responses compared to SE in two independent C57/BL6 vaccination studies, suggesting a balanced and productive T(H1/T(H2 response. GLA and 3M-051 similarly enhanced the protective efficacy of CS/D against challenge with a transgenic P. berghei parasite and most importantly, high levels of cytophilic IgG2 antibodies were associated with protection in this model. Our data indicated that the cGMP-grade, soluble CS/D antigen combined with the TLR4-containing adjuvant GLA/SE warrants

  4. STUDY ON SEROPREVALENCE OF MUMPS - SPECIFIC IgG ANTIBODIES IN A HEALTHY POPULATION

    Directory of Open Access Journals (Sweden)

    Milena Karcheva

    2010-09-01

    Full Text Available Mumps is a vaccine preventable viral infection. Its typical clinical manifestations are characterized by pain and swelling of the salivary glands, fever, and fatigue. Often other organs are affected - testes in males after puberty (orchitis, ovaries in women (ooforitis, pancreas (pancreatitis, central nervous system (meningities. The use of specific immune prophylaxis led to a significant success in the fight against mumps, but there are still unresolved issues related to the immunological and epidemiological effectiveness of the vaccines. The disease continues to interest researchers today. The main issues being tackled are related to the conduct of virological, clinical and sero-epidemiological studies in different countries. Objectives of the study is to determine the frequency distribution of mumps-specific IgG antibodies in healthy populations in the region of Pleven, Bulgaria. Methods: a cross-sectional sero - epidemiological representative population - based survey in the area was made. Enzyme immunoassay method was used for an indirect proof of mumps - specific IgG serum antibodies. 410 people were examined at an average age of 25 (1 to 84. Of these, 250 (61 % were women and 160 (39 % - men. Results: Of all test results, the negative were 72 (19 %, the borderline were 12 (3 %, the positive were 182 (44 %, and highly positive were 144 (35 %. The vaccination status showed that 242 (69 % of all surveyed were immunized with a vaccine against mumps. According to the immunization schedule in Bulgaria, 132 (33 % people were immunized with monovaccine during the years - 1 intake, 80 (20 % with trivaccine - 1 intake, and 64 (16 % - 2 doses. Conclusion: We believe that despite the specific immunprophylaxis carried out against mumps decades on end, the necessary level of protection leading to its elimination has not yet been reached.

  5. IgG4相关性肺疾病1例及文献复习%A review of 1 case of IgG4-related lung disease

    Institute of Scientific and Technical Information of China (English)

    李燕; 黄妹; 蔡后荣; 孙琦; 苗立云; 孟凡青; 肖永龙

    2016-01-01

    positive plasma cells was about 40/HP. The serum IgG4 concen-tration was 4. 07g/L (0. 03 g/L~2 g/L). The patient was diagnosed as IgG4-related lung disease. After treatment of glucocorticoid, the clinical symptoms were relieved. Two months later, his chest CT revealed improvement and serum IgG4 concentration decreased to normal level. Conclusion IgG4-related disease is a new concept of multi-organ dis-ease that is characterized by infiltration into organs of IgG4-positive plasma cells and high serum IgG4 concentrations. There have been very few reports in China. This is a case of IgG4-related disease in which only complication was lung involvement. This study could help clinicians improve recognition and knowledge of this rare disease.

  6. IgG4-Associated Cholangitis--A Mimic of PSC.

    Science.gov (United States)

    Beuers, Ulrich; Hubers, Lowiek M; Doorenspleet, Marieke; Maillette de Buy Wenniger, Lucas; Klarenbeek, Paul L; Boonstra, Kirsten; Ponsioen, Cyriel; Rauws, Erik; de Vries, Niek

    2015-01-01

    IgG4-associated cholangitis (IAC) is an inflammatory disorder of the biliary tract representing a major manifestation of IgG4-related disease (IgG4-RD) often with elevation of serum IgG4 levels, infiltration of IgG4+ plasma cells in the affected tissue and good response to immunosuppressive treatment. Its first description may go back to 150 years ago. The clinical presentation of IAC is often misleading, mimicking other biliary diseases such as primary sclerosing cholangitis (PSC) or cholangiocarcinoma. The HISORt criteria--histopathological, imaging, and serological features (sIgG4), other organ manifestations of IgG4-RD and response to treatment--are the standard for the diagnosis of IAC. In this overview of a recent lecture, we summarize our original findings on IgG4-RD that (i) dominant IgG4+ B-cell clones identified by advanced next generation sequencing (NGS) are highly specific for IgG4-RD (meanwhile confirmed by others), are a highly accurate diagnostic marker to distinguish IgG4-RD from PSC and biliary/pancreatic malignancies and may be crucial in unravelling the pathophysiology of IgG4-RD; (ii) sIgG4/sIgG1 >0.24 have additional diagnostic value in comparison to sIgG4 in differentiating IAC from PSC; (iii) blood IgG4 mRNA is a highly accurate diagnostic marker comparable to NGS and may become an easily available and affordable diagnostic standard for distinguishing IgG4-RD from PSC and biliary/pancreatic malignancies; and (iv) 'blue collar work' with long-term exposure to solvents, paints, oil products or industrial gases may be a risk factor for development of IgG4-RD. These findings may contribute to the understanding of the pathophysiology and to the early diagnosis and adequate treatment of IgG4-RD.

  7. IgG subclass deficiency and sinopulmonary bacterial infections in patients with alcoholic liver disease.

    Science.gov (United States)

    Spinozzi, F; Cimignoli, E; Gerli, R; Agea, E; Bertotto, A; Rondoni, F; Grignani, F

    1992-01-01

    Abnormalities in IgG subclass distribution were sought in serum samples and bronchoalveolar lavage fluid from 15 patients with alcoholic liver disease to explain their increased susceptibility to bacterial respiratory infections. Serum IgG4 deficiency alone or in association with low IgG2 levels was revealed in approximately 30% of patients with alcoholic liver disease. This fact prompted us to further investigate the immunoglobulin concentrations in broncho-alveolar lavage fluid, paying special attention to the distribution of IgA and IgG subclasses. IgA levels were found to be normal or slightly elevated. However, there were substantial defects in total IgG and IgG1 concentrations, often associated with reduced IgG2 and IgG4 levels, in approximately 70% of patients with alcoholic liver disease, which proved to be closely correlated with the number and type (pneumonia) of bacterial respiratory infections. A prospective study of intravenous immunoglobulin substitutive therapy involving two patients with recurrent pneumonia and very low serum IgG2 values demonstrated a reduction in the number of respiratory infectious episodes as well as an increase in both serum and, to a lesser extent, bronchoalveolar lavage fluid IgG1 and IgG2 levels. We identified immune defects that may represent an important pathogenetic mechanism that, when considered together with the alcohol-related suppression of alveolar macrophage and ciliary functions and the inhibition of leukocyte migration into the lungs, should help clarify the complex relationships between alcohol and immune defense. PMID:1728935

  8. Understanding the Relationship Between Biotherapeutic Protein Stability and Solid–Liquid Interfacial Shear in Constant Region Mutants of IgG1 and IgG4

    OpenAIRE

    Tavakoli-Keshe, R.; Phillips, J.J.; Turner, R.; Bracewell, D. G.

    2013-01-01

    Relative stability of therapeutic antibody candidates is currently evaluated primarily through their response to thermal degradation, yet this technique is not always predictive of stability in manufacture, shipping, and storage. A rotating disk shear device is proposed that produces defined shear conditions at a known solid–liquid interface to measure stability in this environment. Five variants of IgG1 and IgG4 antibodies were created using combinations of two discrete triple amino acid seq...

  9. IgG4-Related Autoimmune Prostatitis: Is It an Unusual or Underdiagnosed Manifestation of IgG4-Related Disease?

    Directory of Open Access Journals (Sweden)

    María T. Bourlon

    2013-01-01

    Full Text Available IgG4-related disease (IgG4-RD encompasses a wide range of extrapancreatic manifestations. Albeit some are relatively well known, others such as autoimmune prostatitis remain poorly described. We present a 61-year-old Latin-American male with autoimmune pancreatitis (AIP who presented with lower urinary tract symptoms (LUTS, normal prostate specific antigen (PSA test, and prostate enlargement attributed to benign prostatic hyperplasia (BPH. He underwent a transurethral resection of the prostate (TURP after which symptoms were resolved. On histopathology, prostatic stroma had a dense inflammatory infiltrate rich in plasma cells and lymphocytes; immunohistochemical morphometric assessment showed >10 IgG4-positive plasma cells/high power field (HPF. The diagnosis of IgG4-related prostatitis was postoperatively. We compared the patient characteristics with those of previous reports on Asian patients. Shared findings included prostate enlargement, LUTS (symptoms that can be confused with BPH, and PSA within normal limits or mild elevations. IgG4-related prostatitis is rarely considered as a preprocedural diagnosis, even in patients with evidence of IgG4-RD. Involved prostate zones include mainly central and transitional zones and less frequently the peripheral. Currently, there is insufficient data about the natural history and outcome. Whether steroids, transurethral resection, or both are the treatment of choice needs to be elucidated.

  10. A Monosaccharide Residue Is Sufficient to Maintain Mouse and Human IgG Subclass Activity and Directs IgG Effector Functions to Cellular Fc Receptors

    Directory of Open Access Journals (Sweden)

    Daniela Kao

    2015-12-01

    Full Text Available Immunoglobulin G (IgG glycosylation modulates antibody activity and represents a major source of heterogeneity within antibody preparations. Depending on their glycosylation pattern, individual IgG glycovariants present in recombinant antibody preparations may trigger effects ranging from enhanced pro-inflammatory activity to increased anti-inflammatory activity. In contrast, reduction of IgG glycosylation beyond the central mannose core is generally believed to result in impaired IgG activity. However, this study reveals that a mono- or disaccharide structure consisting of one N-acetylglucosamine with or without a branching fucose residue is sufficient to retain the activity of the most active human and mouse IgG subclasses in vivo and further directs antibody activity to cellular Fcγ receptors. Notably, the activity of minimally glycosylated antibodies is not predicted by in vitro assays based on a monomeric antibody-Fcγ-receptor interaction analysis, whereas in vitro assay systems using immune complexes are more suitable to predict IgG activity in vivo.

  11. Antibody isotypes, including IgG subclasses, in Ecuadorian patients with pulmonary Paragonimiasis

    Directory of Open Access Journals (Sweden)

    Angel Guevara E.

    1995-08-01

    Full Text Available An ELISA test was developed to detect Paragonimus-specific antibodies, including IgG subclasses, using P. mexicanus crude water-soluble antigens. The test was standardized to detect antibodies in sera of Ecuadorian patients with pulmonary paragonimiasis and negative controls from the endemic area. The detected mean levels of IgG (0.753, SEM: 0.074 and IgM (0.303, SEM: 0.033 were significantly elevated (P<0.05. Within the IgG subclasses, IgG4 showed the highest detected mean level (0.365, SEM: 0.116 and the other three subclasses showed considerably lower mean levels (IgG1, 0.186 SEM: 0.06; IgG2, 0.046 SEM: 0.01; IgG3, 0.123 SEM: 0.047. The number of P. mexicanus eggs found in sputum of infected individuals showed a positive correlation with the level of antibodies detected for IgM, IgG and its subclasses (P<0.001. The relevance of these findings in Ecuadorian patients suffering from pulmonary paragonimiasis is discussed.

  12. Peroxynitrite-induced structural perturbations in human IgG: A physicochemical study.

    Science.gov (United States)

    Arfat, Mir Yasir; Arif, Zarina; Chaturvedi, Sumit Kumar; Moinuddin; Alam, Khursheed

    2016-08-01

    IgG is an important defence protein. To exhibit optimum function the molecule must maintain its native structure. Peroxynitrite is a potent oxidizing and nitrating agent produced in vivo under pathophysiological conditions. It can oxidize and/or nitrate various amino acids causing changes in the structure and function of proteins. Such proteins may be involved in the pathogenesis of many inflammatory diseases, including rheumatoid arthritis. In the present work, peroxynitrite-induced structural changes in IgG have been studied by UV-visible, fluorescence, CD, FT-IR, DLS spectroscopy and DSC as well as by SDS-PAGE. Peroxynitrite-modified IgG exhibited hyperchromicity at 280 nm, quenching of tryptophan fluorescence, increase in ANS fluorescence, loss of β-sheet, shift in the positions of amide I and amide II bands, appearance of new peak in FT-IR, attachment of nitro residues and increase in melting temperature, compared to native IgG. Furthermore, peroxynitrite-modified IgG exhibited an additional peak at 420 nm, quenching in tyrosine fluorescence and enhancement in dityrosine fluorescence compared to native IgG. Generation of nitrotyrosine, dityrosine and nitrotryptophan was also observed in peroxynitrite-modified IgG. Gross structural changes in IgG caused by peroxynitrite and observed in vitro may favour autoantibodies induction in vivo under similar conditions. PMID:27210739

  13. Sialylation of IgG Fc domain impairs complement-dependent cytotoxicity.

    Science.gov (United States)

    Quast, Isaak; Keller, Christian W; Maurer, Michael A; Giddens, John P; Tackenberg, Björn; Wang, Lai-Xi; Münz, Christian; Nimmerjahn, Falk; Dalakas, Marinos C; Lünemann, Jan D

    2015-11-01

    IgG molecules exert both pro- and antiinflammatory effector functions based on the composition of the fragment crystallizable (Fc) domain glycan. Sialylated IgG Fc domains have antiinflammatory properties that are attributed to their ability to increase the activation threshold of innate effector cells to immune complexes by stimulating the upregulation of the inhibitory Fcγ receptor IIB (FcγRIIB). Here, we report that IgG Fc sialylation of human monoclonal IgG1 molecules impairs their efficacy to induce complement-mediated cytotoxicity (CDC). Fc sialylation of a CD20-targeting antibody had no impact on antibody-dependent cellular cytotoxicity and did not change the affinity of the antibody for activating Fcγ receptors. In contrast, the presence of sialic acid abrogated the increased binding of C1q to Fc-galactosylated IgG1 and resulted in decreased levels of C3b deposition on the cell surface. Similar to monoclonal antibodies, sialic acid inhibited the increased C1q binding to galactosylated Fc fragments in human polyclonal IgG. In sera derived from patients with chronic inflammatory demyelinating polyneuropathy, an autoimmune disease of the peripheral nervous system in which humoral immune responses mediate tissue damage, induction of IgG Fc sialylation was associated with clinical disease remission. Thus, impairment of CDC represents an FcγR-independent mechanism by which Fc-sialylated glycovariants might limit proinflammatory IgG effector functions.

  14. Salivary IgG assay to detect Helicobacter pylori infection in an Indian adult population

    Directory of Open Access Journals (Sweden)

    Ramya Thirumala Krishnaswamy

    2012-01-01

    Conclusion: EIAgen H. pylori IgG assay is a noninvasive, moderately accurate, and sensitive method for the detection of H. pylori infection in saliva. Salivary anti H. pylori IgG test prior to endoscopy is a useful screening test for seroepidemiological studies.

  15. IgG4-related disease manifesting the gastric wall thickening.

    Science.gov (United States)

    Kawano, Hiroo; Ishii, Aya; Kimura, Tokuhiro; Takahashi, Tsuyoshi; Hironaka, Hideharu; Kawano, Michitaka; Yamaguchi, Michiya; Oishi, Keiji; Kubo, Makoto; Matsui, Shoko; Notohara, Kenji; Ikeda, Eiji

    2016-01-01

    IgG4-related disease (IgG4-RD) is a recently designated disease entity and its full picture has not yet been elucidated. Here, we report an unusual case of a patient with gastric wall thickening secondary to IgG4-RD. A 68-year-old male visited our hospital with itchy skin lesions and an episode of organizing pneumonia. On the suspicion of malignancy-associated skin lesions, computed tomography (CT) was performed. The CT revealed prominent thickening of the gastric wall. Due to the possibility of malignancy, the patient underwent distal gastrectomy. Histopathological examination showed fibrosis of the submucosa and prominent thickening of the muscularis propria. Most of infiltrating cells were IgG4-positive plasma cells. Post-operative blood test revealed significantly high serum levels of total IgG and IgG4. Based on these histological features, the patient was given a definitive diagnosis of IgG4-RD. Further accumulation of cases like the present case that develop IgG4-RD with rare manifestations would lead to the elucidation of pathogenesis. PMID:26603834

  16. Design and Evaluation of the Highly Concentrated Human IgG Formulation Using Cyclodextrin Polypseudorotaxane Hydrogels.

    Science.gov (United States)

    Higashi, Taishi; Tajima, Anna; Ohshita, Naoko; Hirotsu, Tatsunori; Abu Hashim, Irhan Ibrahim; Motoyama, Keiichi; Koyama, Sawako; Iibuchi, Ruriko; Mieda, Shiuhei; Handa, Kenji; Kimoto, Tomoaki; Arima, Hidetoshi

    2015-12-01

    To achieve the potent therapeutic effects of human immunoglobulin G (IgG), highly concentrated formulations are required. However, the stabilization for highly concentrated human IgG is laborious work. In the present study, to investigate the potentials of polypseudorotaxane (PPRX) hydrogels consisting of polyethylene glycol (PEG) and α- or γ-cyclodextrin (α- or γ-CyD) as pharmaceutical materials for highly concentrated human IgG, we designed the PPRX hydrogels including human IgG and evaluated their pharmaceutical properties. The α- and γ-CyDs formed PPRX hydrogels with PEG (M.W. 20,000) even in the presence of highly concentrated human IgG (>100 mg/mL). According to the results of (1)H-NMR, powder X-ray diffraction, and Raman microscopy, the formation of human IgG/CyD PPRX hydrogels was based on physical cross-linking arising from their columnar structures. The release profiles of human IgG from the hydrogels were in accordance with the non-Fickian diffusion model. Importantly, the stabilities of human IgG included into the hydrogels against thermal and shaking stresses were markedly improved. These findings suggest that PEG/CyD PPRX hydrogels are useful to prepare the formulation for highly concentrated human IgG.

  17. Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis.

    Science.gov (United States)

    Ohmi, Yuhsuke; Ise, Wataru; Harazono, Akira; Takakura, Daisuke; Fukuyama, Hidehiro; Baba, Yoshihiro; Narazaki, Masashi; Shoda, Hirofumi; Takahashi, Nobunori; Ohkawa, Yuki; Ji, Shuting; Sugiyama, Fumihiro; Fujio, Keishi; Kumanogoh, Atsushi; Yamamoto, Kazuhiko; Kawasaki, Nana; Kurosaki, Tomohiro; Takahashi, Yoshimasa; Furukawa, Koichi

    2016-01-01

    Rheumatoid arthritis (RA)-associated IgG antibodies such as anti-citrullinated protein antibodies (ACPAs) have diverse glycosylation variants; however, key sugar chains modulating the arthritogenic activity of IgG remain to be clarified. Here, we show that reduced sialylation is a common feature of RA-associated IgG in humans and in mouse models of arthritis. Genetically blocking sialylation in activated B cells results in exacerbation of joint inflammation in a collagen-induced arthritis (CIA) model. On the other hand, artificial sialylation of anti-type II collagen antibodies, including ACPAs, not only attenuates arthritogenic activity, but also suppresses the development of CIA in the antibody-infused mice, whereas sialylation of other IgG does not prevent CIA. Thus, our data demonstrate that sialylation levels control the arthritogenicity of RA-associated IgG, presenting a potential target for antigen-specific immunotherapy. PMID:27046227

  18. IgG Adhesion on Hydrophobic Surfaces: Theory, Modelling, and Application to ELISA

    CERN Document Server

    de Thier, P

    2016-01-01

    Enzyme-Linked ImmunoSorbent Assays (ELISA) are a range of widely used analytical methods whose implementation requires to build antibodies (IgG) thin films onto surfaces predominantly made of polystyrene. The high hydrophobicity of polystyrene ensures a spontaneous and strong adhesion of proteins allowing to easily build IgG monolayers. Since the ELISA improvements definitely lie in the comprehension of physico-chemical mechanisms on which IgG immobilization on hydrophobic surfaces are relied, this work develops a theorization essay (thermodynamics of the so-called hydrophobic effect and of thin films building) emphasized by numerical modelling (random sequential additions model, i.e. RSA) and experimental estimations by atomic force microscopy (AFM) and ELISA. Keeping in mind the hydrophobic effect, thermodynamics (of irreversible processes) allows to explain why IgG adhesion on polystyrene occurs whereas numerical modelling approaches show a way of surface saturation leading to promote IgG orientations expe...

  19. Low avidity IgG antibodies in diagnosis of recent human schistosomiasis.

    Science.gov (United States)

    Mostafa, Nahed E; Awad, Adel; Shalaby, Mohsen

    2002-12-01

    One hundred thirty school children from a schistosomiasis endemic area in Sharkia Governorate, were selected on parasitological findings. Seventy persons were negative on the first screen and turned positive after 3 months of the screening (recently infected). Stool examination, ELISA (IgG & IgM), low avid IgG, and circulating antigens were performed for all patients and controls. ELISA detected IgM in all cases. IgG and circulating antigens in 90% of schistosomiasis patients. Low avidity IgG were detected in 85.71% of recent cases. The specificity of ELISA appeared to be >99%. The IgM/IgG ratio was >1 in patients with recent infection. The percentage of fall of O.D. readings of IgG after addition of 6 molar urea was high among cases with recent infection. Low avid lgG appears to be good and valuable in diagnosis of recent schistosomiasis in man. PMID:12512829

  20. Isolation and characterization of a monoclonal anti-protein kinase CK2 beta-subunit antibody of the IgG class for the direct detection of CK2 beta-subunit in tissue cultures of various mammalian species and human tumors

    DEFF Research Database (Denmark)

    Nastainczyk, W; Schmidt-Spaniol, I; Boldyreff, B;

    1995-01-01

    A murine monoclonal anti-protein kinase CK2 beta antibody was isolated and characterized. The antibody detects 1 pmol of purified recombinant CK2 beta-subunit after analysis on SDS-PAGE. Alternatively undenatured CK2 beta-subunit was detected by an ELISA assay either as recombinant CK2 beta-subun...

  1. The Study of IgG Subclass Profiles of Anti-HBc in Populations with Different Status of HBV Infection

    Institute of Scientific and Technical Information of China (English)

    Yu-Yen Yang; Chi-Chiang Yang; Chien-Fu Huang; James Cheng-Chung Wei; Mei-Shang Ho; Lina Wang; Shyh-Jye Lin; Wei-Yu Tsai; Chien-Chou Lin; Fangling Xu

    2005-01-01

    To study IgG subclasses for the hepatitis B virus (HBV) core antigen (anti-HBc) in different populations, a comparison was made between 104 chronic carriers (60 male and 44 female) and 434 recovered individuals (247 male and 192 female). Biochemistry analyses of AST (aspartate aminotransferase) and ALT (alanine aminotransferase) were also performed. Among the 104 chronic carriers, 21 patients were found to be ALT and AST abnormal (> 25 IU/ml). After comparing these ALT and AST abnormal patients with other ALT and AST normal chronic carriers, no statistical difference was observed in the OD values of the anti-HBe (p > 0.05). The ELISA results showed the anti-HBc IgG subclass pattern was IgG1 > IgG3 > IgG4 in chronic carriers and IgG3 > IgG1 > IgG4 in recovered individuals (p < 0.05). This result suggests the IgG1/IgG3 ratio may be related with HBV status. However, in spite of the different anti-HBc IgG1/IgG3 patterns demonstrated in different populations, both anti-HBc IgG1 and IgG3 concentrations were significantly higher in chronic carriers (p < 0.05). Therefore, both the anti-HBc IgG1/IgG3 ratio and their amounts differed. They may play a significant role in chronic carriers and recovered individuals. The anti-HBc IgG subclass profiles of chronic carriers were not changed regardless of liver inflammation, and were independent of sex and age. Cellular & Molecular Immunology.

  2. Protective role of mouse IgG1 in cryoglobulinaemia; insights from an animal model and relevance to human pathology.

    Science.gov (United States)

    Chemouny, Jonathan Maurice; Hurtado-Nedelec, Margarita; Flament, Héloïse; Ben Mkaddem, Sanae; Daugas, Eric; Vrtovsnik, François; Berthelot, Laureline; Monteiro, Renato C

    2016-08-01

    Strait et al. described a novel mouse model of cryoglobulinaemia by challenging mice deficient in the immunoglobulin (Ig)G1 subclass (γ1(-) mice) with goat anti-mouse IgD [5]. The phenotype of wild-type mice was not remarkable, whereas γ1(-) mice developed IgG3 anti-goat IgG cryoglobulins as well as severe and lethal glomerulonephritis. Renal phenotype could not be rescued in γ1(-) mice by the deletion of C3, fragment crystalline γ receptor (FcγR) or J chain. On the other hand, early injection of IgG1, IgG2a or IgG2b inhibited the pathogenic effects of IgG3 in an antigen-dependent manner even in the absence of the FcγRIIb, an anti-inflammatory receptor. The authors concluded that the pathogenic role of IgG3 and the protective characteristic of IgG1 in this model were not explained by their abilities to bind to FcRs or effector molecules but are rather due to structural discrepancies enhancing the precipitation properties/solubility of IgG3/IgG1-containing immune complexes. The present article aims to discuss the current knowledge on IgG biology and the properties of IgGs explaining their differential propensity to acquire cryoglobulin activity. PMID:26410885

  3. Assessing drivers of the IgG4 antibody reactivity to recombinant antigen Bm14 in Wuchereria bancrofti endemic populations in East Africa.

    Science.gov (United States)

    Damgaard, Johanne; Meyrowitsch, Dan W; Rwegoshora, Rwehumbiza T; Magesa, Stephen M; Mukoko, Dunstan A; Simonsen, Paul E

    2016-09-01

    A high proportion of the human population in lymphatic filariasis (LF) endemic areas is positive for filarial specific IgG4 antibodies, including many individuals without microfilariae (mf; circulating larvae in the human blood) or circulating filarial antigens (CFA; marker of adult worm infection). The antibodies are commonly regarded as markers of infection and/or exposure to filarial larvae, but a direct association between the antibodies and these indices has not been well documented. The present study assessed the role and relative effect of potential drivers of the human IgG4 antibody reactivity to the recombinant filarial antigen Bm14 in Wuchereria bancrofti endemic populations in East Africa. Sera collected during previous studies from 395 well characterized individuals with regard to age, sex, mf, CFA, household vector biting and household exposure to infective filarial larvae were tested for IgG4 antibodies to Bm14, and associations between antibody reactivity and the different variables were statistically analyzed. IgG4 reactivity to Bm14 was highly positively associated with CFA, and to a lesser extent with age. However, an expected association with household exposure to infective filarial larvae was not found. Bm14 antibody reactivity thus appeared mainly to reflect actual infection of individuals with adult filarial worms rather than ongoing exposure to transmission. The analyses moreover suggested that many of the CFA negative but Bm14 positive individuals had early or low level infections where antibodies had been induced but where CFA was not (yet?) measurable. Although the study indicated that IgG4 reactivity to Bm14 is a marker of filarial infection, assessment of this reactivity, especially in children, will still be useful for indirect monitoring of changes in transmission intensity, including break of transmission and post-elimination surveillance, in LF control. PMID:27172877

  4. Diagnosis and treatment advances of IgG4-related disease%IgG4相关性疾病的诊治及进展

    Institute of Scientific and Technical Information of China (English)

    高丽霞

    2016-01-01

    IgG4相关性疾病(IgG4 related disease,IgG4-RD)是一类病因不明的慢性系统性自身免疫性疾病.IgG4-RD临床谱广泛,常累及全身多部位腺体、腹膜后组织、肾脏、垂体及淋巴结.IgG4-RD的主要临床特征是受累器官肿胀、纤维化和硬化,血清IgG4水平明显升高,受累组织和器官中大量淋巴细胞和IgG4阳性的浆细胞浸润.IgG4-RD的确诊主要依赖组织病理学活检,该疾病的组织病理学特征为:大量淋巴细胞和浆细胞浸润、组织席纹状纤维化和硬化以及闭塞性静脉炎.糖皮质激素是诱导缓解的首选药物,有些患者需要联合免疫抑制剂或生物制剂.%IgG4 related disease (IgG4-RD)is a kind of chronic systemic autoimmune disease,whose etiology is unknown.The clinical spectrum of IgG4-RD is wide. The disease always involves systemic glandular organs, retroperitoneum,kidney,pituitary gland and lymph nodes.IgG4-RD is characterized by swelling and fibrosclerosing change of affected organs,elevated serum IgG4 level,a large number of lymphocytes and IgG4 positive plasma cells infiltration in involved organ and tissue.The diagnosis is confirmed by biopsy,the histopathological features include:dense lymphocytes and plasmacytes infiltration,storiform fibrosis and sclerosis,obliterative phlebitis.Glucocorticoids are the first-line agent for remission induction,some IgG4-RD patients require the use of immunosuppressive drugs or biological agents.

  5. Prognostic value of intrathecal IgG synthesis in multiple sclerosis: a study in 54 patients

    Directory of Open Access Journals (Sweden)

    Aghamohammadi A

    2008-06-01

    Full Text Available Background: Multiple sclerosis (MS is an inflammatory disease of the central nervous system with multifocal areas of demyelination. Despite an increased understanding of the mechanisms causing MS, immunological factors that indicate disease activity are only starting to be discovered. Chronic brain inflammation is often associated with an increase in production of IgG in the CSF as determined by the IgG index (normal ≤0.77 and oligoclonal bands (OCBs. Different studies have found variable correlations between these two factors and disease progression. We herein evaluate the correlation of IgG index and OCB with disease progression in Iranian MS patients.Methods: The IgG index was measured in 54 patients with multiple sclerosis. The progression index (PI, type of disease course and the presence of OCBs were compared in patients with normal, high and very high IgG index.Results: PI was higher in patients with very high IgG indexes (0.10±0.13 vs. patients with high (0.06±0.05 and normal IgG indexes (0.05±0.07; p>0.05. Secondary progressive (SP patients had higher IgG indexes than those with relapsing-remitting (RR courses (2.04±1.24 for SP vs. 1.78±1.45 for RR; p>0.05. The PI was higher in OCB-positive MS patients (0.08±0.10 vs. OCB-negative patients (0.05±0.04 (p>0.05.Conclusion: Although the findings of this study need to be treated with some caution since this is not a prospective evaluation, the results indicate a trend toward better prognosis of the disease in patients with lower IgG index values. We think that the IgG index is a useful marker of disease activity in MS. Patients with IgG indexes above 1.1 could have an increased risk of progression and they would benefit from early treatment with immunomodulator agents. Our results did not reveal statistically significant prognostic value for IgG index in patients with multiple sclerosis. Thus the results warrant prospective studies to verify the prognostic value of intrathecal IgG

  6. Concurrent systemic AA amyloidosis can discriminate primary sclerosing cholangitis from IgG4-associated cholangitis

    Institute of Scientific and Technical Information of China (English)

    Takehiro Kato; Atsumasa Komori; Sung-Kwan Bae; Kiyoshi Migita; Masahiro Ito; Yasuhide Motoyoshi; Seigo Abiru; Hiromi Ishibashi

    2012-01-01

    Chronic hepatobiliary inflammatory diseases are not widely acknowledged as underlying disorders of systemic AA amyloidosis, except epidemic schistosomiasis. Among them, primary sclerosing cholangitis (PSC) might initiate amyloid A protein deposition in diverse tissues, giving rise to systemic amyloidosis, due to a progressive and unresolved inflammatory process, and its possible association with inflammatory bowel diseases. Nevertheless, only one such case has been reported in the literature to date. We report a 69-yearold Japanese woman with cirrhosis who was diagnosed with PSC complicated with systemic AA amyloidosis, without any evidence of other inflammatory disorders. As a result of cholestasis in conjunction with biliary strictures and increased serum IgG4, the presence of IgG4+ plasma cells was examined systemically, resulting in unexpected documentation of Congo-red-positive amyloid deposits, but not IgG4+ plasma cells, in the liver, stomach and salivary glands. Elevated serum IgG4 is the hallmark of IgG4-related disease, including IgG4-associated cholangitis, but it has also been demonstrated in certain patients with PSC. Amyloid A deposits in multiple organs associated with an indolent clinical course that progresses over many years might have a diagnostic value in discriminating PSC from IgG4-associated cholangitis.

  7. Concurrent systemic AA amyloidosis can discriminate primary sclerosing cholangitis from IgG4-associated cholangitis.

    Science.gov (United States)

    Kato, Takehiro; Komori, Atsumasa; Bae, Sung-Kwan; Migita, Kiyoshi; Ito, Masahiro; Motoyoshi, Yasuhide; Abiru, Seigo; Ishibashi, Hiromi

    2012-01-14

    Chronic hepatobiliary inflammatory diseases are not widely acknowledged as underlying disorders of systemic AA amyloidosis, except epidemic schistosomiasis. Among them, primary sclerosing cholangitis (PSC) might initiate amyloid A protein deposition in diverse tissues, giving rise to systemic amyloidosis, due to a progressive and unresolved inflammatory process, and its possible association with inflammatory bowel diseases. Nevertheless, only one such case has been reported in the literature to date. We report a 69-year-old Japanese woman with cirrhosis who was diagnosed with PSC complicated with systemic AA amyloidosis, without any evidence of other inflammatory disorders. As a result of cholestasis in conjunction with biliary strictures and increased serum IgG4, the presence of IgG4(+) plasma cells was examined systemically, resulting in unexpected documentation of Congo-red-positive amyloid deposits, but not IgG4(+) plasma cells, in the liver, stomach and salivary glands. Elevated serum IgG4 is the hallmark of IgG4-related disease, including IgG4-associated cholangitis, but it has also been demonstrated in certain patients with PSC. Amyloid A deposits in multiple organs associated with an indolent clinical course that progresses over many years might have a diagnostic value in discriminating PSC from IgG4-associated cholangitis.

  8. Igg Subclasses Targeting the Flagella of Salmonella enterica Serovar Typhimurium Can Mediate Phagocytosis and Bacterial Killing

    Science.gov (United States)

    Goh, Yun Shan; Armour, Kathryn L; Clark, Michael R; Grant, Andrew J; Mastroeni, Pietro

    2016-01-01

    Invasive non-typhoidal Salmonella are a common cause of invasive disease in immuno-compromised individuals and in children. Multi-drug resistance poses challenges to disease control, with a critical need for effective vaccines. Flagellin is an attractive vaccine candidate due to surface exposure and high epitope copy number, but its potential as a target for opsonophacytic antibodies is unclear. We examined the effect of targeting flagella with different classes of IgG on the interaction between Salmonella Typhimurium and a human phagocyte-like cell line, THP-1. We tagged the FliC flagellar protein with a foreign CD52 mimotope (TSSPSAD) and bacteria were opsonized with a panel of humanised CD52 antibodies with the same antigen-binding V-region, but different constant regions. We found that IgG binding to flagella increases bacterial phagocytosis and reduces viable intracellular bacterial numbers. Opsonisation with IgG3, followed by IgG1, IgG4, and IgG2, resulted in the highest level of bacterial uptake and in the highest reduction in the intracellular load of viable bacteria. Taken together, our data provide proof-of-principle evidence that targeting flagella with antibodies can increase the antibacterial function of host cells, with IgG3 being the most potent subclass. These data will assist the rational design of urgently needed, optimised vaccines against iNTS disease. PMID:27366588

  9. Optimization of the cutoff value for a commercial anti-dengue virus IgG immunoassay.

    Science.gov (United States)

    Marrero-Santos, Karla M; Beltrán, Manuela; Carrión-Lebrón, Jessica; Sanchez-Vegas, Carolina; Hamer, Davidson H; Barnett, Elizabeth D; Santiago, Luis M; Hunsperger, Elizabeth A

    2013-03-01

    A commercial anti-dengue virus (anti-DENV) indirect IgG enzyme-linked immunosorbent assay (ELISA) for serological diagnosis was evaluated for its utility in determining previous DENV exposure in U.S. travelers. The Boston Area Travel Medicine Network clinics used Focus Diagnostics anti-DENV IgG ELISA to measure anti-DENV IgG antibodies in 591 pretravel specimens from U.S. residents who had traveled to countries where dengue is endemic. When using the manufacturer's index cutoff value for this ELISA, false-positive results were observed that overestimated the perceived past DENV exposure in U.S. travelers. Validation of 121 of these anti-DENV IgG results by plaque reduction neutralization test (PRNT) was used for receiver operating characteristic (ROC) curve optimization of the index cutoff value from 1 to 3.0, improving the specificity of the anti-DENV IgG ELISA from 24% to 95.7%. Additionally, previous vaccination with yellow fever virus contributed to 52.8% of the false-positive rate in the anti-DENV IgG ELISA results. Optimization of the cutoff value of the anti-DENV IgG ELISA provided better interpretation and confidence in the results and eliminated the need for confirmation by PRNT. The travel history of U.S. travelers was also useful for categorizing these travelers into groups for analysis of previous DENV exposure. PMID:23302742

  10. IgG4-related tubulointerstitial nephritis associated with only lymphadenopathy and without elevated serum IgG4 or renal imaging abnormalities: a case report and literature review.

    Science.gov (United States)

    Qiao, Xi; Wang, Lihua; Wang, Chen; Gao, Lifang; Yao, Shulei; Wu, Liran; Zhang, Xiaoqin

    2015-01-01

    IgG4-related tubulointerstitial nephritis (IgG4-TIN) is the most common renal manifestation of IgG4-related kidney disease (IgG4-RKD) and may cause acute or chronic renal dysfunction. Imaging often shows heterogeneous densities in the kidneys, such as a mass or multiple nodules. Serology usually demonstrates high levels of serum IgG4 and total IgG. Most patients have other organs involvement by IgG4 related disease. Although lymphadenopathy is frequently observed in patients with IgG4-TIN, it is rarely presented as the only extrarenal lesion. Herein, we present a rare case of IgG4-TIN associated with only lymphadenopathy and without elevated serum IgG4 or renal imaging abnormalities. A 61-year-old Chinese man was admitted to our hospital with seven months history of generalized lymphadenopathy and five months history of renal dysfunction. His renal imaging was normal. He had no current or previous clinical, radiographic, and/or histologic evidence of other organ involvement except for the lymphadenopathy. Renal biopsy indicated plasma cell-rich TIN with an increased number of IgG4-positive plasma cells and storiform fibrosis. Repeated lymph nodes biopsy revealed IgG4-related lymphadenopathy. However, he did not have elevated serum IgG4 or total IgG levels. Oral prednisone therapy improved his renal function and lymphadenopathy. These findings supported our final diagnosis of IgG4-TIN. Clinicians should be aware of this condition and steroid therapy should be considered for such patients. An early diagnosis and appropriate therapy can induce remission and preserve renal function. PMID:26770608

  11. Comparison patterns of 4 T1 antigens recognized by humoral immune response mediated by IgG and IgM antibodies in female and male mice with breast cancer using 2D-immnunoblots.

    Science.gov (United States)

    Díaz-Zaragoza, Mariana; Hernández-Ávila, Ricardo; Govezensky, Tzipe; Mendoza, Luis; Meneses-Ruíz, Dulce María; Ostoa-Saloma, Pedro

    2015-09-01

    The early detection of cancer is one of the most promising approaches to reduce its growing burden and develop a curative treatment before the tumor is established. The early diagnosis of breast cancer is the most demanding of all tumors, because it is the most common cancer in women worldwide. We have described a new approach to analyze humoral immune reactions against 4 T1 cell antigens in female mice, reporting that the IgG and IgM responses differed and varied over time and between individuals. In this study, we compared and analyzed the detection of tumor antigens with IgG and IgM from the sera of male mice that were injected with 4 T1 cells into the mammary gland nipple in 2D immunoblot images. The variability in IgM and IgG responses in female and male mice with breast cancer at various stages of disease was characterized, and the properties with regard to antigen recognition were correlated statistically with variables that were associated with the individuals and tumors. The ensuing IgG and IgM responses differed. Only the IgG response decreased over time in female mice--not in male mice. The IgM response was maintained during tumor development in both sexes. Each mouse had a specific pattern of antigen recognition--ie, an immunological signature--represented by a unique set of antigen spots that were recognized by IgM or IgG. These data would support that rationale IgM is a better tool for early diagnosis, because it is not subject to immunosuppression like IgG in female mice with breast cancer. PMID:26026196

  12. Immunoglobulin G4-related cholangitis: a variant of IgG4-related systemic disease.

    Science.gov (United States)

    Novotný, Ivo; Dítě, Petr; Trna, Jan; Lata, Jan; Husová, Libuše; Geryk, Edvard

    2012-01-01

    IgG4-related sclerosing cholangitis as part of IgG4 systemic-related diseases is commonly associated with autoimmune pancreatitis. Major clinical manifestations of IgG4-related sclerosing diseases are apparent in the organs in which tissue fibrosis with obstructive phlebitis is pathologically induced. IgG4-related sclerosing cholangitis is included within the heterogeneous group of 'sclerosing cholangitis'. Sclerosing cholangitis may be associated with choledocholithiasis, infection or biliary malignancies. Sclerosing cholangitis of unknown etiology is called primary sclerosing cholangitis (PSC). Conservative therapy of PSC is usually unsuccessful, the disease involves extra- and/or intrahepatic biliary tree, and the end point of this disease is liver cirrhosis. Typically, PSC is identified at the age of 30 to 40 years, and the disease is frequently associated with inflammatory bowel diseases. On the other hand, IgG4-related sclerosing cholangitis is not associated with inflammatory bowel diseases. In patients with IgG4-related sclerosing cholangitis, a first symptom can be obstructive jaundice, whereas obstructive jaundice is rarely present in PSC. Clinically, patients with IgG4-related sclerosing cholangitis are older at diagnosis compared to patients with PSC. A typical diagnostic feature of IgG4-related sclerosing cholangitis is elevation of serum immunoglobulin G4. In patients with IgG4-related sclerosing cholangitis, response to steroid therapy is high; in patients with PSC corticosteroid therapy is unsuccessful. Histochemically abundant infiltration of IgG4-positive plasma cells is detected in the biliary duct wall. Histologically, we can identify dense lymphoplasmacytic infiltration of the bile duct wall, transmural fibrosis, lymphoplasmacytic infiltration and fibrosis in the periportal area of the liver - a typically obliterative phlebitis. The biliary epithelium is usually intact in contrast to PSC, where mucosal erosion is often present. Steroids are the

  13. IgG4-related lung disease manifested as pneumonia in puerperium: a case report

    OpenAIRE

    Wang, Jinlin; Zeng, Yunxiang; Gu, Yingying; Li, Shiyue

    2015-01-01

    IgG4-related lung disease (IgG4-RLD) is recently emerging entity. Several reports concerned with the clinicopathologic feature have been described, but this disease in puerperium has not been reported previously. Here, we report a 24-year-old woman diagnosed as IgG4-RLD in puerperium, who developed dry cough, low fever and exertional dyspnea following the delivery. The inflammatory markers and pulmonary lesions of the patient suggested pneumonia. However, there was no improvement after antibi...

  14. Optimization of the Cutoff Value for a Commercial Anti-Dengue Virus IgG Immunoassay

    OpenAIRE

    Marrero-Santos, Karla M.; Beltrán, Manuela; Carrión-Lebrón, Jessica; Sanchez-Vegas, Carolina; Hamer, Davidson H; Barnett, Elizabeth D.; Luis M Santiago; Hunsperger, Elizabeth A.

    2013-01-01

    A commercial anti-dengue virus (anti-DENV) indirect IgG enzyme-linked immunosorbent assay (ELISA) for serological diagnosis was evaluated for its utility in determining previous DENV exposure in U.S. travelers. The Boston Area Travel Medicine Network clinics used Focus Diagnostics anti-DENV IgG ELISA to measure anti-DENV IgG antibodies in 591 pretravel specimens from U.S. residents who had traveled to countries where dengue is endemic. When using the manufacturer's index cutoff value for this...

  15. Diagnostic Value of Serum IgG4 for IgG4-Related Disease: A PRISMA-compliant Systematic Review and Meta-analysis.

    Science.gov (United States)

    Hao, Mingju; Liu, Min; Fan, Gaowei; Yang, Xin; Li, Jinming

    2016-05-01

    Many studies about serum IgG4 for the diagnosis of IgG4-related disease (IgG4-RD) have been reported. However, these studies had relatively small sample sizes and the diagnostic accuracy values varied much between them.The aim of this study was to perform a meta-analysis to evaluate the diagnostic value of serum IgG4 for IgG4-RD.We conducted a search of relevant articles using MEDLINE, EMBASE, Web of Science, SCOPUS, and Cochrane Library databases published before December 2015.Studies those assessed the diagnostic accuracy of serum IgG4 for IgG4-RD and those provided the cut-off value for serum IgG4 were included.Data were synthesized using the random-effect model. Statistical analysis was performed using STATA with the MIDAS module and Meta-DiSc 1.4 software.A total of 9 case-control studies were analyzed, which included 1235 patients with IgG4-RD and 5696 overall controls. The pooled estimate, for a cut-off value ranged from 135 to 144 mg/dL, produced a sensitivity of 87.2% (95% CI, 85.2-89.0%) and a specificity of 82.6% (95% CI, 81.6-83.6%). The positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 6.48 (95% CI, 3.98-10.57), 0.14 (95% CI, 0.09-0.21), and 45.15 (95% CI, 23.41-87.06), respectively. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) was 0.94 (0.92-0.96). When a cut-off value of 2-fold the upper limit of normal was used (ranged from 270 to 280 mg/dL), the pooled sensitivity was 63% (95% CI, 60.0-66.0%), and the specificity was 94.8% (95% CI, 94.1-95.4%). The PLR, NLR, and DOR were 13.3 (95% CI, 7.39-24.0), 0.41 (95% CI, 0.29-0.58) and 33.42 (95% CI, 13.88-80.43), respectively. The AUC of the SROC was 0.92 (0.90-0.94).Only a relatively small number of studies were included, and significant heterogeneity was observed in this meta-analysis.Serum IgG4 is a modestly effective marker to diagnose IgG4-RD. Doubling the cut-off value for IgG4 could not improve the

  16. Impairment of pneumococcal antigen specific isotype-switched Igg memory B-cell immunity in HIV infected Malawian adults.

    Directory of Open Access Journals (Sweden)

    Oluwadamilola H Iwajomo

    Full Text Available Pneumococcal disease is associated with a particularly high morbidity and mortality amongst adults in HIV endemic countries. Our previous findings implicating a B-cell defect in HIV-infected children from the same population led us to comprehensively characterize B-cell subsets in minimally symptomatic HIV-infected Malawian adults and investigate the isotype-switched IgG memory B-cell immune response to the pneumococcus. We show that similar to vertically acquired HIV-infected Malawian children, horizontally acquired HIV infection in these adults is associated with IgM memory B-cell (CD19(+ CD27(+ IgM(+ IgD(+ depletion, B-cell activation and impairment of specific IgG B-cell memory to a range of pneumococcal proteins. Our data suggest that HIV infection affects both T-cell independent and T-cell dependent B-cell maturation, potentially leading to impairment of humoral responses to extracellular pathogens such as the pneumococcus, and thus leaving this population susceptible to invasive disease.

  17. Dynamics evaluation of total IgG, IgG1 and IgG2a in the serum of mice immunized with radioattenuated paracoccidioides brasiliensis yeast cells

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Estefania M.N.; Andrade, Antero S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)]. E-mail: estefaniabio@yahoo.com.br; antero@cdtn.br; Reis, Bernardo S.; Goes, Alfredo M. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia]. E-mail: brsgarbi@mono.icb.ufmg.br; goes@mono.icb.ufmg.br

    2007-07-01

    Paracoccidioides brasiliensis is the fungus agent of paracoccidioidomycosis, a deep-seated systemic infection of humans. Up to the moment no vaccine has still been reported. The potential of gamma radiation for pathogens attenuation and vaccine development was explored in this work. In our laboratory we developed radioattenuated yeast cells of P. brasiliensis and the aim of the present work was to evaluate the antibody production dynamics in mice immunized with this cells. Were analyzed the IgG antibodies titers as well as the type of response by analyzing the IgG1 and IgG2a antibody pattern in the course of infection. The mice were divided in two groups that were immunized one time and two times respectively. The mice infected with the virulent P. brasiliensis showed a high level of antibody production while the infection with the radioattenuated yeast did not significantly change the antibody level. The level of IgG raised in both immunized groups after the challenge. In the group immunized one time was not observed a significant difference between the levels of both subclasses when compared with the control. After the challenge of the group immunized two times the IgG2a levels increased significantly when analyzed 90 days post challenge. We concluded that a pattern related to the disease control was apparent in the group submitted to two immunizations. The mice had not developed a totally polarized pattern of TH1/TH2 response but a trend to a TH1 response was evident. (author)

  18. Maternofetal transplacental transport of recombinant IgG antibodies lacking effector functions

    DEFF Research Database (Denmark)

    Mathiesen, Line; Nielsen, Leif K; Andersen, Jan Terje;

    2013-01-01

    alloimmunity, which may be lethal. A novel strategy to control pathogenic antibodies would be administration of a non-destructive IgG antibody blocking antigen binding while retaining binding to FcRn. We report on two human IgG3 antibodies with a hinge deletion and a C131S point mutation (IgG3ΔHinge......) that eliminate complement activation and binding to all classical Fcγ receptors (FcγRs) and to C1q while binding to FcRn is retained. Additionally, one of the antibodies has a single point mutation in the Fc (R435H) at the binding site for FcRn (IgG3ΔHinge:R435H). We compared transplacental transport with wild...

  19. IgG4-related disease: a systemic condition with characteristic microscopic features

    DEFF Research Database (Denmark)

    Detlefsen, Sönke

    2013-01-01

    observation that many patients suffering from autoimmune pancreatitis (AIP), a specific type of chronic pancreatitis, had elevated serum levels of IgG4, it was reported that these patients also had increased numbers of IgG4-positive cells in the inflamed pancreatic tissue. In 2003, it was noted that a...... diseases on their own, others have been included under the umbrella of "multifocal fibrosclerosis". Biopsies or resection specimens from affected organs in IgG4-RD reveal several common microscopic features irrespective of the site of the lesion. Cellular and storiform fibrosis, lymphoplasmacytic...... microscopic features, diagnosis and differential diagnosis of the different organ manifestations of IgG4-RD, and the current concepts of its pathogenesis will also be addressed....

  20. Perivascular fibrosis and IgG4-related disease: a case report

    Directory of Open Access Journals (Sweden)

    S. Monti

    2014-11-01

    Full Text Available Immunoglobulin G4-related disease (IgG4-RD is a newly recognized fibroinflammatory condition which can potentially involve any organ. Some characteristic histopathologic features with lymphoplasmacytic infiltrate, an increased number of IgG4+ cells, storiform fibrosis and obliterative phlebitis are the mainstay for diagnosis. Serum IgG4 levels often increase. We report the case of a patient with perivascular fibrotic lesions involving the aortic arch and the splenic hilum, with a surgical biopsy-proven diagnosis of IgG4-related disease. The patient is now undergoing a low-dose corticosteroid maintenance therapy without evidence of new localizations of the disease. This case highlights the need for increasing awareness and recognition of this new, emerging clinical condition.

  1. The Emerging Importance of IgG Fab Glycosylation in Immunity.

    Science.gov (United States)

    van de Bovenkamp, Fleur S; Hafkenscheid, Lise; Rispens, Theo; Rombouts, Yoann

    2016-02-15

    Human IgG is the most abundant glycoprotein in serum and is crucial for protective immunity. In addition to conserved IgG Fc glycans, ∼15-25% of serum IgG contains glycans within the variable domains. These so-called "Fab glycans" are primarily highly processed complex-type biantennary N-glycans linked to N-glycosylation sites that emerge during somatic hypermutation. Specific patterns of Fab glycosylation are concurrent with physiological and pathological conditions, such as pregnancy and rheumatoid arthritis. With respect to function, Fab glycosylation can significantly affect stability, half-life, and binding characteristics of Abs and BCRs. Moreover, Fab glycans are associated with the anti-inflammatory activity of IVIgs. Consequently, IgG Fab glycosylation appears to be an important, yet poorly understood, process that modulates immunity.

  2. Diagnostic value of CagA IgG in the process to eradicate Helicobacter pylori

    Institute of Scientific and Technical Information of China (English)

    Zhi Bang Yang; Pi Long Wang; Ming Ming Gu; Li Hao Chen; Quan Chen; Lin Zhan

    2000-01-01

    AIM To investigate the diagnostic value of CagA IgG in serum.METHODS Seventy three patients with peptic ulcer infected with HP were eradicated by antibioticstherapy. At pretreatment, wk9 and wk20 after treatment, the detection of Hp in gastric muscosa bybacteriologic method were performed, and CagA and whole-cell antigen of HP igG in serum by ELISAmethod were also performed at the same time.RESULTS The IgG titres of Hp CagA and whole-cell antigen changes in accordance with the efficacy ofHp eradicated. The former with an earlier appearance and a greater number of cases decreased to normallevel in comparison with the latter.CONCLUSION CagA IgG is a better index for observing the effectiveness of the eradication of Hp.

  3. Interactions between DMPC liposomes and the serum blood proteins HSA and IgG.

    Science.gov (United States)

    Sabín, Juan; Prieto, Gerardo; Ruso, Juan M; Messina, Paula V; Salgado, Francisco J; Nogueira, Montserrat; Costas, Miguel; Sarmiento, Félix

    2009-02-12

    The interaction between two serum blood proteins, namely human serum albumin (HSA) and human immunoglobulin G (IgG), with 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) liposomes has been studied in detail using dynamic light scattering, flow cytometry, enzyme-linked immunosorbent assay (ELISA), electrophoretic mobility, differential scanning calorimetry (DSC), and surface tension measurements. HSA and IgG interact with liposomes forming molecular aggregates that remain stable at protein concentrations beyond those of total liposome coverage. Both HSA and IgG penetrate into the liposome bilayer. An ELISA assay indicates that the Fc region of IgG is the one that is immersed in the DMPC membrane. The liposome-protein interaction is mainly of electrostatic nature, but an important hydrophobic contribution is also present.

  4. Recombinant AAV Vectors for Enhanced Expression of Authentic IgG.

    Directory of Open Access Journals (Sweden)

    Sebastian P Fuchs

    Full Text Available Adeno-associated virus (AAV has become a vector of choice for the treatment of a variety of genetic diseases that require safe and long-term delivery of a missing protein. Muscle-directed gene transfer for delivery of protective antibodies against AIDS viruses and other pathogens has been used experimentally in mice and monkeys. Here we examined a number of variations to AAV vector design for the ability to produce authentic immunoglobulin G (IgG molecules. Expression of rhesus IgG from a single single-stranded AAV (ssAAV vector (one vector approach was compared to expression from two self-complementary AAV (scAAV vectors, one for heavy chain and one for light chain (two vector approach. Both the one vector and the two vector approaches yielded considerable levels of expressed full-length IgG. A number of modifications to the ssAAV expression system were then examined for their ability to increase the efficiency of IgG expression. Inclusion of a furin cleavage sequence with a linker peptide just upstream of the 2A self-cleaving sequence from foot-and-mouth disease virus (F2A increased IgG expression approximately 2 fold. Inclusion of these sequences also helped to ensure a proper sequence at the C-terminal end of the heavy chain. Inclusion of the post-transcriptional regulatory element from woodchuck hepatitis virus (WPRE further increased IgG expression 1.5-2.0 fold. IgG1 versions of the two rhesus IgGs that were examined consistently expressed better than the IgG2 forms. In contrast to what has been reported for AAV2-mediated expression of other proteins, introduction of capsid mutations Y445F and Y731F did not increase ssAAV1-mediated expression of IgG as determined by transduction experiments in cell culture. Our findings provide a rational basis for AAV vector design for expression of authentic IgG.

  5. Recombinant AAV Vectors for Enhanced Expression of Authentic IgG.

    Science.gov (United States)

    Fuchs, Sebastian P; Martinez-Navio, José M; Gao, Guangping; Desrosiers, Ronald C

    2016-01-01

    Adeno-associated virus (AAV) has become a vector of choice for the treatment of a variety of genetic diseases that require safe and long-term delivery of a missing protein. Muscle-directed gene transfer for delivery of protective antibodies against AIDS viruses and other pathogens has been used experimentally in mice and monkeys. Here we examined a number of variations to AAV vector design for the ability to produce authentic immunoglobulin G (IgG) molecules. Expression of rhesus IgG from a single single-stranded AAV (ssAAV) vector (one vector approach) was compared to expression from two self-complementary AAV (scAAV) vectors, one for heavy chain and one for light chain (two vector approach). Both the one vector and the two vector approaches yielded considerable levels of expressed full-length IgG. A number of modifications to the ssAAV expression system were then examined for their ability to increase the efficiency of IgG expression. Inclusion of a furin cleavage sequence with a linker peptide just upstream of the 2A self-cleaving sequence from foot-and-mouth disease virus (F2A) increased IgG expression approximately 2 fold. Inclusion of these sequences also helped to ensure a proper sequence at the C-terminal end of the heavy chain. Inclusion of the post-transcriptional regulatory element from woodchuck hepatitis virus (WPRE) further increased IgG expression 1.5-2.0 fold. IgG1 versions of the two rhesus IgGs that were examined consistently expressed better than the IgG2 forms. In contrast to what has been reported for AAV2-mediated expression of other proteins, introduction of capsid mutations Y445F and Y731F did not increase ssAAV1-mediated expression of IgG as determined by transduction experiments in cell culture. Our findings provide a rational basis for AAV vector design for expression of authentic IgG. PMID:27332822

  6. Oxidative Stress and IgG Antibody Modify Periodontitis-CRP Association.

    Science.gov (United States)

    Singer, R E; Moss, K; Kim, S J; Beck, J D; Offenbacher, S

    2015-12-01

    In a previous report, we demonstrated the inverse association of high serum 8-isoprostane levels, a marker for oxidative stress, with decreased serum IgG antibodies to oral bacteria. The association between increased serum IgG with increased plaque and periodontitis (increased probing depths) was attenuated by high systemic oxidative stress. Other investigations have reported a role for systemic oxidative stress as a stimulus of hepatic C-reactive protein (CRP) response. These observations led us to hypothesize that the reported relationship of periodontitis to elevated serum CRP, a systemic inflammatory marker, may be modified by oxidative stress and that the levels of serum antibodies to oral bacteria might be an intermediary explanatory variable linking the association of systemic oxidative stress, periodontal disease, and levels of CRP. This hypothesis was explored as a secondary analysis of the Dental ARIC (Atherosclerosis Risk in Communities) study using serum levels of CRP, serum IgG levels to 16 oral organisms, serum levels of 8-isoprostane, and periodontal status. The findings indicate periodontitis is associated with high CRP in the presence of elevated oxidative stress that serves to suppress the IgG response. Only within the highest 8-isoprostane quartile was periodontitis (pocket depth) associated with increased serum CRP levels (P = 0.0003). Increased serum IgG antibody levels to oral bacteria were associated with lowered serum CRP levels. Thus, systemic oxidative stress, which has been demonstrated to be associated with increased levels of CRP in other studies, appears to be associated with the suppression of bacterial-specific IgG levels, which in the presence of periodontal disease can result in an enhanced systemic CRP response. Conversely, individuals with increased serum IgG antibodies to plaque bacteria exhibit lowered serum CRP levels. These 2 factors, oxidative stress and the serum IgG response, appear to function in opposing directions to

  7. A study on indirect radiolabeling of IgG with carrier free 188Re

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    188Re labeled monoclonal antibodies are potential candidates for use in radioimmunotherapy. S-Bz-MAG3 as a bifunctional chelating agent was used for labeling of IgG with carrier free 188Re by pre-radiolabeling of the chelating approach. The conjugation conditions were optimized. The stability of 188Re-MAG3-IgG in vitro was high. The results may be useful to the studies of 188Re labeled MAbs for radioimmunotherapy.

  8. Utility of FDG PET/CT in IgG4-related systemic disease

    Energy Technology Data Exchange (ETDEWEB)

    Nakatani, K., E-mail: koyakn@kuhp.kyoto-u.ac.jp [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto (Japan); Nakamoto, Y.; Togashi, K. [Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto (Japan)

    2012-04-15

    IgG4-related systemic disease (IgG4-RSD) is an emerging clinical entity about which much remains to be elucidated, in terms of its aetiology, pathogenesis, diagnosis, treatment and outcome. Autoimmune pancreatitis (AIP) and Mikulicz disease (MD) are the two major, well-studied constituents of IgG4-RSD. AIP and MD have common characteristics of forming tumour-mimicking lesions that consist of lymphoplasmacytic infiltrates and fibrosclerosis with numerous immunoglobulin G4 (IgG4)-positive plasma cells, as well as various multi-organ manifestations of IgG4-RSD. 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose positron-emission tomography/ computed tomography (FDG PET/CT) enables the acquisition of whole-body images and provides functional information about disease activity; as such it has a valuable role in staging extent of disease, guiding biopsy, and monitoring response to treatment. However, FDG PET/CT is likely to be only one component of the management strategy, and clinical, laboratory, imaging and histological findings are crucial in the overall diagnosis of the condition. At present FDG PET/CT does not have a well-established role in the assessment of patients with IgG4-RSD and future prospective studies are required to define the cost-effectiveness and clinical impact in this patient group more accurately.

  9. THE EFFECT OF SLEEP DEPRIVATION ON SERUM IGG RESPONSES TO AEROBIC ACTIVITY IN COLLEGE STUDENT ATHLETES

    Directory of Open Access Journals (Sweden)

    Saeed Jamshidi Far

    2014-11-01

    Full Text Available Background & Aims: Sleep is a restorative process for the immune system. There are many situations in which sleep is disturbed prior to an athletic event. However, the effect of sleep deprivation on immune indices in response to exercise remains unknown. The aim of this study was to investigate the effects of sleep deprivation on serum IgG responses to aerobic activity. Materials & Methods: In this quasi-experimental study, 10 male physical education students were voluntarily participated. Study was performed in two separate occasions; control and experimental within two weeks. In the control occasion, normal sleep and aerobic activity and in the experimental occasion, sleep deprivation and aerobic activity was applied. Aerobic activity was performed on bicycle ergometer for 30 minutes at intensity of 70 to 75 percent of maximum heart rate. Changes in serum IgG concentrations in pre-test, before and after aerobic activity in both occasions were analyzed by the two repeated measures ANOVA and dependent T-test using SPSS software. Results: The results showed that sleep deprivation not significantly effect on Serum IgG response to aerobic activity (p=0.130. Also, aerobic activity not significantly effect on Serum IgG concentration (p=0.357. But sleep deprivation caused a significantly increase in serum IgG concentration (p=0.035. Conclusion: No significant effect of sleep deprivation on serum IgG concentrations response to aerobic activity.

  10. Elbow- and hinge-bending motions of IgG: Dielectric response and dynamic feature.

    Science.gov (United States)

    Hayashi, Yoshihito; Yagihara, Shin

    2016-09-01

    Immunoglobulin G (IgG) is a Y-shaped globular protein consisting of two Fab segments connecting to an Fc segment with a flexible hinge region, in which the Fab segments show secondary flexibility at an "elbow" region. In the present work, the hinge-bending and elbow-bending motions of aqueous solutions of IgG by microwave dielectric measurements below the freezing point of bulk water was observed. The presence of unfreezable water around the macromolecules reduced the effects of steric hindrance normally generated by ice and enabled the intramolecular motions of IgG. At the same time, the overall IgG molecule rotation was restricted by ice. Papain digestion and reduction of the disulfide linkage at the hinge region was used to generate Fab and Fc fragments. In solutions of these fragments, the dielectric relaxation process of the hinge-bending motion was absent, although the elbow-bending motion remained. Three relaxation processes were observed for papain-digested IgG. The high, middle, and low frequency processes were attributed to unfrozen water, local peptide motions cooperating with bound water, and the elbow-bending motion, respectively. In the case of the intact IgG, an additional relaxation process due to the hinge-bending motion was observed at frequencies lower than that of the elbow-bending motion. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 626-632, 2016. PMID:27018805

  11. Enhancement of anti-OVA IgG2c production in vivo by enalapril

    Directory of Open Access Journals (Sweden)

    L.C. Almeida

    2016-01-01

    Full Text Available Angiotensin-converting enzyme (ACE inhibitors have non-hemodynamic, pleiotropic effects on the immune response. The effects of ACE inhibitors on the production of cytokines and T-cell functions are well established. However, little is known on the effects of these medicines on humoral response to foreign antigens. In this study, we investigated the effect of enalapril treatment on ovalbumin (OVA-specific IgG1 and IgG2c production in mice determined by ELISA. Two groups of 8-week-old C57BL/6 females mice (3–4/group were subcutaneously immunized with OVA (10 μg/animal in presence of Alhydrogel (1 mg/mouse and boosted at day 21. The mice were treated with enalapril (5 mg/kg daily, po or were left without treatment for one month. The animals were bled from the orbital plexus on days 0, 7, 14, 21, and 28 after the first immunization and the sera were stored at –20°C until usage. OVA-specific serum IgG1 and IgG2c were determined by ELISA using serum from each individual animal. The results showed that enalapril significantly increased anti-OVA serum IgG2c in the secondary response without affecting IgG1 synthesis. These data expand our understanding on the properties of enalapril on the immune response, including antibody production.

  12. Enhancement of anti-OVA IgG2c production in vivo by enalapril.

    Science.gov (United States)

    Almeida, L C; Muraro, L S; Albuquerque, D A

    2016-07-11

    Angiotensin-converting enzyme (ACE) inhibitors have non-hemodynamic, pleiotropic effects on the immune response. The effects of ACE inhibitors on the production of cytokines and T-cell functions are well established. However, little is known on the effects of these medicines on humoral response to foreign antigens. In this study, we investigated the effect of enalapril treatment on ovalbumin (OVA)-specific IgG1 and IgG2c production in mice determined by ELISA. Two groups of 8-week-old C57BL/6 females mice (3-4/group) were subcutaneously immunized with OVA (10 μg/animal) in presence of Alhydrogel (1 mg/mouse) and boosted at day 21. The mice were treated with enalapril (5 mg/kg daily, po) or were left without treatment for one month. The animals were bled from the orbital plexus on days 0, 7, 14, 21, and 28 after the first immunization and the sera were stored at -20°C until usage. OVA-specific serum IgG1 and IgG2c were determined by ELISA using serum from each individual animal. The results showed that enalapril significantly increased anti-OVA serum IgG2c in the secondary response without affecting IgG1 synthesis. These data expand our understanding on the properties of enalapril on the immune response, including antibody production. PMID:27409332

  13. T-bet regulates T-independent IgG2a class switching.

    Science.gov (United States)

    Gerth, Andrea J; Lin, Ling; Peng, Stanford L

    2003-08-01

    The IgG2a Ig subclass plays a critical role in the pathogenesis of humoral autoimmunity and protection against pathogens. The T-box transcription factor T-bet has been implicated as a critical mediator of class-switch recombination (CSR) to IgG2a, but its relative importance to this process in various immune contexts remains incompletely defined. We report here that, surprisingly, T-bet is selectively required for IgG2a class switching in response to T-independent, but not T-dependent, stimuli. Specifically, T-dependent signaling through CD40, in contrast to T-independent signaling via lipopolysaccharide, can bypass a requirement for T-bet in IgG2a germline transcription and subsequent isotype switching. In contrast, T-bet-deficient B cells undergo class switching to other IgG isotypes at least as well as wild-type counterparts. Thus, T-bet is a class-specific regulator of IgG CSR and represents a unique regulator of B cell differentiation by participating in a T-independent, but not a T-dependent, activation pathway. T-bet-deficient B cells therefore represent a novel paradigm by which to investigate the regulation of humoral immune responses. PMID:12882831

  14. Serum IgG antibodies to C1q in hypocomplementemic urticarial vasculitis syndrome.

    Science.gov (United States)

    Wisnieski, J J; Naff, G B

    1989-09-01

    Urticaria, angioedema, and arthritis are cardinal features of hypocomplementemic urticarial vasculitis syndrome (HUVS). Considered to be an immune complex-mediated disorder, HUVS has been differentiated from systemic lupus erythematosus (SLE), based on its clinical manifestations and the C1q precipitin (C1q-p) reaction, which is manifested as gel precipitation of C1q by a small percentage of HUVS IgG molecules. This phenomenon has been attributed to an Fc region abnormality, and the responsible IgG molecules are said to possess C1q-p activity. We purified IgG from 4 HUVS patients and confirmed that HUVS IgG contains C1q binding activity. F(ab')2 fragments from these patients also bound to C1q, as measured by 2 different C1q binding methods at physiologic ionic strength; HUVS IgG Fc fragments did not bind to C1q. Preincubation of HUVS F(ab')2 fragments with antibody to human F(ab')2 prevented subsequent binding to C1q. We conclude that IgG antibodies to C1q are present in HUVS serum, and it is likely that these antibodies are C1q-p. Because the clinical manifestations of HUVS and the presence of anti-C1q antibodies have been described in patients with SLE, our findings support the concept that HUVS is an autoimmune syndrome related to SLE. PMID:2528353

  15. Active Immunity Induced by Passive IgG Post-Exposure Protection against Ricin

    Directory of Open Access Journals (Sweden)

    Charles Chen Hu

    2014-01-01

    Full Text Available Therapeutic antibodies can confer an instant protection against biothreat agents when administered. In this study, intact IgG and F(ab’2 from goat anti-ricin hyperimmune sera were compared for the protection against lethal ricin mediated intoxication. Similar ricin-binding affinities and neutralizing activities in vitro were observed between IgG and F(ab’2 when compared at the same molar concentration. In a murine ricin intoxication model, both IgG and F(ab’2 could rescue 100% of the mice by one dose (3 nmol administration of antibodies 1 hour after 5 × LD50 ricin challenge. Nine days later, when the rescued mice received a second ricin challenge (5 × LD50, only the IgG-treated mice survived; the F(ab’2-treated mice did not. The experimental design excluded the possibility of residual goat IgG responsible for the protection against the second ricin challenge. Results confirmed that the active immunity against ricin in mice was induced quickly following the passive delivery of a single dose of goat IgG post-exposure. Furthermore, it was demonstrated that the induced active immunity against ricin in mice lasted at least 5 months. Therefore, passive IgG therapy not only provides immediate protection to the victim after ricin exposure, but also elicits an active immunity against ricin that subsequently results in long term protection.

  16. Expression of murine Fc receptors for IgG.

    Science.gov (United States)

    Schreiber, R E; Buku, A; Unkeless, J C

    1990-06-15

    There are two distinct genes that encode murine low affinity Fc gamma RII, murine Fc gamma RII alpha, and murine Fc gamma RII beta, which are transcribed in specific cell lineages. Fc gamma RII alpha transcripts are present in macrophages, NK cells, and mesangial cells; Fc gamma RII beta transcripts are expressed in Fc gamma R-bearing B cells, T cells, and macrophages. We have devised a sandwich ELISA to quantify the expression of Fc gamma RII alpha protein. The ELISA is specific for Fc gamma RII alpha, and does not detect the closely related Fc gamma RII beta protein. Upon stimulation with IFN-gamma the Fc gamma RII beta- macrophage cell line J774a expressed a twelvefold enhanced level of Fc gamma RII alpha protein. Peritoneal macrophages synthesized varying amounts of Fc gamma RII alpha. High levels of Fc gamma RII alpha were observed in resident and thioglycollate-elicited peritoneal macrophages, but no Fc gamma RII alpha was detected in Bacillus Calmette Guérin-elicited macrophages. J774a cells stimulated with rIL-6 bound approximately twice as much anti-Fc gamma RII mAb 2.4G2 IgG as did unstimulated controls. However, the Fc gamma RII alpha-specific ELISA showed no change in the amount of Fc gamma RII alpha expressed. A probe encompassing the extracellular coding sequence of Fc gamma RII beta hybridized to two distinct transcripts that were elevated in rIL-6-stimulated J774a cells. One of these transcripts had the same mobility in electrophoresis as Fc gamma RII alpha mRNA and hybridized to an Fc gamma RII alpha-specific probe, whereas the other transcript was larger and did not hybridize to probes specific for either Fc gamma RII alpha or Fc gamma RII beta. Moreover, we confirmed, with an Fc gamma RII beta-specific probe, that J774a cells do not make Fc gamma RII beta mRNA. Thus, the larger transcript appears to encode a novel Fc gamma RII. We suggest that the increased level of binding of the anti-Fc gamma RII mAb 2.4G2 to rIL-6-induced cells represents

  17. Antiradiation Antitoxin IgG : Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava

    Introduction: High doses of radiation induce apoptotic necrosis of radio-sensitive cells. Mild doses of radiation induce apoptosis or controlled programmed death of radio-sensitive cells with-out development of inflammation and formation of Radiation Toxins. Cell apoptotic necrosis initiates Radiation Toxins (RT)formation. Radiation Toxins play an important role as a trig-ger mechanism for inflammation development and cell lysis. If an immunotherapy approach to treatment of the acute radiation syndromes (ARS) were to be developed, a consideration could be given to neutralization of radiation toxins (Specific Radiation Determinants-SRD) by specific antiradiation antibodies. Therapeutic neutralization effects of the blocking anti-radiation antibodies on the circulated RT had been studied. Radiation Toxins were isolated from the central lymph of irradiated animals with Cerebrovascular(Cv ARS),Cardiovascular (Cr ARS),Gastrointestinal(Gi ARS) and Haemopoietic (Hp ARS) forms of ARS. To accomplish this objective, irradiated animals were injected with a preparation of anti-radiation immunoglobulin G (IgG) obtained from hyperimmune donors. Radiation-induced toxins that we call Specific Radiation Determinants (SRD) possess toxic (neurotoxic, haemotoxic) characteristics as well as specific antigenic properties. Depending on direct physiochemical radiation damage, they can induce development of many of the pathological processes associated with ARS. We have tested several specific hyperimmune IgG preparations against these radiation toxins and ob-served that their toxic properties were neutralized by the specific antiradiation IgGs. Material and Methods: A scheme of experiments was following: 1.Isolation of radiation toxins (RT) from the central lymph of irradiated animals with different form of ARS. 2.Transformation of a toxic form of the RT to a toxoid form of the RT. 3.Immunization of radiation naive animals. Four groups of rabbits were inoculated with a toxoid form of SRD

  18. Clinical fluctuations in MuSK myasthenia gravis are related to antigen-specific IgG4 instead of IgG1

    NARCIS (Netherlands)

    Niks, E H; van Leeuwen, Y; Leite, M I; Dekker, F W; Wintzen, A R; Wirtz, P W; Vincent, A; van Tol, M J D; Jol-van der Zijde, C M; Verschuuren, J J G M

    2008-01-01

    We studied the longitudinal relation between disease severity and titers of antigen-specific IgG subclasses in sera of patients with myasthenia gravis and antibodies to Muscle Specific Kinase (MuSK MG). Six patients were included of whom 55 samples had been collected during 2.5-13.4 years. Anti-MuSK

  19. IgG2 immunodeficiency: association to pediatric patients with bacterial meningoencephalitis Inmunodeficiencia de IgG2: asociación en pacientes pediátricos con meningoencefalitis bacterianas

    Directory of Open Access Journals (Sweden)

    XIOMARA ESCOBAR-PÉREZ

    2000-03-01

    Full Text Available An IgG subclass deficiency is often associated with bacterial infections. We studied four pediatric patients suffering from meningoencephalitis, two of them due to Streptococcus pneumoniae and two due to Haemophilus influenzae type b. Simultaneous diagnostic serum and cerebrospinal fluid samples were taken during income. The four subclasses of IgG and albumin were quantified in both biologic fluids by radial immunodiffusion. Very low levels of seric IgG2 with non detectable cerebrospinal fluid IgG2 were found in the patients. No intrathecal IgG subclass synthesis was found in two patients. One patient with S. pneumoniae had IgG3 intrathecal synthesis. Intrathecal IgG1, IgG3 and IgG4 synthesis was found in one patient suffering from H. influenzae according with reibergrams. Substitutive therapy with intravenous gammaglobulin was given to the patients as part of the treatment.Las deficiencias por subclases de IgG se asocian frecuentemente con infecciones de origen bacteriano. Se estudian cuatro pacientes en edad pediátrica con meningoencefalitis, dos de ellos a Streptococcus pneumoniae y dos a Haemophilus influenzae tipo b. Se toman muestras simultáneas diagnósticas de suero y líquido cefalorraquídeo en el momento del ingreso. Se cuantificaron las cuatro sublclases de IgG y albúmina en ambos líquidos biológicos por inmunodifusión radial. Se encontró que los pacientes presentaban cifras muy disminuidas de IgG2 sérico y ningun exhibia IgG2 en el líquido cefalorraquídeo. Dos pacientes no sintetizaron ninguna subclase de IgG intratecalmente. Un paciente con S. pneumoniae sintetizó IgG3 intratecal. Uno de los pacientes con meningoencefalitis a H. influenzae sintetizó IgG1, IgG3 e IgG4 intratecalmente de acuerdo com el reibergrama. Estos pacientes recibieron terapia substitutiva com gammaglobulina intravenosa como parte de la medicación.

  20. APPRAISAL OF PRENATAL ANTI-TOXOPLASMA GONDII (IGG+IGM)- IHA/IGM-ELISA SCREENING IN SINGLE SAMPLES VIA IGG AVIDITY TEST.

    Science.gov (United States)

    El-Bali, Mohammed; Zaglool, Dina A M; Khodari, Yousif A W; Al-Harthi, Saeed A

    2016-04-01

    Congenital toxoplasmosis is associated with important morbidity and mortality. Since vertical transmission of Toxoplasma gondii can occur in acute cases, antenatal screening for recent infections is vital. Accurate determination of acute toxoplasmosis requires a combination of immunoassays, usually not routinely applied for screening purposes. This study evaluated the anti-T. gondii (IgG+IgM)/IgM prenatal screening procedure by IgG avidity assay. The routine prenatal screening for (IgG+IgM) anti-T. gondii by indirect hemagglutination (IHA) in serum samples was done of 2247 pregnant women who attended two hospitals between 2011 and 2013 revealed 487 (21.7%) positive samples. Examination of IHA-positive sera by IgM and IgG/IgG-avidity concurrent ELISA tests revealed 7 positive and 3 border-line IgM-ELISA titers during the initial check-up of 10 women, who were then followed up at 3-4 week-intervals. Among these, 4 (40%) showed simultaneous high avidity IgG antibodies, indicating distant infection by the parasite, and no anti-T. gondii specific IgG could be detected in follow-up sera of two cases (20%), indicating false IgM initial positive results. Only 4 (40%) women showed simultaneous IgM and low avidity IgG antibodies indicating active infections. Avoidance of an over-diagnosis of acute toxoplasmosis Anti-T. gondii (IgG+IgM)/IgM prenatal screening must be supplemented by a discriminative test like IgG avidity ELISA. PMID:27363056

  1. IL-21 promotes the production of anti-DNA IgG but is dispensable for kidney damage in lyn-/- mice.

    Science.gov (United States)

    Gutierrez, Toni; Mayeux, Jessica M; Ortega, Sterling B; Karandikar, Nitin J; Li, Quan-Zhen; Rakheja, Dinesh; Zhou, Xin J; Satterthwaite, Anne B

    2013-02-01

    The autoimmune disease systemic lupus erythematosus is characterized by loss of tolerance to nuclear Ags and a heightened inflammatory environment, which together result in end organ damage. Lyn-deficient mice, a model of systemic lupus erythematosus, lack an inhibitor of B-cell and myeloid cell activation. This results in B-cell hyper-responsiveness, plasma cell accumulation, autoantibodies, and glomerulonephritis (GN). IL-21 is associated with autoimmunity in mice and humans and promotes B-cell differentiation and class switching. Here, we explore the role of IL-21 in the autoimmune phenotypes of lyn(-/-) mice. We find that IL-21 mRNA is reduced in the spleens of lyn(-/-) IL-6(-/-) and lyn(-/-) Btk(lo) mice, neither of which produce pathogenic autoantibodies or develop significant GN. While IL-21 is dispensable for plasma cell accumulation and IgM autoantibodies in lyn(-/-) mice, it is required for anti-DNA IgG antibodies and some aspects of T-cell activation. Surprisingly, GN still develops in lyn(-/-) IL-21(-/-) mice. This likely results from the presence of IgG autoantibodies against a limited set of non-DNA Ags. These studies identify a specific role for IL-21 in the class switching of anti-DNA B cells and demonstrate that neither IL-21 nor anti-DNA IgG is required for kidney damage in lyn(-/-) mice.

  2. In utero sensitization modulates IgG isotype, IFN-γ and IL-10 responses of neonates in bancroftian filariasis.

    Science.gov (United States)

    Achary, K G; Mandal, N N; Mishra, S; Mishra, R; Sarangi, S S; Satapathy, A K; Kar, S K; Bal, M S

    2014-10-01

    In utero exposure has been considered as a risk factor for filarial infection. To evaluate the influence of maternal infection on filarial-specific IgG subclass response in neonates and their correlation with plasma levels IL-10 and interferon-γ, 145 pairs of mothers and their respective cord bloods were examined. Transplacental transfer of circulating filarial antigen (CFA) was observed in 34·8% cord bloods from CFA positive mothers. Filarial-specific IgG1, IgG2 and IgG4 responses of cord bloods were found to be positively correlated with CFA of mothers. In contrast, IgG3 responses negatively correlated with CFA of mothers. The % of similarity of recognition pattern in the cord blood with maternal blood was high for IgG3 response than IgG4 in all three groups. An increased levels of IL-10 and decreased levels of interferon gamma (IFN-γ) were observed in cord blood of infected mothers. Interferon gamma was positively correlated with IgG3 and negatively correlated with IgG4 level. On the other hand, IL-10 was positively correlated with IgG4 and CFA, indicating that cytokines may play a role in modulating the immune responses in cord bloods of sensitized foetus. The findings of the study reveal that in utero tolerance or sensitization may influence the filarial-specific immunity to infection in neonates.

  3. Conformational difference in human IgG2 disulfide isoforms revealed by hydrogen/deuterium exchange mass spectrometry.

    Science.gov (United States)

    Zhang, Aming; Fang, Jing; Chou, Robert Y-T; Bondarenko, Pavel V; Zhang, Zhongqi

    2015-03-17

    Both recombinant and natural human IgG2 antibodies have several different disulfide bond isoforms, which possess different global structures, thermal stabilities, and biological activities. A detailed mapping of the structural difference among IgG2 disulfide isoforms, however, has not been established. In this work, we employed hydrogen/deuterium exchange mass spectrometry to study the conformation of three major IgG2 disulfide isoforms known as IgG2-B, IgG2-A1, and IgG2-A2 in two recombinant human IgG2 monoclonal antibodies. By comparing the protection factors between amino acid residues in isoforms B and A1 (the classical form), we successfully identified several local regions in which the IgG2-B isoform showed more solvent protection than the IgG2-A1 isoform. On the basis of three-dimensional structural models of IgG2, these identified regions were located on the Fab domains, close to the hinge, centered on the side where the two Fab arms faced each other in spatial proximity. We speculated that in the more solvent-protected B isoform, the two Fab arms were brought into contact by the nonclassical disulfide bonds, resulting in a more compact global structure. Loss of Fab domain flexibility in IgG2-B could limit its ability to access cell-surface epitopes, leading to reduced antigen binding potency. The A2 isoform was previously found to have disulfide linkages similar to those of the classical A1 isoform, but with different biophysical behaviors. Our data indicated that, compared to IgG2-A1, IgG2-A2 had less solvent protection in some heavy-chain Fab regions close the hinge, suggesting that the A2 isoform had more flexible Fab domains. PMID:25730439

  4. Effect of biotherapeutics on antitoxin IgG in experimentally induced Clostridium difficile infection

    Directory of Open Access Journals (Sweden)

    S Kaur

    2012-01-01

    Full Text Available Purpose: Recurrent diarrhoea after successful treatment of primary Clostridium difficile associated disease (CDAD occurs due to bowel flora alterations and failure to mount an effective antibody response. Apart from antibiotics, risk factors include immunosuppressive and acid-suppressive drug administration. Biotherapeutics such as probiotic and epidermal growth factor (EGF may offer potential effective therapy for CDAD. Materials and Methods: The effect of biotherapeutics in mounting an antibody response against C. difficile toxins was studied in BALB/c mice challenged with C. difficile after pre-treatment with ampicillin, lansoprazole or cyclosporin. Sera from sacrificed animals were estimated for antitoxin IgG by enzyme linked immunosorbent assay. Results: Antitoxin IgG was significantly higher (P0.05 in animals in which C. difficile was given after pre-treatment with cyclosporin compared to those without any pre-treatment, or pre-treatment with antibiotic or lansoprazole. In inter-subgroup comparisons also significant anomaly in production of antitoxin IgG was found. The antitoxin IgG levels were raised in animals administered C. difficile after pre-treatment with ampicillin, but lower in animals administered cyclosporin. High levels of antitoxin IgG were also found in the serum samples of animals receiving lansoprazole and C. difficile. Conclusions: Probiotics showed their beneficial effect by boosting the immune response as seen by production of antitoxin IgG. Oral administration of EGF did not affect the immune response to C. difficile toxins as significant increase was not observed in the serum antitoxin IgG levels in any of the groups investigated.

  5. IgG4-related disease: A relatively new concept for clinicians.

    Science.gov (United States)

    Vasaitis, Lilian

    2016-01-01

    IgG4-related disease (IgG4-RD) is a recently recognized chronic fibrotic inflammation, which can affect almost every organ, and may come to clinical attention first due to visible organ swelling or organ dysfunction, or is identified incidentally by imaging and specific biopsy. The disorder has an allergic background and is immune-mediated. Up-regulated responses of T helper 2 and T regulatory cells and their cytokines play a major role in disease progression. About 30-50% of patients are atopic or have mild eosinophilia. IgG4-RD predominantly affects middle-aged male patients. The cornerstones of diagnosis of the disease are compatible clinical features and typical histopathology. Swelling of salivary and lacrimal glands, lymphadenopathy, and type 1 autoimmune pancreatitis (AIP) are the most common manifestations of the disease. However, other tissues and organs, such as retroperitoneum, lung, kidney, aorta, upper airways, thyroid gland, meninges, heart, mesenterium and skin may be involved. Typical histopathology is lymphoplasmacytic infiltration abundant in IgG4-positive plasma cells, storiform-type fibrosis, and obliterative phlebitis. Elevated serum IgG4 concentration supports the diagnosis. Characteristic imaging features such as a "capsule-like rim" surrounding the pancreatic lesions is highly specific to type 1 AIP. 18F-fluorodeoxyglucose positron emission tomography/computed tomography enables mapping the sites of inflammation, permits evaluation of the extent of the disease, helps in guiding biopsy decision, and may be used in monitoring response to treatment. Glucocorticoids alone or in combination with B-cell depletion with rituximab induces prompt clinical response to IgG4-RD. This article reviews the current understanding, different clinical manifestations, and approaches to diagnosis and treatment of IgG4-RD. PMID:26481243

  6. Production of heterologous IgG antibody against Heymann nephritis antigen by injections of immune complexes.

    Science.gov (United States)

    Barabas, Arpad Z; Cole, Chad D; Sensen, Maria; Lafreniere, Rene

    2012-02-01

    Heterologous IgG antibody (ab) can be produced against Heymann nephritis (HN) antigen (ag) in rabbits by administering it in Freund's complete adjuvant. The developing abs reacted at high titre with rat kidney brush border (BB) regions of the renal proximal tubules in an indirect fluorescence ab test. A single IV injection of the heterologous ab into a susceptible strain of rat resulted in the localization of IgG ab to glomerular fixed ags, producing immune complex glomerular nephritis. The injected ab also reacted with the BB region of the renal proximal tubules. The aim of this experiment was to find out whether heterologous IgG ab against the HN ag can also be produced in recipient rabbits by injecting immune complexes (ICs) composed of a rat kidney tubular preparation [rat kidney fraction 3 (rKF3)] and donor rabbit-derived rabbit anti-rKF3 IgG ab. We found that anti-rKF3 IgG ab--against the BB region of the renal proximal tubules--could be induced in rabbits injected with ICs, and the resulting ab was able to initiate passive HN in rats. This was the first time a pathogenic IgG ab was produced against HN ag in rabbits without the use of adjuvant. Ab responses in recipient rabbits were achieved by ab information transfer. Recipient rabbits injected with the IC produced the same class of immunoglobulin with the same specificity against the target ag rKF3, as was present in the innoculum, namely rabbit anti-rKF3 IgG ab. PMID:22103575

  7. Conformational plasticity of IgG during protein A affinity chromatography.

    Science.gov (United States)

    Gagnon, Pete; Nian, Rui

    2016-02-12

    Single step elution of a protein A column with 100mM acetate pH 3.5 produced a curvilinear gradient with pH dropping steeply at first then more gradually as it approached endpoint. IgG with a native hydrodynamic diameter of 11.5 nm began to elute at pH 6.0 with a size of 9.4 nm. IgG size continued to decrease across the peak, reaching a minimum of 2.2 nm at pH 3.9. Secondary structure of early eluting IgG was only mildly affected but later eluting fractions became increasingly non-native with the 2.2 nm population exhibiting the highest proportion of β-sheet and lowest random coil of all conformations. Size reduction and structural change of IgG through this portion of the elution peak were attributed dominantly to a pre-existing tendency of highly concentrated IgG to adopt reduced size conformations at low pH and conductivity, facilitated by the known conformational relaxation of IgG by its interaction with protein A. IgG size increased to 10.4 nm as elution pH approached 3.5 across the tailing fractions. Major loss of β-sheet and increase of α-helix and random coil were observed in parallel. Late elution of this population was attributed to it being eluted from interactions with 2 distinct protein A domains, one bound to each side of the Fc region, creating a higher dissociation constant than single-site Fc-protein A interactions, and requiring more severely disruptive conditions for elution. The high degree of conformational disruption was attributed to simultaneous interaction of both heavy chains with protein A. PMID:26805601

  8. Sialoadenitis progression in nonobese diabetic mice and its correlation with expression of apoptosis-associated proteins in salivary glands and serum IgG levels

    Institute of Scientific and Technical Information of China (English)

    QI Ge; HUA Hong; GAO Yan; LIN Qin; YU Guang-yan

    2007-01-01

    Background Sj(o)gren syndrome (SS) is an autoimmune disorder characterized by chronic lymphocytic infiltration and decreased secretion in salivary glands. Apoptosis is one of the possible mechanisms involved in acinar epithelial destruction in SS. The role of apoptosis in the initiation and effect phase of sialoadenitis is still controversial. The aim of this study was to observe the roles of apoptosis-associated proteins and serum IgG levels in sialoadenitis progression in nonobese diabetic (NOD) mice.Methods 2-, 5-, 10-, 15-, 20-week female NOD and matched BALB/c control mice were selected. Saliva and tear flow rate were measured. Serum IgG level was tested by enzyme-linked immunosorbent assay (ELISA). Number of lymphocyte foci (NLF) in submandibular glands (SMGs) was counted under routine hematoxylin/eosin-stained sections.Expression of Fas, Bcl-2 and procaspase3 proteins as well as apoptotic cells in the SMGs were detected by immunohistochemical staining and by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay respectively.Results Decreased stimulated total flow rate (STFR) and lymphocyte foci in SMGs were first observed in the 10-week NOD group. STFR was negatively correlated with NLF (P<0.05). Serum IgG in NOD mice was significantly higher than that of the control group (P<0.05) and showed a positive correlation with NLF (P<0.05). Fas expression in SMGs acinar cells in NOD mice increased with age and was significantly higher compared with that in the control group. Bcl-2 expression and procaspase3 expression in SMG acinar cells in each NOD group were lower compared with those of the age-matched control mice.Conclusion Abnormal expression of Fas and Bcl-2 in the SMGs and higher level of serum IgG may contribute to the initiation of sialoadenitis and cause the glandular destruction in NOD mice.

  9. IgG subclass antibodies to human and bacterial HSP60 are not associated with disease activity and progression over time in axial spondyloarthritis

    DEFF Research Database (Denmark)

    Carlsen, Thomas Gelsing; Hjelholt, Astrid Johannesson; Jurik, Anne Grethe;

    2013-01-01

    and patient follow-up. In this study, we have focused on these parameters in a cohort of axial SpA patients with a well-established set of clinical characteristics, including MRI changes and human leukocyte antigen B27. METHODS: IgG subclass antibodies (IgG1, IgG2, IgG3 and IgG4) against recombinant HSP60...... and the disease parameters. RESULTS: Elevated levels of IgG1 and IgG3 to human HSP60 and IgG1 to HSP60 of Salmonella enterica Enteritidis were observed in SpA patients compared with healthy controls at both time points. The antibody levels were almost constant over time for IgG1, whereas high levels of IgG3...

  10. Characterization of methacrylate chromatographic monoliths bearing affinity ligands.

    Science.gov (United States)

    Černigoj, Urh; Vidic, Urška; Nemec, Blaž; Gašperšič, Jernej; Vidič, Jana; Lendero Krajnc, Nika; Štrancar, Aleš; Podgornik, Aleš

    2016-09-16

    We investigated effect of immobilization procedure and monolith structure on chromatographic performance of methacrylate monoliths bearing affinity ligands. Monoliths of different pore size and various affinity ligands were prepared and characterized using physical and chromatographic methods. When testing protein A monoliths with different protein A ligand densities, a significant nonlinear effect of ligand density on dynamic binding capacity (DBC) for IgG was obtained and accurately described by Langmuir isotherm curve enabling estimation of protein A utilization as a function of ligand density. Maximal IgG binding capacity was found to be at least 12mg/mL exceeding theoretical monolayer adsorption value of 7.8mg/mL assuming hexagonal packing and IgG hydrodynamic diameter of 11nm. Observed discrepancy was explained by shrinkage of IgG during adsorption on protein A experimentally determined through calculated adsorbed IgG layer thickness of 5.4nm from pressure drop data. For monoliths with different pore size maximal immobilized densities of protein A as well as IgG dynamic capacity linearly correlates with monolith surface area indicating constant ligand utilization. Finally, IgGs toward different plasma proteins were immobilized via the hydrazide coupling chemistry to provide oriented immobilization. DBC was found to be flow independent and was increasing with the size of bound protein. Despite DBC was lower than IgG capacity to immobilized protein A, ligand utilization was higher. PMID:27554023

  11. Effects of adjuvants on IgG subclasses elicited by virus-like Particles

    Directory of Open Access Journals (Sweden)

    Visciano Maria Luisa

    2012-01-01

    Full Text Available Abstract Background Virus-Like Particles (VLPs represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C adjuvants, has been evaluated in an animal model. Results Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced TH2 pattern, VLPs formulated with either adjuvant elicited a TH1-biased IgG subclasses (IgG2a and IgG3, with poly(I:C more potent than CpG ODN1826. Conclusions The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen.

  12. Label-free Raman mapping of surface distribution of protein a and IgG biomolecules.

    Science.gov (United States)

    Combs, Zachary A; Chang, Sehoon; Clark, Tolecia; Singamaneni, Srikanth; Anderson, Kyle D; Tsukruk, Vladimir V

    2011-03-15

    We have demonstrated a nanoengineered substrate composed of micropatterned silver nanoparticles to be used for the label-free mapping of adsorbed biomolecules. We utilized surface-enhanced Raman scattering (SERS) phenomenon to monitor the known bioanalytes, protein A and human immunoglobulin G (IgG). The SERS substrate was composed of a poly(alylamine hydrochloride) (PAH)/poly(styrenesulfonate) (PSS) layer-by-layer (LbL) nanocoating micropatterned with silver nanoparticles confined to microscopic stripes. Selective adsorption of biomacromolecules is facilitated by the amine-terminated LbL nanocoating, which prevents the surface adsorption of positively charged protein A across the surface except on the patterned regions containing negatively charged silver nanoparticles. Furthermore, adsorption of IgG on predetermined regions is facilitated by the selective binding of the Fc region of IgG to protein A. This label-free SERS approach provides accurate, selective, and fast detection of protein A and IgG solutions with a nanomolar concentration, down to below 1 nM for IgG in solution. This method could also be utilized for the facile detection of proteins in field conditions as well as in clinical, forensic, industrial, and environmental laboratories. PMID:21294559

  13. IgG4-Related Disease Presenting as Recurrent Mastoiditis With Central Nervous System Involvement

    Directory of Open Access Journals (Sweden)

    April L. Barnado MD

    2013-09-01

    Full Text Available We report a case of a 43-year-old female who presented with right ear fullness and otorrhea. She was initially diagnosed with mastoiditis that was not responsive to multiple courses of antibiotics and steroids. She was then diagnosed with refractory inflammatory pseudotumor, and subsequent treatments included several mastoidectomies, further steroids, and radiation therapy. The patient went on to develop mastoiditis on the contralateral side as well as central nervous system involvement with headaches and right-sided facial paresthesias. Reexamination of the mastoid tissue revealed a significantly increased number of IgG4-positive cells, suggesting a diagnosis of IgG4-related disease. The patient improved clinically and radiographically with rituximab and was able to taper off azathioprine and prednisone. IgG4-related disease should be considered in patients with otologic symptoms and be on the differential diagnosis in patients with inflammatory pseudotumor. Staining for IgG and IgG4 is essential to ensure a prompt diagnosis and treatment.

  14. Increased Levels of IgG Antibodies against Human HSP60 in Patients with Spondyloarthritis

    DEFF Research Database (Denmark)

    Nielsen, Astrid Hjelholt; Carlsen, Thomas; Deleuran, Bent;

    2013-01-01

    Introduction: Spondyloarthritis (SpA) comprises a heterogeneous group of inflammatory diseases, with strong association to human leukocyte antigen (HLA)-B27. SpA is suggested triggered by bacterial infection, and bacterial heat shock protein (HSP) seems to be a strong T cell antigen. Since...... severity in relation to HLA-B27 was evaluated. Material & Methods: Serum samples from 82 patients and 50 controls were analysed by enzyme-linked immunosorbent assay (ELISA) for immunoglobulin (Ig)G1, IgG2, IgG3 and IgG4 antibodies against human HSP60 and HSP60 from Chlamydia trachomatis, Salmonella...... against human HSP60, but not antibodies against bacterial HSP60, were elevated in the SpA group compared with the control group. Association between IgG3 antibodies against human HSP60 and BASMI was shown in HLA-B27+ patients. Only weak correlation between antibodies against bacterial and human HSP60 was...

  15. Activation of complement by an IgG molecule without a genetic hinge.

    Science.gov (United States)

    Brekke, O H; Michaelsen, T E; Sandin, R; Sandlie, I

    1993-06-17

    The hinge region links the two Fab arms to the Fc portion of the IgG molecule. It mediates flexibility to the molecule and serves as a connecting structure between the two heavy chains. In addition it provides space between the Fab and Fc parts. All three properties have been proposed to be important for the ability of IgG to initiate complement activation leading to complement-mediated cell lysis (CML). Here we report the construction of a hinge-deleted mouse-human chimaeric IgG3 molecule with specificity for the hapten NIP (3-iodo-4-hydroxy-5-nitrophenacetyl), HM-1. HM-1 lacks the genetic hinge, but has an introduced cysteine between Ala 231 (EU numbering) and Pro 232 in the lower hinge encoded by the CH2 exon. The introduced cysteine forms a disulphide bond between the two heavy chains of the molecule. In CML, HM-1 shows a greater activity than IgG3 wild type. This is the first time an IgG molecule without a genetic hinge has been found to be active in CML. We conclude that the hinge functioning as a spacer is not a prerequisite for complement activation. Rather, its major role seems to be to connect the heavy chains to each other in the amino-terminal part of CH2. Because HM-1 is expected to have low Fab-Fc flexibility, this molecular feature is probably of no importance for complement activation.

  16. Bancroftian filariasis: the patterns of filarial-specific immunoglobulin G1 (IgG1), IgG4, and circulating antigens in an endemic community of northeastern Tanzania

    DEFF Research Database (Denmark)

    Simonsen, P E; Lemnge, M M; Msangeni, H A;

    1996-01-01

    The profile of filarial-specific immunoglobulin G1 (IgG1), IgG4, and Wuchereria bancrofti-specific circulating antigen (Og4C3) was analyzed in individuals one year of age and older in a community with high endemicity for Bancroftian filariasis. The overall microfilarial (mf) prevalence in the exa......The profile of filarial-specific immunoglobulin G1 (IgG1), IgG4, and Wuchereria bancrofti-specific circulating antigen (Og4C3) was analyzed in individuals one year of age and older in a community with high endemicity for Bancroftian filariasis. The overall microfilarial (mf) prevalence...

  17. Characterization of IgG4 anti-neurofascin 155 antibody-positive polyneuropathy

    OpenAIRE

    Ogata, Hidenori; Yamasaki, Ryo; Hiwatashi, Akio; Oka, Nobuyuki; Kawamura, Nobutoshi; Matsuse, Dai; Kuwahara, Motoi; Suzuki, Hidekazu; Kusunoki, Susumu; Fujimoto, Yuichi; Ikezoe, Koji; Kishida, Hitaru; Tanaka, Fumiaki; Matsushita, Takuya; Murai, Hiroyuki

    2015-01-01

    Objective To investigate anti-neurofascin 155 (NF155) antibody-positive chronic inflammatory demyelinating polyneuropathy (CIDP). Methods Sera from 50 consecutive CIDP patients diagnosed in our clinic, 32 patients with multiple sclerosis, 40 patients with other neuropathies including 26 with Guillain–Barré syndrome (GBS)/Fisher syndrome, and 30 healthy controls were measured for anti-NF antibodies by flow cytometry using HEK293 cell lines stably expressing human NF155 or NF186. Four additiona...

  18. Microscale characterization of the binding specificity and affinity of a monoclonal antisulfotyrosyl IgG antibody

    DEFF Research Database (Denmark)

    Lassen, K.S.; Bradbury, A.R.; Heegaard, N.H.;

    2008-01-01

    peptides and proteins. The data show that the anti-Tyr(SO(3)H) antibody is completely specific for compounds containing sulfated tyrosyls. Affinity electrophoresis experiments allowed us to estimate dissociation constants for sulfated hirudin fragment (56-65), gastrin-17, and cholecystokinin octapeptide...... (CCK8) in the 1-3 microM range. The affinity of the antibody toward complement 4 protein that contains three sulfotyrosines was analyzed by surface plasmon resonance technology and modeled according to a bivalent-binding model which yielded a K(d1) of 20.1 microM for the monovalent complex. The same...... binding was studied by CE and found to be in the micromolar scale albeit with some uncertainty due to complex separation patterns. The work illustrates the amount of information on antibody-antigen interactions that may be obtained with microelectrophoretic methods consuming minute quantities of material...

  19. Intrathecal IgG synthesis and autoantibody-secreting cells in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Jensen, Claus V; Christiansen, Michael

    2000-01-01

    We studied intrathecal IgG synthesis and autoantibody-secreting cells in 148 patients with possible onset symptoms of MS (POSMS) or clinically definite MS (CDMS). In POSMS intrathecal synthesis of IgG oligoclonal bands and abnormalities on T2-weighted magnetic resonance imaging were associated...... but the former were more prevalent. The cerebrospinal fluid (CSF) leukocyte count and the number of anti-protelipid protein antibody-secreting cells in cerebrospinal fluid (CSF) correlated with disease activity in POSMS. Intrathecal IgG synthesis levels and the number of anti-myelin basic protein antibody......-secreting cells in CSF correlated with disease activity in CDMS. Our results support recent reports of pathogenetic heterogeneity and a pathogenetic role of the antibody response in MS...

  20. Recurrent meningitis in a child with IgG3 subclass deficiency.

    Science.gov (United States)

    Vehapoglu, Aysel; Ozgurhan, Gamze; Demir, Aysegul Dogan; Uzuner, Selcuk; Nursoy, Mustafa Atilla; Turkmen, Serdar

    2014-08-01

    Recurrent meningitis is an uncommon life-threatening condition. Here, the case of a 6-year-old boy is reported who had two episodes of meningitis with an IgG3 subclass deficiency. The boy had aseptic meningitis at the age of 3 years, followed by bacterial meningitis at the age of 4 years. Primary immunoglobulin deficiencies are a group of disorders associated with an increased incidence and/or severity of infection. Recurrent infections, sinusitis, bronchitis, and pneumonia are the most frequently observed illnesses in patients with IgG subclass deficiencies, of which an IgG3 subclass deficiency is the most common, especially in adults. Although cases of recurrent viral or bacterial meningitis have been reported, herein a patient is presented with recurrence of aseptic and bacterial meningitis 1 year after the initial episode. Some researchers recommend that all children with episodes of recurrent meningitis should be screened for primary immunoglobulin or complement deficiencies.

  1. The many faces of Merlin: IgG4-associated pulmonary-renal disease.

    Science.gov (United States)

    Sprangers, Ben; Lioen, Pieter; Meijers, Björn; Lerut, Evelyne; Meersschaert, Joke; Blockmans, Daniel; Claes, Kathleen

    2011-09-01

    Pulmonary-renal syndrome is a common and serious disorder with a broad differential diagnosis. We describe a case of a middle-aged man presenting with interstitial pulmonary disease and severe renal impairment caused by a hypocomplementemic immune-complex-mediated interstitial nephritis. Serum levels of IgG4 were elevated, and renal biopsy specimens revealed the presence of interstitial IgG4(+) plasma cells. There was a rapid improvement of both pulmonary and renal abnormalities after the initiation of corticosteroids. To our knowledge, this report is the first to show interstitial pulmonary disease in association with interstitial kidney disease as the predominant and presenting symptoms of IgG4-related disease. PMID:21896524

  2. Homogeneous Detection of Human IgG by Gold Nanoparticle Probes

    Institute of Scientific and Technical Information of China (English)

    CAO Qihua; YUAN Hong; CAI Ruxiu

    2009-01-01

    A simple,and homogeneous detection system for human IgG based on the optical properties of aggregated gold nanoparticles probes were investigated.When gold nanoparticles with about 13 nm in diameter were modified by goat anti-human IgG,the addition of human IgG could change the absorption of colloidal gold solution,and the absorption intensity at 740 nm depended on the amount of human IgG.The aggregation of gold nanoparticles was also validated using transmission electron microscopy(TEM).A series of experiments were carried out to study the effects of pH value, the reaction temperature,and non-specific adsorption on the assay.A dynamic range of 10-500μg/~3 mL human IgG was observed.The new bioassay could be used for the rapid and ho-mogeneous detection of antibodies in bioanalytical chemistry.

  3. Isolation and Purification of Bovine Colostrum sIgA and IgG

    Institute of Scientific and Technical Information of China (English)

    YAO Yonghao; GAO Xuejun; LIU Xiaofei

    2008-01-01

    To further utilize bioactive substance such as bovine colostrum sIgA and lgG, slgA and IgG were isolated and purified simultaneously by salting out,ultrafiltration and gel chromatography,etc.The analysis of results were showed quantitatively by nonhydrogenized SDS-PAGE,and quanlities of sIgA and IgG were respectively detected by Western Blot. The results showed that the purity and yield of bovine colostrum slgA were 85.3% and 42.8%,respectively,while the purity and yield of bovine colostrum IgG were respectively 97.2% and 64.4%.This preparative method provides theoretical and experimental foundation for sIgA industrial production.

  4. Voltage-driven translocation behaviors of IgG molecule through nanopore arrays

    Science.gov (United States)

    Liu, Lei; Wang, Bing; Sha, Jingjie; Yang, Yue; Hou, Yaozong; Ni, Zhonghua; Chen, Yunfei

    2013-05-01

    Nanopore-based biosensing has attracted more and more interests in the past years, which is also regarded as an emerging field with major impact on bio-analysis and fundamental understanding of nanoscale interactions down to single-molecule level. In this work, the voltage-driven translocation properties of goat antibody to human immunoglobulin G (IgG) are investigated using nanopore arrays in polycarbonate membranes. Obviously, the background ionic currents are modulated by IgG molecules for their physical place-holding effect. However, the detected ionic currents do `not' continuously decrease as conceived; the currents first decrease, then increase, and finally stabilize with increasing IgG concentration. To understand this phenomenon, a simplified model is suggested, and the calculated results contribute to the understanding of the abnormal phenomenon in the actual ionic current changing tendency.

  5. Dectin-1 agonist selectively induces IgG1 class switching by LPS-activated mouse B cells.

    Science.gov (United States)

    Seo, Beom-Seok; Park, Ha-Yan; Yoon, Hee-Kyung; Yoo, Yung-Choon; Lee, Junglim; Park, Seok-Rae

    2016-10-01

    Heat-killed Saccharomyces cerevisiae (HKSC) is an agonist for Dectin-1, a major fungal cell wall β-glucan receptor. We previously reported that HKSC selectively enhances IgG1 production by LPS-activated mouse B cells. To determine if this IgG1 selectivity is caused by selective IgG1 class switching, we performed RT-PCRs for measuring germline transcripts (GLTs), flow cytometric analyses for detecting Ig-expressing cells, and ELISPOT assays for measuring the number of Ig-secreting cells in HKSC/LPS-stimulated mouse B cell cultures. HKSC selectively enhanced expression of GLTγ1, the number of IgG1-expressing cells, and the number of IgG1-secreting B cells in the presence of LPS stimulation. In addition, HKSC induced the expression of CD69, an activation marker for B lymphocytes, and the expression of surface Dectin-1. Two Dectin-1 antagonists, laminarin and a neutralizing Dectin-1 antibody, selectively diminished HKSC-reinforced IgG1 production by LPS-stimulated B cells. Furthermore, depleted zymosan (dzn), a Dectin-1 agonist with increased selectivity, also selectively enhanced GLTγ1 transcription. The Dectin-1 antagonists blocked dzn-induced IgG1 production by LPS-activated B cells. Collectively, these results suggest that Dectin-1 agonists selectively induce IgG1 class switching by direct stimulation of Dectin-1 on LPS-activated B cells resulting in selective production of IgG1.

  6. Comparison of Salivary Anti Helicobacter pylori IgG with Serum IgG and Bacteriological Tests in Detecting Helicobacter pylori Infections

    OpenAIRE

    H Ghasemian safaei; Fazeli, A.; H Tamizifar; Rashidi, N.(Department of Physics, Faculty of Basic Sciences, University of Mazandaran, P.O. Box 47416-1467, Babolsar, Iran)

    2005-01-01

    Background: This study was conducted to compare the efficacy of enzyme-linked immunosorbent assay (ELISA) for detecting anti-Helicobacter pylori (H. pylori) specific IgG antibodies in specimens of oral fluid and serum with bacteriological tests. Methods: Antral biopsy specimens, as well as serum and oral fluid samples were collected from 97 patients who underwent upper gastrointestinal endoscopy. The presence or absence of current H. pylori infection was determined by culture, ...

  7. High Serum IgG4 Concentrations in Patients with Hashimoto’s Thyroiditis

    Directory of Open Access Journals (Sweden)

    Anna Popławska-Kita

    2015-01-01

    Full Text Available Purpose. Since recent reports suggest that Hashimoto thyroiditis (HT may be associated with IgG4-related disease, we aimed to find out whether the measurement of serum IgG4 allows for the identification of distinct types of HT, with different clinical, sonographic, and serologic characteristics. Methods. The group studied consisted of 53 patients with HT and 28 healthy individuals who underwent thyroid ultrasonography and body composition analysis. Serum concentrations of IgG4, TSH, anti-peroxidase antibodies (TPOAb, anti-TSH receptor antibodies, TNF-α, TGF-β1, Fas Ligand, TRAIL, and chemokines (CXCL9, CXCL11, and CXCL10 were measured by ELISA or radioimmunoassay. Results. The group with IgG4 level >135 IU/ml accounted for 32.5% of the patients. The signs of fibrosis were present in 27.0% of the high-IgG4 patients and in 9.1% of the normal-IgG4 group. The patients with elevated IgG4 required higher doses of L-thyroxine and had significantly lower level of TPOAb (P=0.02 than the non-IgG4-HT individuals and higher TNF-α level in comparison with the controls (P=0.01. Conclusions. Our results suggest that the measurement of serum IgG4 allows for an identification of patients with more rapid progression of HT, requiring higher doses of L-thyroxine. Low TPOAb level and the absence of coexisting autoimmune diseases may suggest distinct pathomechanism of this type of thyroiditis.

  8. Production of double antibody for radioimmunoassay (sheep anti-rabbit IgG antiserum)

    International Nuclear Information System (INIS)

    A second antibody (sheep anti-rabbit IgG antiserum) to be used in RIAs in which the first antibody is raised in rabbits was produced. For this production, initially the IgG was isolated from rabbit serum and purified by sodium sulphate precipitation followed by ion exchange chromatography on DEAE-cellulose. Four sheep were immunized with 500 u g of purified rabbit IgG, emulsified in Freund Complete Adjuvant and administered by multisite subcutaneous injections. These injections were repeated at 20-days intervals and blood samples (40 ml) were taken from the jugular vein 10 days after the boosts for the evaluation of the antisera title. After each four boosts a great bleeding was done by the same route. Approximately 500 ml of serum were obtained in each bleeding per animal. The antisera were evaluated by the human thyrotropin RIA developed at IPEN laboratories employing reagents provided by NIDDKD, USA. These evaluations referred to the determination of the antisera title and of the ideal concentration of carrier IgG, to the study of the kinetic of precipitation and to the confirmation of the inexistent cross-reactivity with human IgG, in comparison with a reference antiserum of know precipitation characteristics supplied by the Radioassay System Laboratories. Approximately 3,6 l of antiserum (sheep anti-rabbit IgG serum) were produced from the four sheep, which presented title and precipitation characteristics very similar to those exhibited by the imported commercial product, even presenting higher titles. The results obtained in this work indicated that it was created enough experience for the production of this biological reagent for RIA, that could be done integrally in the country in greater scale, and at a very reduced cost. (author). 81 refs, 36 figs, 33 tabs

  9. The Accuracy of IgG Avidity for Detection of Acute Toxoplasmosis among Pregnant Saudi Women

    Directory of Open Access Journals (Sweden)

    Eman El Masry El Damarany

    2010-02-01

    Full Text Available AIM: The diagnosis of acute toxoplasmosis depends on the presence of immunoglobulin M (IgM, but it may persist for a long time in some cases. The objective of this study was to determine the role and accuracy of IgG avidity for the detection of acute Toxoplasmosis in early pregnancy. METHOD: The study included 160 women. Sera were screened for anti-Toxoplasma IgG and IgM and for IgG-avidity using ELIZA. PCR was done for confirmation in selected group of specimens. This study was performed at the College of Medicine, King Faisal University, Saudi Arabia from January 2008 through April 2009. RESULTS: 32 cases of low avidity were negative IgM while 15 cases of high avidity were positive IgM. 16 cases of low avidity were positive IgG. The accuracy of low avidity in relation to positive IgM revealed a sensitivity, specificity, positive predictive value, negative predictive value and likelihood ratio of 77.0%, 51.5%, 64.0%, 66.7% and 1.58 respectively. The accuracy of low IgG avidity in comparison with PCR demonstrated 91%, 45.7%, 60.4% and 84.2% respectively. CONCLUSION: Negative IgM didn’t exclude recent Toxoplasma infection and positive IgG may be present with recent infection. IgG avidity testing help in accurate differentiation of recent infections. [TAF Prev Med Bull 2010; 9(1.000: 7-14

  10. Overlapping IgG4 Responses to Self- and Environmental Antigens in Endemic Pemphigus Foliaceus.

    Science.gov (United States)

    Qian, Ye; Jeong, Joseph S; Ye, Jian; Dang, Bim; Abdeladhim, Maha; Aoki, Valeria; Hans-Filhio, Gunter; Rivitti, Evandro A; Valenzuela, Jesus G; Diaz, Luis A

    2016-03-01

    The etiology of human autoimmune diseases in general remains largely unknown, although the genetic and environmental interplay may be relevant. This applies to the autoimmune diseases of the skin such as the pemphigus phenotypes and others. In this group, there is an endemic form of pemphigus foliaceus (also known as fogo selvagem [FS]) in which the pathogenic IgG4 autoantibody response to the self-antigen desmoglein 1 (Dsg1) cross-reacts with the LJM11 sand fly salivary gland Ag. In this investigation, we dissected the IgG4 autoantibody repertoires used by FS patients in response to endogenous self-Dsg1 and exogenous LJM11 sand fly Ag. Based on analyses of the genetic clonal signatures of these Abs, our results indicate that there is a significant overlap between these two responses, as all identified IgG4 mAbs cross-react to both Dsg1 and LJM11 Ags. Germline H- and L-chain V gene Abs generated according to mutated cross-reactive mAbs preserved their reactivity to both Ags. Our findings suggest that both Dsg1 autoantigen and LJM11 environmental Ag could be the initial antigenic stimulants for the IgG4 autoimmune responses in FS. These results support our hypothesis that LJM11 Ag plays a substantial role in triggering the IgG4 autoantibody development in FS and provide new insights on how noninfectious environmental Ag(s) may drive the generation of autoantibodies in IgG4-related autoimmune diseases. PMID:26826247

  11. Comparison of Four Commercial Kits to Detect HSV-2 IgG Antibody

    Institute of Scientific and Technical Information of China (English)

    Song Biao(宋彪); Chen Xiangsheng(陈祥生); Yin Yueping(尹跃平); Yao Xu(姚煦); Li Wengzhong(李文忠)

    2004-01-01

    Objectives: To compare the efficiency of four commercial ELISA kits in detecting type-specific HSV-2 IgG antibodies. Materials and Methods: A total of 125 subjects, including 105 with genital ulcers, and 20 controls without any history of STDs were recruited from the STD clinic for detection of type-specific HSV-2 IgG antibody with different kits. Four kinds of commercially available ELISA kits, including Quida HSV2 IgG ELISA (Aifulang Biochem Co. Ltd., Hangzhou), TORCH-HSV2 IgG (Jingmei Biotech Co. Ltd., Shanghai), CaptiaTM HSV2 IgG (Trinity biotech, USA ) and HerpeSelect TM 2 ELISA IgG (Focus technologies, USA) were used for evaluation. Western Blot assay was performed as a gold standard.Results: Compared to Western Blot results, the sensitivity and specificity of the kits (Quida HSV2, TORCHHSV2, CaptiaTM HSV2 and HerpeSelectTM 2) were 13.1% and 98.4%, 7.5% and 100%, 100% and 11.1%,87.7 % and 96.7 %, respectively. The positive predictive value (PV) and negative PV of the four kits were 88.9%and 54.3%, 100% and 55.5%, 55.6% and 100%, 96.2%and 89.2%, respectively. The areas under the ROC curve of three kits (Quida HSV2, CaptiaTM HSV2 andHerpeSelectTM 2) were 0.885 (0.822~0.948), 0.825 (0.747- 0.902), 0.974 (0.950 - 0.998), respectively Conclusion: The performance of HerpeSelectTM 2 is the best among the four kits. The results also indicate that the commercially available kits for detection of type-specific HSV2 antibody should be re-evaluated in terms of their validity.

  12. Profiling IgG N-glycans as potential biomarker of chronological and biological ages

    Science.gov (United States)

    Yu, Xinwei; Wang, Youxin; Kristic, Jasminka; Dong, Jing; Chu, Xi; Ge, Siqi; Wang, Hao; Fang, Honghong; Gao, Qing; Liu, Di; Zhao, Zhongyao; Peng, Hongli; Pucic Bakovic, Maja; Wu, Lijuan; Song, Manshu; Rudan, Igor; Campbell, Harry; Lauc, Gordan; Wang, Wei

    2016-01-01

    Abstract As an important post-translation modifying process, glycosylation significantly affects the structure and function of immunoglobulin G (IgG) molecules and is essential in many steps of the inflammatory cascade. Studies have demonstrated the potential of using glycosylation features of IgG as a component of predictive biomarkers for chronological age in several European populations, whereas no study has been reported in Chinese. Herein, we report various patterns of changes in IgG glycosylation associated with age by analyzing IgG glycosylation in 701 community-based Han Chinese (244 males, 457 females; 23–68 years old). Eleven IgG glycans, including FA2B, A2G1, FA2[6]G1, FA2[3]G1, FA2[6]BG1, FA2[3]BG1, A2G2, A2BG2, FA2G2, FA2G2S1, and FA2G2S2, change considerably with age and specific combinations of these glycan features can explain 23.3% to 45.4% of the variance in chronological age in this population. This indicates that these combinations of glycan features provide more predictive information than other single markers of biological age such as telomere length. In addition, the clinical traits such as fasting plasma glucose and aspartate aminotransferase associated with biological age are strongly correlated with the combined glycan features. We conclude that IgG glycosylation appears to correlate with both chronological and biological ages, and thus its possible role in the aging process merits further study. PMID:27428197

  13. IgG1 and IgG4 antibody responses to the Anopheles gambiae salivary protein gSG6 in the sympatric ethnic groups Mossi and Fulani in a malaria hyperhendemic area of Burkina Faso.

    Directory of Open Access Journals (Sweden)

    Cinzia Rizzo

    Full Text Available Human antibody response to the Anopheles gambiae salivary protein gSG6 has recently emerged as a potentially useful tool for malaria epidemiological studies and for the evaluation of vector control interventions. However, the current understanding of the host immune response to mosquito salivary proteins and of the possible crosstalk with early response to Plasmodium parasites is still very limited. We report here the analysis of IgG1 and IgG4 subclasses among anti-gSG6 IgG responders belonging to Mossi and Fulani from Burkina Faso, two ethnic groups which are known for their differential humoral response to parasite antigens and for their different susceptibility to malaria. The IgG1 antibody response against the gSG6 protein was comparable in the two groups. On the contrary, IgG4 titers were significantly higher in the Fulani where, in addition, anti-gSG6 IgG4 antibodies appeared in younger children and the ratio IgG4/IgG1 stayed relatively stable throughout adulthood. Both gSG6-specific IgG1 and IgG4 antibodies showed a tendency to decrease with age whereas, as expected, the IgG response to the Plasmodium circumsporozoite protein (CSP exhibited an opposite trend in the same individuals. These observations are in line with the idea that the An. gambiae gSG6 salivary protein induces immune tolerance, especially after intense and prolonged exposure as is the case for the area under study, suggesting that gSG6 may trigger in exposed individuals a Th2-oriented immune response.

  14. Turnover rate of anti-D IgG injected during pregnancy.

    OpenAIRE

    Eklund, J; M. Hermann; Kjellman, H; Pohja, P

    1982-01-01

    Anti-D IgG was injected into 15 Rh-negative women in the 28th week of gestation and into three non-pregnant women. The uptake of anti-D after the intramuscular injections was calculated by measuring the concentration of antibody in the plasma with an autoanalyser. The biological half life and the catabolic rate of anti-D IgG were calculated according to a compartmental model. The recovery in vivo of anti-D was an average 24% in the non-pregnant women and 21% in the pregnant women. The half li...

  15. Neuromyelitis optica IgG in the cerebrospinal fluid induces astrocytopathy in optic nerve

    DEFF Research Database (Denmark)

    Soelberg, Kerstin; Lillevang, Søren Thue; Mørch, Marlene;

    Background: Serum immunoglobulin G targeting the astrocyte water channel aquaporin-4 (AQP4) in the central nervous system (CNS) is a biomarker for neuromyelitis optica spectrum disease (NMOSD). Optic neuritis (ON) is believed to be immune-mediated and is associated with AQP4-IgG in NMOSD-ON. The ......Background: Serum immunoglobulin G targeting the astrocyte water channel aquaporin-4 (AQP4) in the central nervous system (CNS) is a biomarker for neuromyelitis optica spectrum disease (NMOSD). Optic neuritis (ON) is believed to be immune-mediated and is associated with AQP4-IgG in NMOSD...

  16. ADAMTS13-binding IgG are present in patients with thrombotic thrombocytopenic purpura

    OpenAIRE

    Tsai, Han-Mou; Raoufi, Mojgan; Zhou, Wenhua; Guinto, Enriqueta; Grafos, Nickolas; Ranzurmal, Safi; Greenfield, Robert S.; Rand, Jacob H.

    2006-01-01

    Functional assays are commonly used to measure the antibodies of ADAMTS13 found in patients of thrombotic thrombocytopenic purpura (TTP). In this study we used an enzyme-linked immunoassay to analyze the ADAMTS13-binding IgG levels in six groups of individuals: normal, random hospitalized patients, acute TTP,TTP after receiving plasma therapy, TTP in remission, and other types of thrombotic microangiopathy (TMA). The results showed thatADAMTS13-binding IgG levels were elevated in 100% of the ...

  17. Significantly lower anti-Leishmania IgG responses in Sudanese versus Indian visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Tapan Bhattacharyya

    2014-02-01

    Full Text Available BACKGROUND: Visceral leishmaniasis (VL, a widely distributed systemic disease caused by infection with the Leishmania donovani complex (L. donovani and L. infantum, is almost always fatal if symptomatic and untreated. A rapid point-of-care diagnostic test for anti-Leishmania antibodies, the rK39-immunochromatographic test (rK39-ICT, has high sensitivity and specificity in South Asia but is less sensitive in East Africa. One of the underlying reasons may be continent-specific molecular diversity in the rK39 antigen within the L. donovani complex. However, a second reason may be differences in specific IgG anti-Leishmania levels in patients from different geographical regions, either due to variable antigenicity or immunological response. METHODOLOGY/PRINCIPAL FINDINGS: We determined IgG titres of Indian and Sudanese VL patients against whole cell lysates of Indian and Sudanese L. donovani strains. Indian VL patients had significantly higher IgG titres against both L. donovani strains compared to Sudanese VL patients (p<0.0001. Mean reciprocal log10 50% end-point titres (1/log10t50 were i 3.80 and 3.88 for Indian plasma and ii 2.13 and 2.09 for Sudanese plasma against Indian and Sudanese antigen respectively (p<0.0001. Overall, the Indian VL patients therefore showed a 46.8-61.7 -fold higher mean ELISA titre than the Sudanese VL patients. The higher IgG titres occurred in children (<16 years old and adults of either sex from India (mean 1/log10t50: 3.60-4.15 versus Sudan (mean 1/log10t50: 1.88-2.54. The greatest difference in IgG responses was between male Indian and Sudanese VL patients of ≥ 16 years old (mean 1/log10t50: 4.15 versus 1.99 = 144-fold (p<0.0001. CONCLUSIONS/SIGNIFICANCE: Anti-Leishmania IgG responses among VL patients in Sudan were significantly lower than in India; this may be due to chronic malnutrition with Zn(2+ deficiency, or variable antigenicity and capacity to generate IgG responses to Leishmania antigens. Such

  18. IgG antibodies to dengue in dry blood samples in filter paper.

    OpenAIRE

    Carmen Acosta; Regla Herrera; Pedro Almenarez; Susana Vázquez

    2003-01-01

    En este trabajo se presentan los resultados de la normalización del procedimiento de detección de anticuerpos IgG contra el virus dengue en muestras de sangre colectadas sobre papel de filtro. Las muestras se obtuvieron de 216 individuos que acudieron al banco de sangre de Marianao de los cuales 25 presentaron resultados con títulos superiores a 1:40 por la técnica de Inhibición de la Hemaglutinación. En todas las muestras se determinó la presencia de anticuerpos IgG contra el virus dengue me...

  19. IgG antibodies to Aspergillus fumigatus in cystic fibrosis: a laboratory correlate of disease activity.

    OpenAIRE

    Forsyth, K D; Hohmann, A W; Martin, A J.; Bradley, J

    1988-01-01

    Serum was collected from 50 patients with cystic fibrosis, and IgG antibodies to Aspergillus fumigatus were measured by enzyme linked immunosorbent assay (ELISA). In addition, total IgE and Aspergillus specific IgE antibodies were measured in 41 of the 50. A close association was found between pulmonary function and clinical state, and IgG antibodies to Aspergillus. There was no association between pulmonary function or clinical state and IgE antibodies. It is postulated that in patients with...

  20. IgG is transported across the mouse yolk sac independently of FcγRIIb

    OpenAIRE

    Mohanty, Sudhasri; Kim, Jonghan; Latha P Ganesan; Phillips, Gary S.; Hua, Keding; Jarjoura, David; Hayton, William L.; Robinson, John M.; Anderson, Clark L.

    2009-01-01

    It is generally accepted that FcRn is the major IgG transporter in human syncytiotrophoblast and the mouse yolk sac endoderm, however the finding of a different Fc receptor FcγRIIb (RIIb) in the human placental endothelium has suggested the existence of an additional IgG transporter. To test this hypothesis in the mouse, we utilized wild-type (RIIb+/+) mice and mice with a null mutation in the gene encoding RIIb (RIIb−/− mice). We found that while RIIb is expressed in the placental yolk sac v...

  1. The study of 3-dimensional structures of IgG with atomic force microscopy

    Institute of Scientific and Technical Information of China (English)

    YU Yi-gang; XU Ru-xiang; JIANG Xiao-dan; KE Yi-quan

    2005-01-01

    Objective: To detect 3-dimensional images of anti-N-methyl-D-aspartate receptor Nr1 (NMDAr1) polycolonal IgG affixed on mica in physiological environment. Methods: The images and data were obtained from a contact mode and commercial Si3N4 probed tip by using atomic force microscope (AFM). Conclusions: Using AFM to investigate biomacromolecule can make us deeply understand the structure of IgG, which will instruct us to detect the membrane receptor protein as a labelling agent.

  2. Leishmania mexicana infection induces IgG to parasite surface glycoinositol phospholipids that can induce IL-10 in mice and humans.

    Directory of Open Access Journals (Sweden)

    Laurence U Buxbaum

    Full Text Available Infection with the intracellular protozoan parasite Leishmania mexicana causes chronic disease in C57BL/6 mice, in which cutaneous lesions persist for many months with high parasite burdens (10(7-10(8 parasites. This chronic disease process requires host IL-10 and FcγRIII. When Leishmania amastigotes are released from cells, surface-bound IgG can induce IL-10 and suppress IL-12 production from macrophages. These changes decrease IFN-γ from T cells and nitric oxide production in infected cells, which are both required for Leishmania control. However, antibodies targets and the kinetics of antibody production are unknown. Several groups have been unsuccessful in identifying amastigote surface proteins that bind IgG. We now show that glycoinositol phospholipids (GIPLs of L. mexicana are recognized by mouse IgG1 by 6 weeks of infection, with a rapid increase between 12 and 16 weeks, consistent with the timing of chronic disease in C57BL/6 mice vs. healing in FcγRIII-deficient mice. A single prominent spot on TLC is recognized by IgG, and the glycolipid is a glycosyl phosphatidylinositol containing a branched mannose structure. We show that the lipid structure of the GIPL (the sn-2 fatty acid is required for antibody recognition. This GIPL is abundant in L. mexicana amastigotes, rare in stationary-phase promastigotes, and absent in L. major, consistent with a role for antibodies to GIPLs in chronic disease. A mouse monoclonal anti-GIPL IgG recognizes GIPLs on the parasite surface, and induces IL-10 from macrophages. The current work also extends this mouse analysis to humans, finding that L. mexicana-infected humans with localized and diffuse cutaneous leishmaniasis have antibodies that recognize GIPLs, can bind to the surface of amastigotes, and can induce IL-10 from human monocytes. Further characterization of the target glycolipids will have important implications for drug and vaccine development and will elucidate the poorly understood role of

  3. Association of Schistosoma mansoni-specific IgG and IgE antibody production and clinical schistosomiasis status in a rural area of Minas Gerais, Brazil.

    Directory of Open Access Journals (Sweden)

    Deborah Negrão-Corrêa

    Full Text Available BACKGROUND: Studies in murine models and human populations have indicated that the collagen-rich granulomatous response against parasite eggs trapped in the liver is associated with the development of severe hepatosplenic schistosomiasis, characterized by periportal fibrosis and portal hypertension. The role of the humoral response in parasite susceptibility has been well established, but its participation in disease severity remains poorly understood. In this work, we evaluated the relationship between parasite-reactive IgE and IgG levels and schistosomiasis morbidity in infected patients with similar parasite burdens. METHODOLOGY/PRINCIPAL FINDINGS: Ninety-seven Schistosoma mansoni-infected individuals were subjected to clinical examination and abdominal ultrasound analysis. IgG reactivity and IgE concentration against Schistosoma mansoni soluble egg antigens (SEA and adult worm antigen preparation (SWAP were evaluated by ELISA assay. Multivariable linear regression models were used to evaluate the relationship between parasite-reactive antibodies and the co-variables investigated. The study population showed low parasite burden (median 30 eggs/g feces, constant re-infection, and signs of fibrosis was detected in more than 30% of individuals. Most infected individuals showed IgG reactivity, and the median concentrations of IgE anti-SEA and anti-SWAP antibodies were 1,870 and 1,375 ng/mL, respectively. There was no association between parasite burden and antibody response or any parameter of disease severity. However, IgG anti-SWAP level was positively associated with morbidity parameters, such as spleen size and thickness of portal vein at the entrance and secondary branch. In contrast, the data also revealed independent inverse correlations between concentration of parasite-reactive IgE and gallbladder wall thickness, a marker of fibrosis in schistosomiasis. CONCLUSIONS/SIGNIFICANCE: The data indicate that IgG anti-SWAP is positively

  4. Detection of FMD virus type specific IgG1, IgG2 and IgA antibodies in milk and serum of buffaloes vaccinated with oil adjuvanted polyvalent FMD vaccine

    Directory of Open Access Journals (Sweden)

    R. Sharma

    2010-02-01

    Full Text Available The present investigation was carried out on 15 randomly selected milch buffaloes divided into three groups on the basis of lactation at an organized farm, to study the foot and mouth disease virus type specific antibodies in milk and serum following FMD vaccination. Milk and serum samples collected before vaccination i.e. 0 day and on 7, 14, 28, 42 and 56 days post vaccination, were analyzed for the detection of FMD virus specific IgG1, IgG2 and IgA antibody response by indirect double antibody sandwich ELISA. Significant FMD virus type specific antibody titres (IgG1, IgG2 and IgA were detected in milk and serum of buffaloes on different days post vaccination, though the levels of antibodies were lower in milk as compared to serum. FMD virus type specific IgG1 was found to be the predominant subclass as compared to IgG2 and IgA both in milk and serum of vaccinated buffaloes. Milk and serum IgG1, IgG2 and IgA antibody titres were positively correlated with values of regression coefficient (R as 0.506, 0.434 and 0.396, respectively.

  5. Quantitative analysis of the IgG and IgG subclass immune responses to chromosomal Pseudomonas aeruginosa beta-lactamase in serum from patients with cystic fibrosis by western blotting and laser scanning densitometry

    DEFF Research Database (Denmark)

    Petersen, T D; Ciofu, O; Pressler, T;

    1996-01-01

    lung infection with P aeruginosa was further investigated by correlating the a beta ab IgG subclasses with pulmonary function in patients with cystic fibrosis. METHODS: Immunoglobulin G (IgG) and IgG subclass a beta ab were investigated by western blotting and quantified by laser scanning densitometry......BACKGROUND: Antibodies against chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) are markers of the development of resistance of P aeruginosa to beta-lactam antibiotics in patients with cystic fibrosis and chronic lung infection. The role of these antibodies in patients with chronic....... A longitudinal study on 43 consecutive patients with cystic fibrosis who developed chronic lung infection with P aeruginosa was performed. RESULTS: IgG subclass a beta ab appeared in all patients with chronic infection with P aeruginosa. Eleven years after the onset of infection all the patients had IgG1, 79...

  6. Mannose metabolism in recombinant CHO cells and its effect on IgG glycosylation.

    Science.gov (United States)

    Slade, Peter G; Caspary, R Guy; Nargund, Shilpa; Huang, Chung-Jr

    2016-07-01

    Understanding the causes of high-mannose (HM) glycosylation of recombinant IgG in CHO cells would facilitate the production of therapeutics. CHO cells grown with mannose as the major carbon source demonstrated a dramatic increase in total HM glycosylation in recombinant IgG, with no effect on cell growth, viability, or titer. Quantitative metabolomics and (13) C flux analysis were used to explore the mechanism for increased HM glycosylation and understand the metabolism of mannose in CHO cells. It was demonstrated that mannose was a good carbon source for CHO cell growth and IgG production, readily entering both glycolysis and the TCA Cycle. Previous mechanisms for increased HM glycosylation during antibody production have been attributed to changes in pH, osmolality, increased specific productivity, and nutrient limitation. The results from this study propose a novel mechanism where an increased carbon flux in the GDP-mannose synthetic pathway increased the intracellular concentration of mannose-containing metabolites. The abnormally high concentration of mannose and mannose-metabolites were shown to inhibit α-mannosidase activity and it was proposed that this inhibition in the ER and Golgi caused the production of IgG with increased high-mannose glycosylation. Biotechnol. Bioeng. 2016;113: 1468-1480. © 2016 Wiley Periodicals, Inc. PMID:26724786

  7. Effects of sterilizing radiation dose on the amino acid composition of normal human Ig(G)

    International Nuclear Information System (INIS)

    In order to verify gamma radiation effect of 60Co, samples of Normal human Ig(G) in a) pH 7 solutions with different concentrations, and b) in liophilized state, were irradiated. In both, the quali and quantitative amino acid compositions have been studied. No changes in amino acid composition were observed, for doses up to 10 Mrad delivered to the liophilized samples. Nevertheless, when 5 mg/ml and 10 mg/ml solutions of Ig(G) were irradiated with a 2 Mrad gamma dose, both were affected. The damage appeared in greater proportion in the samples with lower concentration. Cistine was the amino acid most damaged and the loss of methionine, proline histidine, arginine, tirosine and phenilalanine, decreased in this order. The analysis of the experimental data shows that liophilized human Ig(G) can be treated with doses higher than those required to achieve sterilization, without modifying its immunologic and primary proteic structure properties. Therefore, gamma sterilization feasibility has been proved for normal human Ig(G) only in the liophilized state. (author)

  8. Investigation of Hepatitis E Virus IgG Seroprevalence in Women of Reproductive Age

    Directory of Open Access Journals (Sweden)

    Erdal Özbek

    2016-03-01

    Full Text Available Objective: Hepatitis E virus (HEV infection can cause fa­tal hepatitis particularly in pregnant women. In this study, it was aimed to investigate the rate of anti HEV IgG se­roprevalence in women of childbearing age and whether there are differences in seroprevalence among people liv­ing in urban and rural areas or not. Methods: A total of 158 women volunteers aged 15-49 years living in rural or urban areas were included in this study. Anti-HEV IgG antibodies were performed with en­zyme immunoassay method. The obtained data were presented as numbers and percentages and statistically analyzed. Results: Anti-HAV IgG was detected positive in 41 of the 158 volunteers (25.9%. Anti-HEV IgG was found positive in 25 of the 92 volunteers living in urban areas (27.2% and in 16 of the 66 volunteers in rural areas (24.2%. Conclusion: In our city, HEV seroprevalence is above the average in Turkey. We think that epidemiological fac­tors should be investigated and that screening HEV serol­ogy can be useful in pregnancy monitoring. J Clin Exp Invest 2016; 7 (1: 69-72

  9. Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia

    OpenAIRE

    Miura, Yumako; Devaux, Jérôme J.; Fukami, Yuki; Manso, Constance; Belghazi, Maya; Wong, Anna Hiu Yi; Yuki, Nobuhiro

    2015-01-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is clinically heterogeneous and shows varying responses to immunotherapy. In a cohort of 533 Japanese patients with CIDP, Miura et al. identify 13 patients with IgG4 antibodies against the axonal adhesion molecule, contactin-1. Antibodies are associated with subacute onset, sensory ataxia and good response to corticosteroids.

  10. IgG Responses to Tissue-Associated Antigens as Biomarkers of Immunological Treatment Efficacy

    Directory of Open Access Journals (Sweden)

    Heath A. Smith

    2011-01-01

    Full Text Available We previously demonstrated that IgG responses to a panel of 126 prostate tissue-associated antigens are common in patients with prostate cancer. In the current report we questioned whether changes in IgG responses to this panel might be used as a measure of immune response, and potentially antigen spread, following prostate cancer-directed immune-active therapies. Sera were obtained from prostate cancer patients prior to and three months following treatment with androgen deprivation therapy (=34, a poxviral vaccine (=31, and a DNA vaccine (=21. Changes in IgG responses to individual antigens were identified by phage immunoblot. Patterns of IgG recognition following three months of treatment were evaluated using a machine-learned Bayesian Belief Network (ML-BBN. We found that different antigens were recognized following androgen deprivation compared with vaccine therapies. While the number of clinical responders was low in the vaccine-treated populations, we demonstrate that ML-BBN can be used to develop potentially predictive models.

  11. Amplified Immunoassay of Human IgG Using Real-time Biomolecular Interaction Analysis (BIA) Technology

    Institute of Scientific and Technical Information of China (English)

    PEI,Ren-Jun(裴仁军); CUI,Xiao-Qiang(崔小强); YANG,Xiu-Rong(杨秀荣); WANG,Er-Kang(汪尔康)

    2002-01-01

    An automated biomolecular interaction analysis instrument (BIAcore) based on surface plasmon resonance (SPR) has been used to determine human immunoglobulin G (IgG) in real time. Polyclonal anti-human IgG antibody was covalently immobilized to a carboxymethyldextran-modified gold film surface. The samples of human IgG prepared in HBS buffer were poured over the immobilized surface. The signal amplification antibody was applied to amplify the response signal. After each measurement, the surface was regenerated with 0.1 mol/L H3PO4. The assay was rapid, requiring only 30 min for antibody immobilization and 20 min for each subsequent process of immune binding, antibody amplification and regeneration. The antibody immobilized surface had good response to human IgG in the range of 0.12-60 nmol/L with a detection limit of 60 pmoL/L. The same antibody immobilized surface could be used for more than 110 cycles of binding, amplificafion and regeneration. The results demonstrate that the sensitivity, specificity and reproducibility of amplified immunoassay using real-time BIA technology are satisfactory.

  12. A novel chemiluminescent immunoassay for detection of Toxoplasma gondii IgG in human sera.

    Science.gov (United States)

    Holec-Gąsior, Lucyna; Ferra, Bartłomiej; Czechowska, Justyna; Serdiuk, Illia E; Krzymiński, Karol; Kur, Józef

    2016-08-01

    This study describes Toxoplasma gondii IgG chemiluminescent immunoassay (CLIA) based on the use of a novel immunochemical reagents in the form of the conjugates of original acridinium ester (AE) labels attached to antibodies and SAG2-GRA1-ROP1L chimeric antigen and shows that this test is useful for diagnostic purposes.

  13. Aquaporin-4 IgG autoimmune syndrome and immunoreactivity associated with thyroid cancer

    DEFF Research Database (Denmark)

    Soelberg, Kerstin; Larsen, Stine Rosenkilde; Mørch, Marlene;

    2016-01-01

    pathogenicity of autoantibodies vary between neurologic diseases. By contrast, anti-aquaporin-4 (AQP4) IgG from patients with neuromyelitis optica spectrum disorder (NMOSD) is a specific biomarker for NMOSD. AQP4 is the most abundant water channel in the CNS, particularly abundant on astrocytes, forming...

  14. [IgG antibodies against toxic shock syndrome toxin 1 in human immunoglobulins].

    Science.gov (United States)

    Dickgiesser, N; Kustermann, B

    1986-07-15

    IgG antibodies against toxic shock syndrome toxin-1 in human immunoglobulins were determined using the ELISA technique. Of the drugs for intramuscular application, hemogamma and beriglobin contained the highest amount of antibodies. The highest concentration of antibodies in drugs for intravenous application was found in Pseudomonas polyglobin and in Venimmun. PMID:3762013

  15. Current Concepts and Diagnosis of IgG4-Related Pancreatitis (Type 1 AIP).

    Science.gov (United States)

    Kawa, Shigeyuki

    2016-08-01

    Although now considered to be a member of the systemic entity of immunoglobulin G4- (IgG4-) related disease, IgG4-related pancreatitis is generally referred to as type 1 autoimmune pancreatitis (AIP). Type 1 AIP was established based on a pathological background of lymphoplasmacytic sclerosing pancreatitis, high serum IgG4 concentration, and abundant IgG4-bearing plasma cell infiltration. The characteristic clinical features of type 1 AIP, such as elderly male preponderance, obstructive jaundice, and mass-forming lesions in the pancreas, often mimic those of pancreatic cancer. However, because AIP responds favorably to corticosteroid treatment, careful differentiation from pancreatic cancer is required. An AIP diagnosis is currently based on the 2011 International Consensus Diagnostic Criteria for AIP, which are based on high sensitivity, selectivity, and accuracy. Over the long term, AIP can progress to a chronic condition, with pancreatic stone formation and atrophy resembling that of chronic pancreatitis. Although AIP has been linked to the complication of malignancies, it remains controversial whether an association exists between the disease and tumor formation. PMID:27466795

  16. The Contribution of Allergen-Specific IgG to the Development of Th2-Mediated Airway Inflammation

    Directory of Open Access Journals (Sweden)

    Jesse W. Williams

    2012-01-01

    Full Text Available In both human asthmatics and animal models of allergy, allergen-specific IgG can contribute to Th2-mediated allergic inflammation. Mouse models have elucidated an important role for IgG and Fc-gamma receptor (FcγR signaling on antigen presenting cells (APC for the induction of airway inflammation. These studies suggest a positive feedback loop between IgG produced by the adaptive B cell response and FcγR signaling on innate immune cells. Studies of IgG and FcγRs in humans with asthma or allergic lung disease have been more controversial. Some reports have identified associations between allergen-specific IgG and severity of allergic responses, while other studies have found associations of IgG subclass IgG4 with allergic tolerance. In this paper, we review the literature to help define the nature of IgG and FcγR signaling on innate immune cells and how it contributes to the development of allergic immune responses.

  17. Cross-sectional Serosurvey of Crimean-Congo Hemorrhagic Fever Virus IgG in Livestock, India, 2013-2014.

    Science.gov (United States)

    Mourya, Devendra T; Yadav, Pragya D; Shete, Anita M; Sathe, Padmakar S; Sarkale, Prasad C; Pattnaik, Bramhadev; Sharma, Gaurav; Upadhyay, Kamlesh J; Gosavi, Surekha; Patil, Deepak Y; Chaubal, Gouri Y; Majumdar, Triparna D; Katoch, Vishwa M

    2015-10-01

    We conducted a cross-sectional serosurvey of Crimean-Congo hemorrhagic fever (CCHF) among livestock in 22 states and 1 union territory of India. A total of 5,636 samples from bovines, sheep, and goats were screened for CCHF virus IgG. IgG was detected in 354 samples, indicating that this virus is widespread in this country.

  18. Indigenous Greenlanders have a higher sero-prevalence of IgG antibodies to Helicobacter pylori than Danes

    DEFF Research Database (Denmark)

    Milman, Nils; Byg, Keld-Erik; Andersen, Leif P;

    2003-01-01

    To assess the sero-prevalence of IgG antibodies to Helicobacter pylori (H. pylori) in Greenlanders and compare with the sero-prevalence in Caucasian Danes.......To assess the sero-prevalence of IgG antibodies to Helicobacter pylori (H. pylori) in Greenlanders and compare with the sero-prevalence in Caucasian Danes....

  19. Development of fully automated determination of marker-specific immunoglobulin G (IgG) avidity based on the avidity competition assay format: application for Abbott Architect cytomegalovirus and Toxo IgG Avidity assays.

    Science.gov (United States)

    Curdt, Ingo; Praast, Gerald; Sickinger, Eva; Schultess, Jan; Herold, Iris; Braun, Hans Bertram; Bernhardt, Stephanie; Maine, Gregory T; Smith, Darwin D; Hsu, Stephen; Christ, Heike M; Pucci, Dominick; Hausmann, Michael; Herzogenrath, Jörg

    2009-03-01

    Determination of the avidity of immunoglobulin G (IgG) directed against a specific marker has become an established diagnostic tool for identifying or excluding acute infections with pathogens. A novel assay format termed AVIcomp (avidity competition based on mass action) circumventing the conventional chaotropic format has been developed for determination of the avidity of marker-specific IgG in patient specimens. Its applications for cytomegalovirus (CMV) and Toxoplasma gondii are presented. Specific high-avidity IgG from the patient specimen is selectively blocked using a soluble antigen in a sample pretreatment reagent, and the amount of remaining specific low-avidity IgG is determined relative to that in an untreated control. The comparison of the conventional chaotropic format, represented by the Radim CMV IgG Avidity assay, and the newly developed AVIcomp method, as exemplified by the Architect CMV IgG Avidity assay, on blood drawn within 4 months after seroconversion revealed a sensitivity of 100% (97.3% by an alternative calculation) for the AVIcomp format versus 87.5% (75.7% by an alternative calculation) for the chaotropic avidity assay. The specificity on 312 CMV IgG reactive and CMV IgM nonreactive specimens from pregnant women was 100% for the AVIcomp assay and 99.7% for the conventional avidity assay. The Architect Toxo IgG Avidity assay showed an agreement of 97.2% with the bioMérieux Vidas Toxo IgG Avidity Assay employing chaotropic reagents. These performance data suggest that the AVIcomp format shows superior sensitivity and equivalent specificity for the determination of IgG avidity to assays based on the chaotropic method and that the AVIcomp format may also be applicable to other disease states.

  20. Increased levels of IgG antibodies against human HSP60 in patients with spondyloarthritis.

    Directory of Open Access Journals (Sweden)

    Astrid Hjelholt

    Full Text Available Spondyloarthritis (SpA comprises a heterogeneous group of inflammatory diseases, with strong association to human leukocyte antigen (HLA-B27. A triggering bacterial infection has been considered as the cause of SpA, and bacterial heat shock protein (HSP seems to be a strong T cell antigen. Since bacterial and human HSP60, also named HSPD1, are highly homologous, cross-reactivity has been suggested in disease initiation. In this study, levels of antibodies against bacterial and human HSP60 were analysed in SpA patients and healthy controls, and the association between such antibodies and disease severity in relation to HLA-B27 was evaluated.Serum samples from 82 patients and 50 controls were analysed by enzyme-linked immunosorbent assay (ELISA for immunoglobulin (IgG1, IgG2, IgG3 and IgG4 antibodies against human HSP60 and HSP60 from Chlamydia trachomatis, Salmonella enteritidis and Campylobacter jejuni. Disease severity was assessed by the clinical scorings Bath Ankylosing Spondylitis Disease Activity Index (BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI and Bath Ankylosing Spondylitis Metrology Index (BASMI. Levels of IgG1 and IgG3 antibodies against human HSP60, but not antibodies against bacterial HSP60, were elevated in the SpA group compared with the control group. Association between IgG3 antibodies against human HSP60 and BASMI was shown in HLA-B27⁺ patients. Only weak correlation between antibodies against bacterial and human HSP60 was seen, and there was no indication of cross-reaction. These results suggest that antibodies against human HSP60 is associated with SpA, however, the theory that antibodies against human HSP60 is a specific part of the aetiology, through cross-reaction to bacterial HSP60, cannot be supported by results from this study. We suggest that the association between elevated levels of antibodies against human HSP60 and disease may reflect a general activation of the immune system and an increased

  1. A simple set of validation steps identifies and removes false results in a sandwich enzyme-linked immunosorbent assay caused by anti-animal IgG antibodies in plasma from arthritis patients

    OpenAIRE

    Kragstrup, Tue W; Vorup-Jensen, Thomas; Deleuran, Bent; Hvid, Malene

    2013-01-01

    Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are chronic diseases characterized by activation of the immune system and production of antibodies. Thus, rheumatoid factor, anti-animal IgG antibodies and heterophilic antibodies in plasma samples from arthritis patients can interfere with immunoassays such as sandwich enzyme-linked immunosorbent assay (ELISA) systems often used in arthritis research. However, standard methodologies on how to test for false results caused by these antibod...

  2. Antitumor Efficacy of Anti-GD2 IgG1 Is Enhanced by Fc Glyco-Engineering.

    Science.gov (United States)

    Xu, Hong; Guo, Hongfen; Cheung, Irene Y; Cheung, Nai-Kong V

    2016-07-01

    The affinity of therapeutic antibodies for Fcγ receptors (FcγRs) strongly influences their antitumor potency. To generate antibodies with optimal binding and immunologic efficacy, we compared the affinities of different versions of an IgG1 Fc region that had an altered peptide backbone, altered glycans, or both. To produce IgG1 with glycans that lacked α1,6-fucose, we used CHO cells that were deficient in the enzyme UDP-N-acetylglucosamine: α-3-d-mannoside-β-1,2-N-acetylglucosaminyltransferase I (GnT1), encoded by the MGAT1 gene. Mature N-linked glycans require this enzyme, and without it, CHO cells synthesize antibodies carrying only Man5-GlcNAc2, which were more effective in antibody-dependent cell-mediated cytotoxicity (ADCC). Our engineered IgG1, hu3F8-IgG1, is specific for GD2, a neuroendocrine tumor ganglioside. Its peptide mutant is IgG1-DEL (S239D/I332E/A330L), both produced in wild-type CHO cells. When produced in GnT1-deficient CHO cells, we refer to them as IgG1n and IgG1n-DEL, respectively. Affinities for human FcγRs were measured using Biacore T-100 (on CD16 and CD32 polymorphic alleles), their immunologic properties compared for ADCC and complement-mediated cytotoxicity (CMC) in vitro, and pharmacokinetics and antitumor effects were compared in vivo in humanized mice. IgG1n and IgG1n-DEL contained only mannose and acetylglucosamine and had preferential affinity for activating CD16s, over inhibitory CD32B, receptors. In vivo, the antitumor effects of IgG1, IgG1-DEL, and IgG1n-DEL were similar but modest, whereas IgG1n was significantly more effective (P < 0.05). Thus, IgG1n antibodies produced in GnT1-deficient CHO cells may have potential as improved anticancer therapeutics. Cancer Immunol Res; 4(7); 631-8. ©2016 AACR. PMID:27197064

  3. The evaluation of rubella and sitomegalovirus IgG avidity tests in pregnants: four-year experience

    Directory of Open Access Journals (Sweden)

    Berrin Uzun

    2014-09-01

    Full Text Available Objective: In this study, we aim to evaluate the retrospective IgG avidity index (AI test results of the pregnant, who have applied to our hospital and had pregnancy screening test and have been asked for rubella and cytomegalovirus antibody tests and IgG AI test in 4 year period. Methods: Anti-rubella IgM, anti-rubella IgG, anti-CMV IgM and anti-CMV antibodies were performed by IMMULITE 2000XPi™ Immunoassay System (Siemens, Germany whereas IgG AI tests were performed by commercial kits of rubella and cytomegalovirus antibody tests (Dia.Pro® Diagnostic, Milano-Italy. Results: Between January 2010 and December 2013, 23 (7.32 % of 314 pregnant women tested rubella IgG AI had low AI, and 266 cases had high AI rate; 14 (17.28% of 81 pregnant women tested CMV IgG AI, had lower AI rate, 52 of them had high AI. 9 out of 23 pregnant women, who were detected low rubella were requested only AI without any IgM and IgG value; the IgG antibody of 13 pregnant was reactive, and IgM antibody was not requested; IgG and IgM antibody of 1 pregnant was detected positive. When 5 pregnant, who were detected low CMV AI were requested AI without IgG and IgM value; the IgG and IgM of 4 was reactive; 4 of them had IgG reactive but IgM negative; 1 had IgG and IgM negative. Conclusion: As a result, our low rubella AI rate has been detected lower than the rates in our country since our study population contains only the pregnant. Our low CMV AI rate varies due to the same reasons as literature data. During pregnancy scanning, performing of AI testing together with specific IgG and IgM will save both time and will be more meaningful in clinical evaluation for pregnant women. J Clin Exp Invest 2014; 5 (3: 420-423

  4. Determination of Antibodies (IgG, IgM against Toxoplasma gondii in Patients with Cancer

    Directory of Open Access Journals (Sweden)

    M Pedram

    2007-08-01

    Full Text Available Background: The aim of this study was determination of antibodies (IgG, IgM against Toxoplasma in malignant patients in order to refer the patients on time to the physician for treatment.Methods: This study was carried out on 252 malignant patients and 252 healthy normal subjects (as control obtained from Shafa Hospital and Medical Diagnostic Laboratory (Iran-Zamin, in Ahwaz city. Patient's information was recorded in a questionnaire before sampling. Serum samples of patients were examined for IgG and IgM antibodies by ELISA technique using Trinity kits. Results: The results of this study revealed the presence of Toxoplasma antibodies in 114 (45.2% cases of patients who were positive for Toxoplasma IgG antibodies, and 26 (10.3% cases were confirmed to be positive for Toxoplasma IgM antibodies and also 17 (6.7% of cases had both IgG and IgM antibodies against Toxoplasma gondii. In control group 92 (36.5% cases and 15 (6% cases revealed seropositive for IgG and IgM antibodies, respectively. There were no significant differences between sex, close contact with cat, living region, chemotherapy, and seropositivity rate of toxoplasmosis in patients. Comparing the age groups, the highest seropositive rate showed in the age of 51 years or higher, and their rates had tendency to increase with age in both groups. No seropositivity significant relationship was found between patients and control group.Conclusion: According to the prevalence of positive cases in these patients, it is necessary to examine the patients for toxoplasmosis before, during and after chemotherapy.

  5. Association Between HLA Haplotypes and Increased Serum Levels of IgG4 in Patients With Primary Sclerosing Cholangitis.

    Science.gov (United States)

    Berntsen, Natalie L; Klingenberg, Olav; Juran, Brian D; Benito de Valle, Maria; Lindkvist, Björn; Lazaridis, Konstantinos N; Boberg, Kirsten Muri; Karlsen, Tom H; Hov, Johannes Roksund

    2015-05-01

    Increased serum levels of IgG4 have been reported in 9%-15% of patients with primary sclerosing cholangitis (PSC); it is not clear whether this increase contributes to pathogenesis. We performed genetic analyses of the HLA complex in patients with PSC from Norway, Sweden, and from the United States. We found an association between levels of IgG4 above the upper reference limit and specific HLA haplotypes. These patients had a significantly lower frequency of the strongest PSC risk factor, HLA-B*08, than patients without increased IgG4, and significantly higher frequencies of HLA-B*07 and HLA-DRB1*15. HLA genotype therefore might affect the serum concentration of IgG4, and increased IgG4 might be a marker of a distinct phenotype of PSC.

  6. Recent advances in the concept and pathogenesis of IgG4-related disease in the hepato-bilio-pancreatic system.

    Science.gov (United States)

    Okazaki, Kazuichi; Yanagawa, Masahito; Mitsuyama, Toshiyuki; Uchida, Kazushige

    2014-09-01

    Recent studies have proposed nomenclatures of type 1 autoimmune pancreatitis (AIP) (IgG4-related pancreatitis), IgG4-related sclerosing cholangitis (IgG4-SC), IgG4-related cholecystitis, and IgG4-related hepatopathy as IgG4-related disease (IgG4-RD) in the hepato-bilio-pancreatic system. In IgG4-related hepatopathy, a novel concept of IgG4-related autoimmune hepatitis (AIH) with the same histopathological features as AIH has been proposed. Among organs involved in IgG4-RD, associations with pancreatic and biliary lesions are most frequently observed, supporting the novel concept of "biliary diseases with pancreatic counterparts." Targets of type 1 AIP and IgG4-SC may be periductal glands around the bile and pancreatic ducts. Based on genetic backgrounds, innate and acquired immunity, Th2-dominant immune status, regulatory T (Treg) or B cells, and complement activation via a classical pathway may be involved in the development of IgG4-RD. Although the role of IgG4 remains unclear in IgG4-RD, IgG4-production is upregulated by interleukin 10 from Treg cells and by B cell activating factor from monocytes/basophils with stimulation of toll-like receptors/nucleotide-binding oligomerization domain-like receptors. Based on these findings, we have proposed a hypothesis for the development of IgG4-RD in the hepato-bilio-pancreatic system. Further studies are necessary to clarify the pathogenic mechanism of IgG4-RD. PMID:25228969

  7. Comparison of Salivary Anti Helicobacter pylori IgG with Serum IgG and Bacteriological Tests in Detecting Helicobacter pylori Infections

    Directory of Open Access Journals (Sweden)

    H Ghasemian safaei

    2005-01-01

    Full Text Available Background: This study was conducted to compare the efficacy of enzyme-linked immunosorbent assay (ELISA for detecting anti-Helicobacter pylori (H. pylori specific IgG antibodies in specimens of oral fluid and serum with bacteriological tests. Methods: Antral biopsy specimens, as well as serum and oral fluid samples were collected from 97 patients who underwent upper gastrointestinal endoscopy. The presence or absence of current H. pylori infection was determined by culture, histology and urease detection. Anti-H. pylori specific IgG was detected in serum and oral fluid, using an established lab-made, and a commercial ELISA kit. The obtained data were compared with results of bacteriological tests. Results: In all, 62 (64% of 97 patients were positive for H. pylori by one or more of the gold standard tests (culture, histology and urease detection. Lab-made enzyme-linked immunoassay of oral fluid had a sensitivity and specificity of 92% and 83% respectively. A sensitivity and specificity of 87% and 83%, respectively, was obtained with the commercial kit. Lab-made enzyme-linked immunoassay of serum samples had a sensitivity and specificity of 90% and 88%, respectively. A sensitivity of 86% and specificity of 86% was obtained with the commercial kit. Conclusion: Detection of anti-H. pylori specific IgG in oral fluid by ELISA is comparable in sensitivity and specificity with serum based methods. Oral fluid based ELISA could provide a reliable, non-invasive method for the diagnosis of H. pylori infection. Saliva testing may have a role in epidemiological studies. Keywords: Helicobacter pylori, ELISA, Oral fluid

  8. Early differentiated CD138(high MHCII+ IgG+ plasma cells express CXCR3 and localize into inflamed kidneys of lupus mice.

    Directory of Open Access Journals (Sweden)

    Stéphanie Lacotte

    Full Text Available Humoral responses are central to the development of chronic autoimmune diseases such as systemic lupus erythematosus. Indeed, autoantibody deposition is responsible for tissue damage, the kidneys being one of the main target organs. As the source of pathogenic antibodies, plasma cells are therefore critical players in this harmful scenario, both at systemic and local levels. The aim of the present study was to analyze plasma cells in NZB/W lupus mice and to get a better understanding of the mechanisms underlying their involvement in the renal inflammation process. Using various techniques (i.e. flow cytometry, quantitative PCR, ELISpot, we identified and extensively characterized three plasma cell intermediates, according to their B220/CD138/MHCII expression levels. Each of these cell subsets displays specific proliferation and antibody secretion capacities. Moreover, we evidenced that the inflammation-related CXCR3 chemokine receptor is uniquely expressed by CD138(highMHCII(+ plasma cells, which encompass both short- and long-lived cells and mostly produce IgG (autoantibodies. Expression of CXCR3 allows efficient chemotactic responsiveness of these cells to cognate chemokines, which production is up-regulated in the kidneys of diseased NZB/W mice. Finally, using fluorescence and electron microscopy, we demonstrated the presence of CD138(+CXCR3(+IgG(+ cells in inflammatory areas in the kidneys, where they are very likely involved in the injury process. Thus, early differentiated CD138(highMHCII(+ rather than terminally differentiated CD138(highMHCII(low plasma cells may be involved in the renal inflammatory injury in lupus, due to CXCR3 expression and IgG secretion.

  9. Evaluation of cysticercus-specific IgG (total and subclasses and IgE antibody responses in cerebrospinal fluid samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies

    Directory of Open Access Journals (Sweden)

    Lisandra Akemi Suzuki

    2013-02-01

    Full Text Available In the present study, an enzyme-linked immunosorbent assay (ELISA standardized with vesicular fluid of Taenia solium cysticerci was used to screen for IgG (total and subclasses and IgE antibodies in cerebrospinal fluid (CSF samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies and patients with other neurological disorders. The following results were obtained: IgG-ELISA: 100% sensitivity (median of the ELISA absorbances (MEA=1.17 and 100% specificity; IgG1-ELISA: 72.7% sensitivity (MEA=0.49 and 100% specificity; IgG2-ELISA: 81.8% sensitivity (MEA=0.46 and 100% specificity; IgG3-ELISA: 63.6% sensitivity (MEA=0.12 and 100% specificity; IgG4-ELISA: 90.9% sensitivity (MEA=0.85 and 100% specificity; IgE-ELISA 93.8% sensitivity (MEA=0.60 and 100% specificity. There were no significant differences between the sensitivities and specificities in the detection of IgG-ELISA and IgE-ELISA, although in CSF samples from patients with neurocysticercosis the MEA of the IgG-ELISA was significantly higher than that of the IgE-ELISA. The sensitivity and MEA values of the IgG4-ELISA were higher than the corresponding values for the other IgG subclasses. Future studies should address the contribution of IgG4 and IgE antibodies to the physiopathology of neurocysticercosis.

  10. Understanding the Relationship Between Biotherapeutic Protein Stability and Solid–Liquid Interfacial Shear in Constant Region Mutants of IgG1 and IgG4

    Science.gov (United States)

    Tavakoli-Keshe, Roumteen; Phillips, Jonathan J; Turner, Richard; Bracewell, Daniel G

    2014-01-01

    Relative stability of therapeutic antibody candidates is currently evaluated primarily through their response to thermal degradation, yet this technique is not always predictive of stability in manufacture, shipping, and storage. A rotating disk shear device is proposed that produces defined shear conditions at a known solid–liquid interface to measure stability in this environment. Five variants of IgG1 and IgG4 antibodies were created using combinations of two discrete triple amino acid sequence mutations denoted TM and YTE. Antibodies were ranked for stability based on shear device output (protein decay coefficient, PDC), and compared with accelerated thermal stability data and the melting temperature of the CH2 domain (Tm1) from differential scanning calorimetry to investigate technique complimentarity. Results suggest that the techniques are orthogonal, with thermal methods based on intramolecular interaction and shear device stability based on localized unfolding revealing less stable regions that drive aggregation. Molecular modeling shows the modifications’ effects on the antibody structures and indicates a possible role for Fc conformation and Fab-Fc docking in determining suspended protein stability. The data introduce the PDC value as an orthogonal stability indicator, complementary to traditional thermal methods, allowing lead antibody selection based on a more full understanding of process stability. © 2013 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:437–444, 2014 PMID:24357426

  11. The IgG avidity value for the prediction of Toxoplasma gondii infection in the amniotic fluid.

    Science.gov (United States)

    Tanimura, Kenji; Nishikawa, Akira; Tairaku, Shinya; Shinozaki, Nanae; Deguchi, Masashi; Morizane, Mayumi; Ebina, Yasuhiko; Morioka, Ichiro; Yamada, Hideto

    2015-09-01

    Primary Toxoplasma gondii (T. gondii) infection during pregnancy may lead to congenital toxoplasmosis. Maternal screening using T. gondii IgG avidity measurement and multiplex nested PCR was performed. The aim of this prospective cohort study was to determine a cut-off value of IgG avidity index (AI) for the prediction of the presence of T. gondii DNA in the amniotic fluid. One hundred thirty-nine women with positive or equivocal tests for IgM underwent both serum IgG avidity measurement and PCR analysis for the amniotic fluid. Nine had positive PCR results, and three of them were diagnosed as having congenital infection. A cut-off value of IgG AI was determined using receiver operating characteristic analysis. IgG AI (mean 13%) in women with positive PCR results was significantly lower than that (39%) in women with negative results. A cut-off value of amniotic fluid. None of women with IgG AI of ≥30% had a positive PCR result or congenital infection. This study firstly demonstrated that a cut-off value of 25-30% IgG AI might be useful for the prediction of the presence of T. gondii DNA in the amniotic fluid and congenital infection.

  12. IgG4-related Lung Disease Associated with Autoimmune Hemolytic Anemia: A Case Report and a Literature Review.

    Science.gov (United States)

    Noguchi, Shingo; Yatera, Kazuhiro; Jinbo, Mitsutaka; Yamada, Sohsuke; Shimabukuro, Ikuko; Yamasaki, Kei; Kido, Takashi; Ishimoto, Hiroshi; Yoshii, Chiharu; Mukae, Hiroshi

    2016-01-01

    We herein report a case of IgG4-related lung disease (IgG4-RLD) associated with autoimmune hemolytic anemia (AIHA). A 73-year-old Japanese female visited our hospital for an examination following an abnormal chest X-ray in 1999. She was diagnosed with bronchiolitis and AIHA, and treatment with prednisolone was started. After seven years, she visited our department due to a cough. Chest computed tomography (CT) demonstrated focal consolidation with ground-glass attenuations and thickened bronchial walls in the bilateral lungs. She was clinically diagnosed and treated for bronchial asthma. CT findings had shown no changes, and a lung biopsy was performed using video-assisted thoracic surgery at eleven years from the first diagnosis of AIHA. The pathological findings demonstrated the presence of peribronchovascular lymphoplasmacytic infiltrates with stromal fibrotic changes, admixed with many IgG4-positive plasma cells. Furthermore, the patient's serum IgG4 level was high, and her CT findings did not show any obvious abnormal findings in the any organs other than the lungs. She was diagnosed with IgG4-RLD based on the findings. We believe that this case report of IgG4-RLD associated with AIHA is clinically helpful for a better understanding of these diseases, although there are five reported cases of IgG4-related disease associated with AIHA. PMID:27580552

  13. IgG4相关硬化性胆管炎的研究进展%Recent advances in research of immunoglobulin G4-related sclerosing cholangitis

    Institute of Scientific and Technical Information of China (English)

    黄颖秋

    2012-01-01

    免疫球蛋白G4相关硬化性胆管炎(immunoglobulin G4-related sclerosing cholangitis,IgG4-SC)是一种新近认识的以血清IgG4升高、慢性进行性阻塞性黄疸、弥漫性或局限性IgG4阳性浆细胞和淋巴细胞组织浸润、纤维化及闭塞性静脉炎为特征的慢性炎症性疾病,常并发自身免疫性胰腺炎(autoimmune pancreatitis,AIP),其临床、生化及影像学特征与原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)或胆管癌(cholangiocarcinoma,CC)相似.类固醇激素是IgG4-SC的主要治疗手段,而肝移植是PSC唯一的有效治疗方法,CC则需外科手术治疗.因此,IgG4-SC与PSC或CC间的准确鉴别是目前面临的一个十分重要的课题.本文详尽地阐述了免疫球蛋白G4(immunoglobulin G4,IgG4)的特征和功能,IgG4-SC的诊断和治疗,IgG4-SC与AIP、PSC及CC之间关系等研究进展,为IgG4-SC的精确诊断和治疗提供了新的思路.%Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is a recently defined disease entity characterized by elevated serum IgG4, chronic progressive obstructive jaundice, and diffuse or mass-forming inflammatory reaction rich in IgG4-positive plasma cells and lymphocytes associated with fibrosclerosis and obliterative phlebitis, which shares a number of clinical, biochemical, and radiological features with primary sclerosing cholangitis (PSC) or cholangiocarcino-ma (CC). IgG4-SC is commonly associated with autoimmune pancreatitis (AIP). Steroid therapy comprises the mainstay of treatment for IgG4-SC patients. However, liver transplantation is the only useful treatment for PSC patients, and CC patients require surgical therapy. Therefore, the accurate discrimination between IgG4-SC and PSC or CC is a very important issue. In this article, we will review the features and role of immunoglobulin G4 (IgG4), the diagnosis and therapy of IgG4-SC, and the relations between IgG4-SC and AIP, PSC or CC.

  14. IgG4-related kidney disease: MRI findings with emphasis on the usefulness of diffusion-weighted imaging

    International Nuclear Information System (INIS)

    Objectives: To investigate the imaging findings of immunoglobulin G4 (IgG4)-related kidney disease (IgG4-KD) on magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) and to evaluate the usefulness of DWI in lesion detection. Methods: This retrospective cohort study included 31 patients with IgG4-KD who underwent MRI covering both kidneys. Two radiologists reviewed in consensus the MR images to determine the distribution pattern (location, laterality, and multiplicity) and the visually assessed signal intensity (hypointense, isointense or hyperintense) of the renal lesions compared to the normal renal parenchyma on each sequence. Per-patient sensitivity for detecting IgG4-KD and the number of detectable lesions were compared in T2-weighted images, DWI, and dynamic contrast-enhanced images. Results: IgG4-KD typically manifested as bilateral (83.9%), multiple (93.5%), and renal parenchymal (87.1%) nodules appearing isointense (93.5%) on T1-weighted images, hypointense (77.4%) on T2-weighted images, hyperintense (100%) on DWI (b = 1000), and hypointense (83.3%) in the arterial phase and with a progressive enhancement pattern on dynamic contrast-enhanced images. The sensitivity of DWI for detecting IgG4-KD was significantly higher than that of T2-weighted images (100% vs. 77.4%, P = 0.034). The median number of detectable lesions was significantly greater in DWI (n = 9) than in T2-weighted images (n = 2) and dynamic contrast-enhanced images (n = 5) (P ≤ 0.008). Conclusions: The characteristic MRI findings of IgG4-KD were bilateral, multiple, renal parenchymal nodules with T2 hypointensity, diffusion restriction, and a progressive enhancement pattern. As DWI was useful in the detection of IgG4-KD, adding DWI to conventional MRI for patients suspected of having IgG4-KD may enhance the diagnosis

  15. Hepatitis C viremia is associated with cytomegalovirus IgG antibody levels in HIV-infected women.

    Directory of Open Access Journals (Sweden)

    Mark H Kuniholm

    Full Text Available BACKGROUND: Individuals with HIV infection exhibit high cytomegalovirus (CMV IgG levels, but there are few data regarding the association of hepatitis C virus (HCV with the immune response against CMV. METHODS: Associations of HCV with CMV seropositivity and CMV IgG levels were studied in 635 HIV-infected women, 187 of whom were HCV-seropositive, with adjustment in multivariable models for age, race/ethnicity, and HIV disease characteristics. Eighty one percent of the women reported receipt of highly active antiretroviral therapy (HAART prior to or at CMV testing. RESULTS: In adjusted models women with chronic HCV had higher CMV IgG levels than those without HCV RNA (β = 2.86, 95% CI:0.89 - 4.83; P = 0.004. The association of HCV RNA with CMV IgG differed by age (P(interaction = 0.0007, with a strong association observed among women in the low and middle age tertiles (≤ 45.3 years of age; β = 6.21, 95% CI:3.30 - 9.11, P<0.0001 but not among women in the high age tertile. CMV IgG levels were not associated with non-invasive measures of liver disease, APRI and FIB-4, or with HCV RNA level and adjustment for Epstein-Barr virus (EBV IgG levels did not affect the association between HCV and CMV. CONCLUSIONS: CMV IgG levels are higher in HCV/HIV co-infected women than in HIV mono-infected women. Further research on the association of HCV with CMV IgG is indicated because prior studies have found CMV IgG to be associated with morbidity and mortality in the general population and subclinical carotid artery disease in HIV-infected patients.

  16. Clearance of red cells by monoclonal IgG3 anti-D in vivo is affected by the VF polymorphism of Fc gamma RIIIa (CD16)

    NARCIS (Netherlands)

    Kumpel, BM; De Haas, M; Koene, HR; Van de Winkel, JGJ; Goodrick, MJ

    2003-01-01

    Human red cells (RBC) coated with IgG anti-D are cleared from the circulation to the spleen by macrophages which express IgG receptors (Fcgamma R). Polymorphisms of Fcgamma RIIa and Fcgamma RIIIa affect IgG binding in vitro , and may alter the efficiency of clearance of immune complexes in vivo. In

  17. Human IgG is produced in a pro-form that requires clipping of C-terminal lysines for maximal complement activation

    DEFF Research Database (Denmark)

    van den Bremer, E. T. J.; Beurskens, F. J.; Voorhorst, M.;

    2015-01-01

    . Interestingly, IgG1 mutants containing either a negative C-terminal charge or multiple positive charges lost CDC almost completely; however, CDC was fully restored by mixing C-terminal mutants of opposite charge. Our data indicate a novel post-translational control mechanism of human IgG: human IgG molecules...

  18. Correlation of isotopic cisternographic patterns in multiple sclerosis with CSF IgG values

    International Nuclear Information System (INIS)

    Thirty-eight patients with multiple sclerosis (MS) were examined with isotopic cisternography (IC) in order to study cerebrospinal fluid (CSF) dynamics. Cisternography was also performed in 15 patients with amyotrophic lateral sclerosis and in 14 with senile dementia of the Alzheimer type as controls. IC pattern of ''mixed'' type was found in 18 MS patients and all those with Alzheimer senile dementia examined, while the IC examination did not show abnormality in any of 15 patients with amyotrophic lateral sclerosis. In MS patients, the abnormal IC picture proved to be significantly correlated with the CSF IgG values as calculated by Link's and Tourtelotte's formulas. The abnormal IC in MS may be due to altered CSF reabsorption or increased transependymal flow, or it may be related to the abnormal concentration of IgG

  19. Unique features of monoclonal IgG2b in the cleavage reaction with pepsin.

    Directory of Open Access Journals (Sweden)

    Sumii,Hiroshi

    1989-06-01

    Full Text Available Preparations of IgG2b purified from several mouse hybridoma clones were highly susceptible, compared to other subclasses, to peptic digestion under conditions usually used to prepare F (ab'2 fragments. Analyses of the digestion products revealed that no F (ab'2 was produced and that the main product was a Fab-like fragment. Demonstration of the hinge disulfides in the Fc portion clearly indicated that in IgG2b the primary peptic cleavage occurs on the NH2-terminal side of the inter-heavy chain disulfide bridge. The resulting Fab failed to bind with antigen, suggesting the importance of the CH1-hinge region in maintaining the native conformation of the antigen-binding site.

  20. Detection of IgG antibodies against Bordetella pertussis with /sup 125/I-protein A

    Energy Technology Data Exchange (ETDEWEB)

    Wirsing von Koenig, C.H.; Finger, H.

    1981-01-01

    A method for the detection of IgG antibodies against Bordetella pertussis is described, based on the principle of 'sandwich' radioimmunoassay. /sup 125/I protein A is used as radioactive tracer. The influence of amounts of antigen, antibody, radioactive tracer, incubation time and temperature were tested and the optimal conditions for the assay are described. The procedure offers a simple, quick, and sensitive method for detecting antibodies against B. pertussis. Application and limitation of the test are discussed.

  1. Seroprevalence of parvovirus B19 IgG in children affected by juvenile idiopathic arthritis

    OpenAIRE

    Weissbrich, Benedikt; Süß-Fröhlich, Yvonne; Girschick, Hermann J.

    2007-01-01

    Parvovirus (PV) B19 is the causative agent of the childhood disease erythema infectiosum. An association of PV B19 with chronic arthropathies, sometimes resembling rheumatoid arthritis or juvenile idiopathic arthritis (JIA), has repeatedly been described. Other studies, however, have failed to identify any such relationship. In order to study further whether there is a link between PV B19 and JIA, we determined the prevalence of PV B19 specific IgG antibodies in serum samples from children wi...

  2. Toxocara Canis IgG Seropositivity in Patients with Chronic Urticaria.

    Science.gov (United States)

    Burak Selek, Mehmet; Baylan, Orhan; Kutlu, Ali; Özyurt, Mustafa

    2015-08-01

    We aimed to investigate IgG antibody levels specific to Toxocara canis (T. canis), a parasite which subsists in dog's intestine, on serum samples obtained from patients with chronic urticaria (CU) to evaluate effective risk in CU etiopathogenesis. In this study, 73 patients diagnosed with CU and 109 healthy individuals as control group, were included. Various factors such as sex, age, education and income, daily hand washing habits, history of dog owning and soil eating were questioned in patient anamnesis. T. canis IgG antibodies were detected using an enzyme linked immunosorbent assay (ELISA) kit prepared with T. canis larval excretory-secretory antigens. Positive results were confirmed with western blot (WB) WB test. We found T. canis IgG positivity in 17.8% (n=13) of patients (n=73) with CU. But we did not observe any T. canis IgG positivity in healthy controls (n=109). Low molecular weight bands (24-35 kDa) were observed in 11 samples in WB analyses while two of the samples were weakly positive. It is revealed that dog owning history increases T. canis seropositivity 12.9 times while insufficient daily hand washing habit (less than six times a day) increases seropositivity 20.7 times. Our study showed that T. canis may trigger CU since we found 17.8% seropositivity in 73 patients with CU and none in 109 healthy individuals. Moreover, various socio-demographic characteristics have been shown to affect T. canis seropositivity in patients with CU.

  3. Assessing Immunity to Rubella Virus: a Plea for Standardization of IgG (Immuno)assays.

    Science.gov (United States)

    Bouthry, Elise; Furione, Milena; Huzly, Daniela; Ogee-Nwankwo, Adaeze; Hao, LiJuan; Adebayo, Adebola; Icenogle, Joseph; Sarasini, Antonella; Revello, Maria Grazia; Grangeot-Keros, Liliane; Vauloup-Fellous, Christelle

    2016-07-01

    Immunity to rubella virus (RV) is commonly determined by measuring specific immunoglobulin G (RV IgG). However, RV IgG results and their interpretation may vary, depending on the immunoassay, even though most commercial immunoassays (CIAs) have been calibrated against an international standard and results are reported in international units per milliliter. A panel of 322 sera collected from pregnant women that tested negative or equivocal for RV IgG in a prior test (routine screening) was selected. This panel was tested with two reference tests, immunoblotting (IB) and neutralization (Nt), and with 8 CIAs widely used in Europe. IB and Nt gave concordant results on 267/322 (82.9%) sera. Of these, 85 (26.4%) sera were negative and 182 (56.5%) sera were positive for both tests. All 85 IB/Nt-negative samples were classified as negative with all CIAs. Of the 182 IB/Nt-positive samples, 25.3 to 61.5% were classified as equivocal and 6 to 64.8% were classified as positive with the CIAs. Wide variations in titers in international units per milliliter were observed. In our series, more than half of the women considered susceptible to RV based on CIA results tested positive for RV antibodies by IB/Nt. Our data suggest that (i) sensitivity of CIAs could be increased by considering equivocal results as positive and (ii) the definition of immunity to RV as the 10-IU/ml usual cutoff as well as the use of quantitative results for clinical decisions may warrant reconsideration. A better standardization of CIAs for RV IgG determination is needed. PMID:27147722

  4. A prominent lack of IgG1-Fc fucosylation of platelet alloantibodies in pregnancy.

    Science.gov (United States)

    Kapur, Rick; Kustiawan, Iwan; Vestrheim, Anne; Koeleman, Carolien A M; Visser, Remco; Einarsdottir, Helga K; Porcelijn, Leendert; Jackson, Dave; Kumpel, Belinda; Deelder, André M; Blank, Dennis; Skogen, Björn; Killie, Mette Kjaer; Michaelsen, Terje E; de Haas, Masja; Rispens, Theo; van der Schoot, C Ellen; Wuhrer, Manfred; Vidarsson, Gestur

    2014-01-23

    Immunoglobulin G (IgG) formed during pregnancy against human platelet antigens (HPAs) of the fetus mediates fetal or neonatal alloimmune thrombocytopenia (FNAIT). Because antibody titer or isotype does not strictly correlate with disease severity, we investigated by mass spectrometry variations in the glycosylation at Asn297 in the IgG Fc because the composition of this glycan can be highly variable, affecting binding to phagocyte IgG-Fc receptors (FcγR). We found markedly decreased levels of core fucosylation of anti-HPA-1a-specific IgG1 from FNAIT patients (n = 48), but not in total serum IgG1. Antibodies with a low amount of fucose displayed higher binding affinity to FcγRIIIa and FcγRIIIb, but not to FcγRIIa, compared with antibodies with a high amount of Fc fucose. Consequently, these antibodies with a low amount of Fc fucose showed enhanced phagocytosis of platelets using FcγRIIIb(+) polymorphonuclear cells or FcγRIIIa(+) monocytes as effector cells, but not with FcγRIIIa(-) monocytes. In addition, the degree of anti-HPA-1a fucosylation correlated positively with the neonatal platelet counts in FNAIT, and negatively to the clinical disease severity. In contrast to the FNAIT patients, no changes in core fucosylation were observed for anti-HLA antibodies in refractory thrombocytopenia (post platelet transfusion), indicating that the level of fucosylation may be antigen dependent and/or related to the immune milieu defined by pregnancy.

  5. Distribution of the IgG Fc Receptor, FcRn, in the Human Fetal Intestine

    OpenAIRE

    Shah, Uzma; Dickinson, Bonny L.; Blumberg, Richard S.; Simister, Neil E.; Lencer, Wayne I.; Walker, W. Allan

    2003-01-01

    The intestinal Fc receptor, FcRn, functions in the maternofetal transfer of gamma globulin (IgG) in the neonatal rodent. In humans, most of this transfer is presumed to occur in utero via the placenta. Although the fetus swallows amniotic fluid that contains immunoglobulin, it is unknown whether this transfer also occurs via the fetal intestine. A human FcRn has been identified in the syncytiotrophoblast that mediates the maternofetal transfer of antibody. It has also been identified in human...

  6. Serum IgG Antibody Levels to Periodontal Microbiota Are Associated with Incident Alzheimer Disease

    OpenAIRE

    Noble, James M.; Nikolaos Scarmeas; Celenti, Romanita S.; Elkind, Mitchell S. V.; Wright, Clinton B; Nicole Schupf; Papapanou, Panos N.

    2014-01-01

    Background Periodontitis and Alzheimer disease (AD) are associated with systemic inflammation. This research studied serum IgG to periodontal microbiota as possible predictors of incident AD. Methods Using a case-cohort study design, 219 subjects (110 incident AD cases and 109 controls without incident cognitive impairment at last follow-up), matched on race-ethnicity, were drawn from the Washington Heights-Inwood Columbia Aging Project (WHICAP), a cohort of longitudinally followed northern M...

  7. Salivary IgG assay to detect Helicobacter pylori infection in an Indian adult population

    OpenAIRE

    Ramya Thirumala Krishnaswamy; Chaya Manoranjini David; Savitha Govindaiah; Ramnarayan Belur Krishnaprasad; Sanjay Chikkarasinakere Jogigowda

    2012-01-01

    Background: Helicobacter pylori infection, the commonest chronic bacterial infection in humans, causes chronic gastritis, peptic ulcer, and possibly gastric carcinoma and lymphoma. Recently, investigators have focused on its role in the development of extra-gastrointestinal diseases with oral manifestations. H. pylori infection can be diagnosed by various methods. Of late, H. pylori IgG antibodies have been detected in saliva using enzyme-linked immunosorbent assay (ELISA). However, local val...

  8. Toxocara Canis IgG Seropositivity in Patients with Chronic Urticaria

    Directory of Open Access Journals (Sweden)

    Mehmet Burak-Selek

    2015-10-01

    Full Text Available We aimed to investigate IgG antibody levels specific to Toxocara canis (T. canis, a parasite which subsists in dog’s intestine, on serum samples obtained from patients with chronic urticaria (CU to evaluate effective risk in CU etiopathogenesis.In this study, 73 patients diagnosed with CU and 109 healthy individuals as control group, were included. Various factors such as sex, age, education and income, daily hand washing habits, history of dog owning and soil eating were questioned in patient anamnesis. T. canis IgG antibodies were detected using an enzyme linked immunosorbent assay (ELISA kit prepared with T. canis larval excretory-secretory antigens. Positive results were confirmed with western blot (WB WB test.We found T. canis IgG positivity in 17.8% (n=13 of patients (n=73 with CU. But we did not observe any T. canis IgG positivity in healthy controls (n=109. Low molecular weight bands (24-35 kDa were observed in 11 samples in WB analyses while two of the samples were weakly positive. It is revealed that dog owning history increases T. canis seropositivity12.9 times while insufficient daily hand washing habit (less than six times a day increasesseropositivity 20.7 times. Our study showed that T. canis may trigger CU since we found17.8% seropositivity in 73 patients with CU and none in 109 healthy individuals.Moreover, various socio-demographic characteristics have been shown to affect T. canisseropositivity in patients with CU. 

  9. Seroprevalence of diphtheria toxoid IgG antibodies in children, adolescents and adults in Poland

    OpenAIRE

    Aleksandra A. Zasada; Rastawicki, Waldemar; Rokosz, Natalia; Jagielski, Marek

    2013-01-01

    Background Recommendations for diphtheria immunization are to apply an effective primary immunization in infancy and to maintain immunity throughout life. Immunity against diphtheria depends primarily on antibody to the diphtheria toxin. This study evaluated the seroprevalence of IgG diphtheria antitoxin in sera of healthy children, adolescents and adults in Poland. Methods A total of 1387 serum samples collected between 2010 and 2012 from individuals with ages ranging from 1 month to 85 year...

  10. THE EFFECT OF SLEEP DEPRIVATION ON SERUM IGG RESPONSES TO AEROBIC ACTIVITY IN COLLEGE STUDENT ATHLETES

    OpenAIRE

    Saeed, Jamshidi Far; Mirza, Hossein Norouzi Kamareh

    2015-01-01

    Background & Aims: Sleep is a restorative process for the immune system. There are many situations in which sleep is disturbed prior to an athletic event. However, the effect of sleep deprivation on immune indices in response to exercise remains unknown. The aim of this study was to investigate the effects of sleep deprivation on serum IgG responses to aerobic activity. Materials & Methods: In this quasi-experimental study, 10 male physical education students were voluntarily participated. St...

  11. THE EFFECT OF SLEEP DEPRIVATION ON SERUM IGG RESPONSES TO AEROBIC ACTIVITY IN COLLEGE STUDENT ATHLETES

    OpenAIRE

    Saeed Jamshidi Far; Mirza Hossein Norouzi Kamareh

    2014-01-01

    Background & Aims: Sleep is a restorative process for the immune system. There are many situations in which sleep is disturbed prior to an athletic event. However, the effect of sleep deprivation on immune indices in response to exercise remains unknown. The aim of this study was to investigate the effects of sleep deprivation on serum IgG responses to aerobic activity. Materials & Methods: In this quasi-experimental study, 10 male physical education students were voluntarily participated. St...

  12. Toxocara Canis IgG Seropositivity in Patients with Chronic Urticaria.

    Science.gov (United States)

    Burak Selek, Mehmet; Baylan, Orhan; Kutlu, Ali; Özyurt, Mustafa

    2015-08-01

    We aimed to investigate IgG antibody levels specific to Toxocara canis (T. canis), a parasite which subsists in dog's intestine, on serum samples obtained from patients with chronic urticaria (CU) to evaluate effective risk in CU etiopathogenesis. In this study, 73 patients diagnosed with CU and 109 healthy individuals as control group, were included. Various factors such as sex, age, education and income, daily hand washing habits, history of dog owning and soil eating were questioned in patient anamnesis. T. canis IgG antibodies were detected using an enzyme linked immunosorbent assay (ELISA) kit prepared with T. canis larval excretory-secretory antigens. Positive results were confirmed with western blot (WB) WB test. We found T. canis IgG positivity in 17.8% (n=13) of patients (n=73) with CU. But we did not observe any T. canis IgG positivity in healthy controls (n=109). Low molecular weight bands (24-35 kDa) were observed in 11 samples in WB analyses while two of the samples were weakly positive. It is revealed that dog owning history increases T. canis seropositivity 12.9 times while insufficient daily hand washing habit (less than six times a day) increases seropositivity 20.7 times. Our study showed that T. canis may trigger CU since we found 17.8% seropositivity in 73 patients with CU and none in 109 healthy individuals. Moreover, various socio-demographic characteristics have been shown to affect T. canis seropositivity in patients with CU. PMID:26547714

  13. Serum IgG antibody levels to periodontal microbiota are associated with incident Alzheimer disease.

    Directory of Open Access Journals (Sweden)

    James M Noble

    Full Text Available Periodontitis and Alzheimer disease (AD are associated with systemic inflammation. This research studied serum IgG to periodontal microbiota as possible predictors of incident AD.Using a case-cohort study design, 219 subjects (110 incident AD cases and 109 controls without incident cognitive impairment at last follow-up, matched on race-ethnicity, were drawn from the Washington Heights-Inwood Columbia Aging Project (WHICAP, a cohort of longitudinally followed northern Manhattan residents aged >65 years. Mean follow-up was five years (SD 2.6. In baseline sera, serum IgG levels were determined for bacteria known to be positively or negatively associated with periodontitis (Porphyromonas gingivalis, Tannerella forsythia, Actinobacillus actinomycetemcomitans Y4, Treponema denticola, Campylobacter rectus, Eubacterium nodatum, and Actinomyces naeslundii genospecies-2. In all analyses, we used antibody threshold levels shown to correlate with presence of moderate-severe periodontitis.Mean age was 72 years (SD 6.9 for controls, and 79 years (SD 4.6 for cases (p640 ng/ml, present in 10% of subjects was associated with increased risk of AD (HR = 2.0, 95%CI: 1.1-3.8. This association was stronger after adjusting for other significant titers (HR = 3.1, 95%CI: 1.5-6.4. In this model, high anti-E. nodatum IgG (>1755 ng/ml; 19% of subjects was associated with lower risk of AD (HR = 0.5, 95%CI: 0.2-0.9.Serum IgG levels to common periodontal microbiota are associated with risk for developing incident AD.

  14. Antigen-binding radioimmunoassays for human IgG antibodies to bovine ν-lactoglobulin

    International Nuclear Information System (INIS)

    A double antibody antigen-binding assay for the detection of human IgG antibodies to the bovine milk allergen ν-lactoglobulin is described. The levels of such antibodies in patients with established cows' milk protein intolerance were significantly higher than the levels observed in a healthy control group (P<0.01). The assay showed excellent correlation with a solid phase antigen binding assay (rsub(s) = 0.8, P<0.001). (Auth.)

  15. Specific IgG and its subclass antibodies after immunotherapy with gynandropsis gynandra

    Directory of Open Access Journals (Sweden)

    Latha G

    2005-01-01

    Full Text Available Background : About 10 to 15 % of the Indian population is known to suffer from major allergic disorders such as Asthma, Rhinitis, Atopic Dermatitis and Urticaria. Aeroallergens play a major role in the pathogenesis of respiratory allergic diseases. Among the aeroallergens, pollens are major causative agents. The predominance of pollen allergens necessitate the need to assess the specific immunotherapy (SIT in allergic patients. Objective : To evaluate the effect of immunotherapy based on the presence of IgG and its subclass antibodies towards whole pollen antigen of Gynandropsis gynandra (G.gynandra and its fractions. Material and Methods : A study was conducted in 30 bronchial asthma patients on immunotherapy, by assessing the levels of IgG and its subclasses specific to G. gynandra pollen. Results : There was a significant increase in IgG and its subclass antibodies to whole pollen antigen and its fractions i.e.> 90kD, 46-37kD and 36-32kD after the course of IT. Conclusion : The use of peptide fractions may be more appropriate instead of the whole pollen antigen to test the effect of immunotherapy.

  16. IgG N-glycans as potential biomarkers for determining galactose tolerance in Classical Galactosaemia.

    LENUS (Irish Health Repository)

    Coss, K P

    2012-02-01

    N-glycan processing and assembly defects have been demonstrated in untreated and partially treated patients with Classical Galactosaemia. These defects may contribute to the ongoing pathophysiology of this disease. The aim of this study was to develop an informative method of studying differential galactose tolerance levels and diet control in individuals with Galactosaemia, compared to the standard biochemical markers. Ten Galactosaemia adults with normal intellectual outcomes were analyzed in the study. Five subjects followed galactose liberalization, increments of 300 mg to 4000 mg\\/day over 16 weeks, and were compared to five adult Galactosaemia controls on a galactose restricted diet. All study subjects underwent clinical and biochemical monitoring of red blood cell galactose-1-phosphate (RBC Gal-1-P) and urinary galactitol levels. Serum N-glycans were isolated and analyzed by normal phase high-performance liquid chromatography (NP-HPLC) with galactosylation of IgG used as a specific biomarker of galactose tolerance. IgG N-glycan profiles showed consistent individual alterations in response to diet liberalization. The individual profiles were improved for all, but one study subject, at a galactose intake of 1000 mg\\/day, with decreases in agalactosylated (G0) and increases in digalactosylated (G2) N-glycans. We conclude that IgG N-glycan profiling is an improved method of monitoring variable galactosylation and determining individual galactose tolerance in Galactosaemia compared to the standard methods.

  17. Saliva and sera IgA and IgG in Egyptian Giardia-infected children.

    Science.gov (United States)

    El-Gebaly, Naglaa Saad M; Halawa, Eman Fawzy; Moussa, Hanaa M Ezzat; Rabia, Ibrahim; Abu-Zekry, Maha

    2012-08-01

    Giardiasis is a gastrointestinal infection of wide distribution that is more prevalent in childhood. Easy and rapid diagnosis of giardiasis is essential for reduction of this infection. This cross-sectional study included 62 children in which collection of saliva, stool and serum samples was performed. An enzyme-linked immunosorbent assay (ELISA) technique was evaluated to detect IgA and IgG responses in both saliva and serum samples. Twenty-two children were positive for Giardia duodenalis infection by direct examination of faecal specimens, 20 non-infected and 20 infected with other parasites. Salivary and serum IgA and IgG responses against G. duodenalis infection were significantly higher in Giardia parasitized than non-Giardia parasitized children (p < 0.001). This concludes that specific salivary IgA may serve as a diagnostic tool and specific salivary IgG as a screening tool in monitoring the exposure of various populations to Giardia duodenalis. The advantage of salivary assays over serum immunoglobulin assay is being easy and non-invasive in sampling technique which is important especially for young children. PMID:22402609

  18. Use of IgG Avidity test in case definitions of toxoplasmosis in pregnancy.

    Science.gov (United States)

    Zotti, C; Charrier, L; Giacomuzzi, M; Moiraghi Ruggenini, A; Mombrò, M; Fabris, C; Marocchetti, P; Alfieri, R; Leto, R; Renzi, N; Milano, R; Lievre, M A; Colozza, M; Zanella, D; Antona, G; Paschero, M C; Tosetti, F; Miglietti, D; Nicoletta, T; De Renzi, G; Tinivella, F; Donati, M; Ferrini, A; Crotti, G; Coucourde, L; Guazzotti, G C; Gera, A; Malabaila, A; Di Natale, C; Rabozzi, M L; Ginardi, C; Bruzzone, T; Canepa, C; Fruttero, M; Mastracchio, G; Valle, S; Toppino, M; Forno, N; Bellingeri, P; Caraccio, W; Lazzara, C; Decaroli, V; Pedrazzi, E; Gomella, S

    2004-01-01

    A survey network for congenital toxoplasmosis (TOXO-NET) was set up in December 1996 in Piedmont (Italy). Participants were asked to classify the infections in pregnant mothers and newborns by the criteria of the European Network on Congenital Toxoplasmosis published by Lebech in 1996. Because the IgG Avidity test is largely employed as a 2nd level test in toxoplasmosis diagnosis and it could be helpful to date infection, the co-ordinators of TOXO-NET suggested including it in the "case definition" of "probable" infection and "unlikely" infection. 117 cases of toxoplasmosis in pregnancy divided into the risk categories under Lebech's criteria were re-examined using the "new" case definitions. 77 out of 117 (65.8%) Toxoplasma gondii infections during pregnancy could be defined with only one serum sample using the IgG Avidity test. The IgG Avidity test proved a useful method to classify the Toxoplasma gondii infections in pregnancy, especially when we had only one serum sample.

  19. Positive IgG Western Blot for Borrelia burgdorferi in Colombia

    Directory of Open Access Journals (Sweden)

    Palacios Ricardo

    1999-01-01

    Full Text Available In order to evaluate the presence of specific IgG antibodies to Borrelia burgdorferi in patients with clinical manifestations associated with Lyme borreliosis in Cali, Colombia, 20 serum samples from patients with dermatologic signs, one cerebrospinal fluid (CSF sample from a patient with chronic neurologic and arthritic manifestations, and twelve serum samples from individuals without clinical signs associated with Lyme borreliosis were analyzed by IgG Western blot. The results were interpreted following the recommendations of the Centers for Diseases Control and Prevention (CDC for IgG Western blots. Four samples fulfilled the CDC criteria: two serum specimens from patients with morphea (localized scleroderma, the CSF from the patient with neurologic and arthritic manifestations, and one of the controls. Interpretation of positive serology for Lyme disease in non-endemic countries must be cautious. However these results suggest that the putative "Lyme-like" disease may correlate with positivity on Western blots, thus raising the possibility that a spirochete genospecies distinct from B. burgdorferi sensu stricto, or a Borrelia species other than B. burgdorferi sensu lato is the causative agent. Future work will focus on a survey of the local tick and rodent population for evidence of spirochete species that could be incriminated as the etiologic agent.

  20. IgG glycan hydrolysis by EndoS inhibits experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Benkhoucha Mahdia

    2012-09-01

    Full Text Available Abstract Studies in experimental autoimmune encephalomyelitis (EAE, a mouse model of multiple sclerosis, have shown that B cells markedly influence the course of the disease, although whether their effects are protective or pathological is a matter of debate. EndoS hydrolysis of the IgG glycan has profound effects on IgG effector functions, such as complement activation and Fc receptor binding, suggesting that the enzyme could be used as an immunomodulatory therapeutic agent against IgG-mediated diseases. We demonstrate here that EndoS has a protective effect in myelin oligodendrocyte glycoprotein peptide amino acid 35–55 (MOG35-55-induced EAE, a chronic neuroinflammatory demyelinating disorder of the central nervous system (CNS in which humoral immune responses are thought to play only a minor role. EndoS treatment in chronic MOG35-55-EAE did not impair encephalitogenic T cell priming and recruitment into the CNS of mice, consistent with a primary role of EndoS in controlling IgG effector functions. In contrast, reduced EAE severity coincided with poor serum complement activation and deposition within the spinal cord, suggesting that EndoS treatment impairs B cell effector function. These results identify EndoS as a potential therapeutic agent against antibody-mediated CNS autoimmune disorders.

  1. Filgrastim-Induced Crescentic Transformation of Recurrent IgG2λ GN.

    Science.gov (United States)

    Batal, Ibrahim; Markowitz, Glen S; Wong, Waichi; Avasare, Rupali; Mapara, Markus Y; Appel, Gerald B; D'Agati, Vivette D

    2016-07-01

    Proliferative GN with monoclonal IgG deposits is an increasingly recognized form of GN, but its relation to hematologic malignancy remains poorly understood. Filgrastim, an analog for granulocyte colony-stimulating factor produced by recombinant DNA technology, is frequently used to stimulate bone marrow release of hematopoietic progenitor cells in preparation for stem cell transplant. We report an exceptional case of proliferative GN with monoclonal IgG2λ deposits in a young man whose disease progressed slowly to CKD, which was followed by a preemptive kidney transplant. The patient developed recurrent GN in the allograft and clinically detectable plasma cell neoplasm 9 years after the first renal manifestations. Contemporaneous with filgrastim administration for stem cell mobilization, the patient's slowly progressive GN underwent severe crescentic transformation, leading to rapidly progressive and irreversible allograft failure. This report explores the spectrum of GN with monoclonal IgG deposits and the pathophysiologic role of granulocyte colony-stimulating factor in exacerbation of preexisting GN. PMID:27147425

  2. Interactions of IgG1 CH2 and CH3 domains with FcRn

    Directory of Open Access Journals (Sweden)

    Tianlei eYing

    2014-04-01

    Full Text Available Antibody fragments are emerging as promising biopharmaceuticals because of their relatively small size and other unique properties. However, when compared to full-size antibodies, most of the current antibody fragments of VH or VL display greatly reduced half-lives. A promising approach to overcome this problem is through the development of novel antibody fragments based on IgG Fc region, which contributes to the long half-life of IgG through its unique pH-dependent association with the neonatal Fc receptor (FcRn. The IgG Fc region comprises two CH2 and two CH3 domains. In this report, we present a comparative study of the FcRn binding capability of the CH2 and CH3 domains. The stability and aggregation resistance of these domains were also investigated and compared. We found that monomeric CH2 and CH3 domains exhibited the pH-dependent FcRn binding while the dimeric forms of CH2 and CH3 domains did not. Although all of these domains had high serum stability, they had aggregation tendencies as measured by dynamic light scattering. By providing a better understanding of the structure-activity relationship of the Fc fragment, these results guide further approaches to generate novel Fc-based small-size antibody fragments that possess pH-dependent FcRn binding capability, desired in vivo half-lives and other favorable biophysical properties for their drugability.

  3. [IgG4- and MPO-ANCA-associated hypertrophic pachymeningitis].

    Science.gov (United States)

    Aragonès, Josep M; Arias-Rivero, Montserrat; García-Barrionuevo, Joan M; Lucchetti, Gianni

    2015-11-16

    Introduccion. La paquimeningitis hipertrofica idiopatica es una enfermedad fibroinflamatoria de la duramadre. Su diagnostico requiere la exclusion de enfermedades infecciosas, tumorales y otras enfermedades inflamatorias. En los ultimos años se han descrito nuevas entidades que pueden presentarse con paquimeningitis hipertrofica: la enfermedad relacionada con IgG4 y la paquimeningitis MPO-ANCA+ como forma de vasculitis limitada al sistema nervioso central. Caso clinico. Varon de 64 años con cefalea y cervicalgia de predominio nocturno y clinica de compresion medular. Tras el diagnostico de paquimeningitis hipertrofica craneocervical facilitado por el estudio de resonancia magnetica, se realizo un estudio etiologico. Se descartaron enfermedades infecciosas y tumorales. La clinica no mostraba afectacion sistemica y en la analitica presentaba IgG4 elevada y MPO-ANCA+. Tras tratamiento con corticoides presento una rapida mejoria de la clinica. Conclusiones. La enfermedad relacionada con IgG4 y la vasculitis asociada a MPO-ANCA limitada al sistema nervioso central pueden representar un alto porcentaje de las paquimeningitis hipertroficas que se consideraban idiopaticas, y su diagnostico requiere biopsia y estudio histologico.

  4. [Central nervous system in IgG4-related disease: case report and literature review].

    Science.gov (United States)

    Vanegas-Garcia, A L; Calle-Lopez, Y; Zapata, C H; Alvarez-Espinal, D M; Saavedra-Gonzalez, Y A; Arango-Viana, J C

    2016-08-01

    Introduccion. La enfermedad relacionada con IgG4 es una entidad clinica multisistemica recientemente descrita y que se presenta con diferentes manifestaciones clinicas. Los organos que estan afectados con mayor frecuencia son el pancreas, la via biliar y las glandulas salivales, y es menos frecuente la afeccion del sistema nervioso central. Caso clinico. Mujer de 33 años con alteraciones cognitivas, alucinaciones, cefalea, sindrome convulsivo, sinusitis maxilar con afeccion osea y evidencia de paquimeningitis y panhipopituitarismo, con biopsia meningea que confirmo una enfermedad relacionada con IgG4, tras haberse descartado causas secundarias. Se inicio tratamiento con glucocorticoides y azatioprina, sin recaidas despues de 12 meses de seguimiento. Conclusiones. Se debe considerar el diagnostico de enfermedad relacionada con IgG4 en casos de paquimeningitis hipertrofica e hipofisitis, incluso sin que se acompañen de otras manifestaciones sistemicas, siempre que se hayan descartado otras causas mas frecuentes. El tratamiento de eleccion son los glucocorticoides, y puede ser necesario añadir otro inmunosupresor como ahorrador de esteroides y para evitar las recaidas. Se necesitan estudios prospectivos para evaluar las diferentes manifestaciones clinicas y paraclinicas y establecer los resultados del tratamiento a largo plazo.

  5. Detection of IgG Anti-Leishmania Antigen by Flow Cytometry as a Diagnostic Test for Cutaneous Leishmaniasis.

    Science.gov (United States)

    Pedral-Sampaio, Geraldo; Alves, Jessé S; Schriefer, Albert; Magalhães, Andréa; Meyer, Roberto; Glesby, Marshall J; Carvalho, Edgar M; Carvalho, Lucas P

    2016-01-01

    Diagnosis of cutaneous leishmaniasis (CL) relies on clinical presentation, parasite isolation, histopathologic evaluation and positive Montenegro skin test. However, the low amounts of parasites in the lesion of these individuals make parasite isolation and histopatologic diagnosis unreliable, often leading to false-negative results. Also, 15% of people living in endemic areas have sub-clinical infection characterized by positive Montenegro skin test, which may contribute to misdiagnosis. Although the main Leishmania killing mechanism is through cell-mediated immune response, antibodies against Leishmania antigens are found in infected individuals. Here our goal was to develop a new serological technique using polystyrene microspheres sensitized with soluble Leishmania antigens as a tool for the detection of IgG in serum from CL patients by flow cytometry. To validate the assay we carried out a comparative test (ELISA) commonly used as a diagnostic test for parasitic diseases. To determine cross-reactivity we used serum from patients with Chagas disease, caused by a trypanosome that has several proteins with high homology to those of the Leishmania genus. We observed that the flow cytometry technique was more sensitive than the ELISA, but, less specific. Our results show that the flow cytometry serologic test can be used to confirm CL cases in L. braziliensis transmission areas, however, presence of Chagas disease has to be ruled out in these individuals. PMID:27622535

  6. Detection of IgG Anti-Leishmania Antigen by Flow Cytometry as a Diagnostic Test for Cutaneous Leishmaniasis

    Science.gov (United States)

    Schriefer, Albert; Magalhães, Andréa; Meyer, Roberto; Glesby, Marshall J.; Carvalho, Edgar M.; Carvalho, Lucas P.

    2016-01-01

    Diagnosis of cutaneous leishmaniasis (CL) relies on clinical presentation, parasite isolation, histopathologic evaluation and positive Montenegro skin test. However, the low amounts of parasites in the lesion of these individuals make parasite isolation and histopatologic diagnosis unreliable, often leading to false-negative results. Also, 15% of people living in endemic areas have sub-clinical infection characterized by positive Montenegro skin test, which may contribute to misdiagnosis. Although the main Leishmania killing mechanism is through cell-mediated immune response, antibodies against Leishmania antigens are found in infected individuals. Here our goal was to develop a new serological technique using polystyrene microspheres sensitized with soluble Leishmania antigens as a tool for the detection of IgG in serum from CL patients by flow cytometry. To validate the assay we carried out a comparative test (ELISA) commonly used as a diagnostic test for parasitic diseases. To determine cross-reactivity we used serum from patients with Chagas disease, caused by a trypanosome that has several proteins with high homology to those of the Leishmania genus. We observed that the flow cytometry technique was more sensitive than the ELISA, but, less specific. Our results show that the flow cytometry serologic test can be used to confirm CL cases in L. braziliensis transmission areas, however, presence of Chagas disease has to be ruled out in these individuals. PMID:27622535

  7. Adaptive Immunity against Streptococcus pyogenes in Adults Involves Increased IFN-gamma and IgG3 Responses Compared with Children

    DEFF Research Database (Denmark)

    Mortensen, Rasmus; Nissen, Thomas Norrelykke; Blauenfeldt, Thomas;

    2015-01-01

    Each year, millions of people are infected with Streptococcus pyogenes, leading to an estimated 500,000 annual deaths worldwide. For unknown reasons, school-aged children have substantially higher infection rates than adults. The goal for this study was to provide, to our knowledge, the first det...... cellular memory response in combination with IgG1/IgG3-dominated humoral immunity that increase with age. The significance of these data regarding both the increased GAS infection rate in children and the development of protective GAS vaccines is discussed.......Each year, millions of people are infected with Streptococcus pyogenes, leading to an estimated 500,000 annual deaths worldwide. For unknown reasons, school-aged children have substantially higher infection rates than adults. The goal for this study was to provide, to our knowledge, the first...... detailed characterization of the human adaptive immune response against S. pyogenes in both children and adults. We report that all adults in our study, as well as most children, showed immunity against the two conserved group A streptococci (GAS) Ags, streptococcal C5a peptidase and immunogenic secreted...

  8. Does the antibody production ability affect the serum anti-Helicobacter pylori IgG titer?

    Science.gov (United States)

    Chung, Hyun Ah; Lee, Sun-Young; Moon, Hee Won; Kim, Jeong Hwan; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan Sup; Han, Hye Seung

    2016-01-01

    AIM To investigate the relationship between serum titers of anti-Helicobacter pylori (H. pylori) immunoglobulin G (IgG) and hepatitis B virus surface antibody (HBsAb). METHODS Korean adults were included whose samples had positive Giemsa staining on endoscopic biopsy and were studied in the hepatitis B virus surface antigen (HBsAg)/HBsAb serologic assay, pepsinogen (PG) assay, and H. pylori serologic test on the same day. Subjects were excluded if they were positive for HBsAg, had a recent history of medication, or had other medical condition(s). We analyzed the effects of the following factors on serum titers of HBsAb and the anti-H. pylori IgG: Age, density of H. pylori infiltration in biopsy samples, serum concentrations of PG I and PG II, PG I/II ratio, and white blood cell count. RESULTS Of 111 included subjects, 74 (66.7%) exhibited a positive HBsAb finding. The serum anti-H. pylori IgG titer did not correlate with the serum HBsAb titer (P = 0.185); however, it correlated with the degree of H. pylori infiltration on gastric biopsy (P < 0.001) and serum PG II concentration (P = 0.042). According to the density of H. pylori infiltration on gastric biopsy, subjects could be subdivided into those with a marked (median: 3.95, range 0.82-4.00) (P = 0.458), moderate (median: 3.37, range 1.86-4.00), and mild H. pylori infiltrations (median: 2.39, range 0.36-4.00) (P < 0.001). Subjects with a marked H. pylori infiltration on gastric biopsy had the highest serological titer, whereas in subjects with moderate and mild H. pylori infiltrations titers were correspondingly lower (P < 0.001). After the successful eradication, significant decreases of the degree of H. pylori infiltration (P < 0.001), serum anti-H. pylori IgG titer (P < 0.001), and serum concentrations of PG I (P = 0.028) and PG II (P = 0.028) were observed. CONCLUSION The anti-H. pylori IgG assay can be used to estimate the burden of bacteria in immunocompetent hosts with H. pylori infection, regardless

  9. Evaluation of Four Commercial IgG- and IgM-specific Enzyme Immunoassays for Detecting Mycoplasma pneumoniae Antibody: Comparison with Particle Agglutination Assay

    OpenAIRE

    Yoo, Soo Jin; Oh, Hye-Jeon; Shin, Bo-Moon

    2007-01-01

    Diagnosis of Mycoplasma pneumoniae infection is important due to its variable clinical manifestations and absence of response to beta-lactams. Introduction of enzyme immunoassays (EIAs) for serologic diagnosis of M. pneumoniae has made it possible to separate the analyses of specific IgG and IgM antibodies. We compared four different commercial EIAs, ImmunoWELL IgG, IgM (GenBio), Medac IgG, IgA, IgM (Medac), Platelia IgG, IgM (Sanofi Pasteur), and Ridascreen IgG, IgA, IgM (r-Biopharm) with in...

  10. Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface.

    Science.gov (United States)

    Lewis, Steven M; Wu, Xiufeng; Pustilnik, Anna; Sereno, Arlene; Huang, Flora; Rick, Heather L; Guntas, Gurkan; Leaver-Fay, Andrew; Smith, Eric M; Ho, Carolyn; Hansen-Estruch, Christophe; Chamberlain, Aaron K; Truhlar, Stephanie M; Conner, Elaine M; Atwell, Shane; Kuhlman, Brian; Demarest, Stephen J

    2014-02-01

    Robust generation of IgG bispecific antibodies has been a long-standing challenge. Existing methods require extensive engineering of each individual antibody, discovery of common light chains, or complex and laborious biochemical processing. Here we combine computational and rational design approaches with experimental structural validation to generate antibody heavy and light chains with orthogonal Fab interfaces. Parental monoclonal antibodies incorporating these interfaces, when simultaneously co-expressed, assemble into bispecific IgG with improved heavy chain-light chain pairing. Bispecific IgGs generated with this approach exhibit pharmacokinetic and other desirable properties of native IgG, but bind target antigens monovalently. As such, these bispecific reagents may be useful in many biotechnological applications.

  11. Diagnostic accuracy and comparison of two assays for Borrelia-specific IgG and IgM antibodies

    DEFF Research Database (Denmark)

    Dessau, Ram

    2013-01-01

    characteristic (ROC) curves to optimize and standardize test interpretation, it was shown that testing with both IDEIA IgG and IgM was comparable to testing with Liaison IgG alone by comparing the area under the curve of the diagnostically relevant 25 % partial ROC curve (P = 0.1). When using the Liaison Osp......M combined) were 85 and 95 % and for the Liaison (VlsE IgG) method were 67 and 96 %, respectively. Methods for test evaluation, test interpretation and statistical testing are presented and discussed. In conclusion, Liaison VlsE IgG alone and IDEIA IgG/IgM combined showed a high and comparable discriminatory...

  12. A homologue of the rabbit kappa-chain allotype b9 ON IgG from a cottontail rabbit.

    Science.gov (United States)

    Tosi, S L; Mage, R G; Tosi, R M

    1976-08-01

    Eight out of 12 anti-b9 antisera tested strongly bound 125IgG of only one of four individual cottontail rabbits (Sylvilagus floridanus). In addition to this apparent polymorphism of a b9 homologue in cottontail rabbits, a polymorphism defined by some anti-b5 antisera was found. Three of 15 anti-b5 antisera reacted with IgG from only two of the four cottontail rabbits. Reactions with anti-b4 and anti-b6 were similar to those with hare IgG. Most anti-b4 and anti-b6 antisera bound the IgG from each animal. The cottontails we tested also resembled the hare with respect to their weak reactivity with some anti-a2 antisera (Vh allotype) and strong reactivity with anti-15 (an allotype localized in the Fc portion of rabbit gamma-chains). PMID:820806

  13. Infants aged 12 months can mount adequate serotype-specific IgG responses to pneumococcal polysaccharide vaccine

    OpenAIRE

    Balloch, Anne; Licciardi, Paul V.; Russell, Fiona M.; Edward K Mulholland; Tang, Mimi L. K.

    2010-01-01

    This is the first study examining serotype-specific IgG responses following immunization with the polysaccharide vaccine Pneumovax® in infants aged 12 months in the absence of prior pneumococcal conjugate vaccine priming.

  14. A Label-Free Immunosensor for IgG Based on an Extended-Gate Type Organic Field Effect Transistor

    Directory of Open Access Journals (Sweden)

    Tsukuru Minamiki

    2014-09-01

    Full Text Available A novel biosensor for immunoglobulin G (IgG detection based on an extended-gate type organic field effect transistor (OFET has been developed that possesses an anti-IgG antibody on its extended-gate electrode and can be operated below 3 V. The titration results from the target IgG in the presence of a bovine serum albumin interferent, clearly exhibiting a negative shift in the OFET transfer curve with increasing IgG concentration. This is presumed to be due an interaction between target IgG and the immobilized anti-IgG antibody on the extended-gate electrode. As a result, a linear range from 0 to 10 µg/mL was achieved with a relatively low detection limit of 0.62 µg/mL (=4 nM. We believe that these results open up opportunities for applying extended-gate-type OFETs to immunosensing.

  15. [Diagnosis of IgG4-related systemic disease in a patient with an ocular tumor associated with lung nodules].

    Science.gov (United States)

    Vandenbos, F; Benchetrit, M; Tieulié, N; Ambrosetti, D; Chanalet, S; Burel-Vandenbos, F

    2012-12-01

    The IgG4-related systemic disease is a recently described entity of fibro-inflammatory systemic damage. Although initially described in some forms of pancreatitis, the disease can affect all organs. The common histological features include a lymphoplasmacytic infiltration (especially to IgG4), fibrosis and phlebitis. Elevated serum level of IgG4 is also often present. This rare but certainly underdiagnosed disease must be kept in mind of all clinician faced to a non-specific inflammatory lesion. We report a case of ocular inflammation and lung tumors in a patient of 84 years for which the diagnosis was made through immunolabelling with IgG4 in lesions biopsied. PMID:23159548

  16. Antigen-Specific IgG ameliorates allergic airway inflammation via Fcγ receptor IIB on dendritic cells

    Directory of Open Access Journals (Sweden)

    Karasuyama Hajime

    2011-04-01

    Full Text Available Abstract Background There have been few reports on the role of Fc receptors (FcRs and immunoglobulin G (IgG in asthma. The purpose of this study is to clarify the role of inhibitory FcRs and antigen presenting cells (APCs in pathogenesis of asthma and to evaluate antigen-transporting and presenting capacity by APCs in the tracheobronchial mucosa. Methods In FcγRIIB deficient (KO and C57BL/6 (WT mice, the effects of intratracheal instillation of antigen-specific IgG were analysed using the model with sensitization and airborne challenge with ovalbumin (OVA. Thoracic lymph nodes instilled with fluorescein-conjugated OVA were analysed by fluorescence microscopy. Moreover, we analysed the CD11c+ MHC class II+ cells which intaken fluorescein-conjugated OVA in thoracic lymph nodes by flow cytometry. Also, lung-derived CD11c+ APCs were analysed by flow cytometry. Effects of anti-OVA IgG1 on bone marrow dendritic cells (BMDCs in vitro were also analysed. Moreover, in FcγRIIB KO mice intravenously transplanted dendritic cells (DCs differentiated from BMDCs of WT mice, the effects of intratracheal instillation of anti-OVA IgG were evaluated by bronchoalveolar lavage (BAL. Results In WT mice, total cells and eosinophils in BAL fluid reduced after instillation with anti-OVA IgG1. Anti-OVA IgG1 suppressed airway inflammation in hyperresponsiveness and histology. In addition, the number of the fluorescein-conjugated OVA in CD11c+ MHC class II+ cells of thoracic lymph nodes with anti-OVA IgG1 instillation decreased compared with PBS. Also, MHC class II expression on lung-derived CD11c+ APCs with anti-OVA IgG1 instillation reduced. Moreover, in vitro, we showed that BMDCs with anti-OVA IgG1 significantly decreased the T cell proliferation. Finally, we demonstrated that the lacking effects of anti-OVA IgG1 on airway inflammation on FcγRIIB KO mice were restored with WT-derived BMDCs transplanted intravenously. Conclusion Antigen-specific IgG ameliorates

  17. Milk protein IgG and IgA: The association with milk-induced gastrointestinal symptoms in adults

    Institute of Scientific and Technical Information of China (English)

    Sari Anthoni; Erkki Savilahti; Hilpi Rautelin; Kaija-Leena Kolho

    2009-01-01

    AIM: To study the association between serum levels of milk protein IgG and IgA antibodies and milk-related gastrointestinal symptoms in adults.METHODS: Milk protein IgG and IgA antibodies were determined in serum samples of 400 subjects from five outpatient clinics in Southern Finland. Subjects were randomly selected from a total of 1900 adultsundergoing laboratory investigations in primary care. All 400 participants had completed a questionnaire onabdominal symptoms and dairy consumption while waiting for the laboratory visit. The questionnairecovered the nature and frequency of gastrointestinal problems, the provoking food items, family history and allergies. Twelve serum samples were disqualified due to insufficient amount of sera. The levels of specific milkprotein IgG and IgA were measured by using the ELISA technique. The association of the milk protein-specific antibody level was studied in relation to the milk-related gastrointestinal symptoms and dairy consumption.RESULTS: Subjects drinking milk ( n = 265) had higher levels of milk protein IgG in their sera than non-milk drinkers ( n = 123, P < 0.001). Subjects with gastrointestinal problems related to milk drinking ( n = 119) consumed less milk but had higher milk protein IgG levels than those with no milk-related gastrointestinal symptoms ( n = 198, P = 0.02). Among the symptomatic subjects, those reporting dyspeptic symptoms had lower milk protein IgG levels than non-dyspeptics ( P < 0.05). However, dyspepsia was not associated with milk drinking ( P = 0.5). The association of high milk protein IgG levels with constipation was close to the level of statistical significance. Diarrhea had no association with milk protein IgG level ( P = 0.5). With regard to minor symptoms, flatulence and bloating ( P = 0.8), were not associated with milk protein IgG level. Milk protein IgA levels did not show any association with milk drinking or abdominal symptoms. The levels of milk protein IgA and IgG declined as the

  18. Agglutinating mouse IgG3 compares favourably with IgMs in typing of the blood group B antigen: Functionality and stability studies.

    Science.gov (United States)

    Klaus, Tomasz; Bzowska, Monika; Kulesza, Małgorzata; Kabat, Agnieszka Martyna; Jemioła-Rzemińska, Małgorzata; Czaplicki, Dominik; Makuch, Krzysztof; Jucha, Jarosław; Karabasz, Alicja; Bereta, Joanna

    2016-01-01

    Mouse immunoglobulins M (IgMs) that recognize human blood group antigens induce haemagglutination and are used worldwide for diagnostic blood typing. Contrary to the current belief that IgGs are too small to simultaneously bind antigens on two different erythrocytes, we obtained agglutinating mouse IgG3 that recognized antigen B of the human ABO blood group system. Mouse IgG3 is an intriguing isotype that has the ability to form Fc-dependent oligomers. However, F(ab')2 fragments of the IgG3 were sufficient to agglutinate type B red blood cells; therefore, IgG3-triggered agglutination did not require oligomerization. Molecular modelling indicated that mouse IgG3 has a larger range of Fab arms than other mouse IgG subclasses and that the unique properties of mouse IgG3 are likely due to the structure of its hinge region. With a focus on applications in diagnostics, we compared the stability of IgG3 and two IgMs in formulated blood typing reagents using an accelerated storage approach and differential scanning calorimetry. IgG3 was much more stable than IgMs. Interestingly, the rapid decrease in IgM activity was caused by aggregation of the molecules and a previously unknown posttranslational proteolytic processing of the μ heavy chain. Our data point to mouse IgG3 as a potent diagnostic tool. PMID:27484487

  19. Pulmonary hyalinizing granuloma with associated elevation in serum and tissue IgG4 occurring in a patient with a history of sarcoidosis.

    Science.gov (United States)

    Chapman, Erin M; Gown, Allen; Mazziotta, Robert; Churg, Andrew

    2012-05-01

    Pulmonary hyalinizing granulomas (PHGs) are unusual fibrosclerotic inflammatory lung lesions. The organ-based manifestations of the recently defined IgG4-related sclerosing disease typically show dense fibrosis and heavy lymphoplasmacytic infiltrates. IgG4-related sclerosing disease is also defined by increased serum IgG4 levels and increased tissue levels of IgG4-positive plasma cells. The morphologic features of PHG overlap with those seen in IgG4-related sclerosing disease, and this suggests that PHG may be a form of IgG4-related sclerosing disease. We present a case of a 51-year-old man with a history of sarcoidosis who presented with slowly enlarging pulmonary nodules. Histologic evaluation of one of the nodules yielded a diagnosis of PHG. Further investigation demonstrated both elevated serum IgG4 and elevated tissue IgG4-positive plasma cells in the PHG. In previous reports, lesions that are now considered part of IgG4-related sclerosing disease were documented in patients also diagnosed with PHG, although these reports date from before the description of IgG4 sclerosing disease. This case provides the first definitive evidence that PHG is part of the spectrum of IgG4-related sclerosing disease. PMID:22498827

  20. Titer IgG Pertusis pada Usia Remaja, Dewasa, dan Orang Tua Mempergunakan Metode ELISA dan Mikroaglutinasi Pertusis

    Directory of Open Access Journals (Sweden)

    Novilia Sjafri Bachtiar

    2011-03-01

    Full Text Available Pertussis antigen which only given in primary immunization, could not protect for a long period. In some countries whooping cough became an reemerging disease. The objective of this study was to evaluate the correlation between age and percentage of positive IgG pertussis in adolescent, adult, and elderly population using enzyme link immunosorbent assay (ELISA and microagglutination. This observational analytic with cross sectional study was done on 402 subjects, consisted of 134 adolescents (12–18 years, 187 adults (19–49 years, and 81 elderly (50–64 years in Bandung, period 2008–2010. Titer of pertussis IgG was measured using ELISA and microagglutination of pertussis (MAP. The ELISA results showed positive IgG pertussis in 92 (68.7% adolescent, 143 (76.5% adults, and 72 (88.9% elderly (p=0.003. The results of MAP showed positive pertussis IgG in adolescent, adults, and elderly were 27 (20.1%, 9 (4.8%, and 3 (3.37%, respectively, which was decreased with age (p<0.001. If MAP positive samples were excluded from the analysis in ELISA positive samples, which express the IgG pertussis due to contact with circulate B, the pertussis IgG positive was 68.9%. In conclusion, there is a correlation between age and percentage of positive IgG pertussis titer in adolescent, adult, and ederly population in Bandung using ELISA and MAP methods. Positive pertussis IgG by ELISA is increased with age.

  1. Chronic inflammatory demyelinating polyneuropathy (CIDP): change of serum IgG dimer levels during treatment with intravenous immunoglobulins

    OpenAIRE

    Ritter, Christian; Bobylev, Ilja; Helmar C Lehmann

    2015-01-01

    Background Intravenous immunoglobulin (IVIg) is an effective treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). In most patients, the optimal IVIg dose and regime is unknown. Polyvalent immunoglobulin (Ig) G form idiotypic/anti-idiotypic antibody pairs in serum and IVIg preparations. We determined IgG dimer levels before and after IVIg treatment in CIDP patients with the aim to explore their utility to serve as a surrogate marker for treatment response. Methods IgG was pur...

  2. Serological analysis of human IgG and IgE anti-insulin antibodies by solid-phase radioimmunoassays

    International Nuclear Information System (INIS)

    A single solid-phase assay system which is useful for quantitative measurement of both IgG and IgE anti-insulin antibodies in human serum has been developed. Insulin-specific immunoglobulins are absorbed from human serum by excess quantities of insulin-agarose. After washes to remove unbound immunoglobulins, radioiodinated Staph A or rabbit anti-human IgE is added to detect bound IgG or IgE anbitodies, respectively

  3. Increased sialylation of oligosaccharides on IgG paraproteins--a potential new tumour marker in multiple myeloma.

    OpenAIRE

    Fleming, S C; Smith, S.; Knowles, D; Skillen, A.; Self, C H

    1998-01-01

    AIMS: To investigate whether changes in carbohydrate structure of IgG are related to malignancy and stage of disease in myeloma and monoclonal gammopathy of uncertain significance (MGUS). METHODS: 61 patients were studied at diagnosis: 14 with MGUS, nine with stage I multiple myeloma, 11 with stage II, 21 with stage III, and five with solitary plasmacytoma. IgG was extracted from serum by protein G affinity chromatography. Oligosaccharides were cleaved from the protein backbone enzymatically ...

  4. Recurrent membranous nephropathy in an allograft caused by IgG3κ targeting the PLA2 receptor.

    Science.gov (United States)

    Debiec, Hanna; Hanoy, Melanie; Francois, Arnaud; Guerrot, Dominique; Ferlicot, Sophie; Johanet, Catherine; Aucouturier, Pierre; Godin, Michel; Ronco, Pierre

    2012-12-01

    Up to 80% of patients with idiopathic membranous nephropathy have non-complement-fixing IgG4 autoantibodies to the phospholipase A2 receptor (PLA2R). Membranous nephropathy recurs in approximately 40% of patients after kidney transplantation, but the mechanism is unknown. Here, we describe a patient with recurrent membranous nephropathy 13 days after kidney transplantation whose graft biopsy specimen showed granular staining for C3, C5b-9, C1q, and IgG3κ; electron microscopy revealed subepithelial nonorganized deposits. A search for hematologic disorders was negative. Retrospective evaluation of a biopsy sample from the native kidney revealed a similar pattern: monotypic IgG3κ deposits together with C3, C1q, and C5b-9. Glomerular deposits contained PLA2R in both the graft and the native kidney, suggesting that the recurrence was the result of circulating anti-PLA2R antibodies binding to PLA2R antigen expressed on donor podocytes. Confocal analysis of anti-PLA2R and antihuman IgG3 showed co-localization, and the patient had IgG3κ-restricted circulating anti-PLA2R antibodies. Treatment with rituximab stabilized both proteinuria and serum creatinine, and circulating anti-PLA2R became undetectable. In summary, this case of recurrent membranous nephropathy in a graft suggests that circulating monoclonal anti-PLA2R IgG3κ caused the disease and activated complement by the classic pathway.

  5. A case of non-lacrimal immunoglobulin G4 (IgG4)-related orbital disease with mastitis.

    Science.gov (United States)

    Farooq, Tahir Ali; Mudhar, Hardeep; Sandramouli, S

    2016-01-01

    IgG4-related orbital disease is a recognised cause for orbital inflammation. As its awareness increases and diagnostic accuracy improves there will be an increased number of cases being identified. This unique case demonstrates for the first time, with histological evidence, a case of a non-lacrimal IgG4-related orbital disease with concurrent IgG4-related mastitis. We describe a 47 year old who presented with a supraorbital swelling and mass. This was initially successfully treated with oral steroids and was later excised on recurrence. Immunohistochemical and blood serum analysis confirmed IgG4-related orbital disease. On systemic enquiry she was found to have a mass of the breast, which was shown to be IgG4-related mastitis. She is currently asymptomatic with no sign of recurrence and is under long-term surveillance. This case highlights the importance of systemic work up in patients presenting with orbital foci of IgG4 disease.

  6. Evaluation of mixed-mode chromatographic resins for separating IgG from serum albumin containing feedstock.

    Science.gov (United States)

    Wang, Rong-Zhu; Lin, Dong-Qiang; Tong, Hong-Fei; Lu, Hui-Li; Yao, Shan-Jing

    2013-10-01

    Mixed-mode chromatography has been focused as a cost-effective new technique for antibody purification. In this study, four mixed-mode resins with N-benzyl-N-methyl ethanol amine, 2-benzamido-4-mercaptobutanoic acide, 4-mercapto-ethyl-pyridine and phenylpropylamine as the ligands were tested and the multi-functional interactions between ligand and protein were discussed. Immunoglobulin G (IgG), bovine serum albumin (BSA) and the binary mixture of BSA and IgG were used as the model feedstock to compare the separation behaviors by pH gradient elution. The comparison analysis showed mixed-mode resin with N-benzyl-N-methyl ethanol amine as the ligand had the best ability to separate IgG and BSA. The results indicated that for four resins tested ionic interaction might play the dominant role in the separation of IgG and BSA while the hydrophobic interactions and hydrogen bonding have some subsidiary effects. The pH stepwise elution and sample loading were optimized to improve the IgG purification from serum albumin containing feedstock. High purity (92.3%) and high recovery (95.6%) of IgG were obtained. The results indicated that mixed-mode chromatography would be a potential option for antibody purification with the control of loading and elution conditions. PMID:23973532

  7. PURIFIED IGG F C-BINDING PROTEINS FROM M22 GROUP A STREPTOCOCCUS ARE ABLE TO INDUCE EXPERIMENTAL GLOMERULONEPHRITIS

    Directory of Open Access Journals (Sweden)

    L. A. Burova

    2012-01-01

    Full Text Available Abstract. Pathogenesis of acute post-streptococcal glomerulonephritis (APSGN, a major complication of group A streptococcal (GAS throat or skin disease, remains unclear. Over years, various theories were based on distinct streptococcal extracellular factors, as well as immunological mimicry of streptococci for renal tissue antigens was considered. Previously we reported that a lot of clinical GAS isolates with proven nephritogenic ability show a non-immune binding of monomeric or aggregated IgG. Moreover, using a rabbit model of APSGN, we obtained evidence for important causative role of streptococcal IgG Fc-binding proteins (IgG FcBPs belonging to the M family surface proteins. I.e., rabbits injected by whole IgG FcBP-positive streptococci showed induction of renal glomerular changes, with deposition of IgG and complement C3, resembling the picture recorded in human APSGN. These typical renal changes were always preceded by development of circulating anti-IgG antibodies. Present study was performed in the same rabbit model. Both purified IgG FcBPs isolated from type M22 GAS were found to elicit glomerular degenerative damage of renal glomeruli comparable to those caused by whole bacteria, as well as induce anti-IgG antibodies, deposition of IgG and C3 complement and production of proinflammatory cytokines (IL-1β, TNFα, IL-6 by glomerular mesangial and endothelial cells. By contrast, rabbits injected with proteins A or G, IgG FcBPs of S. aureus and group G streptococci, respectively, exhibited only low levels of circulating anti-IgG and reversible glomerular changes. In these settings, we have not observed any features of membranousproliferative glomerulonephritis (GN resembling morphological traits of acute post-streptococcal GN in humans. These data correlated with results obtained after injection of intact Staphylococcus aureus (Cowan 1 strain or group G streptococci (G148 strain. Both microbial types are known to harbor IgG Fc

  8. Binding of fusion protein FLSC IgG1 to CCR5 is enhanced by CCR5 antagonist Maraviroc.

    Science.gov (United States)

    Latinovic, Olga; Schneider, Kate; Szmacinski, Henryk; Lakowicz, Joseph R; Heredia, Alonso; Redfield, Robert R

    2014-12-01

    The CCR5 chemokine receptor is crucial for human immunodeficiency virus type 1 (HIV-1) infection, acting as the principal coreceptor for HIV-1 entry and transmission and is thus an attractive target for antiviral therapy. Studies have suggested that CCR5 surface density and its conformational changes subsequent to virion engagement are rate limiting for entry, and consequently, infection. Not all CCR5 antibodies inhibit HIV-1 infection, suggesting a need for more potent reagents. Here we evaluated full length single chain (FLSC) IgG1, a novel IgG-CD4-gp120(BAL) fusion protein with several characteristics that make it an attractive candidate for treatment of HIV-1 infections, including bivalency and a potentially increased serum half-life over FLSC, the parental molecule. FLSC IgG1 binds two domains on CCR5, the N-terminus and the second extracellular loop, lowering the levels of available CCR5 viral attachment sites. Furthermore, FLSC IgG1 synergizes with Maraviroc (MVC), the only licensed CCR5 antagonist. In this study, we used both microscopy and functional assays to address the mechanistic aspects of the interactions of FLSC IgG1 and MVC in the context of CCR5 conformational changes and viral infection. We used a novel stochastic optical reconstruction microscopy (STORM), based on high resolution localization of photoswitchable dyes to visualize direct contacts between FLSC IgG1 and CCR5. We compared viral entry inhibition by FLSC IgG1 with that of other CCR5 blockers and showed FLSC IgG1 to be the most potent. We also showed that lower CCR5 surface densities in HIV-1 infected primary cells result in lower FLSC IgG1 EC50 values. In addition, CCR5 binding by FLSC IgG1, but not CCR5 Ab 2D7, was significantly increased when cells were treated with MVC, suggesting MVC allosterically increases exposure of the FLSC IgG1 binding site. These data have implications for future antiviral therapy development.

  9. Stabilization of IgG1 in spray-dried powders for inhalation.

    Science.gov (United States)

    Schüle, S; Schulz-Fademrecht, T; Garidel, P; Bechtold-Peters, K; Frieb, W

    2008-08-01

    The protein stabilizing capabilities of spray-dried IgG1/mannitol formulations were evaluated. The storage stability was tested at different residual moisture levels prepared by vacuum-drying or equilibration prior to storage. Vacuum-drying at 32 degrees C/0.1mbar for 24h reduced the moisture level below 1%, constituting an optimal basis for improved storage stability. The crystalline IgG1/mannitol powders with a weight ratio of 20/80 up to 40/60 failed to prevent the antibody aggregation as assessed by size exclusion chromatography during storage. Ratios of 60/40 up to 80/20 IgG1/mannitol provided superior stability of the antibody and the powders could be produced with high yields. The lower the residual moisture, the better was the stabilizing capability. An amount of 20% mannitol provided the best stabilization. Storage stability of 60/40, 70/30, and 80/20 IgG1/mannitol formulations over one year was adequate at 2-8 degrees C and 25 degrees C. Closed storage (sealed in vials) at 40 degrees C/75% RH and open storage at 25 degrees C/60% RH revealed that the stability still required optimization. The lower the protein content, the better was the powder flowability. The aerodynamic properties of powders spray-dried with 10% solids content were inadequate, as the particle size ranged between 5.1 and 7.2 microm and the fine particle fraction accounted for only 4-11%. Reduction of the solids content to 2.5% did improve the aerodynamic properties as the mass mean aerodynamic diameter was reduced to 3.6 microm and the fine particle fraction was increased to about 14%. The reduction of the solids content did not influence the storage stability significantly. Also spray-drying at higher temperatures had no significant impact on the storage stability, despite a higher tendency to form amorphous systems. In order to improve the storage stability and to maintain the good flowability of 70/30 IgG1/mannitol powder or to keep the storage stability but to improve the flowability

  10. Hypermethylation of MST1 in IgG4-related autoimmune pancreatitis and rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Fukuhara, Takataro; Tomiyama, Takashi [Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, JST CREST, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010 (Japan); Yasuda, Kaneki [Department of Urology and Andrology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010 (Japan); Ueda, Yoshihiro [Department of Molecular Genetics, Institute of Biomedical Science, and JST CREST, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010 (Japan); Ozaki, Yoshio; Son, Yonsu; Nomura, Shosaku [Department of the First Department of Internal Medicine, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010 (Japan); Uchida, Kazushige; Okazaki, Kazuichi [Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, JST CREST, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010 (Japan); Kinashi, Tatsuo, E-mail: kinashi@takii.kmu.ac.jp [Department of Molecular Genetics, Institute of Biomedical Science, and JST CREST, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010 (Japan)

    2015-08-07

    The serine/threonine kinase Mst1 plays important roles in the control of immune cell trafficking, proliferation, and differentiation. Previously, we reported that Mst1 was required for thymocyte selection and regulatory T-cell functions, thereby the prevention of autoimmunity in mice. In humans, MST1 null mutations cause T-cell immunodeficiency and hypergammaglobulinemia with autoantibody production. RASSF5C(RAPL) is an activator of MST1 and it is frequently methylated in some tumors. Herein, we investigated methylation of the promoter regions of MST1 and RASSF5C(RAPL) in leukocytes from patients with IgG4-related autoimmune pancreatitis (AIP) and rheumatoid arthritis (RA). Increased number of CpG methylation in the 5′ region of MST1 was detected in AIP patients with extrapancreatic lesions, whereas AIP patients without extrapancreatic lesions were similar to controls. In RA patients, we detected a slight increased CpG methylation in MST1, although the overall number of methylation sites was lower than that of AIP patients with extrapancreatic lesions. There were no significant changes of the methylation levels of the CpG islands in the 5′ region of RASSF5C(RAPL) in leukocytes from AIP and RA patients. Consistently, we found a significantly down-regulated expression of MST1 in regulatory T cells of AIP patients. Our results suggest that the decreased expression of MST1 in regulatory T cells due to hypermethylation of the promoter contributes to the pathogenesis of IgG4-related AIP. - Highlights: • Mst1 controls immune cells trafficking, cell proliferation and differentiation. • Autoimmune pancreatitis (AIP) is an idiopathic pancreatitis affecting multiple organs. • Decreased MST1 expression and increased CpG methylation of promoter of MST1 in AIP. • Slight increased CpG methylation of MST1 in rheumatoid arthritis patients. • MST1 contributes pathogenesis of IgG4-related AIP.

  11. "Evaluation of Rubella IgG Antibodies among High School Girls in Uremia City"

    Directory of Open Access Journals (Sweden)

    H Mohaddesi

    2003-09-01

    Full Text Available Rubella or German measles is a mild contagious disease in non-pregnant women, but in pregnant affected mother’s possibility of fetus infection in the first twelve weeks of gestation is 80%. Between 13-14 weeks of gestation is 54% and by the end of the second trimester is 25%. If fetus gets infected severe anomalies will progress. At present no vaccination against rubella is begin envisaged by the National Immunization Program in Iran. Because of serious complications of the rubella in pregnancy, it’s very important to determine the immune status of young girls at their pre-marriage age. Five hundred eighty nine high school girls were selected at random from different high schools and then a questionnaire was filled up. Blood samples were obtained and anti-rubella IgG titre was detected in each sera by using American Diaplus Diagnostics ELISA kits. From 589 samples 500 students (89.4% showed positive and 89 students (15.1% revealed negative results for anti-rubella IgG. Of all 63 students (10.69% had previously been vaccinated against rubella. The results indicated that 15.1% of all students and 20.7% of precollege girls would be mothers, are seronegative. Comparison of these results with the conclusions obtained in other cities of Iran shows that it would be necessary to screen rubella IgG antibodies in premarriage young girls on other regions of country and vaccination against rubella could be considered as a part of National Immunization Program.

  12. Interleukin-33 primes mast cells for activation by IgG immune complexes.

    Directory of Open Access Journals (Sweden)

    Shinjiro Kaieda

    Full Text Available Mast cells (MCs are heterogeneous cells whose phenotype is modulated by signals received from the local microenvironment. Recent studies have identified the mesenchymal-derived cytokine IL-33 as a potent direct activator of MCs, as well as regulator of their effector phenotype, and have implicated this activity in the ability of mast cells to contribute to murine experimental arthritis. We explored the hypothesis that IL-33 enables participation of synovial MCs in murine K/BxN arthritis by promoting their activation by IgG immune complexes. Compared to wild-type (WT control mice, transgenic animals lacking the IL-33 receptor ST2 exhibited impaired MC-dependent immune complex-induced vascular permeability (flare and attenuated K/BxN arthritis. Whereas participation of MCs in this model is mediated by the activating IgG receptor FcγRIII, we pre-incubated bone marrow-derived MCs with IL-33 and found not only direct induction of cytokine release but also a marked increase in FcγRIII-driven production of critical arthritogenic mediators including IL-1β and CXCL2. This "priming" effect was associated with mRNA accumulation rather than altered expression of Fcγ receptors, could be mimicked by co-culture of WT but not ST2(-/- MCs with synovial fibroblasts, and was blocked by antibodies against IL-33. In turn, WT but not ST2(-/- MCs augmented fibroblast expression of IL-33, forming a positive feedback circuit. Together, these findings confirm a novel role for IL-33 as an amplifier of IgG immune complex-mediated inflammation and identify a potential MC-fibroblast amplification loop dependent on IL-33 and ST2.

  13. IgG subclass switching and clonal expansion in cutaneous melanoma and normal skin.

    Science.gov (United States)

    Saul, Louise; Ilieva, Kristina M; Bax, Heather J; Karagiannis, Panagiotis; Correa, Isabel; Rodriguez-Hernandez, Irene; Josephs, Debra H; Tosi, Isabella; Egbuniwe, Isioma U; Lombardi, Sara; Crescioli, Silvia; Hobbs, Carl; Villanova, Federica; Cheung, Anthony; Geh, Jenny L C; Healy, Ciaran; Harries, Mark; Sanz-Moreno, Victoria; Fear, David J; Spicer, James F; Lacy, Katie E; Nestle, Frank O; Karagiannis, Sophia N

    2016-01-01

    B cells participate in immune surveillance in human circulation and tissues, including tumors such as melanoma. By contrast, the role of humoral responses in cutaneous immunity is underappreciated. We report circulating skin-homing CD22+CLA+B cells in healthy volunteers and melanoma patients (n = 73) and CD22+ cells in melanoma and normal skin samples (n = 189). Normal and malignant skin featured mature IgG and CD22 mRNA, alongside mRNA for the transiently-expressed enzyme Activation-induced cytidine Deaminase (AID). Gene expression analyses of publically-available data (n = 234 GEO, n = 384 TCGA) confirmed heightened humoral responses (CD20, CD22, AID) in melanoma. Analyses of 51 melanoma-associated and 29 normal skin-derived IgG sequence repertoires revealed lower IgG1/IgGtotal representation compared with antibodies from circulating B cells. Consistent with AID, comparable somatic hypermutation frequencies and class-switching indicated affinity-matured antibodies in normal and malignant skin. A melanoma-associated antibody subset featured shorter complementarity-determining (CDR3) regions relative to those from circulating B cells. Clonal amplification in melanoma-associated antibodies and homology modeling indicated differential potential antigen recognition profiles between normal skin and melanoma sequences, suggesting distinct antibody repertoires. Evidence for IgG-expressing B cells, class switching and antibody maturation in normal and malignant skin and clonally-expanded antibodies in melanoma, support the involvement of mature B cells in cutaneous immunity. PMID:27411958

  14. Hypermethylation of MST1 in IgG4-related autoimmune pancreatitis and rheumatoid arthritis

    International Nuclear Information System (INIS)

    The serine/threonine kinase Mst1 plays important roles in the control of immune cell trafficking, proliferation, and differentiation. Previously, we reported that Mst1 was required for thymocyte selection and regulatory T-cell functions, thereby the prevention of autoimmunity in mice. In humans, MST1 null mutations cause T-cell immunodeficiency and hypergammaglobulinemia with autoantibody production. RASSF5C(RAPL) is an activator of MST1 and it is frequently methylated in some tumors. Herein, we investigated methylation of the promoter regions of MST1 and RASSF5C(RAPL) in leukocytes from patients with IgG4-related autoimmune pancreatitis (AIP) and rheumatoid arthritis (RA). Increased number of CpG methylation in the 5′ region of MST1 was detected in AIP patients with extrapancreatic lesions, whereas AIP patients without extrapancreatic lesions were similar to controls. In RA patients, we detected a slight increased CpG methylation in MST1, although the overall number of methylation sites was lower than that of AIP patients with extrapancreatic lesions. There were no significant changes of the methylation levels of the CpG islands in the 5′ region of RASSF5C(RAPL) in leukocytes from AIP and RA patients. Consistently, we found a significantly down-regulated expression of MST1 in regulatory T cells of AIP patients. Our results suggest that the decreased expression of MST1 in regulatory T cells due to hypermethylation of the promoter contributes to the pathogenesis of IgG4-related AIP. - Highlights: • Mst1 controls immune cells trafficking, cell proliferation and differentiation. • Autoimmune pancreatitis (AIP) is an idiopathic pancreatitis affecting multiple organs. • Decreased MST1 expression and increased CpG methylation of promoter of MST1 in AIP. • Slight increased CpG methylation of MST1 in rheumatoid arthritis patients. • MST1 contributes pathogenesis of IgG4-related AIP

  15. An improved recombinant IgG immunoblot for serodiagnosis of Lyme borreliosis.

    Science.gov (United States)

    Wilske, B; Habermann, C; Fingerle, V; Hillenbrand, B; Jauris-Heipke, S; Lehnert, G; Pradel, I; Rössler, D; Schulte-Spechtel, U

    1999-12-01

    We have previously described the use of the following recombinant antigens for serodiagnostic immunoblots: p83/100, p39, OspC and p41 (flagellin) internal fragment [Wilske et al. (1993) Med Microbiol Immunol 182:255-270; Rossler et al. (1997) J Clin Microbiol 35:2752-2758]. In our currently used immunoblot p83/100 is derived from strain PKo (Borrelia afzelii), p39 (BmpA) and OspC from strains PKa2 (B. hurgdorferi sensu stricto), PKo and PBi (B. garinii), respectively; the p41 (flagellin) internal fragments were cloned from strains PKo and PBi. In this study we describe the use of two additional recombinantly expressed highly immunogenic proteins Osp 7 (derived from PKo) and p58 (derived from PBi). A clinically well-defined panel of sera from 147 Lyme borreliosis patients and 139 controls previously tested by a standardized whole cell lysate immunoblot [Hauser et al. (1997) J Clin Microbiol 35:1433-1444] was investigated in the recombinant immunoblot without (old recombinant immunoblot) and with Ospl7 and p58 (new recombinant immunoblot) for IgG antibodies. The sensitivity of the recombinant IgG immunoblot for diagnosis of stage II and stage III could be significantly improved by addition of Osp17 and p58 without loss of specificity. With the exception of sera from patients with erythema migrans the diagnostic sensitivity is comparable to the whole cell lysate IgG immunoblot. The main advantage of the recombinant immunoblot is the easy identification of diagnostic bands, whereas the identification of bands in the whole cell lysate immunoblot is difficult. The recombinant immunoblot is especially suitable where large series of sera need to be investigated.

  16. Reliable classifier to differentiate primary and secondary acute dengue infection based on IgG ELISA.

    Directory of Open Access Journals (Sweden)

    Marli Tenório Cordeiro

    Full Text Available BACKGROUND: Dengue virus infection causes a wide spectrum of illness, ranging from sub-clinical to severe disease. Severe dengue is associated with sequential viral infections. A strict definition of primary versus secondary dengue infections requires a combination of several tests performed at different stages of the disease, which is not practical. METHODS AND FINDINGS: We developed a simple method to classify dengue infections as primary or secondary based on the levels of dengue-specific IgG. A group of 109 dengue infection patients were classified as having primary or secondary dengue infection on the basis of a strict combination of results from assays of antigen-specific IgM and IgG, isolation of virus and detection of the viral genome by PCR tests performed on multiple samples, collected from each patient over a period of 30 days. The dengue-specific IgG levels of all samples from 59 of the patients were analyzed by linear discriminant analysis (LDA, and one- and two-dimensional classifiers were designed. The one-dimensional classifier was estimated by bolstered resubstitution error estimation to have 75.1% sensitivity and 92.5% specificity. The two-dimensional classifier was designed by taking also into consideration the number of days after the onset of symptoms, with an estimated sensitivity and specificity of 91.64% and 92.46%. The performance of the two-dimensional classifier was validated using an independent test set of standard samples from the remaining 50 patients. The classifications of the independent set of samples determined by the two-dimensional classifiers were further validated by comparing with two other dengue classification methods: hemagglutination inhibition (HI assay and an in-house anti-dengue IgG-capture ELISA method. The decisions made with the two-dimensional classifier were in 100% accordance with the HI assay and 96% with the in-house ELISA. CONCLUSIONS: Once acute dengue infection has been determined, a 2-D

  17. Diagnostic utility of IgG and IgM immunohistochemistry in autoimmune liver disease

    Institute of Scientific and Technical Information of China (English)

    Roger; Klein; Moreira; Frank; Revetta; Elizabeth; Koehler; Mary; Kay; Washington

    2010-01-01

    AIM:To assess the role of IgM and IgG immunohistochemistry(IHC) in the evaluation of autoimmune liver conditions-autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC),and primary sclerosing cholangitis(PSC).METHODS:Forty one biopsies from untreated patients diagnosed with autoimmune liver disease(AIH,n = 20;PBC,n = 13;PSC,n = 8) and fourteen biopsies of patients with chronic hepatitis C were selected.IgM and IgG-positive plasma cells were counted in each sample.RESULTS:A predominance of IgG-positive plas...

  18. An interesting cause of esophageal ulcer etiology: Multiple myeloma of IgG kappa subtype

    Institute of Scientific and Technical Information of China (English)

    Yavuz Pehlivan; Alper Sevinc; Ibrahim Sari; Murat T Gulsen; Mehmet Buyukberber; Mehmet E Kalender; Celalettin Camci

    2006-01-01

    Multiple myeloma is a neoplasm of mature and immature plasma cells. A 50-year-old woman with lumbago,dysphagia, and left arm pain was presented. Upper endoscopical examination was performed. There was an exudate-covered ulcer in the distal esophagus, located at 30-32 cm from the incisors, covering the whole mucosa.Histopathological examination of the specimens obtained from the lesion showed the involvement of plasma cells consistent with multiple myeloma of IgG kappa subtype.Esophageal involvement of multiple myeloma should be kept in mind in patients presenting with dysphagia.

  19. Human anti-rhesus D IgG1 antibody produced in transgenic plants

    DEFF Research Database (Denmark)

    Bouquin, Thomas; Thomsen, Mads Jonas Birkbak; Nielsen, Leif Kofoed;

    2002-01-01

    Transgenic plants represent an alternative to cell culture systems for producing cheap and safe antibodies for diagnostic and therapeutic use. To evaluate the functional properties of a 'plantibody', we generated transgenic Arabidopsis plants expressing full-length human IgG1 against the Rhesus D...... antigen, which is responsible for alloimmunization of RhD- mothers carrying an RhD+ fetus. Anti-RhD extracted from plants specifically reacted with RhD+ cells in antiglobulin technique, and elicited a respiratory burst in human peripheral blood mononuclear cells. Plant-derived antibody had equivalent...

  20. Anti-S. typhi Vi IgG levels in children with and without typhoid vaccinations

    Directory of Open Access Journals (Sweden)

    Sriandayani

    2014-09-01

    Full Text Available Background Typhoid fever is endemic to Indonesia, with an annual incidence of 13/10,000 people. Vaccination has been shown to be an effective method to prevent typhoid fever. Of several vaccine types, the polysaccharide Vi vaccine is the most commonly used typhoid vaccine in developing countries. Results of previous studies remain inconclusive on the necessity of revaccination every 3 years. Objective To compare the mean serum antibody titers of anti-S. typhi Vi IgG and the proportion of children with protective antibody levels between children with and without typhoid Vi vaccination. Methods We conducted a cross-sectional study at Tuminting District, Manado from June to September 2012. Data was analyzed using independent T-test and Fisher’s test. Serum anti-S. typhi Vi IgG levels were measured by enzyme-linked immunosorbent assay (ELISA method. Results Seventy-six subjects were divided into two groups: 38 children who had received the typhoid Vi vaccination more than 3 years prior to this study and 38 children who never had typhoid vaccinations as a control group. No statistically significant difference in age and gender was found between the two groups. The mean serum anti-Vi IgG level was 0.55 ug/mL (SD 0.58; 95%CI 0.36 to 0.74 in the vaccinated group, significantly higher than that of the control group [0.31 ug/mL (SD 0.42; 95%CI 0.17 to 0.44; P=0.038]. The proportion of children with protective anti-Vi antibody level was higher in the vaccinated group (23.7% than in the control group (10.5%, however, this difference was not statistically significant (P=0.128. Conclusion The mean serum anti-S. typhi Vi IgG antibody level in children who had been vaccinated more than 3 years prior to the study is higher than in children who had never received typhoid vaccinations. Nevertheless, the mean antibody titers are generally non-protective in both groups. Also, the proportion of children with protective antibody levels is not significantly different

  1. Antigen recognition by IgG4 antibodies in human trichinellosis

    Directory of Open Access Journals (Sweden)

    Pinelli E.

    2001-06-01

    Full Text Available The antibody isotype response to Trichinella spiralis excretory/secretory (ES products of muscle larva was examined using sera from patients with confirmed trichinellosis. Using Western blots we identify components of the ES antigen that are recognized by IgM and IgG antibodies. A 45 kDa component was strongly recognized by different antibody classes and subclasses. We observed a 45 kDa-specific lgG4 response that was detected exclusively using sera of patients with trichinellosis and not of patients with echinococcosis, filariasis, cysticercosis, ascariasis, strongyloidiasis or toxocariasis. These results are relevant for the diagnosis of human trichinellosis.

  2. Hepatic nodular lymphoid lesion with increased IgG4-positive plasma cells associated with primary biliary cirrhosis: a report of two cases.

    Science.gov (United States)

    Calvo, Jessica; Carbonell, Nicolas; Scatton, Olivier; Marzac, Christophe; Ganne-Carrie, Nathalie; Wendum, Dominique

    2015-11-01

    The nodular lymphoid lesion of the liver known as reactive lymphoid hyperplasia or pseudolymphoma is rare and its pathogenesis is unknown. We report two cases of nodular lymphoid lesions of the liver with numerous IgG4-positive plasma cells in patients with primary biliary cirrhosis. Histologically, in both cases, the lesion showed a dense lymphoplasmacytic infiltrate with lymphoid follicles and granulomas. Fibrous tissue was scarce and without a storiform pattern. Obliterative phlebitis was not identified. The IgG4+ plasma cell counts were 82 and 76 per high power field, with an IgG4/IgG ratio of 75 and 64 %, respectively, which qualifies the lesions according to the diagnostic criteria for IgG4-related disease as « probable histological feature of IgG4-related disease ». There were no rearrangements of immunoglobulin heavy-chain genes and plasma cells had a polytypic pattern of kappa and lambda light-chain expression. The non-tumor liver showed primary biliary cirrhosis with destructive cholangitis without IgG4 plasma cells. In both cases, IgG4-related disease was not found in other organs neither at the time of diagnosis nor 3 years later. Serum IgG4 levels normalized after local ablation of the lesions. It seems unlikely that these lesions are a manifestation of IgG4-related disease. However, because the pathogenesis of both nodular lymphoid lesions and IgG4-related disease remains unclear, further studies are needed to elucidate a potential link between nodular lymphoid lesions of the liver and an increased number of IgG4 plasma cells. More definite conclusions will be possible when the pathogenesis of IgG4-related disease has been clarified.

  3. Anti-Lipid IgG Antibodies Are Produced via Germinal Centers in a Murine Model Resembling Human Lupus

    Science.gov (United States)

    Wong-Baeza, Carlos; Reséndiz-Mora, Albany; Donis-Maturano, Luis; Wong-Baeza, Isabel; Zárate-Neira, Luz; Yam-Puc, Juan Carlos; Calderón-Amador, Juana; Medina, Yolanda; Wong, Carlos; Baeza, Isabel; Flores-Romo, Leopoldo

    2016-01-01

    Anti-lipid IgG antibodies are produced in some mycobacterial infections and in certain autoimmune diseases [such as anti-phospholipid syndrome, systemic lupus erythematosus (SLE)]. However, few studies have addressed the B cell responses underlying the production of these immunoglobulins. Anti-lipid IgG antibodies are consistently found in a murine model resembling human lupus induced by chlorpromazine-stabilized non-bilayer phospholipid arrangements (NPA). NPA are transitory lipid associations found in the membranes of most cells; when NPA are stabilized they can become immunogenic and induce specific IgG antibodies, which appear to be involved in the development of the mouse model of lupus. Of note, anti-NPA antibodies are also detected in patients with SLE and leprosy. We used this model of lupus to investigate in vivo the cellular mechanisms that lead to the production of anti-lipid, class-switched IgG antibodies. In this murine lupus model, we found plasma cells (Gr1−, CD19−, CD138+) producing NPA-specific IgGs in the draining lymph nodes, the spleen, and the bone marrow. We also found a significant number of germinal center B cells (IgD−, CD19+, PNA+) specific for NPA in the draining lymph nodes and the spleen, and we identified in situ the presence of NPA in these germinal centers. By contrast, very few NPA-specific, extrafollicular reaction B cells (B220+, Blimp1+) were found. Moreover, when assessing the anti-NPA IgG antibodies produced during the experimental protocol, we found that the affinity of these antibodies progressively increased over time. Altogether, our data indicate that, in this murine model resembling human lupus, B cells produce anti-NPA IgG antibodies mainly via germinal centers. PMID:27746783

  4. The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation

    Directory of Open Access Journals (Sweden)

    Christoph Fickentscher

    2015-01-01

    Full Text Available To analyze the glycosylation of anti-β2GP1, we investigated purified IgG from healthy children, patients with APS, and asymptomatic adult carriers of antiphospholipid antibodies. We observed that in the sera of healthy children and of patients with APS, IgG3 and IgG2 were predominant, respectively. The potentially protective anti-β2GP1-IgM was lower in the sera of healthy children. Although anti-β2GP1-associated C1q did not differ between children and patients with antiphospholipid syndrome, the associated C3c was significantly higher in the sera of healthy children. This indicates a more efficient clearance of anti-β2GP1 immune complexes in the healthy children. This clearance is not accompanied by inflammation or coagulatory events. It is likely that the most important pathogenic factor of the anti-β2GP1-IgG is related to the different glycosylation observed in healthy and diseased individuals. We detected a significantly higher sialylation of anti-β2GP1-IgG isolated from the sera of healthy children and asymptomatic adults when compared with that of patients with clinically apparent antiphospholipid syndrome. Low sialylated IgG reportedly ameliorates inflammation and inflammation promotes hyposialylation. Thus, both reactions create a vicious circle that precipitates the pathology of the antiphospholipid syndrome including thrombus-formation. We conclude that the increased sialylation of anti-β2GP1-IgG of sera of healthy individuals limits their pathogenicity.

  5. Anti-HIV-1 antibody-dependent cellular cytotoxicity mediated by hyperimmune bovine colostrum IgG.

    Science.gov (United States)

    Kramski, Marit; Lichtfuss, Gregor F; Navis, Marjon; Isitman, Gamze; Wren, Leia; Rawlin, Grant; Center, Rob J; Jaworowski, Anthony; Kent, Stephen J; Purcell, Damian F J

    2012-10-01

    Antibodies with antibody-dependent cellular cytotoxicity (ADCC) activity play an important role in protection against HIV-1 infection, but generating sufficient amounts of antibodies to study their protective efficacy is difficult. HIV-specific IgG can be easily and inexpensively produced in large quantities using bovine colostrum. We previously vaccinated cows with HIV-1 envelope gp140 and elicited high titers of anti-gp140-binding IgG in colostrum. In the present study, we determined whether bovine antibodies would also demonstrate specific cytotoxic activity. We found that bovine IgG bind to Fcγ-receptors (FcγRs) on human neutrophils, monocytes, and NK cells in a dose-dependent manner. Antibody-dependent killing was observed in the presence of anti-HIV-1 colostrum IgG but not nonimmune colostrum IgG. Killing was dependent on Fc and FcγR interaction since ADDC activity was not seen with F(ab')(2) fragments. ADCC activity was primarily mediated by CD14(+) monocytes with FcγRIIa (CD32a) as the major receptor responsible for monocyte-mediated ADCC in response to bovine IgG. In conclusion, we demonstrate that bovine anti-HIV colostrum IgG have robust HIV-1-specific ADCC activity and therefore offer a useful source of antibodies able to provide a rapid and potent response against HIV-1 infection. This could assist the development of novel Ab-mediated approaches for prevention of HIV-1 transmission. PMID:22730083

  6. Anti-neutrophil cytoplasmic antibody-enriched IgG induces adhesion of human T lymphocytes to extracellular matrix proteins.

    Science.gov (United States)

    Tomer, Y; Lider, O; Gilburd, B; Hershkoviz, R; Meroni, P L; Wiik, A; Shoenfeld, Y

    1997-06-01

    Recent studies have shown that anti-neutrophil cytoplasmic antibodies (ANCA) can activate neutrophils to adhere to endothelium, degranulate, and cause endothelial cell injury. These data have lead to the hypothesis that the T cell inflammatory response causing the vasculitis in Wegener's granulomatosis (WG) is secondary to stimulation of neutrophils by ANCA. So far there is no evidence for a direct effect of ANCA on lymphocytes. The present study was designed to examine whether lymphocytes can be directly stimulated by ANCA to adhere to endothelial extracellular matrix (ECM) proteins. Human and mouse ANCA-enriched IgG were tested for their ability to increase adhesion of human T lymphocytes to fibronectin, laminin, and intact ECM. Incubation of human T lymphocytes with human ANCA-enriched IgG increased adhesion of the lymphocytes in a dose-dependent manner to fibronectin, laminin, and intact ECM (the percentage adhesion to intact ECM was 55.7 +/- 3.1 and 45.0 +/- 1.0% for lymphocytes incubated with human IgG containing ANCA or control human IgG, respectively; P = 0.0045). The same induction of adhesion to fibronectin, laminin, and intact ECM was observed when the cells were incubated with the F(ab)2 fragment of ANCA-enriched IgG. Similarly, ANCA-enriched IgG produced in mice increased the adhesion of lymphocytes to fibronectin (the percentage adhesion to fibronectin was 29.7 +/- 4.3 and 16.6 +/- 1.9% for lymphocytes incubated with mouse IgG-ANCA or control mouse IgG, respectively; P = 0.0008). These results may suggest that ANCA can directly stimulate lymphocytes to adhere to endothelial ECM and to induce the vasculitic lesions of WG. It remains to be shown by which mechanisms ANCA stimulate lymphocytes to adhere to ECM. PMID:9175913

  7. Highly sensitive detection of human IgG using a novel bio-barcode assay combined with DNA chip technology

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhenbao [Central South University, School of Pharmaceutical Sciences (China); Zhou, Bo, E-mail: zhoubo1771@163.com [The Affiliated Zhongda Hospital of Southeast University, Department of Gerontology (China); Wang, Haiqing; Lu, Feng; Liu, Tianjun; Song, Cunxian; Leng, Xigang, E-mail: lengxigyky@163.com [Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College (China)

    2013-09-15

    A simple and ultrasensitive detection of human IgG based on signal amplification using a novel bio-barcode assay and DNA chip technology was developed. The sensing platform was a sandwich system made up of antibody-modified magnetic microparticles (Ab-MMPs)/human IgG/Cy3-labeled single-stranded DNA and antibody-modified gold nanoparticles (Cy3-ssDNA-Ab-AuNPs). The MMPs (2.5 {mu}m in diameter) modified with mouse anti-human IgG monoclonal-antibodies could capture human IgG and further be separated and enriched via a magnetic field. The AuNPs (13 nm in diameter) conjugated with goat anti-human IgG polyclonal-antibodies and Cy3-ssDNA could further combine with the human IgG/Ab-MMP complex. The Cy3-ssDNA on AuNPs was then released by TCEP to hybridize with the DNA chip, thus generating a detectable signal by the fluorescence intensity of Cy3. In order to improve detection sensitivity, a three-level cascaded signal amplification was developed: (1) The MMP enrichment as the first-level; (2) Large quantities of Cy3-ssDNA on AuNPs as the second-level; (3) The Cy3-ssDNA conjugate with DNA chip as the third-level. The highly sensitive technique showed an increased response of the fluorescence intensity to the increased concentration of human IgG through a detection range from 1 pg mL{sup -1} to 10 ng mL{sup -1}. This sensing technique could not only improve the detection sensitivity for the low concentration of human IgG but also present a robust and efficient signal amplification model. The detection method has good stability, specificity, and reproducibility and could be applied in the detection of human IgG in the real samples.

  8. Highly sensitive detection of human IgG using a novel bio-barcode assay combined with DNA chip technology

    International Nuclear Information System (INIS)

    A simple and ultrasensitive detection of human IgG based on signal amplification using a novel bio-barcode assay and DNA chip technology was developed. The sensing platform was a sandwich system made up of antibody-modified magnetic microparticles (Ab-MMPs)/human IgG/Cy3-labeled single-stranded DNA and antibody-modified gold nanoparticles (Cy3-ssDNA-Ab-AuNPs). The MMPs (2.5 μm in diameter) modified with mouse anti-human IgG monoclonal-antibodies could capture human IgG and further be separated and enriched via a magnetic field. The AuNPs (13 nm in diameter) conjugated with goat anti-human IgG polyclonal-antibodies and Cy3-ssDNA could further combine with the human IgG/Ab-MMP complex. The Cy3-ssDNA on AuNPs was then released by TCEP to hybridize with the DNA chip, thus generating a detectable signal by the fluorescence intensity of Cy3. In order to improve detection sensitivity, a three-level cascaded signal amplification was developed: (1) The MMP enrichment as the first-level; (2) Large quantities of Cy3-ssDNA on AuNPs as the second-level; (3) The Cy3-ssDNA conjugate with DNA chip as the third-level. The highly sensitive technique showed an increased response of the fluorescence intensity to the increased concentration of human IgG through a detection range from 1 pg mL−1 to 10 ng mL−1. This sensing technique could not only improve the detection sensitivity for the low concentration of human IgG but also present a robust and efficient signal amplification model. The detection method has good stability, specificity, and reproducibility and could be applied in the detection of human IgG in the real samples

  9. The Prevalence and Levels of Anti-HEV IgG in the Population of Jiangsu Province, China

    Institute of Scientific and Technical Information of China (English)

    Xin Yao; Jun-zhi Wang; Ting Wu; Cheng Zhou; Yi-min Li; Feng-cai Zhu; Qiang Yan; Wei-jin Huang; Chuan Ji; Zheng-lun Liang

    2013-01-01

    Objective To investigate the prevalence and levels of anti-HEV IgG in the population of Jiangsu Province. Methods Total of 2 656 samples from Qindong and 11 463 samples from Anfeng were colleted. The anti-HEV antibody was qualitatively and quantitatively detected using ELISA kits and the references had been established. Results The positive rates of anti-HEV IgG in male and female were 55.6% and 40.1%, respectively. The positive rate of anti-HEV IgM in male and female were both 3.4%. In opposite to anti-HEV IgG, the positive rate of anti-HEV IgM in Anfeng was signiifcant higher than that in Qindong. The mean anti-HEV IgG titers for 6 age groups were 0.94, 0.92, 1.07, 1.46, 1.27, 1.19 and 0.68, 1.31, 1.08, 1.14, 1.31, 1.68 IU/ml, in Qindong and Anfeng region, respectively. The positive rate of anti-HEV IgG tended to increase with age and the titer of anti-HEV IgG was associated with age (R>0.90). Conclusions The results in this study showed that HEV was widely prevalent in both Qindong and Anfeng of Jiansu Province and the prevalence and the anti-HEV IgG titer were associated with gender and age.

  10. Seroprevalence of hepatitis B e antigen (HBe antigen and B core antibodies (IgG anti-HBcore and IgM anti-HBcore among hepatitis B surface antigen positive blood donors at a Tertiary Centre in Nigeria

    Directory of Open Access Journals (Sweden)

    Akinbami Akinsegun A

    2012-03-01

    Full Text Available Abstract Background Hepatitis B virus (HBV is a common cause of liver disease throughout the world. HBV is transmitted through blood and other body fluids, including semen and saliva. Chronic replication of HBV virons is characterized by persistence circulation of HBsAg, HBeAg and HBV DNA; usually with anti-HBc and occasionally with anti-HBs. Aim: To determine the prevalence of HBeAg, IgG anti-HBcore and IgM anti-HBcore amongst HBsAg positive blood donors. These parameters are reflective of transmissibility and active hepatitis B infection. A cross sectional study was carried out at the blood donor clinics of Lagos State University Teaching Hospital Ikeja and Lagos University Teaching Hospital Idiaraba. A total of 267 donors were recruited to determine HBe antigen, IgG and IgM anti-HBcore antibodies amongst hepatitis BsAg positive donors. Five milliliters of blood was collected from those who tested positive to HBsAg screen during donation. The sera were subjected to enzyme linked immunosorbent assay (ELISA. Pearson chi-squared test was used for the analytical assessment. Findings A total number of 267 HBsAg positive blood donors were studied. A seroprevalence of 8.2% (22 of 267 HBeAg was obtained, 4 of 267 (1.5% were indeterminate while 241 (90.3% tested negative. Only 27 out of 267 donors (10.1% tested positive to IgM anti-HBcore, 234(87.6% tested negative, while 6(2.2% were indeterminate. A higher percentage of 60.7% (162 of 267 tested positive to IgG anti-HBcore, while 39.3% (105 of 267 tested negative. Conclusion There is a low seroprevalence rate of HBeAg-positive chronic hepatitis and relatively high IgG anti-HBcore and IgM anti-HBcore rates in South West Nigeria.

  11. Effect of high mannose glycan pairing on IgG antibody clearance.

    Science.gov (United States)

    Liu, Yaoqing Diana; Flynn, Gregory C

    2016-05-01

    IgG antibodies contain N-linked glycans on the Fc portion of each heavy chain. The glycan on one heavy chain can either match the glycan on the other heavy chain (symmetrical pairing) or be different (asymmetrical pairing). These Fc glycans influence effector functions and can alter clearance rates. Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. Traditional analytical methods, which are used to measure glycans in such studies, do not determine the number of HM glycans per antibody. With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. The two HM paired forms cleared at the same rate, indicating that the effect on clearance was not proportional to the degree of modification. Since both forms can exist on therapeutic antibodies and the ratio can differ between products, measuring their relative levels is necessary to properly estimate effects on clearance. PMID:26992607

  12. High-fat-diet exposure induces IgG accumulation in hypothalamic microglia

    Directory of Open Access Journals (Sweden)

    Chun-Xia Yi

    2012-09-01

    The mediobasal hypothalamic arcuate nucleus (ARC, with its relatively ‘leaky’ blood-brain barrier that allows more circulating molecules to enter the brain, has emerged as a key sensor of blood-borne signals. In both the ARC and white adipose tissue (WAT, consumption of a high-fat diet (HFD rapidly induces infiltration of microglia (ARC or macrophages (WAT. Animals with HFD-induced obesity (DIO and insulin resistance additionally accumulate B cells in WAT, increasing the local production of pathogenic antibodies. We therefore investigated whether DIO mice or genetically obese ob/ob mice have increased IgG in the ARC, analogous to the recent observations in WAT. Following 16 weeks of exposure to a HFD, wild-type (WT mice had significantly increased IgG-immunoreactivity (ir signaling that was specific to the ARC and was exclusively concentrated in microglia. By contrast, IgG-ir of age-matched obese ob/ob mice fed standard chow had ARC IgG levels comparable with those in chow-fed WT control mice. However, following 2 weeks of HFD exposure, ob/ob mice also had a significant increase of IgG-ir in the ARC. In summary, our findings reveal a novel pathophysiological phenomenon, specific for the hypothalamic ARC, that is induced by exposure to a HFD and can be enhanced, but not caused, by genetic obesity.

  13. Subcutaneous IgG in immune-mediate diseases: proposed mechanisms of action and literature review.

    Science.gov (United States)

    Danieli, Maria Giovanna; Gelardi, Chiara; Pedini, Veronica; Moretti, Romina; Gabrielli, Armando; Logullo, Francesco

    2014-12-01

    Intravenous immunoglobulin (IVIg) constitutes a relevant treatment option in various immune-mediated disorders, such as chronic inflammatory neuropathies and idiopathic inflammatory myopathies (IIM). Several advantages are linked to IVIg immunomodulatory and steroid sparing effects and to the possibility to withdraw the immunosuppressant therapy. However, the use of IVIg is not always easy to manage. It is associated with the need of an intravenous route of administration, high costs, and the risk of serious systemic adverse effects. More recently, the subcutaneous administration of immunoglobulin (SCIg) has been used in immunological practice as an alternative to IVIg, administered at lower dosages and more frequent intervals. This results in higher and more stable IgG serum levels and may prevent end-of-dose reduction and adverse effects caused by sudden IgG serum elevation. Moreover, the use of SCIg is more feasible, patient-friendly and cost-effective compared to the intravenous administration. In this context we compared IVIg and SCIg long term efficacy in the treatment of chronic inflammatory neuropathies and IIM, by reviewing the current literature and reporting the data obtained from our clinical experience about the use of SCIg in patients with myositis. We also described the most recent evidence on the immunomodulatory role of immunoglobulin, the pharmacokinetic properties of SCIg compared to the IVIg treatment, and the consequent clinical, laboratory and immunological implications. PMID:25172241

  14. Diagnosis of autoimmune neutropenia by neutrophil-bound IgG and IgM antibodies.

    Science.gov (United States)

    Ito, Taichi; Taniuchi, Shoichiro; Tsuji, Shoji; Iharada, Anna; Hasui, Masafumi; Kaneko, Kazunari

    2011-10-01

    Autoimmune neutropenia (AIN) in infancy is caused by antineutrophil (granulocyte-specific) autoantibodies. These antibodies are rarely found in circulation because their serum levels are extremely low. We hypothesized that a direct granulocyte immunofluorescence test (D-GIFT) that enables us to detect neutrophil-bound autoantibodies consisting of both immunoglobulin (Ig) G and IgM has better diagnostic value than the detection of circulating autoantibodies. Whole blood (100 μL) was obtained from 50 infants with AIN, 12 infants with transient neutropenia, and 37 control infants. D-GIFT was performed using both fluorescein isothiocyanate-conjugated antihuman IgG Fc portion monoclonal antibodies and fluorescein isothiocyanate antihuman IgM monoclonal antibodies. Results were assessed as relative fluorescence intensity (RFI). The RFIs of antineutrophil IgG-bound and antineutrophil IgM-bound cells in patients with AIN were significantly higher than those in patients with transient neutropenia and in controls. Positive results, as assessed by RFI scores of more than 1.81 in either antineutrophil IgG-bound or antineutrophil IgM-bound cells, showed the sensitivity and specificity of D-GIFT, and the areas under the receiver operating characteristic curve (0.98, 0.98, and 0.997, respectively) in the diagnosis of AIN. D-GIFT detecting both neutrophil-bound IgG autoantibodies and IgM autoantibodies has discriminatory power for identifying patients with AIN and, therefore, can be a useful diagnostic test. PMID:21941149

  15. Renal Cell Carcinoma Mimicking Igg4-Related Pseudotumor in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Khan

    2014-09-01

    Full Text Available Context Autoimmune pancreatitis is classified into two distinct clinical profiles. Care report Type 1 autoimmunepancreatitis (AIP is considered to be a manifestation of a novel clinicopathological entity called IgG4 related sclerosingdisease, diagnosed using the Mayo Clinic HISORt criteria. Extra-pancreatic manifestations can include involvement of bileducts, salivary gland, lung nodules, thyroiditis, tubulointerstitial nephritis, renal masses, and retroperitoneal fibrosis. Type2 autoimmune pancreatitis on the other hand is confirmed by histologically seen duct centric pancreatitis without elevationof IgG4 or involvement of other organs. In type 1 autoimmune pancreatitis, extrapancreatic manifestations like bile ductstrictures, tubulointerstitial nephritis, renal nodules, retroperitoneal fibrosis respond to steroid therapy. Conclusion Wepresent a case of type 1 autoimmune pancreatitis in which the renal mass did not respond to steroid therapy and was later on found to be renal cell carcinoma. To the best of our knowledge this is only the third reported case of autoimmune pancreatitis in which the patient had renal cell carcinoma. Our case highlights the importance of close follow up of lesions that do not respond to steroid treatment which in this case proved to be renal cell cancer.

  16. Maternal and Other Risk Factors Including Bovine IgG in Developing Infantile Colic

    Directory of Open Access Journals (Sweden)

    Masoud Omidian

    2007-04-01

    Full Text Available Objective: Infantile colic is one of the most current problems in the first few months of life. It is suggested that organic or psychologic and behavioral factors can predispose to involve this disorder. Here, we have studied the role of some maternal risk factors including bovine IgG levels in breast milk for appearing the colic in young babies. Material & Methods: This retrospective study was performed on 50 infants as case group and 30 infants aged 3 weeks to 3 months who had normal growth and development as control group for one year in Mashad. Data was analyzed with Pearson Chi-Square and Fisher’s exact tests. Findings: Most colicky infants were male (62% vs 38% female. They were mainly symptomatic at neonatal period. In 64% of cases, it occurred in the first offspring. Infantile colic was more common in babies who delivered normally than by cesarean section and in mothers aged 20-30 years. According to our finding, there was no relationship between bovine IgG in breast milk and infantile colic. It revealed that anxious pregnant women had more colicky babies and paternal smoking seemed to develop colic in young infants. Conclusion: In order to reduce the occurrence of colic in infants, primigravid mothers aged 20-30 years should have a stressfree environment especially during pregnancy and no smoking exposure in this period.

  17. Engineering upper hinge improves stability and effector function of a human IgG1.

    Science.gov (United States)

    Yan, Boxu; Boyd, Daniel; Kaschak, Timothy; Tsukuda, Joni; Shen, Amy; Lin, Yuwen; Chung, Shan; Gupta, Priyanka; Kamath, Amrita; Wong, Anne; Vernes, Jean-Michel; Meng, Gloria Y; Totpal, Klara; Schaefer, Gabriele; Jiang, Guoying; Nogal, Bartek; Emery, Craig; Vanderlaan, Martin; Carter, Paul; Harris, Reed; Amanullah, Ashraf

    2012-02-17

    Upper hinge is vulnerable to radical attacks that result in breakage of the heavy-light chain linkage and cleavage of the hinge of an IgG1. To further explore mechanisms responsible for the radical induced hinge degradation, nine mutants were designed to determine the roles that the upper hinge Asp and His play in the radical reactions. The observation that none of these substitutions could inhibit the breakage of the heavy-light chain linkage suggests that the breakage may result from electron transfer from Cys(231) directly to the heavy-light chain linkage upon radical attacks, and implies a pathway separate from His(229)-mediated hinge cleavage. On the other hand, the substitution of His(229) with Tyr showed promising advantages over the native antibody and other substitutions in improving the stability and function of the IgG1. This substitution inhibited the hinge cleavage by 98% and suggests that the redox active nature of Tyr did not enable it to replicate the ability of His to facilitate radical induced degradation. We propose that the lower redox potential of Tyr, a residue that may be the ultimate sink for oxidizing equivalents in proteins, is responsible for the inhibition. More importantly, the substitution increased the antibody's binding to FcγRIII receptors by 2-3-fold, and improved ADCC activity by 2-fold, while maintaining a similar pharmacokinetic profile with respect to the wild type. Implications of these observations for antibody engineering and development are discussed.

  18. [Expression of human IL-35-IgG4 (Fc) fusion protein in CHO/DG44 cells].

    Science.gov (United States)

    Tang, Jing; Gao, Wenda; Zhang, Qing; Zhang, Dawei; Chen, Yang; He, Bo; Liu, Quansheng

    2009-01-01

    We constructed the eukaryotic expression vector of human IL-35-IgG4 (Fc)-pOptiVEC-TOPO by gene recombination technique and expressed the fusion protein human IL-35-IgG4 (Fc) in CHO/DG44 cells. The two components of the newly discovered cytokine human IL-35, EBI3 and IL-12p35, were amplified by PCR from the cDNA library derived from the KG-I cells after LPS induction. The two PCR-amplified cDNA fragments of human IL-35 were linked by over-lapping PCR and then cloned into the IgG4 (Fc)-pOptiVEC-TOPO vector. The constructed plasmid with the recombinant cDNA IL-35-IgG4 (Fc) was verified by restriction enzyme digestion analysis, PCR and DNA sequencing. The verified plasmid with the recombinant cDNA was transfected into CHO/DG44 cells using Lipofectamine 2000. The success of the transfection was examined and confirmed by RT-PCR. After selection in alpha-MEM (-) medium, the IL-35-Ig G4 (Fc) positive CHO/DG44 clones were chosen and the media from these positive clones were collected to be used to purify the fusion protein. The positive CHO/DG44 clones were further cultured in increasing concentrations of MTX and the expression levels of the fusion protein IL-35-Ig G4 (Fc) were repetitively induced by MTX-induced gene amplification. The IL-35-IgG4 (Fc) fusion protein was purified from the media collected from the positive CHO/DG44 clones by protein G affinity chromatography and then identified by SDS-PAGE and Western blotting. The results showed that one protein band was found to match well with the predicted relative molecular mass of human IL-35-IgG4 (Fc) and this protein could specifically bind to anti-human IgG4 (Fc) monoclonal antibody. In conclusion, our study successfully established an IL-35-IgG4 (Fc) positive DG44 cell line which could stably express IL-35-IgG4 (Fc) fusion protein.

  19. Induction of IgG3 to LPS via Toll-like receptor 4 co-stimulation.

    Directory of Open Access Journals (Sweden)

    Francisco J Quintana

    Full Text Available B-cells integrate antigen-specific signals transduced via the B-cell receptor (BCR and antigen non-specific co-stimulatory signals provided by cytokines and CD40 ligation in order to produce IgG antibodies. Toll-like receptors (TLRs also provide co-stimulation, but the requirement for TLRs to generate T-cell independent and T-cell dependent antigen specific antibody responses is debated. Little is known about the role of B-cell expressed TLRs in inducing antigen-specific antibodies to antigens that also activate TLR signaling. We found that mice lacking functional TLR4 or its adaptor molecule MyD88 harbored significantly less IgG3 natural antibodies to LPS, and required higher amounts of LPS to induce anti-LPS IgG3. In vitro, BCR and TLR4 signaling synergized, lowering the threshold for production of T-cell independent IgG3 and IL-10. Moreover, BCR and TLR4 directly associate through the transmembrane domain of TLR4. Thus, in vivo, BCR/TLR synergism could facilitate the induction of IgG3 antibodies against microbial antigens that engage both innate and adaptive B-cell receptors. Vaccines might exploit BCR/TLR synergism to rapidly induce antigen-specific antibodies before significant T-cell responses arise.

  20. Resonance scattering spectral detection of ultratrace IgG using immunonanogold-HAuCl4-NH2OH catalytic reaction

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Nanogold particles of 10 nm were used to label goat anti-human IgG (GIgG) to obtain nanogold-labeled GIgG (AuGIgG). In a citrate-HCl buffer solution of pH 2.27,AuGIgG showed a strong catalytic effect on the reaction between HAuCl4 and NH2OH to form big gold particles that exhibited a resonance scatter-ing (RS) peak at 796 nm. Under the chosen conditions,AuGIgG combined with IgG to form immuno-complex AuGIgG-IgG that can be removed by centrifuging at 16000 r/min. AuGIgG in the centrifuging solution also showed catalytic effect on the reaction. On those grounds,an immunonanogold catalytic RS assay for IgG was designed. With addition of IgG,the amount of AuGIgG in the centrifuging solution decreased; the RS intensity at 796 nm (I796 nm) decreased linearly. The decreased intensity ΔI796 nm was linear with respect to the IgG concentration in the range of 0.08-16.0 ng·mL-1 with a detection limit of 0.02 ng·mL-1. This assay was applied to analysis of IgG in sera with satisfactory sensitivity,selectivity and rapidity.

  1. Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection.

    Science.gov (United States)

    French, Martyn A; Abudulai, Laila N; Fernandez, Sonia

    2013-01-01

    The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of "protective" immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8⁺ T-cell responses restricted by "protective" HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.

  2. Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection

    Directory of Open Access Journals (Sweden)

    Sonia Fernandez

    2013-08-01

    Full Text Available The development of vaccines to treat and prevent human immunodeficiency virus (HIV infection has been hampered by an incomplete understanding of “protective” immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8+ T-cell responses restricted by “protective” HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK cell responses and plasmacytoid dendritic cell (pDC responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.

  3. Natural Mosquito-Pathogen Hybrid IgG4 Antibodies in Vector-Borne Diseases: A Hypothesis

    Science.gov (United States)

    Londono-Renteria, Berlin; Cardenas, Jenny C.; Troupin, Andrea; Colpitts, Tonya M.

    2016-01-01

    Chronic exposure to antigens may favor the production of IgG4 antibodies over other antibody types. Recent studies have shown that up to a 30% of normal human IgG4 is bi-specific and is able to recognize two antigens of different nature. A requirement for this specificity is the presence of both eliciting antigens in the same time and at the same place where the immune response is induced. During transmission of most vector-borne diseases, the pathogen is delivered to the vertebrate host along with the arthropod saliva during blood feeding and previous studies have shown the existence of IgG4 antibodies against mosquito salivary allergens. However, there is very little ongoing research or information available regarding IgG4 bi-specificity with regard to infectious disease, particularly during immune responses to vector-borne diseases, such as malaria, filariasis, or dengue virus infection. Here, we provide background information and present our hypothesis that IgG4 may not only be a useful tool to measure exposure to infected mosquito bites, but that these bi-specific antibodies may also play an important role in modulation of the immune response against malaria and other vector-borne diseases in endemic settings. PMID:27746778

  4. Binding of IgM rheumatoid factor to group A, C and G streptococci with IgG Fc receptors.

    Science.gov (United States)

    Schröder, A K; Christensen, P; Svensson, M L

    1986-01-01

    The possibility that IgM rheumatoid factors bind to streptococci was studied. Using a sequence of Sephadex G200 gel filtration, protein A-Sepharose CL-4B chromatography and preparatory electrophoresis, IgM was isolated from the sera of 2 patients with rheumatoid arthritis and then radiolabelled with 125I. There was significant binding of radiolabelled IgM to group-A streptococci types M1, M15 and M22, and to a group-C and a group-G strain, all expressing IgG Fc receptors, but none to Staphylococcus aureus, Escherichia coli or to 11 other strains of streptococci without IgG Fc receptors. The radiolabelled IgM was separated by affinity chromatography on a column containing human IgG. Types M1 and M15 bound the fraction retained on the column, whereas M22 bound both this fraction and the non-retained fraction. Commercial human IgG, even at high concentrations, did not inhibit binding. The binding reaction, which is perhaps triggered either by the IgM rheumatoid factor or by IgG complexed with rheumatoid factor, could be a useful tool for removal of anti-immunoglobulin from the blood of patients with rheumatoid arthritis.

  5. Investigation of serum oxidized low-density lipoprotein IgG levels in patients with angiographically defined coronary artery disease.

    Science.gov (United States)

    Moohebati, Mohsen; Kabirirad, Vahid; Ghayour-Mobarhan, Majid; Esmaily, Habibollah; Tavallaie, Shima; Akhavan Rezayat, Amir; Pourghadamyari, Hossein; Sahebkar, Amirhossein

    2014-01-01

    It has been suggested that antioxidized low-density lipoprotein (anti-oxLDL) antibodies play a role in the pathogenesis of atherosclerosis. The aim of this study was to measure serum ox-LDL IgG levels in 31 patients with angiographically defined coronary artery disease (CAD) (≥50% stenosis in at least one major coronary artery; CAD(+) group) and compare these levels with those of 32 subjects with coronary stenosis (CAD(-) group) and 24 healthy age- and sex-matched controls using ELISA. We did not find any significant difference between CAD(+), CAD(-), and control groups in regard to oxLDL IgG levels (P = 0.83). Serum oxLDL IgG levels did not differ between 1VD (one vessel disease), 2VD (2 vessels disease), and 3VD (3 vessels disease) subgroups of CAD(+) patients (P = 0.20). Serum anti-oxLDL titers were only significantly correlated with LDL-C in the CAD(+) group (P cardiovascular risk factors was associated with serum ox-LDL IgG levels. The present results suggest that serum levels of ox-LDL IgG are neither associated with the presence and severity of CAD nor with the conventional cardiovascular risk factors.

  6. High prevalence of human anti-bovine IgG antibodies as the major cause of false positive reactions in two-site immunoassays based on monoclonal antibodies

    DEFF Research Database (Denmark)

    Andersen, Ditte C; Koch, Claus; Jensen, Charlotte H;

    2004-01-01

    were purified by protein G affinity chromatography from culture supernatant containing 10% (v/v) fetal calf serum (FCS). Human anti-animal IgG (bovine, mouse, horse, and swine) antibodies and human anti-bovine serum albumin antibodies were measured using an ELISA design, with direct bridging of the...... human anti-mouse IgG antibodies (HAMA), described to create false positive results, may be due to a crossreacting fraction of the polyclonal circulating antibodies against bovine IgG....

  7. High concentrations of therapeutic IgG1 antibodies are needed to compensate for inhibition of antibody-dependent cellular cytotoxicity by excess endogenous immunoglobulin G.

    Science.gov (United States)

    Preithner, Susanne; Elm, Stefanie; Lippold, Sandra; Locher, Mathias; Wolf, Andreas; da Silva, Antonio J; Baeuerle, Patrick A; Prang, Nadja S

    2006-03-01

    A common feature of human IgG1 antibodies used for cancer treatment is that their anti-tumour efficacy requires high serum trough levels and continued therapy for several months. Treatment cycles, thereby, consume several grams of IgG1 translating into significant drug needs and costs. The basis for the low in vivo efficacy, which is in contrast to high in vitro antibody-dependent cellular cytotoxicity (ADCC), is not well understood. Here, we have explored factors contributing to this discrepancy using adecatumumab (MT201), a fully human monoclonal IgG1 against epithelial cell adhesion molecule (Ep-CAM) and trastuzumab (Herceptin), a humanized IgG1 with specificity for the human epithelial growth factor receptor type 2 (HER-2) antigen. We found that physiological levels of human sera strongly inhibited ADCC of both IgG1 antibodies. Effects showed some dependence on the density of Ep-CAM and HER-2 targets, the tumour cell line tested and on effector cell and serum donors. Removal of IgG by affinity chromatography abolished the inhibitory effect of a serum pool. Inhibition of ADCC was fully restored by adding back the IgG fraction or by an equal amount of IgG from a commercial source. We further demonstrate that CD56-positive lymphocytes within human PBMC contributed >90% to ADCC and that normal serum levels of IgG effectively competed for in vitro binding of an IgG1 antibody to low-affinity Fcgamma receptor type III (CD16), as is present on natural killer (NK) cells. Competition of serum IgG for binding of therapeutic IgG1 to NK cell may be one important reason why high antibody doses are required in the clinic for treatment of cancer by an ADCC-based mechanism. PMID:16102830

  8. Pattern of pre-existing IgG subclass responses to a panel of asexual stage malaria antigens reported during the lengthy dry season in Daraweesh, Sudan

    DEFF Research Database (Denmark)

    Nasr, A; Iriemenam, N C; Troye-Blomberg, M;

    2011-01-01

    The anti-malarial IgG immune response during the lengthy and dry season in areas of low malaria transmission as in Eastern Sudan is largely unknown. In this study, ELISA was used for the measurement of pre-existing total IgG and IgG subclasses to a panel of malaria antigens, MSP2-3D7, MSP2-FC27, ...

  9. IgG subclass distributions of anti-horse serum antibodies and natural venom-antibodies produced in response to antivenom injection or snake bite in humans.

    Science.gov (United States)

    Ameno, S; Ameno, K; Fuke, C; Kiryu, T; Ijiri, I

    1990-01-01

    The Japanese Mamushi (Agkistrodon halys blomhoffi, BOIE) is the most common snake in Japan. Bite victims treated with antivenom (horse serum) can produce antibodies against the horse serum and the snake venom. We studied distributions of the IgG subclasses of both these antibodies produced in response to antivenom injection and snake bite. We found that IgG1 and IgG4 of each antibody in the victims' serum were present for a long period of time. PMID:2343468

  10. Detection of FMD virus type specific IgG1, IgG2 and IgA antibodies in milk and serum of buffaloes vaccinated with oil adjuvanted polyvalent FMD vaccine

    OpenAIRE

    Sharma, R.; Sharma, A.; Yadav, V.

    2010-01-01

    The present investigation was carried out on 15 randomly selected milch buffaloes divided into three groups on the basis of lactation at an organized farm, to study the foot and mouth disease virus type specific antibodies in milk and serum following FMD vaccination. Milk and serum samples collected before vaccination i.e. 0 day and on 7, 14, 28, 42 and 56 days post vaccination, were analyzed for the detection of FMD virus specific IgG1, IgG2 and IgA antibody response by indirect double antib...

  11. Two distinct classes of IgG Fc receptors on a human monocyte line (U937) defined by differences in binding of murine IgG subclasses at low ionic strength

    International Nuclear Information System (INIS)

    Two distinct classes of IgG Fc receptors (FcR) on cells of a human monocytic line (U937) by analyzing the direct binding of murine IgG subclasses in medium of low ionic strength. Four lines of evidence support this contention. (1) The binding of aggregated murine IgB2b (AggmIgG2b) to U937 and Daudi cells was enhanced at low ionic strength, whereas monomeric murine IgG2a (mIgG2a) did not bind to Daudi cells and its high affinity binding to U937 cells was unaffected by changes in ionic strength. (2) Double reciprocal inhibition experiments with U937 cells indicated that the binding of both ligands was inhibited 30 to 135 times more efficiently by the homologous ligand than by the heterologous one. That is, the binding of 125I-AggmIgG2b was inhibited 50% by 3.5 μg/ml of AggmIgG2b and 100 μg/ml of mIgG2a. Similarly, the binding of 125I-mIgG2a was inhibited 50% by 2.5 μg/ml of mIgG2a and only 44% by 243 μg/ml of AggmIgG2b. (3) A monoclonal antibody of the IgG2b subclass raised against an IgG FcR on K562 cells inhibited binding to U937 cells of AggmIgG2b but not of mIgG2a. (4) Trypsinization of U937 cells abrogated by 32% the binding of mIgG2a but did not affect the binding of AggmIgG2b. Human IgG inhibited binding of both AggmIgG2b and mIgG2a t U937 cells. They propose that the newly recognized FcR that binds AggmIgG2b is the human homologue of the murine macrophage IgG2b/1 FcR (FcRII), and that the previously described 72,000 dalton high-affinity FcR on U937 cells that binds mIgG2a is the human equivalent of the murine macrophage IgG2a FcR (FcRI)

  12. Detection of oligoclonal IgG kappa and IgG lambda bands in cerebrospinal fluid and serum with Hevylite™ antibodies. comparison with the free light chain oligoclonal pattern

    OpenAIRE

    Zeman David; Hradílek Pavel; Švagera Zdeněk; Mojžíšková Eva; Woznicová Ivana; Zapletalová Olga

    2012-01-01

    Abstract Background Oligoclonal IgG bands in cerebrospinal fluid that are absent in serum indicate intrathecal IgG synthesis and are a sensitive marker of CNS inflammatory diseases, in particular multiple sclerosis. It may be of interest to determine whether these bands are predominantly IgGκ or IgGλ. Methods We have used Hevylite™ antibodies and developed a technique for detection of oligoclonal IgGκ and IgGλ bands by means of isoelectric focusing followed by immunoblotting. The same techniq...

  13. Seroprevalence of hepatitis B e antigen (HBe antigen) and B core antibodies (IgG anti-HBcore and IgM anti-HBcore) among hepatitis B surface antigen positive blood donors at a Tertiary Centre in Nigeria

    OpenAIRE

    Akinbami Akinsegun A; Oshinaike Olajumoke O; Dosunmu Owolabi A; Adeyemo Titilope A; Adediran Adewumi; Akanmu Sulaiman; Wright Kikelomo O; Ilori Seun; Aile Kinsley

    2012-01-01

    Abstract Background Hepatitis B virus (HBV) is a common cause of liver disease throughout the world. HBV is transmitted through blood and other body fluids, including semen and saliva. Chronic replication of HBV virons is characterized by persistence circulation of HBsAg, HBeAg and HBV DNA; usually with anti-HBc and occasionally with anti-HBs. Aim: To determine the prevalence of HBeAg, IgG anti-HBcore and IgM anti-HBcore amongst HBsAg positive blood donors. These parameters are reflective of ...

  14. Perspective: hypothesis: serum IgG antibody is sufficient to confer protection against infectious diseases by inactivating the inoculum.

    Science.gov (United States)

    Robbins, J B; Schneerson, R; Szu, S C

    1995-06-01

    The theory proposed is that a critical level of specific serum IgG is sufficient to confer protection against infectious diseases by inactivating the inoculum of the pathogen. This theory relies heavily on evaluation of licensed vaccines and includes the following: Measurement of serum antibodies only reliably predicts the efficacy of vaccines, according to regulatory agencies. Serum IgG antibodies alone account for the protection conferred by passive immunization. "Herd" immunity conferred by vaccines on viral and bacterial diseases is best explained by serum antibodies that inactivate the inoculum on mucosal surfaces, thus reducing the pathogen's transmission. Once the disease is manifest, serum antibodies induced by active immunization will neither relieve symptoms nor eliminate the pathogen; specific IgG must be present when the host encounters the pathogen in order to confer protective immunity. Information about the initial pathogen-host contact is vital, whereas knowledge of the symptomatology of the disease may not be essential for vaccine development.

  15. Structure of full-length human anti-PD1 therapeutic IgG4 antibody pembrolizumab.

    Science.gov (United States)

    Scapin, Giovanna; Yang, Xiaoyu; Prosise, Winifred W; McCoy, Mark; Reichert, Paul; Johnston, Jennifer M; Kashi, Ramesh S; Strickland, Corey

    2015-12-01

    Immunoglobulin G4 antibodies exhibit unusual properties with important biological consequences. We report the structure of the human full-length IgG4 S228P anti-PD1 antibody pembrolizumab, solved to 2.3-Å resolution. Pembrolizumab is a compact molecule, consistent with the presence of a short hinge region. The Fc domain is glycosylated at the CH2 domain on both chains, but one CH2 domain is rotated 120° with respect to the conformation observed in all reported structures to date, and its glycan chain faces the solvent. We speculate that this new conformation is driven by the shorter hinge. The structure suggests a role for the S228P mutation in preventing the IgG4 arm exchange. In addition, this unusual Fc conformation suggests possible structural diversity between IgG subclasses and shows that use of isolated antibody fragments could mask potentially important interactions, owing to molecular flexibility.

  16. IgG4-related disease presenting as a lung mass and weight loss: Case report and review of the literature.

    Science.gov (United States)

    Grewal, Kevin; Cohen, Paul; Kwon, Jeff S; Kaufman, David A

    2016-01-01

    We describe a case of IgG4-related lung disease presenting as a lung mass with associated weight loss. IgG4-related disease is a systemic sclerosing disorder that causes fibrotic, often tumor-like manifestations that variably effect different organ systems. The clinical presentation of IgG4-related disease is protean. Timely recognition and diagnosis requires awareness on the part of clinicians and pathologists to the variable manifestations of this newly recognized disorder. We offer a concise review of the pulmonary manifestations, diagnosis and treatment of IgG4-related lung disease. PMID:27222780

  17. IgG4-related disease presenting as a lung mass and weight loss: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Kevin Grewal

    2016-01-01

    Full Text Available We describe a case of IgG4-related lung disease presenting as a lung mass with associated weight loss. IgG4-related disease is a systemic sclerosing disorder that causes fibrotic, often tumor-like manifestations that variably effect different organ systems. The clinical presentation of IgG4-related disease is protean. Timely recognition and diagnosis requires awareness on the part of clinicians and pathologists to the variable manifestations of this newly recognized disorder. We offer a concise review of the pulmonary manifestations, diagnosis and treatment of IgG4-related lung disease.

  18. Measurement of Anti-Erythropoiesis-Stimulating Agent IgG4 Antibody as an Indicator of Antibody-Mediated Pure Red Cell Aplasia

    Science.gov (United States)

    Weeraratne, Dohan K.; Kuck, Andrew J.; Chirmule, Narendra

    2013-01-01

    Patients treated with erythropoietin-based erythropoiesis-stimulating agents (ESAs) can develop a rare but life-threatening condition called antibody-mediated pure red cell aplasia (amPRCA). The antibody characteristics in a nephrology patient with amPRCA include high antibody concentrations with neutralizing activity and a mixed IgG subclass including anti-ESA IgG4 antibodies. In contrast, anti-ESA IgG4 antibody is generally not detected in baseline samples and antibody-positive non-PRCA patients. Therefore, we validated a highly sensitive immunoassay on the ImmunoCAP 100 instrument to quantitate anti-ESA IgG4 antibodies using a human recombinant anti-epoetin alfa (EPO) IgG4 antibody as a calibrator. The biotinylated ESA was applied to a streptavidin ImmunoCAP, and bound anti-ESA IgG4 antibodies were detected using a β-galactosidase-conjugated mouse anti-human IgG4 antibody. The validated assay was used to detect anti-ESA IgG4 in amPRCA and non-PRCA patients. The immunoassay detected 15 ng/ml of human anti-EPO IgG4 antibody in the presence of a 200 M excess of human anti-ESA IgG1, IgG2, or IgM antibody and tolerated 2 μg/ml of soluble erythropoietin. All patient samples with confirmed amPRCA had measurable anti-ESA IgG4 antibodies. In addition, 94% (17/18) of non-PRCA patient samples were antibody negative or had below 15 ng/ml of anti-ESA IgG4 antibodies. This novel immunoassay can measure low-nanogram quantities of human anti-ESA IgG4 antibodies in the presence of other anti-ESA antibodies. An increased concentration of anti-ESA IgG4 antibody is associated with the development of amPRCA. We propose that the measurement of anti-ESA specific IgG4 antibodies may facilitate early detection of amPRCA in patients receiving all ESAs structurally related to human erythropoietin. PMID:23114696

  19. Neutralization and purification of thyroid stimulating antibody (TSAb) and thyroid blocking antibody (TBAb) by heterophilic antibody to animal IgG in Graves' disease.

    Science.gov (United States)

    Ochi, Yukio; Kajita, Yoshihiro; Hachiya, Takashi; Hamaoki, Masaru

    2012-01-01

    There are several reports that sera from Graves' patients contain heterophilic antibody (Ab) to animal IgG such as human anti-mouse antibody (HAMA). We examined the binding of TSAb and TBAb with heterophilic Ab. The binding of animal IgG with patient's IgG was examined by the inhibition of animal IgG on the binding of labeled bovine (b) IgG with patient's IgG. The binding to labeled bIgG was detected in the serum of 5 patients (2.7 %) among 185 patients with Graves' disease. The binding of the labeled bIgG with patient's IgG was inhibited by animal serum or the crude IgG (45% ammonium sulfate fraction of serum)(such as dog, horse, bovine, porcine, goat, ovine, rabbit, guinea-pig, rat, mouse) except human, monkey and chick. This heterophilic Ab which had cross-reaction with mammalian IgG (except human, monkey) was used as human anti-animal IgG Ab. TBII and TSAb activity of TSAb-positive serum, and TBII activity of TBAb-positive serum were neutralized by incubation with this Ab-bound column. Partial purification of TSAb- or TBAb- IgG from Protein A-purified TSAb- or TBAb-IgG was possible using this Ab-bound column. TBII and TSAb activity of TSAb-IgG and TBII activity of TBAb-IgG were neutralized by incubation with rabbit anti-human (h) IgG Ab (having cross-reaction with animal IgG). Further purification of Protein A-purified TSAb-IgG or TBAb-IgG by rabbit anti-hIgG Ab-bound column was impossible. The binding of TSAb and TBAb with heterophlic Ab means that TSAb-and TBAb-specific IgG have immunological similarity with mammalian species IgG compared to human IgG. PMID:22082836

  20. Anti-aquaporin-4 IgG in patients presenting with unilateral optic neuritis: A cohort study

    Directory of Open Access Journals (Sweden)

    Masoud Etemadifar

    2012-01-01

    Full Text Available Background: Optic neuritis (ON can be the first presentation of multiple sclerosis (MS or neuromyelitis optica (NMO. Anti-aquaporin-4 IgG (AQP4 IgG is a highly specific and moderately sensitive biomarker for NMO. This study was designed to assess the rate of seropositivity for AQP4 IgG, and the short-term outcome of patients presenting with single isolated ON (SION. Methods: A cohort of 41 consecutive patients experiencing severe (< 20 / 200 SION (not fulfilling the diagnostic criteria for MS or NMO, was prospectively recruited. Blood sampling was carried out immediately after the diagnosis of ON, and AQP4 IgG was tested qualitatively, using an indirect immunofluorescence kit. After clinical and paraclinical investigations, all the patients were followed up for a short-term period of at least 18 months. Results: The seroprevalence among the initial ON patients was 9.7% (4 / 41. The short-term conversion rate to MS and NMO was estimated to be about 7.3 and 4.9%, respectively. The conversion rate to NMO in initially seropositive patients was greater than that for the whole cohort [2 / 4 (50% vs. 2 / 41 (4.9%; P = 0.035; Odds ratio: 19.5, 95% confidence interval: 1.73 to 219.50]. Conclusion: AQP4 IgG seropositive SION patients were more likely to develop NMO in comparison to the total SION population. Further studies, with a longer follow-up period and larger sample sizes are warranted to assess the clinical and prognostic value of assessing AQP4 IgG in SION.

  1. Cytomegalovirus IgG Level and Avidity in Breastfeeding Infants of HIV-Infected Mothers in Malawi

    Science.gov (United States)

    Wiener, Jeffrey; Chang, Tiffany S.; Dollard, Sheila C.; Amin, Minal M.; Ellington, Sascha; Kayira, Dumbani; van der Horst, Charles; Jamieson, Denise J.

    2015-01-01

    Cytomegalovirus (CMV) infection is common among infants of HIV-infected mothers in resource-limited settings. We examined the prevalence and timing of infant CMV infection during the first year of life using IgG antibody and avidity among HIV-exposed infants in Malawi and correlated the results with the presence of detectable CMV DNA in the blood. The Breastfeeding, Antiretrovirals and Nutrition (BAN) study randomized 2,369 mothers and their infants to maternal antiretrovirals, infant nevirapine, or neither for 28 weeks of breastfeeding, followed by weaning. Stored plasma specimens were tested for CMV IgG and antibody avidity from a random subset of infants who had been previously tested with blood CMV PCR and had available specimens at birth and at 24 and 48 weeks of age. Ninety-four of 127 infants (74.0%) tested at 24 weeks of age had CMV IgG of low or intermediate avidity, signifying primary CMV infections. An additional 22 infants (17.3%) had IgG of high avidity; 19 of them had CMV DNA detected in their blood, indicating infant infections. Taken together, these results show that the estimated prevalence of CMV infection at 24 weeks was 88.9%. By 48 weeks of age, 81.3% of infants had anti-CMV IgG; most of them (70.9%) had IgG of high avidity. The CMV serology and avidity testing, combined with the PCR results, confirmed a high rate of primary CMV infection by 6 months of life among breastfeeding infants of HIV-infected mothers. The CMV PCR in blood detected most, but not all, infant CMV infections. PMID:26424831

  2. A role for fetal hemoglobin and maternal immune IgG in infant resistance to Plasmodium falciparum malaria.

    Directory of Open Access Journals (Sweden)

    Chanaki Amaratunga

    Full Text Available BACKGROUND: In Africa, infant susceptibility to Plasmodium falciparum malaria increases substantially as fetal hemoglobin (HbF and maternal immune IgG disappear from circulation. During the first few months of life, however, resistance to malaria is evidenced by extremely low parasitemias, the absence of fever, and the almost complete lack of severe disease. This resistance has previously been attributed in part to poor parasite growth in HbF-containing red blood cells (RBCs. A specific role for maternal immune IgG in infant resistance to malaria has been hypothesized but not yet identified. METHODS AND FINDINGS: We found that P. falciparum parasites invade and develop normally in fetal (cord blood, CB RBCs, which contain up to 95% HbF. However, these parasitized CB RBCs are impaired in their binding to human microvascular endothelial cells (MVECs, monocytes, and nonparasitized RBCs--cytoadherence interactions that have been implicated in the development of high parasite densities and the symptoms of malaria. Abnormal display of the parasite's cytoadherence antigen P. falciparum erythrocyte membrane protein-1 (PfEMP-1 on CB RBCs accounts for these findings and is reminiscent of that on HbC and HbS RBCs. IgG purified from the plasma of immune Malian adults almost completely abolishes the adherence of parasitized CB RBCs to MVECs. CONCLUSIONS: Our data suggest a model of malaria protection in which HbF and maternal IgG act cooperatively to impair the cytoadherence of parasitized RBCs in the first few months of life. In highly malarious areas of Africa, an infant's contemporaneous expression of HbC or HbS and development of an immune IgG repertoire may effectively reconstitute the waning protective effects of HbF and maternal immune IgG, thereby extending the malaria resistance of infancy into early childhood.

  3. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    DEFF Research Database (Denmark)

    Gaini, Shahin

    2015-01-01

    A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode...... revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis...... and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine....

  4. C3b covalently bound to IgG demonstrates a reduced rate of inactivation by factors H and I

    OpenAIRE

    1984-01-01

    We have prepared C3b covalently linked to IgG via a hydroxylamine- sensitive bond between the C3b alpha' chain and sites predominantly, but not exclusively, located in the IgG heavy chain. This C3b species displays relative resistance to inactivation by factors H and I when compared with free C3b. This resistance appears to be due entirely to reduced affinity of C3b-IgG for factor H. Resistance to inactivation is not conferred on C3b by binding to another serum glycoprotein of similar size, c...

  5. Radioimmunoassay of serum IgE, IgG, SIgA in patients of bronchial asthma

    International Nuclear Information System (INIS)

    The contents of serum IgE, IgG, SIgA in 176 patients of bronchial asthma and 50 healthy persons are measured by RIA. The results show that the serum IgE of 112 patients (occupied 63.6%) rise obviously (P<0.01). The serum IgG of 66 patients (occupied 37.5%) is much lower than the one of healthy persons (P<0.05). The serum SIgA of 123 patients (occupied 68.9%) is much lower than the one of healthy persons (P<0.05)

  6. A simple set of validation steps identifies and removes false results in a sandwich enzyme-linked immunosorbent assay caused by anti-animal IgG antibodies in plasma from arthritis patients.

    Science.gov (United States)

    Kragstrup, Tue W; Vorup-Jensen, Thomas; Deleuran, Bent; Hvid, Malene

    2013-12-01

    Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are chronic diseases characterized by activation of the immune system and production of antibodies. Thus, rheumatoid factor, anti-animal IgG antibodies and heterophilic antibodies in plasma samples from arthritis patients can interfere with immunoassays such as sandwich enzyme-linked immunosorbent assay (ELISA) systems often used in arthritis research. However, standard methodologies on how to test for false results caused by these antibodies are lacking. The objective of this study was to design a simple set of steps to validate a sandwich ELISA before using it for measuring analytes in plasma from arthritis patients. An interleukin-24 (IL-24) sandwich ELISA system was prepared with a monoclonal mouse capture antibody and a polyclonal goat detection antibody and tested for interference by rheumatoid factor, anti-animal IgG antibodies and heterophilic antibodies. Plasma samples from 23 patients with RA and SpA were used. No differences were found between plasma samples measured in wells coated with anti-IL-24 specific antibody and in wells coated with isotype control antibody (false positive results), and recombinant human IL-24 was not recovered in spiked samples (false negative results). This interference was removed after preincubating the plasma samples from patients with arthritis with goat or bovine IgG, suggesting that anti-animal IgG antibodies found in the plasma of the arthritis patients caused the false results. Additional testing showed that the signal-to-noise ratio could be increased by titration of the capture and detection antibodies and by using the ELAST amplification system. Finally, the calculated concentration of IL-24 was increased in ethylenediaminetetraacetic acid (EDTA) plasma compared to heparin plasma and serum and decreased with repetitive freeze/thaw cycles of the samples illustrating how sample handling could additionally contribute to the variations reported by different

  7. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children

    Science.gov (United States)

    Chong, Sze Yee; Coleman, Lee; MacGregor, Duncan; Hardikar, Winita; Oliver, Mark R.

    2016-01-01

    We report 3 children who presented with fever and abdominal pain, deranged liver function tests, and on abdominal ultrasound were found to have an enlarged pancreas, substantial abdominal lymphadenopathy, and extrahepatic biliary duct dilatation. After ruling out malignancy, probable immunoglobulin G4-related disease (IgG4RD) associated with autoimmune pancreatitis was considered. This condition was first described in the adults and often mimics pancreatic cancer. It can involve multiple organs, either synchronously or metachronously, and is rarely reported in children. The disorder mostly responds to corticosteroid therapy and other immune suppression. We highlight the difficulty in diagnosing autoimmune pancreatitis/IgG4-related disease in children and illustrate the difference between pediatric and adult presentation. PMID:27622194

  8. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children.

    Science.gov (United States)

    Bolia, Rishi; Chong, Sze Yee; Coleman, Lee; MacGregor, Duncan; Hardikar, Winita; Oliver, Mark R

    2016-07-01

    We report 3 children who presented with fever and abdominal pain, deranged liver function tests, and on abdominal ultrasound were found to have an enlarged pancreas, substantial abdominal lymphadenopathy, and extrahepatic biliary duct dilatation. After ruling out malignancy, probable immunoglobulin G4-related disease (IgG4RD) associated with autoimmune pancreatitis was considered. This condition was first described in the adults and often mimics pancreatic cancer. It can involve multiple organs, either synchronously or metachronously, and is rarely reported in children. The disorder mostly responds to corticosteroid therapy and other immune suppression. We highlight the difficulty in diagnosing autoimmune pancreatitis/IgG4-related disease in children and illustrate the difference between pediatric and adult presentation. PMID:27622194

  9. Strong antitumor activities of IgG3 antibodies to a human melanoma-associated ganglioside

    Energy Technology Data Exchange (ETDEWEB)

    Hellstroem, I.; Brankovan, V.; Hellstroem, K.E.

    1985-03-01

    Three mouse monoclonal IgG3 antibodies, 2B2, IF4, and MG-21, recognize a G/sub D3/ ganglioside antigen that is expressed at the cell surface of most human melanomas. All three antibodies mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro when tested with human lymphocytes or effector cells in a 2-hr or 4-hr /sup 51/Cr-release test, and one antibody, MG-21, also gives strong complement-dependent cytotoxicity with human serum. Antibody 2B2, which gives ADDC also in the presence of mouse lymphocytes, inhibited the outgrowth of a human melanoma in nude mice, but antibody IF4, which showed no ADCC with mouse lymphocyte effectors, did not.

  10. Magnetic enzyme-linked immunosorbent assay (MELISA) for determination of specific IgG in paracoccidioidomycosis.

    Science.gov (United States)

    de Camargo, Z P; Guesdon, J L; Drouhet, E; Improvisi, L

    1984-01-01

    A magnetic solid phase enzyme-linked immunosorbent assay (MELISA) for quantification of IgG antibodies to somatic and metabolic antigens of Paracoccidioides brasiliensis was developed. Activation of magnetic polyacrylamide agarose beads with concanavalin A was superior to glutaraldehyde activation, and test sensitivity was higher for somatic than for metabolic antigens. Comparative MELISA, counterimmunoelectrophoresis and erythroimmunoassay tests with sera from 33 proven cases of paracoccidioidomycosis, 14 cases of histoplasmosis and 20 normal human sera showed the MELISA could distinguish antibody levels in paracoccidioidomycosis from those in normal sera; however two sera from histoplasmosis cases cross-reacted in the MELISA. MELISA is a rapid test (5-6 h) and the results suggest it has considerable potential value for assay of anti-P. brasiliensis antibodies. PMID:6438813

  11. Human anti-rhesus D IgG1 antibody produced in transgenic plants

    DEFF Research Database (Denmark)

    Bouquin, Thomas; Thomsen, Mads; Nielsen, Leif Kofoed;

    2002-01-01

    antigen, which is responsible for alloimmunization of RhD- mothers carrying an RhD+ fetus. Anti-RhD extracted from plants specifically reacted with RhD+ cells in antiglobulin technique, and elicited a respiratory burst in human peripheral blood mononuclear cells. Plant-derived antibody had equivalent......Transgenic plants represent an alternative to cell culture systems for producing cheap and safe antibodies for diagnostic and therapeutic use. To evaluate the functional properties of a 'plantibody', we generated transgenic Arabidopsis plants expressing full-length human IgG1 against the Rhesus D...... properties to CHO cell-produced anti-RhD antibody, indicating its potential usefulness in diagnostic and therapeutic programs....

  12. Oral lichen sclerosus expressing extracellular matrix proteins and IgG4-positive plasma cells.

    Science.gov (United States)

    De Aquino Xavier, Flavia Calo; Prates, Alisio Alves; Gurgel, Clarissa Araujo; De Souza, Tulio Geraldo; Andrade, Rodrigo Guimaraes; Goncalves Ramos, Eduardo Antonio; Pedreira Ramalho, Luciana Maria; Dos Santos, Jean Nunes

    2014-09-16

    Lichen sclerosus (LS) is a mucocutaneous disease with uncommon oral involvement. The etiology is not yet well understood, but LS has been associated with autoimmune, genetic, and immunological factors. We report a 47-year-old man with LS that exhibited an asymptomatic white plaque with red patches on the maxillary alveolar mucosa extending to the labial mucosa. He had no other skin disease. Positive immunostaining for tenascin and scarcity of fibronectin suggested extracellular matrix reorganization. Elastin immunostaining indicated a reduction of elastic fibers. Immunoexpression of collagen IV in blood vessels and its absence in the epithelial basement membrane, together with diffuse MMP-9 immunoexpression, suggested altered proteolytic activity. Mast cell staining bordering areas of sclerosis indicated a possible role in the synthesis of collagen. IgG4 positivity in plasma cells suggested a role in the fibrogenesis. This is an unusual presentation of oral LS and we discuss immunohistochemical findings regarding cellular and extracellular matrix components.

  13. Serum Immunoglobulin Free Light Chain Assessment in IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Aurélie Grados

    2013-01-01

    Full Text Available Immunoglobulin free light chains are produced in excess during normal antibody synthesis. Their evaluation is commonly used in case of a monoclonal gammopathy. In polyclonal hypergammaglobulinemia related to the Sjögren syndrome or systemic lupus, erythematosus serum free light chain levels are increased and could correlate with disease activity. We show here that the κ ( and λ ( free light chains and the κ : λ ratio ( are increased in sixteen patients with IgG4-related disease when compared to healthy controls. The increase of κ and λ free light chains probably reflects the marked polyclonal B cell activation of the disease. We could not assess in this small cohort of patients a significative correlation of serum free light chain levels and disease activity or extension.

  14. IgG antibodies to dengue in dry blood samples in filter paper.

    Directory of Open Access Journals (Sweden)

    Carmen Acosta

    2003-01-01

    Full Text Available En este trabajo se presentan los resultados de la normalización del procedimiento de detección de anticuerpos IgG contra el virus dengue en muestras de sangre colectadas sobre papel de filtro. Las muestras se obtuvieron de 216 individuos que acudieron al banco de sangre de Marianao de los cuales 25 presentaron resultados con títulos superiores a 1:40 por la técnica de Inhibición de la Hemaglutinación. En todas las muestras se determinó la presencia de anticuerpos IgG contra el virus dengue mediante un inmunoensayo enzimático (UMELISA de captura. Cuando se compararon las condiciones de elución de treinta minutos y una hora la coincidencia fue del 93 y 100 % respectivamente. En las dos condiciones evaluadas en el paso de la incubación de las muestras en la placa de reacción; una hora a 37 ºC y una hora a temperatura ambiente; la coincidencia fue del 100 %, manteniendo este paso igual para el procesamiento de muestras de sangre colectadas sobre papel de filtro como las de suero (una hora a 37 ºC. Al analizarse en su conjunto los resultados de las muestras se obtuvo una sensibilidad y especificidad del 100 % en los tiempos ensayados, para la prueba efectuada con sangre total colectada sobre papel de filtro conservada a 4 ºC y las conservadas a temperatura ambiente. Los autores recomiendan la utilización de este método para la detección de anticuerpos anti dengue.

  15. The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria

    Science.gov (United States)

    Weaver, Rupert; Reiling, Linda; Feng, Gaoqian; Drew, Damien R.; Mueller, Ivo; Siba, Peter M.; Tsuboi, Takafumi; Richards, Jack S.; Fowkes, Freya J. I.; Beeson, James G.

    2016-01-01

    Understanding the targets and mechanisms of human immunity to malaria is important for advancing the development of highly efficacious vaccines and serological tools for malaria surveillance. The PfRH5 and PfRipr proteins form a complex on the surface of P. falciparum merozoites that is essential for invasion of erythrocytes and are vaccine candidates. We determined IgG subclass responses to these proteins among malaria-exposed individuals in Papua New Guinea and their association with protection from malaria in a longitudinal cohort of children. Cytophilic subclasses, IgG1 and IgG3, were predominant with limited IgG2 and IgG4, and IgG subclass-specific responses were higher in older children and those with active infection. High IgG3 to PfRH5 and PfRipr were significantly and strongly associated with reduced risk of malaria after adjusting for potential confounding factors, whereas associations for IgG1 responses were generally weaker and not statistically significant. Results further indicated that malaria exposure leads to the co-acquisition of IgG1 and IgG3 to PfRH5 and PfRipr, as well as to other PfRH invasion ligands, PfRH2 and PfRH4. These findings suggest that IgG3 responses to PfRH5 and PfRipr may play a significant role in mediating naturally-acquired immunity and support their potential as vaccine candidates and their use as antibody biomarkers of immunity. PMID:27604417

  16. The role of IgG subclass of mouse monoclonal antibodies in antibody-dependent enhancement of feline infectious peritonitis virus infection of feline macrophages.

    Science.gov (United States)

    Hohdatsu, T; Tokunaga, J; Koyama, H

    1994-01-01

    Antibody-dependent enhancement (ADE) of feline infectious peritonitis virus (FIPV) infection was studied in feline alveolar macrophages and human monocyte cell line U937 using mouse neutralizing monoclonal antibodies (MAbs) directed to the spike protein of FIPV. Even among the MAbs that have been shown to recognize the same antigenic site, IgG 2a MAbs enhanced FIPV infection strongly, whereas IgG 1 MAbs did not. These IgG 2a MAbs enhanced the infection even when macrophages pretreated with the MAb were washed and then inoculated with the virus. Immunofluorescence flow cytometric analysis of the macrophages treated with each of the MAbs showed that the IgG 2a MAbs but not the IgG 1 MAbs bound to feline alveolar macrophages. Treatment of the IgG 2a MAb with protein A decreased the binding to the macrophages and, in parallel, diminished the ADE activity. Although no infection was observed by inoculation of FIPV to human monocyte cell line U937 cells, FIPV complexed with either the IgG 2a MAb or the IgG 1 MAb caused infection in U937 cells which are shown to express Fc gamma receptor (Fc gamma R) I and II that can bind mouse IgG 2a and IgG 1, respectively. These results suggest that the enhancing activity of MAb is closely correlated with IgG subclass and that the correlation is involved in binding of MAb to Fc gamma R on feline macrophage.

  17. The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria.

    Science.gov (United States)

    Weaver, Rupert; Reiling, Linda; Feng, Gaoqian; Drew, Damien R; Mueller, Ivo; Siba, Peter M; Tsuboi, Takafumi; Richards, Jack S; Fowkes, Freya J I; Beeson, James G

    2016-01-01

    Understanding the targets and mechanisms of human immunity to malaria is important for advancing the development of highly efficacious vaccines and serological tools for malaria surveillance. The PfRH5 and PfRipr proteins form a complex on the surface of P. falciparum merozoites that is essential for invasion of erythrocytes and are vaccine candidates. We determined IgG subclass responses to these proteins among malaria-exposed individuals in Papua New Guinea and their association with protection from malaria in a longitudinal cohort of children. Cytophilic subclasses, IgG1 and IgG3, were predominant with limited IgG2 and IgG4, and IgG subclass-specific responses were higher in older children and those with active infection. High IgG3 to PfRH5 and PfRipr were significantly and strongly associated with reduced risk of malaria after adjusting for potential confounding factors, whereas associations for IgG1 responses were generally weaker and not statistically significant. Results further indicated that malaria exposure leads to the co-acquisition of IgG1 and IgG3 to PfRH5 and PfRipr, as well as to other PfRH invasion ligands, PfRH2 and PfRH4. These findings suggest that IgG3 responses to PfRH5 and PfRipr may play a significant role in mediating naturally-acquired immunity and support their potential as vaccine candidates and their use as antibody biomarkers of immunity. PMID:27604417

  18. Effector functions of a monoclonal aglycosylated mouse IgG2a: binding and activation of complement component C1 and interaction with human monocyte Fc receptor.

    Science.gov (United States)

    Leatherbarrow, R J; Rademacher, T W; Dwek, R A; Woof, J M; Clark, A; Burton, D R; Richardson, N; Feinstein, A

    1985-04-01

    Aglycosylated monoclonal anti-DNP mouse IgG2a produced in the presence of tunicamycin was compared with the native monoclonal IgG2a with respect to its ability to interact with the first component of complement, C1, and to compete with human IgG for binding to human monocyte Fc receptors. The aglycosylated IgG2a was found to bind subcomponent C1q with an equivalent capacity to the native IgG2a, but the dissociation constant was found to be increased three-fold. When activation of C1 by the glycosylated and aglycosylated IgG2a was compared, the rate of C1 activation by the aglycosylated IgG2a was reduced approximately three-fold. In contrast aglycosylation was accompanied by a large decrease (greater than or equal to 50-fold) in the apparent binding constant of monomeric IgG2a to human monocytes. The data suggest that the aglycosylated IgG2a has a structure which differs in the CH2 domain from the native IgG2a, and that the heterogeneous N-linked oligosaccharides of this monoclonal IgG2a which occur at a conserved position in the CH2 domain play a role in maintaining the integrity of its monocyte-binding site. This lack of monocyte binding may result either from a localized conformational change occurring in a single CH2 domain or from an alteration in the CH2-CH2 cross-domain architecture which is normally structured by a pair of opposing and interacting oligosaccharides. The minimal changes in C1q binding and C1 activation suggest that the oligosaccharides are, at most, indirectly involved in these events. PMID:4033665

  19. Local IgG synthesis in three pediatric patients with cuban epidemic neuropathy Sintesis local de IgG en tres pacientes pediátricos com neuropatía epidêmica cubana

    Directory of Open Access Journals (Sweden)

    Alberto Dorta-Contreras

    1996-03-01

    Full Text Available Three pediatric patients with Cuban epidemic neuropathy were studied. Cerebrospinal fluid and sera were simultaneously obtained. Albumin and IgG were quantified by immunodifusion. Albumin quotient and local synthesis of IgG were calculated by Reiber/Felgenhauer formula. A patient with optic neuritis had a dysfunction of the blood-cerebrospinal fluid barrier. All the group had local synthesis of IgG.Se estudiaron tres pacientes pediátricos con neuropatia epidêmica cubana. Se obtuvieron suero y liquido cefalorraquídeo simultaneamente. Se cuantificaran los niveles de albúmina e IgG por inmunodifusion radial. Se calculo la razón albúmina y la fórmula de Reiber/Felgenhauer. Un paciente con neuritis óptica tuvo una disfunción de la barrera sangre-líquido cefaloraquídeo. Todo el grupo tuvo síntesis local de IgG.

  20. The Immunoglobulin (IgG) Antibody Response to OspA and OspB Correlates with Severe and Prolonged Lyme Arthritis and the IgG Response to P35 Correlates with Mild and Brief Arthritis

    Science.gov (United States)

    Akin, Evren; McHugh, Gail L.; Flavell, Richard A.; Fikrig, Erol; Steere, Allen C.

    1999-01-01

    In an effort to implicate immune responses to specific Borrelia burgdorferi proteins that may have a role in chronic Lyme arthritis, we studied the natural history of the antibody response to B. burgdorferi in serial serum samples from 25 patients monitored throughout the course of Lyme disease. In these patients, the immunoglobulin G (IgM) and IgG antibody responses to 10 recombinant B. burgdorferi proteins, determined during early infection, early arthritis, and maximal arthritis, were correlated with the severity and duration of maximal arthritis. The earliest responses were usually to outer surface protein C (OspC), P35, P37, and P41; reactivity with OspE, OspF, P39, and P93 often developed weeks later; and months to years later, 64% of patients had responses to OspA and OspB. During early infection and early arthritis, the levels of IgG antibody to P35 correlated inversely with the subsequent severity or duration of maximal arthritis. In contrast, during periods of maximal arthritis, the levels of IgG antibody to OspA and OspB, especially to a C-terminal epitope of OspA, correlated directly with the severity and duration of arthritis. Thus, the higher the IgG antibody response to P35 earlier in the infection, the milder and briefer the subsequent arthritis, whereas during maximal arthritis, the higher the IgG response to OspA and OspB, the more severe and prolonged the arthritis. PMID:9864212

  1. Immune status of health care workers to measles virus: evaluation of protective titers in four measles IgG EIAs

    NARCIS (Netherlands)

    Dorigo-Zetsma, J.W.; Hall, M.A.; Vreeswijk, J.; Vries, J.J. de; Vossen, A.C.; Hulscher, H.I. Ten; Kerkhof, J.; Smits, G.P.; Ruijs, W.L.M.; Koopmans, M.P.; Binnendijk, R.S. van

    2015-01-01

    BACKGROUND: Following the recognition of a measles case in a hospital in The Netherlands, health care workers (HCW) from the premises were screened by a commercial enzyme immunoassay (EIA) for measles IgG to identify persons at risk for measles. At least 10% of the HCW were tested measles IgG-negati

  2. Is immunotherapy-induced birch-pollen-specific IgG4 a marker for decreased allergen-specific sensitivity?

    DEFF Research Database (Denmark)

    Bodtger, U; Ejrnaes, A M; Hummelshoj, L;

    2005-01-01

    The role of IgG4 during allergen-specific immunotherapy (SIT) is still controversial. The available studies present paramount differences in in vitro techniques, allergens, and clinical outcome parameters. By implementing a sensitive method, and pivotal clinical outcome parameters, we wanted to...

  3. Snake venomics of monocled cobra (Naja kaouthia) and investigation of human IgG response against venom toxins

    DEFF Research Database (Denmark)

    Laustsen, Andreas Hougaard; Gutiérrez, José María; Lohse, Brian;

    2015-01-01

    /cardiotoxins. IgGs isolated from a person who had repeatedly self-immunized with a variety of snake venoms were immunoprofiled by ELISA against all venom fractions. Stronger responses against larger toxins, but lower against the most critical α-neurotoxins were obtained. As expected, no neutralization potential...

  4. Continuous milking of dairy cows disrupts timing of peak IgG concentration appearance in mammary secretions

    NARCIS (Netherlands)

    Baumrucker, C.R.; Zbinden, R.S.; Dorland, van H.A.; Remmelink, G.J.; Kemp, B.; Knegsel, van A.T.M.; Bruckmaier, R.M.

    2014-01-01

    The length of the dry period in commercial dairy production is under close scrutiny. While the main concern is the composition and volume of milk produced, the evaluation of colostrum quality under these new paradigms has suggested a decline in IgG concentrations, while some reports indicate no chan

  5. Association of serum immunoglobulin G (IgG) levels against two periodontal pathogens and prothrombotic state: a clinical pilot study

    NARCIS (Netherlands)

    S. Bizzarro; E.A. Nicu; U. van der Velden; M.L. Laine; B.G. Loos

    2010-01-01

    Objective: Periodontitis is associated with cardiovascular diseases (CVD). In our previous studies a prothrombotic state has been observed in periodontitis, which contributes to the risk of CVD. The aim of this study was to investigate whether serum IgG levels against Aggregatibacter actinomycetemco

  6. Glycoprofiling effects of media additives on IgG produced by CHO cells in fed-batch bioreactors

    DEFF Research Database (Denmark)

    Kildegaard, Helene Faustrup; Fan, Yuzhou; Wagtberg Sen, Jette;

    2016-01-01

    . In this study, the effect on IgG N-glycosylation from feeding CHO cells with eight glycosylation precursors during cultivation was investigated. The study was conducted in fed-batch mode in bioreactors with biological replicates to obtain highly controlled and comparable conditions. We assessed charge...

  7. IgG subclasses of anti-FVIII antibodies during immune tolerance induction in patients with hemophilia A

    NARCIS (Netherlands)

    van Helden, Pauline M. W.; van den Berg, H. Marijke; Gouw, Samantha C.; Kaijen, Paul H. P.; Zuurveld, Marleen G.; Mauser-Bunschoten, Evelien P.; Aalberse, Rob C.; Vidarsson, Gestur; Voorberg, Jan

    2008-01-01

    The eradication of inhibitory antibodies in patients with haemophilia A can be accomplished by frequent administration of high or intermediate doses of factor VIII (FVIII), so-called immune tolerance induction (ITI). This study monitored the distribution of IgG subclasses of anti-FVIII antibodies du

  8. Increased blood levels of IgG reactive with secreted Streptococcus pyogenes proteins in chronic plaque psoriasis.

    Science.gov (United States)

    El-Rachkidy, Rana G; Hales, Jonathan M; Freestone, Primrose P E; Young, Helen S; Griffiths, Christopher E M; Camp, Richard D R

    2007-06-01

    A pathogenic role for Streptococcus (S) pyogenes infections in chronic plaque psoriasis is suspected but poorly defined. We separated cellular and supernatant proteins from S. pyogenes cultures by high-resolution two-dimensional gel electrophoresis, and used immunoblotting to demonstrate the diversity of serum or plasma IgGs that react with elements of the proteome of this bacterium. We have shown that a substantial proportion of IgG-reactive proteins from cultured S. pyogenes are secreted. The total secreted protein fraction, including diverse IgG-binding elements, was subsequently used in an ELISA to measure blood titers of reactive IgG. This ELISA showed that blood samples from patients with chronic plaque psoriasis contained significantly higher titers of reactive IgG than samples from age- and sex-matched healthy controls (P=0.0009). In contrast, neither a standard assay measuring antistreptolysin O titers nor ELISAs measuring titers of IgG reactive with protein fractions from Staphylococcus aureus and Staphylococcus epidermidis, were able to distinguish between blood samples from the two groups. These findings justify the hypothesis that S. pyogenes infections are more important in the pathogenesis of chronic plaque psoriasis than has previously been recognized, and indicate the need for further controlled therapeutic trials of antibacterial measures in this common skin disease.

  9. Evaluation of the PANBIO Brucella Immunoglobulin G (IgG) and IgM Enzyme-Linked Immunosorbent Assays for Diagnosis of Human Brucellosis

    OpenAIRE

    Araj, George F.; Kattar, Mireille M.; Fattouh, Layla G.; Bajakian, Kayane O.; Kobeissi, Sara A.

    2005-01-01

    PANBIO Brucella immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays (ELISAs) were assessed against Brucella standard agglutination tube and Coombs tests. The sensitivities of ELISA IgG and IgM were 91% and 100%, respectively, while the specificity was 100% for both. These ELISAs are simple, rapid, and reliable for the diagnosis of human brucellosis.

  10. IgG antibodies in food allergy influence allergen-antibody complex formation and binding to B cells: a role for complement receptors

    NARCIS (Netherlands)

    Meulenbroek, L.A.; Jong, R.J.; Hartog Jager, den C.F.; Monsuur, H.N.; Wouters, D.; Nauta, A.; Knippels, L.M.; Neerven, van R.J.J.; Ruiter, B.; Leusen, J.H.; Hack, C.E.; Bruijnzeel-Koomen, C.A.; Knulst, A.C.; Garssen, J.; Hoffen, van E.

    2013-01-01

    Allergen-IgE complexes are more efficiently internalized and presented by B cells than allergens alone. It has been suggested that IgG Abs induced by immunotherapy inhibit these processes. Food-allergic patients have high allergen-specific IgG levels. However, the role of these Abs in complex format

  11. Comprehensive Analysis of the Therapeutic IgG4 Antibody Pembrolizumab: Hinge Modification Blocks Half Molecule Exchange In Vitro and In Vivo.

    Science.gov (United States)

    Yang, Xiaoyu; Wang, Fengqiang; Zhang, Ying; Wang, Larry; Antonenko, Svetlana; Zhang, Shuli; Zhang, Yi Wei; Tabrizifard, Mohammad; Ermakov, Grigori; Wiswell, Derek; Beaumont, Maribel; Liu, Liming; Richardson, Daisy; Shameem, Mohammed; Ambrogelly, Alexandre

    2015-12-01

    IgG4 antibodies are evolving as an important class of cancer immunotherapies. However, human IgG4 can undergo Fab arm (half molecule) exchange with other IgG4 molecules in vivo. The hinge modification by a point mutation (S228P) prevents half molecule exchange of IgG4. However, the experimental confirmation is still expected by regulatory agencies. Here, we report for the first time the extensive analysis of half molecule exchange for a hinge-modified therapeutic IgG4 molecule, pembrolizumab (Keytruda) targeting programmed death 1 (PD1) receptor that was approved for advanced melanoma. Studies were performed in buffer or human serum using multiple exchange partners including natalizumab (Tysabri) and human IgG4 pool. Formation of bispecific antibodies was monitored by fluorescence resonance energy transfer, exchange with Fc fragments, mixed mode chromatography, immunoassays, and liquid chromatography-mass spectrometry. The half molecule exchange was also examined in vivo in SCID (severe combined immunodeficiency) mice. Both in vitro and in vivo results indicate that the hinge modification in pembrolizumab prevented half molecule exchange, whereas the unmodified counterpart anti-PD1 wt showed active exchange activity with other IgG4 antibodies or self-exchange activity with its own molecules. Our work, as an example expected for meeting regulatory requirements, contributes to establish without ambiguity that hinge-modified IgG4 antibodies are suitable for biotherapeutic applications.

  12. Neuron-derived IgG protects dopaminergic neurons from insult by 6-OHDA and activates microglia through the FcγR I and TLR4 pathways.

    Science.gov (United States)

    Zhang, Jie; Niu, Na; Wang, Mingyu; McNutt, Michael A; Zhang, Donghong; Zhang, Baogang; Lu, Shijun; Liu, Yuqing; Liu, Zhihui

    2013-08-01

    Oxidative and immune attacks from the environment or microglia have been implicated in the loss of dopaminergic neurons of Parkinson's disease. The role of IgG which is an important immunologic molecule in the process of Parkinson's disease has been unclear. Evidence suggests that IgG can be produced by neurons in addition to its traditionally recognized source B lymphocytes, but its function in neurons is poorly understood. In this study, extensive expression of neuron-derived IgG was demonstrated in dopaminergic neurons of human and rat mesencephalon. With an in vitro Parkinson's disease model, we found that neuron-derived IgG can improve the survival and reduce apoptosis of dopaminergic neurons induced by 6-hydroxydopamine toxicity, and also depress the release of NO from microglia triggered by 6-hydroxydopamine. Expression of TNF-α and IL-10 in microglia was elevated to protective levels by neuron-derived IgG at a physiologic level via the FcγR I and TLR4 pathways and microglial activation could be attenuated by IgG blocking. All these data suggested that neuron-derived IgG may exert a self-protective function by activating microglia properly, and IgG may be involved in maintaining immunity homeostasis in the central nervous system and serve as an active factor under pathological conditions such as Parkinson's disease.

  13. Simultaneous use of serum IgG and IgM for risk scoring of suspected early Lyme borreliosis: graphical and bivariate analyses

    DEFF Research Database (Denmark)

    Dessau, Ram B; Ejlertsen, Tove; Hilden, Jørgen

    2010-01-01

    The laboratory diagnosis of early disseminated Lyme borreliosis (LB) rests on IgM and IgG antibodies in serum. The purpose of this study was to refine the statistical interpretation of IgM and IgG by combining the diagnostic evidence provided by the two immunoglobulins and exploiting the whole...

  14. Association of Helicobacter pylori IgG antibody with various demographic and biochemical parameters in kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Azar Baradaran

    2011-01-01

    Full Text Available Few reports are available regarding the promoting factors that affect Helicobacter pylori (H. pylori infection in renal transplant (RTx patients. We report a cross-sectional study that was conducted on a group of stable RTx patients to investigate the relationship of various demographic and biochemical parameters of these patients with serum H. pylori IgG antibody titer as a sign of H. pylori infection. A total of 72 patients who were referred to the clinic for continuing their treatment were enrolled in this study. These patients included 47 males and 25 females. The mean age of the study patients was 44 (±12 years. The mean length of time after they received a transplanted kidney was 67.5 (±42 months (median: 62 months. The mean value of serum H. pylori-specific IgG antibody titer among these patients was 3 (±4.6 U/mL (median: 1 U/mL, and that of intact parathormone (iPTH was 18.4 (±8.2 pg/mL (median: 16.5 pg/mL. The mean serum magnesium (Mg was 1.9 (±0.20 mg/dL (median: 1.9 mg/dL and the mean creatinine clearance was 53 (±11 mL/min (median: 56 mL/min. In this study population, there was no significant difference in the H. pylori IgG antibody titers, serum iPTH, Mg, calcium, alkaline phosphatase and albumin levels as well as body mass index (BMI between males and females or diabetics and non-diabetics. There was no significant relationship between serum H. pylori IgG antibody titers and the age of the patients, BMI, serum Alb, phosphorus, Ca, serum leptin and serum ALP. Significant negative correlation between serum H. pylori IgG antibody titers and serum Mg (r = -0.30, P = 0.01 and serum iPTH (r = -0.25, P = 0.03 was seen. A significant positive correlation was found between serum H. pylori IgG antibody titer and creatinine clearance (r = 0.26, P = 0.02, and a near-significant positive correlation was found with the duration of RTx (r = 0.20, P = 0.08. Our study shows that the correlation of H. pylori IgG antibody titer with some

  15. ROLE OF PREEXISTING VIRUS-SPECIFIC IgG IN PRIMARY DISEASE AND IN REINFECTION WITH RESPIRATORY SYNCYTIAL VIRUS

    Directory of Open Access Journals (Sweden)

    V. Z. Krivitskaya

    2012-01-01

    Full Text Available Abstract. The aim of the study is evaluation of links between presence in blood of specific pre-existing IgG to respiratory-syncytial virus (RSV, clinical course of RSV infection and character specific to RSV humoral immune response in patients of different ages. The antibodies were detected by ELISA using whole RS virus or synthetic peptides corresponded to the selected determinants of the envelope RSV proteins. It was shown that RS specific maternal IgG antibodies passively transferred to babies in utero can circulate in the blood up to 10 months of life. The analysis of paired sera of 45 babies in the age of 1–10 months revealed firstly that presence of maternal IgG specific antibodies to the conservative B-cell immunogenic determinants of the F-protein (amino acids 221–232 and/or the G-protein (amino acids 152–164 and 184–198 is coupled with more high morbidity of primary RSV infection (89% versus 56%, p = 0.023, and also with more high frequency of complicated by bronchus obstruction course of the disease (81% versus 20%, р = 0.001 in compare with babies who were serologically negative to the maternal determinants specific antibodies. The correlation analysis has shown that the high presence of maternal determinant-specific IgG in the blood in babies till 10 months of life is associated in the case of primary infection with disbalance of humoral anti-viral immune response: intensive synthesis of serum RSV IgA. This is evidence of complicated course of infection with simultaneous suppression of response to RSV specific IgG. As opposed to the primary RSV infection in patients older than 3 years (n = 121 it was not detected links between anamnestic determinant-specific IgG synthesized by own immune system as the results of previous disease episodes and synthesis of anti-RSV IgG, IgM, IgE and IgA in RSV re-infections. In the contrast to babies in more older patients the feedback connection between level of pre-existing determinant

  16. Enterococcus faecalis endocarditis severity in rabbits is reduced by IgG Fabs interfering with aggregation substance.

    Directory of Open Access Journals (Sweden)

    Patrick M Schlievert

    Full Text Available BACKGROUND: Enterococcus faecalis is a significant cause of infective endocarditis, an infection of the heart endothelium leading to vegetation formation (microbes, fibrin, platelets, and host cells attached to underlying endothelial tissue. Our previous research determined that enterococcal aggregation substance (AS is an important virulence factor in causation of endocarditis, although endocarditis may occur in the absence of AS production. Production of AS by E. faecalis causes the organism to form aggregates through AS binding to enterococcal binding substance. In this study, we assessed the ability of IgGs and IgG Fabs against AS to provide protection against AS+ E. faecalis endocarditis. METHODOLOGY/PRINCIPAL FINDINGS: When challenged with AS+ E. faecalis, 10 rabbits actively immunized against AS+ E. faecalis developed more significant vegetations than 9 animals immunized against AS⁻E. faecalis, and 9/10 succumbed compared to 2/9 (p<0.005, suggesting enhanced aggregation by IgG contributes significantly to disease. IgG antibodies against AS also enhanced enterococcal aggregation as tested in vitro. In contrast, Fab fragments of IgG from rabbits immunized against purified AS, when passively administered to rabbits (6/group immediately before challenge with AS+E. faecalis, reduced total vegetation (endocarditis lesion microbial counts (7.9 x 10⁶ versus 2.0 x 10⁵, p = 0.02 and size (40 mg versus 10, p = 0.05. In vitro, the Fabs prevented enterococcal aggregation. CONCLUSIONS/SIGNIFICANCE: The data confirm the role of AS in infective endocarditis formation and suggest that use of Fabs against AS will provide partial protection from AS+E. faecalis illness.

  17. Enhanced FcRn-dependent transepithelial delivery of IgG by Fc-engineering and polymerization.

    Science.gov (United States)

    Foss, Stian; Grevys, Algirdas; Sand, Kine Marita Knudsen; Bern, Malin; Blundell, Pat; Michaelsen, Terje E; Pleass, Richard J; Sandlie, Inger; Andersen, Jan Terje

    2016-02-10

    Monoclonal IgG antibodies (Abs) are used extensively in the clinic to treat cancer and autoimmune diseases. In addition, therapeutic proteins are genetically fused to the constant Fc part of IgG. In both cases, the Fc secures a long serum half-life and favourable pharmacokinetics due to its pH-dependent interaction with the neonatal Fc receptor (FcRn). FcRn also mediates transport of intact IgG across polarized epithelial barriers, a pathway that is attractive for delivery of Fc-containing therapeutics. So far, no study has thoroughly compared side-by-side how IgG and different Fc-fusion formats are transported across human polarizing epithelial cells. Here, we used an in vitro cellular transport assay based on the human polarizing epithelial cell line (T84) in which both IgG1 and Fc-fusions were transported in an FcRn-dependent manner. Furthermore, we found that the efficacy of transport was dependent on the format. We demonstrate that transepithelial delivery could be enhanced by Fc-engineering for improved FcRn binding as well as by Fc-polymerization. In both cases, transport was driven by pH-dependent binding kinetics and the pH at the luminal side. Hence, efficient transcellular delivery of IgG-based drugs across human epithelial cells requires optimal pH-dependent FcRn binding that can be manipulated by avidity and Fc-engineering, factors that should inspire the design of future therapeutics targeted for transmucosal delivery. PMID:26718855

  18. [Hypertrophic pachymeningitis secondary to IgG4-related disease: case report and review of the literature].

    Science.gov (United States)

    Rodríguez-Castro, Emilio; Fernández-Lebrero, Aida; López-Dequidt, Iria A; Rodríguez-Osorio, Xiana; López-González, Francisco J; Suárez-Peñaranda, José M; Arias, Manuel

    2015-10-01

    Introduccion. La paquimeningitis hipertrofica es un trastorno infrecuente que produce un engrosamiento focal o difuso de la duramadre. Puede ser idiopatica o secundaria a procesos infecciosos, autoinmunes o neoplasicos. La recientemente descrita 'enfermedad relacionada con IgG4' podria ser la causa de bastantes cuadros considerados criptogenicos. Caso clinico. Mujer de 54 años, con historia de asma bronquial, que consulto por cefalea, vertigo y perdida de audicion por su oido izquierdo. En la resonancia magnetica cerebral con gadolinio se objetivo engrosamiento y realce dural, que se extendia desde la pared lateral del seno cavernoso izquierdo y la parte medial del lobulo temporal al angulo pontocerebeloso y parte del tentorio homolaterales. El liquido cefalorraquideo presentaba 10 leucocitos/µL (90% mononucleares), con 1 g/L de proteinas y sin consumo de glucosa. El estudio anatomopatologico mostro fibrosis y un infiltrado linfoplasmocitario, con 16 celulas plasmaticas IgG4+ por campo de gran aumento. El resto de estudios analiticos y microbiologicos resultaron normales o negativos. La tasa plasmatica de IgG4 estaba dentro de los limites normales. Tratada con esteroides, se produjo mejoria clinica acompañada de la practica desaparicion de las alteraciones detectadas en la neuroimagen. Conclusiones. La paquimeningitis hipertrofica como manifestacion de la enfermedad relacionada con IgG4 puede diagnosticarse basandose en los hallazgos de la resonancia magnetica si la IgG4 plasmatica esta elevada. En casos dudosos, habra que recurrir a la biopsia meningea. La corticoterapia suele ser eficaz y representa la primera linea terapeutica.

  19. Influence of IgG Subclass on Human Antimannan Antibody-Mediated Resistance to Hematogenously Disseminated Candidiasis in Mice.

    Science.gov (United States)

    Nishiya, Casey T; Boxx, Gayle M; Robison, Kerry; Itatani, Carol; Kozel, Thomas R; Zhang, Mason X

    2015-11-16

    Candida albicans is a yeast-like pathogen and can cause life-threatening systemic candidiasis. Its cell surface is enriched with mannan that is resistant to complement activation. Previously, we developed the recombinant human IgG1 antimannan antibody M1g1. M1g1 was found to promote complement activation and phagocytosis and protect mice from systemic candidiasis. Here, we evaluate the influence of IgG subclass on antimannan antibody-mediated protection. Three IgG subclass variants of M1g1 were constructed: M1g2, M1g3, and M1g4. The IgG subclass identity for each variant was confirmed with DNA sequence and subclass-specific antibodies. These variants contain identical M1 Fabs and exhibited similar binding affinities for C. albicans yeast and purified mannan. Yeast cells and hyphae recovered from the kidney of antibody-treated mice with systemic candidiasis showed uniform binding of each variant, indicating constitutive expression of the M1 epitope and antibody opsonization in the kidney. All variants promoted deposition of both murine and human C3 onto the yeast cell surface, with M1g4 showing delayed activation, as determined by flow cytometry and immunofluorescence microscopy. M1g4-mediated complement activation was found to be associated with its M1 Fab that activates the alternative pathway in an Fc-independent manner. Treatment with each subclass variant extended the survival of mice with systemic candidiasis (P candidiasis is influenced by its IgG subclass.

  20. The use of anti-IgG monoclonal antibodies in mapping the monocyte receptor site on IgG.

    Science.gov (United States)

    Partridge, L J; Woof, J M; Jefferis, R; Burton, D R

    1986-12-01

    Monoclonal antibodies (MAbs) directed against epitopes on the C gamma 1, C gamma 2, C gamma 3 and C gamma 2-C gamma 3 interface regions of human IgG were used to attempt to localize the monocyte Fc receptor (FcR) binding site. The MAbs have been assayed for their capacity to inhibit the interaction between 125I-labelled IgG (125I-IgG) and human monocytes or human histiocytic lymphoma U937 cells. Two MAbs specific for epitopes on the N-terminal region of the C gamma 2 domain, and one MAb recognizing an epitope in the C gamma 2-C gamma 3 inter-domain region inhibited binding of 125I-IgG to monocyte FcRs. The remaining MAbs, against a C-terminal C gamma 3 domain epitope, another C gamma 2/C gamma 3 region epitope and the G1m(f) allotope on the C gamma 1 domain did not inhibit the interaction. The capacity of the MAbs to bind to their respective epitopes on cell surface FcR-bound IgG was also studied, using indirect radiobinding and immunofluorescence assays. All of the MAbs, except those with C gamma 2 domain specificities, were able to detect FcR-bound IgG under these conditions. The results confirm the role of the C gamma 2 domain in the interaction of IgG with monocytes and demonstrate that epitopes in the C gamma 3 and C gamma 2-C gamma 3 regions are not involved in the binding site. PMID:2434846

  1. Characterization of IgG monoclonal antibody targeted to both tissue cyst and sporocyst walls of Toxoplasma gondii

    Science.gov (United States)

    Toxoplasma gondii infects approximately one third of the human population and animals habiting terrestrial and aquatic environments. Its environmentally resistant oocysts are excreted by felids, and the stage encysted in tissues (tissue cysts), are important in the horizontal transmission of T. gon...

  2. NRT Atmospheric Water Vapour Retrieval on the Area of Poland at IGG WUELS AC

    Science.gov (United States)

    Kaplon, Jan; Bosy, Jaroslaw; Sierny, Jan; Hadas, Tomasz; Rohm, Witold; Wilgan, Karina; Ryczywolski, Marcin; Oruba, Artur; Kroszczynski, Krzysztof

    2013-04-01

    Global Navigation Satellite Systems (GNSS) are designed for positioning, navigation and amongst other possible applications it can also be used to derive information about the state of the atmosphere. Continuous observations from GNSS receivers provide an excellent tool for studying the neutral atmosphere, currently in near real-time. The Near Real-Time (NRT) neutral atmosphere and water vapour distribution models are currently obtained with high resolution from Ground Base Augmentation Systems (GBAS), where reference stations are equipped with GNSS and meteorological sensors. The Poland territory is covered by dense network of GNSS stations in the frame of GBAS system called ASG-EUPOS (www.asgeupos.pl). This system was established in year 2008 by the Head Office of Geodesy and Cartography in the frame of the EUPOS project (www.eupos.org) for providing positioning services. The GNSS data are available from 130 reference stations located in Poland and neighbour countries. The ground meteorological observations in the area of Poland and neighbour countries are available from ASG-EUPOS stations included in EUREF Permanent Network (EPN) stations, airports meteorological stations (METAR messages stations), and stations managed by national Institute of Meteorology and Water Management (SYNOP messages stations). Institute of Geodesy and Geoinformatics (IGG) of Wroclaw University of Environmental and Life Sciences had created permanent NRT service of ZTD (Zenith Total Delay) estimation for the area of Poland from GPS observations called IGGHZG. The first part of the paper presents the methodology of NRT GNSS data processing for ASG-EUPOS stations for ZTD estimation and its comparison to the results coming from EPN ACs and Military University of Technology in Warsaw AC (MUT AC). Second part covers the procedure of IWV (atmospheric Integrated Water Vapour content) estimation at IGG from IGGHZG product and ZHD (Zenith Hydrostatic Delay) derived from Saastamoinen formula (1972

  3. Análisis inmunoenzimático (ELISA para determinar niveles de IgG anti Bothrops atrox en accidente ofídico Immunoenzymatic determination of IgG anti bothrops atrox levels after snake bites

    Directory of Open Access Journals (Sweden)

    John J. Estrada

    1993-01-01

    Full Text Available Se desarrolló un método de inmunización de conejos con veneno de Bothrops atrox con el fin de preparar antisueros y estandarizar un inmunoanálisis (ELISA para medir niveles de IgG en pacientes con accidente ofídico. La respuesta Inmune de los conejos se siguió por inmunodifusión en doble dimensión (Ouchterlony e inmunoelectroforesis, demostrando la presencia de bandas nítidas desde el día 60 y en todas las sangrias posteriores; se comprobó que hay variabilidad individual en su respuesta inmune. El ELISA para detección de IgG humana anti B. atrox en los indígenas del Chocó fue una prueba simple y sensible (83.3% pero inespecífica por las reacciones cruzadas en individuos que habían sufrido accidentes por B. nasutus. La técnica para detectar IgG equina anti B. atrox en pacientes tratados con antiveneno fue tambIén simple y muy sensible. We developed an immunization method for the production of rabbit antisera against Bothrops atroxvenoms. An enzyme-Ilnked assay (ELISA was standardized in order to measure IgG levels after snake bites. The immune response of rabbits, as determined by Ouchterlony and immunoelectrophoresis techniques, revealed bands of precipitation from the sixtieth day on. Individual variability in the immune response of rabbits was demonstrated. For the measurement of IgG levels In Indians from the Department of Choco (Colombia, ELISA proved to be a sensitive (83.3% and simple but not an specific procedure, since there were cross-reactions in those previously bitten by B. nasutus. ELISA was also simple and sensitive (100% for the determination of equine anti B. atrox IgG antibodies in patients treated with antivenom

  4. Monitoring of Anti-Hepatitis E Virus Antibody Seroconversion in Asymptomatically Infected Blood Donors: Systematic Comparison of Nine Commercial Anti-HEV IgM and IgG Assays

    Science.gov (United States)

    Vollmer, Tanja; Diekmann, Juergen; Eberhardt, Matthias; Knabbe, Cornelius; Dreier, Jens

    2016-01-01

    Diagnosis of hepatitis E virus (HEV) is usually determined serologically by detection of the presence of immunoglobulin (Ig)M antibodies or rising anti-HEV IgG titers. However, serological assays have demonstrated a significant variation in their sensitivities and specificities. In this study, we present the systematic comparison of different immunological anti-HEV assays using complete seroconversion panels of 10 virologically confirmed HEV genotype 3 infected individuals. Assay sensitivities were further evaluated by testing serially diluted World Health Organization (WHO) reference reagent for hepatitis E virus antibody and one patient sample infected with HEV genotype 3. Anti-HEV IgM and IgG antibody presence was determined using the immunological assays Wantai HEV IgM/IgG enzyme-linked immunosorbent assay (ELISA) (Sanbio, Uden, The Netherlands), recomWell HEV IgM/IgG (Mikrogen, Neuried, Germany), HEV IgM ELISA 3.0, HEV ELISA, HEV ELISA 4.0, Assure HEV IgM Rapid Test (all MP Biomedicals Europe, Illkirch Cedex, France) and Anti-HEV ELISA (IgM/IgG, Euroimmun, Lübeck, Germany). The assays showed differences regarding their analytical and diagnostic sensitivities, with anti-HEV IgM assays (n = 5) being more divergent compared to anti-HEV IgG (n = 4) assays in this study. Considerable variations were observed particularly for the detection period of IgM antibodies. This is the first study systematically characterizing serologic assays on the basis of seroconversion panels, providing sample conformity for a conclusive comparison. Future studies should include the assay comparison covering the four different genotypes. PMID:27556482

  5. Cronkhite-Canada syndrome polyps infiltrated with IgG4-positive plasma cells.

    Science.gov (United States)

    Fan, Ru-Ying; Wang, Xiao-Wei; Xue, Li-Jun; An, Ran; Sheng, Jian-Qiu

    2016-08-16

    Cronkhite-Canada syndrome (CCS) is a rare but serious protein-losing enteropathy, but little is known about the mechanism. Further more, misdiagnosis is common due to non-familiarity of its clinical manifestation. A 40-year-old male patient was admitted to our hospital because of diarrhea and hypogeusia associated with weight loss for 4 mo. On physical examination, skin pigmentation, dystrophic nail changes and alopecia were noted. He had no alike family history. Laboratory results revealed low levels of serum albumin (30.1 g/L, range: 35.0-55.0 g/L), serum potassium (2.61 mmol/L, range: 3.5-5.5 mmol/L) and blood glucose (2.6 mmol/L, range: 3.9-6.1 mmol/L). The erythrocyte sedimentation rate was elevated to 17 mm/h (range: 0-15 mm/h). X-ray of chest and mandible was normal. The endoscopic examination showed multiple sessile polyps in the stomach, small bowel and colorectum. Histopathologic examination of biopsies obtained from those polyps showed hyperplastic change, cystic dilatation and distortion of glands with inflammatory infiltration, eosinophilic predominance and stromal edema. Immune staining for IgG4 plasma cells was positive in polyps of stomach and colon. The patient was diagnosed of CCS and treated with steroid, he had a good response to steroid. Both histologic findings and treatment response to steroid suggested an autoimmune mechanism underling CCS. PMID:27574615

  6. Human IgG Fc promotes expression, secretion and immunogenicity of enterovirus 71 VP1 protein.

    Science.gov (United States)

    Xu, Juan; Zhang, Chunhua

    2016-05-01

    Enterovirus (EV71) can cause severe neurological diseases, but the underlying pathogenesis remains unclear. The capsid protein, viral protein 1 (VP1), plays a critical role in the pathogenicity of EV71. High level expression and secretion of VP1 protein are necessary for structure, function and immunogenicity in its natural conformation. In our previous studies, 5 codon-optimized VP1 DNA vaccines, including wt-VP1, tPA-VP1, VP1-d, VP1-hFc and VP1-mFc, were constructed and analyzed. They expressed VP1 protein, but the levels of secretion and immunogenicity of these VP1 constructs were significantly different (P<0.05). In this study, we further investigated the protein levels of these constructs and determined that all of these constructs expressed VP1 protein. The secretion level was increased by including a tPA leader sequence, which was further increased by fusing human IgG Fc (hFc) to VP1. VP1-hFc demonstrated the most potent immunogenicity in mice. Furthermore, hFc domain could be used to purify VP1-hFc protein for additional studies. PMID:27533931

  7. Site-specific conjugation of bifunctional chelator BAT to mouse IgG1 Fab' fragment

    Institute of Scientific and Technical Information of China (English)

    Jun LI; Xue-hao WANG; Xiao-ming WANG; Zhao-lai CHEN

    2006-01-01

    Aim: To perform a site-specific conjugation of Fab' fragments of a mouse monoclonal antibody(MoAb) B43(of IgG1 subtype) to a bifunctional chelator 6-[p-(bromoacetamido) benzyl]-l,4,8,11-tetraazacyclotetradecane-N,N',N",N'"-tetraacetic acid (BAT) via the thiol groups in the hinge distal to the antigenbinding site of the Fab'. Methods: B43 was cleaved using a simple 2-step method.First, stable F(ab')2 was produced by pepsin treatment. Fab' with free thiol in the hinge region was then obtained by cysteine reduction of F(ab')2. Second, a sitespecific conjugation of Fab' to thiol-specific BAT was performed in a one-step reaction. Results: The Fab' fragment had approximately 1.8 free thiol groups per molecule after cysteine reduction. The conjugation efficiency and the chemical yield were approximately 1.28 moles chelator/Fab' and 74% of the initial concentration of Fab', respectively. The F(ab')2, Fab' and Fab'-BAT all maintained reasonable antigen-binding properties. 67Cu labeling of the conjugate under standard conditions did not impair the immunoreactivity of Fab'-BAT. Conclusion: This is a simple and efficient method for producing immunoreactive conjugates of Fab'-BAT, which can be used to make radiometal-labeled conjugates for further diagnostic and therapeutic applications.

  8. Intracellular calcium mobilization in human lymphocytes in the presence of synthetic IgG Fc peptides

    Energy Technology Data Exchange (ETDEWEB)

    Plummer, J.M.; Panahi, Y.P.; McClurg, M.R.; Hahn, G.S.; Naemura, J.R.

    1986-03-01

    Certain synthetic peptides derived from the Fc region of human IgG can suppress the mixed lymphocyte response. These peptides were tested for the ability to induce intracellular calcium mobilization in human lymphocytes using fura-2/calcium fluorescence. T cells were isolated by rosetting and were > 90% OKT3 positive. Lymphocytes were incubated with the acetoxymethyl ester of fura-2 (10 ..mu..M) for 60 minutes at 37/sup 0/C. Fluorescence intensity changes at 505 nm were monitored at an excitation lambda of 340 nm. Fura-2 was not cytotoxic compared to quin-2 since fura-2 loaded mononuclear cells incorporated /sup 3/H-thymidine when stimulated by PHA, succinyl Con A, PWM or LPS-STM whereas quin-2 loaded cells showed a dose dependent inhibition of proliferation. Those synthetic peptides (5 to 400 ..mu..g/ml) that suppressed the MLR induced a dose dependent increase in intracellular calcium in mononuclear cells, lymphocytes, non-T cells and T cells. The fura-2 calcium fluorescence time course response was similar for peptide, PHA and succinyl Con A. These results suggest that these immunoregulatory peptides suppress /sup 3/H-thymidine incorporation at a point after intracellular calcium mobilization and that fura-2 has advantages over quin-2 in measuring intracellular calcium levels in lymphocytes.

  9. Intracellular calcium mobilization in human lymphocytes in the presence of synthetic IgG Fc peptides

    International Nuclear Information System (INIS)

    Certain synthetic peptides derived from the Fc region of human IgG can suppress the mixed lymphocyte response. These peptides were tested for the ability to induce intracellular calcium mobilization in human lymphocytes using fura-2/calcium fluorescence. T cells were isolated by rosetting and were > 90% OKT3 positive. Lymphocytes were incubated with the acetoxymethyl ester of fura-2 (10 μM) for 60 minutes at 370C. Fluorescence intensity changes at 505 nm were monitored at an excitation lambda of 340 nm. Fura-2 was not cytotoxic compared to quin-2 since fura-2 loaded mononuclear cells incorporated 3H-thymidine when stimulated by PHA, succinyl Con A, PWM or LPS-STM whereas quin-2 loaded cells showed a dose dependent inhibition of proliferation. Those synthetic peptides (5 to 400 μg/ml) that suppressed the MLR induced a dose dependent increase in intracellular calcium in mononuclear cells, lymphocytes, non-T cells and T cells. The fura-2 calcium fluorescence time course response was similar for peptide, PHA and succinyl Con A. These results suggest that these immunoregulatory peptides suppress 3H-thymidine incorporation at a point after intracellular calcium mobilization and that fura-2 has advantages over quin-2 in measuring intracellular calcium levels in lymphocytes

  10. Shift in epitope dominance of IgM and IgG responses to Plasmodium falciparum MSP1 block 4

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    Leke Rose GF

    2010-01-01

    Full Text Available Abstract Background Plasmodium falciparum merozoite surface protein-1 (MSP1 has been extensively studied as a blood-stage malaria vaccine candidate, with most work focused on the conserved 19 kDa and semi-conserved 42 kDa C-terminal regions (blocks 16-17 and the hypervariable N-terminal repeat region (block 2. However, recent genotyping studies suggest that additional regions of MSP1 may be under selective pressure, including a locus of intragenic recombination designated as block 4 within the 3' region of the gene. Methods The current study examined the antibody response to the two parental and two recombinant forms of block 4 and to blocks 16-17 (3D7 in study populations from Colombia, Papua New Guinea and Cameroon that differ in malaria transmission intensity and ethnic composition. Results IgM and IgG antibodies were detected against parental and recombinant MSP1 block 4 peptides in all three populations. Overall, 32-44% of the individuals produced IgM to one or more of the peptides, with most individuals having IgM antibodies reactive with both parental and recombinant forms. In contrast, IgG seropositivity to block 4 varied among populations (range 15-65%, with the majority of antibodies showing specificity for one or a pair of block 4 peptides. The IgG response to block 4 was significantly lower than that to blocks 16-17, indicating block 4 is subdominant. Antibodies to block 4 and blocks 16-17 displayed distinct IgG subclass biases, with block 4 responses biased toward IgG3 and blocks 16-17 toward IgG1. These patterns of responsiveness were consistently observed in the three study populations. Conclusions Production of antibodies specific for each parental and recombinant MSP1 block 4 allele in different populations exposed to P. falciparum is consistent with balancing selection of the MSP1 block 4 region by the immune response of individuals in areas of both low and high malaria transmission. MSP1 block 4 determinants may be important

  11. Particle counting assay for anti-toxoplasma IgG antibodies. Comparison with four automated commercial enzyme-linked immunoassays.

    Science.gov (United States)

    Galanti, L M; Dell'Omo, J; Wanet, B; Guarin, J L; Jamart, J; Garrino, M G; Masson, P L; Cambiaso, C L

    1997-09-24

    An assay for anti-toxoplasma IgG antibodies based on agglutination of latex particles was set up and compared with commercial immunoassays. The reaction was measured by instrumental counting of particles remaining unagglutinated. The running time was 45 min. This test (PaC) was compared using 243 serum samples with four automated commercial immunoassays: the Enzymum test Toxo IgG (ES300, Boehringer), the Vidas Toxo IgG (Biomérieux), the IMX Toxo IgG (Abbott), the Magia Toxoplasma gondii IgG (Merck). The mean values (+/- SD) obtained by IMX (25 IU +/- 68) and ES300 (45 IU +/- 142) were significantly lower than the values obtained by Vidas (73 IU +/- 237, p Magia (80 IU +/- 300, p < 10(-4) and p = 0.0005) and by PaC (70 IU +/- 260, p < 10(-4) and p = 0.0126). The correlations between PaC and Toxo IgG Boehringer, Biomérieux, Abbott, Merck were r = 0.97, r = 0.98, r = 0.94, r = 0.98, respectively. The correlation coefficients between the enzyme-immunoassays ranged from 0.96 to 0.99. All positive samples by PaC were found to be positive by enzyme-immunoassays except for eight sera which were doubtful positives by the Enzymum test ToxoIgG from Boehringer. No negative sample by PaC was found positive by any of the enzyme-immunoassays. In PaC, when two latex preparations coated with different antigen were compared, the correlation was rather weak (r = 0.93) suggesting that the selection of the antigen can be critical. In conclusion, the four automated commercial immunoassays now available gave similar results. However, the discrepancies observed in this study underlined the importance of clinical and biological follow-up of the patients and the necessity to confirm the result. The introduction of a new technique such as PaC, which is now available for a large variety of assays in Clinical Chemistry and Microbiology, is justified by its intrinsic advantage of homogeneity. Therefore, automation is easy as well as the control of possible interference.

  12. Detection of oligoclonal IgG kappa and IgG lambda bands in cerebrospinal fluid and serum with Hevylite™ antibodies. comparison with the free light chain oligoclonal pattern

    Directory of Open Access Journals (Sweden)

    Zeman David

    2012-02-01

    Full Text Available Abstract Background Oligoclonal IgG bands in cerebrospinal fluid that are absent in serum indicate intrathecal IgG synthesis and are a sensitive marker of CNS inflammatory diseases, in particular multiple sclerosis. It may be of interest to determine whether these bands are predominantly IgGκ or IgGλ. Methods We have used Hevylite™ antibodies and developed a technique for detection of oligoclonal IgGκ and IgGλ bands by means of isoelectric focusing followed by immunoblotting. The same technique was used for oligoclonal free κ and free λ detection. Among several techniques tested, affinity immunoblotting appears to be the most sensitive; it can detect less than 1 ng of IgGκ or IgGλ paraprotein. We compared oligoclonal IgG profiles with those of oligoclonal IgGκ and IgGλ. There was good agreement concerning the presence or absence of intrathecal synthesis. We observed the ratios between oligoclonal IgGκ and IgGλ bands, and they did not always match the ratios between free κ and free λ bands. We were also able to detect antigen-specific CSF-restricted oligoclonal IgGκ and IgGλ bands in neuroborreliosis. It remains to be determined subsequently by a clinically-oriented prospective study, whether predominant IgGκ/IgGλ or free κ/free λ can be observed more frequently in particular diseases with oligoclonal IgG synthesis. Discussion Very sensitive detection of oligoclonal IgGκ and IgGλ bands in cerebrospinal fluid with Hevylite antibodies is feasible; detection of antigen-specific IgGκ or IgGλ is possible as well. In particular situations, e.g. when difficulties arise in distinguishing between oligoclonal and monoclonal pattern, the test may be of considerable clinical value.

  13. Ectopic Germinal Centers and IgG4-Producing Plasmacytes Observed in Synovia of HLA-B27+ Ankylosing Spondylitis Patients with Advanced Hip Involvement

    Directory of Open Access Journals (Sweden)

    Xiugao Feng

    2015-01-01

    Full Text Available Introduction. Ectopic lymphoid neogenesis and the presence of IgG4-positive plasmacytes have been confirmed in chronic inflammatory sclerosing diseases. This study aims to investigate hip synovial tissues of ankylosing spondylitis (AS patients for IgG4-positive plasma cells and ectopic lymphoid tissues with germinal centers (GCs. Methods. Synovial samples were collected from 7 AS patients who received total hip replacement and were evaluated using immunohistochemistry for the presence of CD20+ B-cells, CD3+ T-cells, CD21+ follicular dendritic cells (FDC, and CD38+ plasma cells. Furthermore, immunoglobulin G (IgG and IgG4, IgA, IgM, and complement components C3d and C4d in synovia were evaluated. Both synovial CD21+ FDCs and IgG4-producing plasmacytes were analyzed. Results. All seven patients had severe fibrosis. Massive infiltrations of lymphocytes were found in 5 out of 7 patients’ synovia. Ectopic lymphoid tissues with CD21+ FDC networks and IgG4-positive plasma cells were observed coincidentally in two patients’ synovia. Conclusion. The pathophysiological mechanism of AS patients’ hip damage might be related to the coincidental presence of ectopic lymphoid tissue with FDCs network and IgG4-positive plasma cells identified here for the first time in AS patients’ inflamed synovial tissue.

  14. Liver-X-receptor activator prevents homocysteine-induced production of IgG antibodies from murine B lymphocytes via the ROS-NF-κB pathway

    International Nuclear Information System (INIS)

    Our previous study showed that homosysteine (Hcy) promotes proliferation of mouse splenic B lymphocytes. In this study, we investigated whether Hcy could stimulate the production of IgG antibodies. Hcy significantly increased the production of IgG antibodies from resting B lymphocytes. B lymphocytes from ApoE-knockout mice with hyperhomocysteinemia showed elevated IgG secretion at either the basal Hcy level or in response to lipopolysaccharide. Hcy promoted reactive oxygen species (ROS) formation, and free radical scavengers, MnTMPyP decreased Hcy-induced IgG secretion. The inhibitor of NF-κB (MG132) also significantly reduced Hcy-induced IgG secretion. Furthermore, Hcy-induced formation of ROS, activation of NF-κB, and secretion of IgG could be inhibited by the liver-X-receptor (LXR) agonist TO 901317. Thus, our data provide strong evidence that HHcy induces IgG production from murine splenic B lymphocytes both in vitro and in vivo. The mechanism might be through the ROS-NF-κB pathway and can be attenuated by the activation of LXR

  15. Recurrent Proliferative Glomerulonephritis With Monoclonal IgG Deposits After a Renal Transplant Which Was Insensitive to Pulse Therapy Remitted by Double Filtration Plasmapheresis.

    Science.gov (United States)

    Wu, Di; Chen, Jin-Song; Cheng, Dong-Rui; Chen, Hao; Li, Xue; Ji, Shu-Ming; Xie, Ke-Nan; Ni, Xue-Feng; Liu, Zhi-Hong; Wen, Ji-Qiu

    2015-10-01

    Proliferative glomerulonephritis with monoclonal IgG deposits manifesting as a nephrotic syndrome recently has been described as a renal disease with the pathological features of mesangial and subendothelial deposits of monoclonal IgG. Eight cases of recurrent proliferative glomerulonephritis with monoclonal IgG deposits after a renal transplant have been reported. Almost all of these patients had a certain remission of proteinuria by steroids alone or with cyclophosphamide, and had further remission through other special treatments (ie, rituximab and plasmapheresis). We present a case of recurrent proliferative glomerulonephritis with monoclonal IgG deposits of the IgG3? subtype after a renal transplant, which was insensitive to pulse intravenous methyl-prednisolone and cyclophosphamide remitted by double filtration plasmapheresis. This case report reveals that recurrent proliferative glomerulo-nephritis with monoclonal IgG deposits may be insensitive to intravenous pulse therapy of methylprednisolone and cyclophosphamide. We advocate double filtration plasmapheresis as an effective treatment of proliferative glomerulo-nephritis with monoclonal IgG deposits on remission of proteinuria.

  16. Elimination of soluble 123I-labeled aggregates of IgG in patients with systemic lupus erythematosus. Effect of serum IgG and numbers of erythrocyte complement receptor type 1

    International Nuclear Information System (INIS)

    Using soluble 123I-labeled aggregates of human IgG (123I-AHIgG) as a probe, we examined the function of the mononuclear phagocyte system in 22 patients with systemic lupus erythematosus (SLE) and 12 healthy controls. In SLE patients, a decreased number of erythrocyte complement receptor type 1 was associated with less binding of 123I-AHIgG to erythrocytes and a faster initial rate of elimination of 123I-AHIgG (mean +/- SEM half-maximal clearance time 5.23 +/- 0.2 minutes, versus 6.58 +/- 0.2 minutes in the controls), with possible spillover of the material outside the mononuclear phagocyte system of the liver and spleen. However, multiple regression analysis showed that serum concentrations of IgG were the most important factor predicting the rate of 123I-AHIgG elimination. IgG concentration may thus reflect immune complex clearance, which in turn, would influence the inflammatory reaction, in SLE

  17. Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide.

    Science.gov (United States)

    Oji, Yusuke; Hashimoto, Naoya; Tsuboi, Akihiro; Murakami, Yui; Iwai, Miki; Kagawa, Naoki; Chiba, Yasuyoshi; Izumoto, Shuichi; Elisseeva, Olga; Ichinohasama, Ryo; Sakamoto, Junichi; Morita, Satoshi; Nakajima, Hiroko; Takashima, Satoshi; Nakae, Yoshiki; Nakata, Jun; Kawakami, Manabu; Nishida, Sumiyuki; Hosen, Naoki; Fujiki, Fumihiro; Morimoto, Soyoko; Adachi, Mayuko; Iwamoto, Masahiro; Oka, Yoshihiro; Yoshimine, Toshiki; Sugiyama, Haruo

    2016-09-15

    We previously evaluated Wilms' tumor gene 1 (WT1) peptide vaccination in a large number of patients with leukemia or solid tumors and have reported that HLA-A*24:02 restricted, 9-mer WT1-235 peptide (CYTWNQMNL) vaccine induces cellular immune responses and elicits WT1-235-specific cytotoxic T lymphocytes (CTLs). However, whether this vaccine induces humoral immune responses to produce WT1 antibody remains unknown. Thus, we measured IgG antibody levels against the WT1-235 peptide (WT1-235 IgG antibody) in patients with glioblastoma multiforme (GBM) receiving the WT1 peptide vaccine. The WT1-235 IgG antibody, which was undetectable before vaccination, became detectable in 30 (50.8%) of a total of 59 patients during 3 months of WT1 peptide vaccination. The dominant WT1-235 IgG antibody subclass was Th1-type, IgG1 and IgG3 . WT1-235 IgG antibody production was significantly and positively correlated with both progression-free survival (PFS) and overall survival (OS). Importantly, the combination of WT1-235 IgG antibody production and positive delayed type-hypersensitivity (DTH) to the WT1-235 peptide was a better prognostic marker for long-term OS than either parameter alone. These results suggested that WT1-235 peptide vaccination induces not only WT1-235-specific CTLs as previously described but also WT1-235-specific humoral immune responses associated with antitumor cellular immune response. Our results indicate that the WT1 IgG antibody against the WT1 peptide may be a useful predictive marker, with better predictive performance in combination with DTH to WT1 peptide, and provide a new insight into the antitumor immune response induction in WT1 peptide vaccine-treated patients. PMID:27170523

  18. Diagnosis of Helicobacter pylori Infection Using ELISA for Detection of Serum IgM, IgG and IgA Antibodies

    Directory of Open Access Journals (Sweden)

    MH K. Ansari

    2007-06-01

    Full Text Available Background: Helicobacter pylori is gram negative bacteria and is the etiologic agent of some gastrointestinal disease are such as chronic gastritis, gastric ulcers, lymphoma and aden carcinoma. Multiple invasive and noninvasive methods for detection of this infection are available, and among non invasive methods diagnostic value of specific IgM, IgG and IgA by ELISAis one of the best methods. The aim of this study to detect H. pylori antibodies for IgM, IgG and IgA by ELISA method. Methods: Blood samples From 131 referred patients (78 female and 53 male for detection of H.pylori was taken and serum separated for detection of IgM, IgG and IgA antibodies. IgG assessed by EIU units (42 was Positive .Also for IgM and IgA antibodies reported by U/ml unit (12 was Positive. Results: 131 Samples were tested for H. pylori IgM, IgG and IgA antibodies and showed 27.47%, 42% and 25.19% positive for IgM, IgG and IgA antibodies respectively. Age group 20-40 years old for IgM, IgG and IgA antibodies 23.3% and 28.3% and 16.7% positive respectively and for 41-80 years old IgM, IgG and IgA antibodies were 31%, 53.5% and 32%, respectively. The above data showing infection is higher at 41- 80 years old patients. Conclusion: The simple method for detection of H. pylori antibodies are available commercially and have sensitivity and specificity for H. pylori diseases. IgG, IgM and IgA have diagnostic importance, therefore regarding acceptable sensitivity and specificity, ease of work with ELISA, being economical and non invasive, it can be employed in diagnosis of H. pylori infections.

  19. Management of a pregnant woman with common variable immunodeficiency and previous reactions to intravenous IgG administration.

    Science.gov (United States)

    Danieli, Maria Giovanna; Moretti, Romina; Pettinari, Lucia; Gambini, Simona

    2012-01-01

    Common variable immunodeficiency is the most common symptomatic primary immunodeficiency in adulthood. Pregnant women with common variable immunodeficiency have different needs from other patients with the same disease. Because of immature state of the fetal and neonatal immune system, transplacental transfer of immunoglobulin G (IgG) has a relevant role in protecting the infant. We here report on a high-risk pregnant woman with common variable immunodeficiency with adverse reactions to intravenous immunoglobulin that was successfully rescued with a new Ig human intravenous, 10% liquid preparation. The treatment was tailored to the health status and characteristics of the patient. The new product was safe and well tolerated. The mother did not report any infections during pregnancy and the baby had a healthy course with 'protective' serum IgG levels. Our case is a further demonstration that intravenous immunoglobulin tolerability in patients with immunodeficiency could be linked to a product's characteristics. PMID:23257273

  20. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    Directory of Open Access Journals (Sweden)

    Shahin Gaini

    2015-01-01

    Full Text Available A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine.

  1. A historical look at the first reported cases of Lassa fever: IgG antibodies 40 years after acute infection.

    Science.gov (United States)

    Bond, Nell; Schieffelin, John S; Moses, Lina M; Bennett, Andrew J; Bausch, Daniel G

    2013-02-01

    Lassa fever is an acute and sometimes severe viral hemorrhagic illness endemic in West Africa. One important question regarding Lassa fever is the duration of immunoglobulin G (IgG) antibody after infection. We were able to locate three persons who worked in Nigeria dating back to the 1940s, two of whom were integrally involved in the early outbreaks and investigations of Lassa fever in the late 1960s, including the person from whom Lassa virus was first isolated. Two persons had high titers of Lassa virus-specific IgG antibody over 40 years after infection, indicating the potential for long-term duration of these antibodies. One person was likely infected in 1952, 17 years before the first recognized outbreak. We briefly recount the fascinating stories of these three pioneers and their important contribution to our understanding of Lassa fever. PMID:23390223

  2. A Historical Look at the First Reported Cases of Lassa Fever: IgG Antibodies 40 Years After Acute Infection

    Science.gov (United States)

    Bond, Nell; Schieffelin, John S.; Moses, Lina M.; Bennett, Andrew J.; Bausch, Daniel G.

    2013-01-01

    Lassa fever is an acute and sometimes severe viral hemorrhagic illness endemic in West Africa. One important question regarding Lassa fever is the duration of immunoglobulin G (IgG) antibody after infection. We were able to locate three persons who worked in Nigeria dating back to the 1940s, two of whom were integrally involved in the early outbreaks and investigations of Lassa fever in the late 1960s, including the person from whom Lassa virus was first isolated. Two persons had high titers of Lassa virus-specific IgG antibody over 40 years after infection, indicating the potential for long-term duration of these antibodies. One person was likely infected in 1952, 17 years before the first recognized outbreak. We briefly recount the fascinating stories of these three pioneers and their important contribution to our understanding of Lassa fever. PMID:23390223

  3. IgG4-Related Mikulicz's Disease Associated with Thyroiditis:a Case Report and Review of the Literature

    Institute of Scientific and Technical Information of China (English)

    Yujiao Zhang; Yi Du; Kaijun Li; Jianfeng He

    2014-01-01

    Purpose:To report an unusual case of IgG4-related Mikulicz's disease associated with thyroiditis. Case report:.We describe a 25-year-old Chinese man who presented with bilateral,.painless swellings of the lachrymal glands,.parotid glands,.and thyroid nodules..The patient un-derwent left-sided dacryoadenectomy and the diagnosis of IgG4-related Mikulicz's disease was pathologically confirmed. The size of the right-sided lachrymal gland and parotid glands recovered fundamentally after one month of glucocorticoid therapy. Conclusion:.IgG4-related Mikulicz's disease associated with thyroiditis should be considered in the differential diagnosis of bilateral swellings of lachrymal glands, salivary glands, and thyroid nodules. Surgical excision is recommended in order to treat the tumor and to ensure the pathological diagnosis. Glu-cocorticoid therapy should be considered in association with surgery after removal. (Eye Science 2014; 29:47-52).

  4. Toxocara canis glycans influence antigen recognition by mouse IgG1 and IgM antibodies.

    Science.gov (United States)

    Długosz, Ewa; Wiśniewski, Marcin

    2016-01-01

    The impact of sugar moieties of Toxocara canis glycoprotein antigens on their recognition by infected mouse antibodies was investigated in this study. Native TES and recombinant Toxocara mucins generated in Pichia pastoris yeast as well as their deglycosylated forms were used in ELISA. TES and recombinant mucins were equally recognized by T. canis infected mouse IgG1 antibodies. IgM immunoglobulins predominantly recognized TES antigens. Among mucins recognition of Tc-MUC-4 was the most significant. Deglycosylation of antigens resulted in significant loss of IgM and IgG1 reactivity to TES, mucins, Tc-MUC-3 and Tc-MUC-4. The presence of sugar moieties had no influence on IgE binding to native or recombinant T. canis antigens. Our results suggest that glycans are involved in epitope formation what should be taken into consideration in production of recombinant helminth antigens for diagnostic purposes. PMID:26751891

  5. IgG antibodies against phospholipase A2 from Crotalus durissus terrificus: cross-reaction with venoms from Bothrops species from Argentina

    OpenAIRE

    JP Rodríguez; MC De Marzi; S Maruñak; P Teibler; O Acosta; EL Malchiodi; LC Leiva

    2009-01-01

    We examined the ability of IgG anti-crotalic PLA2 to cross-react with Bothrops spp. venoms, from snakes found in the northeast of Argentina. Immunoblotting and ELISA tests showed that IgG anti-crotalic PLA2 recognize antigens of bothropic venoms. Indirect hemolytic activity tests showed that the quantity of antibodies that neutralized 50% of Crotalus durissus terrificus venom (ED50: 2.1 mg IgG anti-crotalic PLA2/100 µg of venom) were also able to neutralize venom from other snakes in the foll...

  6. Suppression of polyclonal and antigen-specific murine IgG1 but not IgE responses by neutralizing interleukin-6 in vivo

    OpenAIRE

    Ommen, R.; Vredendaal, Astrid; Savelkoul, Huub

    1994-01-01

    textabstractThe crucial role of interleukin (IL)-4 in the induction of murine IgG1 and IgE responses, which are coupled through the process of sequential isotype switching, has been well documented. Whereas IL-4 is obligatory for the induction of IgE responses, it enhances IgG1 responses. In this study, using neutralizing antibodies, we provide evidence that, besides IL-4, also IL-6 is required for obtaining peak IgG1 responses. The mRNA levels of these two cytokines are coordinately expresse...

  7. Alternative Pathway Dysregulation and the Conundrum of Complement Activation by IgG4 Immune Complexes in Membranous Nephropathy

    Science.gov (United States)

    Borza, Dorin-Bogdan

    2016-01-01

    Membranous nephropathy (MN), a major cause of nephrotic syndrome, is a non-inflammatory immune kidney disease mediated by IgG antibodies that form glomerular subepithelial immune complexes. In primary MN, autoantibodies target proteins expressed on the podocyte surface, often phospholipase A2 receptor (PLA2R1). Pathology is driven by complement activation, leading to podocyte injury and proteinuria. This article overviews the mechanisms of complement activation and regulation in MN, addressing the paradox that anti-PLA2R1 and other antibodies causing primary MN are predominantly (but not exclusively) IgG4, an IgG subclass that does not fix complement. Besides immune complexes, alterations of the glomerular basement membrane (GBM) in MN may lead to impaired regulation of the alternative pathway (AP). The AP amplifies complement activation on surfaces insufficiently protected by complement regulatory proteins. Whereas podocytes are protected by cell-bound regulators, the GBM must recruit plasma factor H, which inhibits the AP on host surfaces carrying certain polyanions, such as heparan sulfate (HS) chains. Because HS chains present in the normal GBM are lost in MN, we posit that the local complement regulation by factor H may be impaired as a result. Thus, the loss of GBM HS in MN creates a micro-environment that promotes local amplification of complement activation, which in turn may be initiated via the classical or lectin pathways by subsets of IgG in immune complexes. A detailed understanding of the mechanisms of complement activation and dysregulation in MN is important for designing more effective therapies. PMID:27199983

  8. p53 Represses Class Switch Recombination to IgG2a through its Antioxidant Function1

    OpenAIRE

    Guikema, Jeroen E. J.; Schrader, Carol E.; Brodsky, Michael H.; Linehan, Erin K.; Richards, Adam; El Falaky, Nahla; Li, Daniel H.; Sluss, Hayla K.; Szomolanyi-Tsuda, Eva; Stavnezer, Janet

    2010-01-01

    Immunoglobulin class switch recombination (CSR) occurs in activated mature B cells, and causes an exchange of the IgM isotype for IgG, IgE or IgA isotypes, which increases the effectiveness of the humoral immune response. DNA double-stranded breaks (DSBs) in recombining switch (S) regions, where CSR occurs, are required for recombination. Activation-induced cytidine deaminase (AID) initiates DSB formation by deamination of cytosines in S regions. This reaction requires reactive oxygen species...

  9. Association of serum immunoglobulin G (IgG) levels against two periodontal pathogens and prothrombotic state: a clinical pilot study

    OpenAIRE

    Laine Marja L; van der Velden Ubele; Nicu Elena A; Bizzarro Sergio; Loos Bruno G

    2010-01-01

    Abstract Objective Periodontitis is associated with cardiovascular diseases (CVD). In our previous studies a prothrombotic state has been observed in periodontitis, which contributes to the risk of CVD. The aim of this study was to investigate whether serum IgG levels against Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) in periodontitis were associated with a prothrombotic state. Materials and methods Patients with moderate (n = 38) and severe periodontitis (n ...

  10. Clinical associations of IgG antibodies to the ribonucleoprotein p67 polypeptide in patients with systemic lupus erythematosus.

    OpenAIRE

    Vencovsky, J; Williams, D G; M. Field; Maini, R N

    1992-01-01

    The ribonucleoprotein (RNP) p67 antigen was purified from rabbit thymus and used in an enzyme linked immunosorbent assay (ELISA) with low interassay variability to detect IgG antibodies to p67 in patients with autoimmune connective tissue diseases. These antibodies were found in eight (80%) patients with a clinical diagnosis of mixed connective tissue disease (MCTD) but also in 27 (40%) patients with systemic lupus erythematosus (SLE). Sixty six per cent of the 12 patients with SLE with high ...

  11. High-yield production of a human monoclonal IgG by rhizosecretion in hydroponic tobacco cultures

    OpenAIRE

    L. M. Madeira; Szeto, T.H.; Henquet, Maurice; Raven, Nicole; Runions, John; Huddleston, Jon; Garrard, Ian; Drake, P.M.W.; Ma, Julian K.C.

    2016-01-01

    Rhizosecretion of recombinant pharmaceuticals from in vitro hydroponic transgenic plant cultures is a simple, low cost, reproducible and controllable production method. Here, we demonstrate the application and adaptation of this manufacturing platform to a human antivitronectin IgG1 monoclonal antibody (mAb) called M12. The rationale for specific growth medium additives was established by phenotypic analysis of root structure and by LC-ESI-MS/MS profiling of the total protein content profile ...

  12. Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations

    OpenAIRE

    Chavez, Brittany K.; Cyrus D. Agarabi; Read, Erik K.; Boyne II, Michael T.; Khan, Mansoor A.; Brorson, Kurt A

    2016-01-01

    Formulating appropriate storage conditions for biopharmaceutical proteins is essential for ensuring their stability and thereby their purity, potency, and safety over their shelf-life. Using a model murine IgG3 produced in a bioreactor system, multiple formulation compositions were systematically explored in a DoE design to optimize the stability of a challenging antibody formulation worst case. The stability of the antibody in each buffer formulation was assessed by UV/VIS absorbance at 280 ...

  13. Management of a pregnant woman with common variable immunodeficiency and previous reactions to intravenous IgG administration

    OpenAIRE

    Danieli, Maria Giovanna; Moretti, Romina; Pettinari, Lucia; Gambini, Simona

    2012-01-01

    Common variable immunodeficiency is the most common symptomatic primary immunodeficiency in adulthood. Pregnant women with common variable immunodeficiency have different needs from other patients with the same disease. Because of immature state of the fetal and neonatal immune system, transplacental transfer of immunoglobulin G (IgG) has a relevant role in protecting the infant. We here report on a high-risk pregnant woman with common variable immunodeficiency with adverse reactions to intra...

  14. Dilazep and dipyridamole inhibit tissue factor expression on monocytes induced by IgG from patients with antiphospholipid syndrome

    Institute of Scientific and Technical Information of China (English)

    Hong ZHON

    2004-01-01

    AIM: To investigate whether antiplatelet agents, dilazep and dipyridamole, inhibit tissue factor (TF) expression on monocytes induced by IgG from patients with antiphospholipid syndrome (APS). METHODS: Freshly isolated peripheral blood monocytes were allowed to adhere on plastic and then cultured in media containing patient or control antibodies and/or other agonists with or without dilazep or dipyridamole. The TF activity on monocytes was investigated by measuring factor VIIa-dependent generation of factor Xa, using a chromogenic substrate and the TF mRNA expression was examined by real-time PCR (TaqMan PCR). RESULTS: The TF activity on monocytes induced by APS IgG (250 mg/L) was inhibited by dilazep (0.15-150 μmol/L) and dipyridamole (0.2-200 μrmol/L) in a dose-dependent fashion. But, the TF mRNA expression induced by APS IgG was not inhibited. Theophylline (500 μmol/L), an adenosine receptor antagonist, could counteract the inhibitory effect of dilazep and dipyridamole on TF activity. CONCLUSION: Antiplatelet agents, dilazep and dipyridamole, block APS IgG-induced monocytes TF expression at a post-transcriptional level, partly by adenosine receptor pathway. Pharmacological agents that block monocytes TF activity, such as dilazep and dipyridamole, are a novel therapeutic approach in APS.

  15. Decrease in binding ability of IgG antibodies by lymphocyte receptors as a result of low dose irradiation effect

    International Nuclear Information System (INIS)

    The effect of low dose irradiation on binding of IgG antibodies by B lymphocyte receptors in peripheral blood is studied for practically health people, living in the Minsk region, and for those people, who live on territories with a high radiation background. A method to determine BIgG+ lymphocytes, carrying the corresponding immunoglobulin determinants (IgA, IgM, IgG, IgD or IgE), in smears was developed and used. Irradiation doses were determined as a sum of contributions of external and internal irradiation. The data on the content of BIgG+ lymphocytes in peripheral blood of the patients depending on their age and irradiation dose are given. The conclusion is made that binding of IgG antibodies by lymphocyte receptors is sensitive to low irradiation doses. The account of BIgG+ lymphocytes in peripheral blood can be useful in formation of groups having increased risk of oncological disease accurrence. 4 refs.; 1 tab

  16. Pregnancy-Associated Changes of IgG and Serum N-Glycosylation in Camel (Camelus dromedarius).

    Science.gov (United States)

    Adamczyk, Barbara; Albrecht, Simone; Stöckmann, Henning; Ghoneim, Ibrahim M; Al-Eknah, Marzook; Al-Busadah, Khalid A S; Karlsson, Niclas G; Carrington, Stephen D; Rudd, Pauline M

    2016-09-01

    The dromedary camel (Camelus dromedarius) is an agriculturally important species of high economic value but of low reproductive efficiency. Serum and IgG N-glycosylation are affected by physiological and pathogenic changes and might therefore be a useful diagnostic tool in camel livestock management. This study presents the first comprehensive annotation of the N-glycome from dromedary camel serum as well as their single-domain and conventional antibodies and its subsequent application for camel pregnancy diagnostics. N-glycans were released by PNGaseF, labeled with 2-aminobenzamide (2-AB), and analyzed by hydrophilic interaction liquid chromatography with fluorescent detection (HILIC-UPLC-FLD), enzymatic sequencing and mass spectrometry (MS). The use of a high-throughput robotic platform for sample preparation allowed the rapid generation of glycomics data from pregnant (n = 8) and nonpregnant (n = 8) camels of the Majaheem and Wadha breed. IgG N-glycans dominate the glycan profile of camel serum and present a mixture of core-fucosylated and noncore-fucosylated N-glycans which can contain N-glycolylneuraminic and N-acetylneuraminic acid. Significant pregnancy-associated but breed-independent increases in galactosylation, core-fucosylation, sialylation, and decreases in serum O-acetylation were observed. The monitoring of IgG and serum N-glycosylation presents an attractive complementary test for camel pregnancy diagnostics and presents an interesting tool for biomarker discovery in camel health and breeding.

  17. An autopsy case of acute pancreatitis with a high serum IgG4 complicated by amyloidosis and rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    Tatsuki Ichikawa; Kazuhiko Nakao; Keisuke Hamasaki; Kazuaki Ohkubo; Kan Toriyama; Katsumi Eguchi

    2005-01-01

    We report an autopsy case of acute pancreatitis with a high serum IgG4 concentration complicated by systemic amyloid A amyloidosis and rheumatoid arthritis (RA). The patient was a 42-year-old Japanese female with a 22-year history of rheumatoid arthritis. She was diagnosed with myasthenia gravis when she was 31-year old. At the onset of pancreatitis, the patient was anti-nuclear antibody-positive,and had high serum gamma globulin and IgG4 levels.Dexamethasone and conventional therapy induced clinical remission and significantly decreased the serum IgG4 and gamma globulin. However, despite the decreased disease parameters, the patient developed a bleeding pseudocyst and died of cardiac failure. In the autopsy examination, it was determined that pancreatitis was probably caused by ischemia due to vascular obstruction caused by amyloid deposition in the pancreas. Even though acute pancreatitis is a rare complication in RA patients, we speculate that an autoimmune pancreatitis-related mechanism and ischemia due to vascular obstruction by amyloid deposition might be attributable to a single source that leads to acute pancreatitis in our particular case.

  18. A Unique Report: Development of Super Anti-Human IgG Monoclone with Optical Density Over Than 3

    Directory of Open Access Journals (Sweden)

    Leili Aghebati Maleki

    2013-08-01

    Full Text Available Purpose: Monoclonal antibodies and related conjugates are key reagents used in biomedical researches as well as, in treatment, purification and diagnosis of infectious and non- infectious diseases. Methods: Balb/c mice were immunized with purified human IgG. Spleen cells of the most immune mouse were fused with SP2/0 in the presence of Poly Ethylene Glycol (PEG. Supernatant of hybridoma cells was screened for detection of antibody by ELISA. Then, the sample was assessed for cross-reactivity with IgM & IgA by ELISA and confirmed by immunoblotting. The subclasses of the selected mAbs were determined. The best clone was injected intraperitoneally to some pristane-injected mice. Anti-IgG mAb was purified from the animals' ascitic fluid by Ion exchange chromatography and then, mAb was conjugated with HRP. Results: In the present study, over than 50 clones were obtained that 1 clone had optical density over than 3. We named this clone as supermonoclone which was selected for limiting dilution. The result of the immunoblotting, showed sharp band in IgG position and did not show any band in IgM&IgA position. Conclusion: Based on the findings of this study, the conjugated monoclonal antibody could have application in diagnosis of infectious diseases like Toxoplasmosis, Rubella and IgG class of other infectious and non- infectious diseases.

  19. EV71 infection correlates with viral IgG preexisting at pharyngo-laryngeal mucosa in children.

    Science.gov (United States)

    Xue, Jingchang; Li, Yaoming; Xu, Xiaoyi; Yu, Jie; Yan, Hu; Yan, Huimin

    2015-04-01

    Enterovirus 71 (EV71) infection causes severe central nervous system damage, particularly for children under the age of 5 years old, which remains a major public health burden worldwide. Clinical data released that children may be repeatedly infected by different members in enterovirus and get even worsen. Mucosa, especially epithelium of alimentary canal, was considered the primary site of EV71 infection. It has been elusive whether the preexsiting viral antibody in mucosa plays a role in EV71 infection. To answer this question, we respectively measured viral antibody response and EV71 RNA copy number of one hundred throat swab specimens from clinically confirmed EV71-infected children. The results released that low-level of mucosal IgG antibody against EV71 broadly existed in young population. More importantly, it further elucidated that the children with mucosal preexsiting EV71 IgG were prone to be infected, which suggested a former viral IgG mediated enhancement of viral infection in vivo.

  20. Toxoplasma gondii IgG antibodies in HIV/AIDS patients attending hospitals in Makurdi metropolis, Benue state, Nigeria

    Directory of Open Access Journals (Sweden)

    Amuta E.U

    2012-01-01

    Full Text Available Background: Toxoplasmosis is caused by Toxoplasma gondii, a parasite that gradually evolved to be the most opportunistic parasite that complicates the course of HIV/AIDS in developing countries. Aim: This study was undertaken to investigate the presence of Toxoplasma gondii IgG antibodies in HIV-infected patients attending hospitals in Makurdi metropolis, Benue State, Nigeria. Materials and Methods: The Enzyme-linked immunosorbent assay (ELISA technique was used to determine the presence of Toxo-IgG antibodies in blood samples collected from the HIV/AIDS patients and their CD4 counts were estimated using flow cytometry. Questionnaires were also administered to obtain information on their socio-demographic status. Results: Thirty-nine, 39 (10.8% were screened positive for Toxo-IgG antibodies out of the 360 HIV/AIDS patients enrolled. Males (10.3% and females (11.2% had similar seroprevalence of Toxo-IgG with no significant difference (χ2= 0.001, p>0.05. The presence of Toxoplasma IgG antibodies was found to be highest in the ≥ 54 years age group. A significant difference was observed in the seroprevalence of Toxoplasma IgG among age groups (χ2=11.56, p 0.05. Conclusion: Further investigations are still needed to clarify the exact relationship of the parasite infection, its effects on the HIV-infected and uninfected individuals and the detection of their major means of transmission.

  1. Human IgG responses against the N-terminal region of Merozoite Surface Protein 1 of Plasmodium vivax

    Directory of Open Access Journals (Sweden)

    Hernando Antonio Del Portillo

    1992-01-01

    Full Text Available The complete primary structure of the gene encoding the Merozoite Surface Protein 1 of Plasmodium vivax (PvMSP-1 revealed the existence of interspecies conserved regions among the analogous proteins of other Plasmodia species. Here, three DNA recombinant clones expressing 50, 200 and 500 amino acids from the N-terminal region of the PvMSP-1 protein were used on ELISA and protein immunoblotting assays to look at the IgG antibody responses of malaria patients from the Brasilian amazon region of Rondônia. The results showed the existance of P. vivax and P. falciparum IgG antibodies directed against PvMSP-1 antigenic determinants expressed in the clones containing the first 200 and the following 500 amino acids of the molecule, but not within the one expressing the most N-terminal 50 amino acids. Interestingly, there was no correlation between the levels of these IgG antibodies and the previous number of malaria infections.

  2. Kinetics and avidity of anti-Toxocara antibodies (IgG) in rabbits experimentally infected with Toxocara canis.

    Science.gov (United States)

    Bin, Lundia Luara Cavalcante; Santarém, Vamilton Alvares; Laposy, Cecília Braga; Rubinsky-Elefant, Guita; Roldán, William Henry; Giuffrida, Rogério

    2016-01-01

    An evaluation was made of the kinetics and avidity of anti-Toxocara antibodies (IgG) in rabbits experimentally infected with embryonated Toxocara canis eggs. Seventeen four month old New Zealand White rabbits were distributed into two groups. In the experimental group, twelve rabbits were infected orally with 1,000 embryonated T. canis eggs. A second group (n = 5), uninfected, was used as a control. Serum samples were collected for analysis on days 7, 14, 21, 28 and 60 post-infection (DPI). An indirect ELISA test was performed to evaluate the reactivity index (RI) of IgG anti-T. canis antibodies and to calculate the avidity index (AI). The animals showed seroconversion from the 14th DPI, with high AI (over 50%) except for one animal, which presented an intermediate AI. At 60 DPI, all the animals were seropositive and maintained a high AI. The data indicated that specific IgG antibodies formed early (14 DPI) in rabbits infected with T. canis, with a high avidity index that persisted throughout the course of the infection. PMID:27027550

  3. Evaluation of the Aspergillus Western blot IgG kit for diagnosis of chronic aspergillosis.

    Science.gov (United States)

    Oliva, A; Flori, P; Hennequin, C; Dubus, J-C; Reynaud-Gaubert, M; Charpin, D; Vergnon, J M; Gay, P; Colly, A; Piarroux, R; Pelloux, H; Ranque, S

    2015-01-01

    Immunoprecipitin detection (IPD) is the current reference confirmatory technique for anti-Aspergillus antibody detection; however, the lack of standardization is a critical drawback of this assay. In this study, we evaluated the performance of the Aspergillus Western blot (Asp-WB) IgG kit (LDBio Diagnostics, Lyon, France), a recently commercialized immunoblot assay for the diagnosis of various clinical presentations of chronic aspergillosis. Three hundred eight serum samples from 158 patients with aspergillosis sensu lato (s.l.) were analyzed. More specifically, 267 serum samples were derived from patients with Aspergillus disease, including 89 cases of chronic pulmonary aspergillosis, 10 of aspergilloma, and 32 of allergic bronchopulmonary aspergillosis, while 41 samples were from patients with Aspergillus colonization, including 15 cystic fibrosis (CF) and 12 non-CF patients. For blood donor controls, the Asp-WB specificity was 94%, while the kit displayed a sensitivity for the aspergillosis s.l. diagnosis of 88.6%, with a diagnostic odds ratio (DOR) of 119 (95% confidence interval [CI], 57 to 251). The DOR values were 185.22 (95% CI,78.79 to 435.45) and 43.74 (95% CI, 15.65 to 122.20) for the diagnosis of Aspergillus disease and Aspergillus colonization, respectively. Among the patients, the sensitivities of the Asp-WB in the diagnosis of Aspergillus colonization were 100% and 41.7% in CF and non-CF patients, respectively. The Asp-WB yielded fewer false-negative results than did IPD. In conclusion, the Asp-WB kit performed well for the diagnosis of various clinical presentations of aspergillosis in nonimmunocompromised patients, with an enhanced standardization and a higher sensitivity than with IPD, which is the current reference method.

  4. Establishment and preliminary application of Dengue virus envelope domain Ⅲ IgG antibody capture enzyme-linked immuno-absorbent assay

    Institute of Scientific and Technical Information of China (English)

    胡冬梅

    2013-01-01

    Objective To establish a highly sensitive and specific assay to detect Dengue virus(DENV) envelope protein domainⅢ(EDⅢ) IgG antibody,and to explore its value in the diagnosis and seroepidemiological survey of dengue

  5. IgE versus IgG4 epitopes of the peanut allergen Ara h 1 in patients with severe allergy

    DEFF Research Database (Denmark)

    Bøgh, Katrine Lindholm; Nielsen, H.; Eiwegger, T.;

    2014-01-01

    , suffering from severe allergic reaction to peanuts, including anaphylaxis, were used to analyse the IgE and IgG4 epitope recognition patterns of the major peanut allergen Ara h 1. Epitope identification was conducted by competitive immuno-screening of a phage-displayed random heptamer peptide library......Background: Development and maintenance of tolerance to food allergens appears to be associated with alterations in antigen specific IgE and IgG4 responses. Previous studies have focused only on comparing IgE and IgG4 linear epitope recognition patterns but take no account of conformational...... epitopes. Objective: The aim of this study was to compare Ara h 1-specific IgE and IgG4 epitope recognition patterns in patients with severe peanut allergy, applying a method allowing for identification of both linear and conformational epitopes. Methods: Polyclonal sera from three individual patients...

  6. Long-term follow-up of treatment with diethylcarbamazine on anti-filarial IgG4: dosage, compliance, and differential patterns in adults and children.

    Science.gov (United States)

    Terhell, A J; Haarbrink, M; van den Biggelaar, A; Mangali, A; Sartono, E; Yazdanbakhsh, M

    2003-01-01

    We have followed a population in an area endemic for Brugia malayi for three years after intensive treatment with diethylcarbamazine (DEC). Microfilariae were cleared from the circulation within four months in all eligible study participants (n = 60). There appeared to be a strong correlation between the maximum reduction in specific IgG4 and the number of days drug was taken under supervision (p = 0.41, P or = 15 years old) showed a gradual decrease in anti-filarial IgG4; 53% of these showed complete clearance of worm burden by the end of the study. In contrast, another group of male IgG4+ adults showed IgG4 patterns that started to increase between nine months and two years after treatment, indicating either a partial efficacy of DEC that allowed recovery of resident adult worms or reinfection. PMID:12556144

  7. Production of anti-horse antibodies induced by IgG, F(ab')2 and Fab applied repeatedly to rabbits. Effect on antivenom pharmacokinetics.

    Science.gov (United States)

    Vázquez, Hilda; Olvera, Felipe; Alagón, Alejandro; Sevcik, Carlos

    2013-12-15

    We separated whole IgG, Fab and F(ab')2 fragments from horse plasma. We previously studied the pharmacokinetics of these immunoglobulins and fragments in rabbits and shown that Fab and F(ab')2 pharmacokinetics were well described by a three-exponential kinetics, while IgG and IgG(T) pharmacokinetics, however, deviated from the three-exponential kinetics 120 h after injecting a bolus of the immunotherapeutics; this departure was shown to be due to a surge of anti-horse antibodies occurring after 120 h, peaking at ≈260 h and decaying slowly afterward (Vázquez et al., 2010). We now describe antivenom pharmacokinetics and anti-horse IgG production in rabbits receiving three boluses (300 μg/kg, I.V.) of Fab, F(ab')2 or IgG separated by 21 days.

  8. Evaluation of the PANBIO Brucella immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays for diagnosis of human brucellosis.

    Science.gov (United States)

    Araj, George F; Kattar, Mireille M; Fattouh, Layla G; Bajakian, Kayane O; Kobeissi, Sara A

    2005-11-01

    PANBIO Brucella immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays (ELISAs) were assessed against Brucella standard agglutination tube and Coombs tests. The sensitivities of ELISA IgG and IgM were 91% and 100%, respectively, while the specificity was 100% for both. These ELISAs are simple, rapid, and reliable for the diagnosis of human brucellosis. PMID:16275951

  9. Comparison of enzyme immunoassays detecting Helicobacter pylori specific IgG in serum and saliva with endoscopic and biopsy findings in patients with dyspepsia

    OpenAIRE

    A El-Mekki; Kumar, A; B Alknawy; Al-Ammari, O; Moosa, R; S Quli; Ahmed, M

    2011-01-01

    Purpose: To compare the performance of two indirect enzyme-linked immunosorbent assays (ELISA) detecting Helicobacter pylori (HP)-specific IgG antibodies in serum and saliva with endoscopic observations and histologic findings of biopsies from dyspeptic patients, in an area of high HP prevalence. Materials and Methods : Sera, saliva and antral biopsies were obtained from 55 dyspeptic patients. IgG antibodies against HP were assayed in sera and saliva utilizing two indirect ELISAs. Biopsies we...

  10. Maternal-fetal immunoglobulin transport: Studies on the binding, internalization, and release of IgG by chick yolk sac tissue and cultured cells

    International Nuclear Information System (INIS)

    Immunoglobulin G (IgG) is transported from the yolk across the endodermal cells of the yolk sac and into the fetal circulation during chick embryonic development, thus providing the chick with passive immunity until it becomes immunocompetent. Saturable, Fc-specific receptors are present on the endodermal cells and are believed to mediate this transfer. In this study, IgG receptors were shown to be present on the yolk sac endodermal cells throughout the 21 days of development, although most of the transport occurs during the last 3 days prior to hatching. Fluorescently conjugated IgG was internalized by a receptor mechanism into small apical vesicles in yolk sac endoderm throughout, but cells from 19 day yolk sacs internalized more conjugate than those from 14 day yolk sacs. This was confirmed and quantitated by assaying the internalization of 125I-IgG into yolk sac tissue. IgG was internalized by a receptor mediated mechanism, reaching a steady state level after 1 to 2 hours. Although both ages of yolk sac tissue possessed the same number of surface IgG receptors, as measured by equilibrium binding assays at 4 degree C, 19 day yolk sac had the capacity to internalize six times as much IgG by a receptor mechanism as 14 day yolk sac

  11. IgG and IgA with Potential Microbial-Binding Activity Are Expressed by Normal Human Skin Epidermal Cells

    Directory of Open Access Journals (Sweden)

    Dongyang Jiang

    2015-01-01

    Full Text Available The innate immune system of the skin is thought to depend largely on a multi-layered mechanical barrier supplemented by epidermis-derived antimicrobial peptides. To date, there are no reports of antimicrobial antibody secretion by the epidermis. In this study, we report the expression of functional immunoglobulin G (IgG and immunoglobulin A (IgA, previously thought to be only produced by B cells, in normal human epidermal cells and the human keratinocyte line HaCaT. While B cells express a fully diverse Ig, epidermal cell-expressed IgG or IgA showed one or two conservative VHDJH rearrangements in each individual. These unique VDJ rearrangements in epidermal cells were found neither in the B cell-derived Ig VDJ databases published by others nor in our positive controls. IgG and IgA from epidermal cells of the same individual had different VDJ rearrangement patterns. IgG was found primarily in prickle cells, and IgA was mainly detected in basal cells. Both epidermal cell-derived IgG and IgA showed potential antibody activity by binding pathogens like Staphylococcus aureus, the most common pathogenic skin bacteria, but the microbial-binding profile was different. Our data indicates that normal human epidermal cells spontaneously express IgG and IgA, and we speculate that these Igs participate in skin innate immunity.

  12. IgG immune responses to different proteins of Helicobacter Pylori as defined by immunoblot assay

    Directory of Open Access Journals (Sweden)

    Raeiszadeh M

    2000-09-01

    Full Text Available Helicobacter pylori (H.pylori is an etiologic factor for chronic gastritis and peptic ulcers. Serological testing of H.pylori infection is common in Iran, as other parts of the world. There are geographical variations in the humoral immune response to various H. pylori strains in different parts of the worl. We studied the immunogenic proteins of H.pylori by means of an Immunoblot assay with antigens of H.pylori strains isolated in Iran. Sera of 64 patients suffering from dyspepsia were analyzed to determine antibodlies which were good marker of infection and the antibody patterns associated with peptic ulcer.54 out of 64 dyspeptic patients were infected by H. pylori based on positive culture or positive results of both rapid urease test and direct examination. 14 out of fity-four had peptic ulcers and the rest were catagoriied as patients with non-ulcer dyspepsia. Some of them had multiple erosions in the gut or deodenum. Tweny –two major bands were identified by immunoblot. Of these, IgG antibodies against 10 protients, and they produced immunoreative bands at 14, 16, 22, 26, 32 , 32, 44, 87, 92, 120 Kda. Antibody patterns were not identical in the patients. The presence of at least one band at 14, 16, 22, 26, 32, 35Kda was the best marker of infection(sensitivity, 90% and specificity, 80% Major serological cross reactions were found at moderate molecular weight bands (50, 52, 54, 60, 66 KDa. The presence of at least one band at 14, 16, 22, 26, 32, 35Kda was the best marker of infection (sensitivity, 90% and specificity, 80%. Major serological crossreactions were found at moderate molerate molecular weight bands (50, 52, 54, 60, 66 KDa. The presence of antibodies to 120 Kda protein (Cag A and 87 Kda Protein (Vac A were not associated with the presence of peptic ulcers. These were in contradiction to results obtained across Europe and U.S but in agreement with Asian studies. However the presence of at least one band at either 32 or 35 Kda was

  13. Non-immune binding of human IgG to M-related proteins confers resistance to phagocytosis of group A streptococci in blood.

    Directory of Open Access Journals (Sweden)

    Harry S Courtney

    Full Text Available The non-immune binding of immunoglobulins by bacteria is thought to contribute to the pathogenesis of infections. M-related proteins (Mrp are group A streptococcal (GAS receptors for immunoglobulins, but it is not known if this binding has any impact on virulence. To further investigate the binding of immunoglobulins to Mrp, we engineered mutants of an M type 4 strain of GAS by inactivating the genes for mrp, emm, enn, sof, and sfbX and tested these mutants in IgG-binding assays. Inactivation of mrp dramatically decreased the binding of human IgG, whereas inactivation of emm, enn, sof, and sfbx had only minor effects, indicating that Mrp is a major IgG-binding protein. Binding of human immunoglobulins to a purified, recombinant form of Mrp indicated that it selectively binds to the Fc domain of human IgG, but not IgA or IgM and that it preferentially bound subclasses IgG₁>IgG₄>IgG₂>IgG₃. Recombinant proteins encompassing different regions of Mrp were engineered and used to map its IgG-binding domain to its A-repeat region and a recombinant protein with 3 A-repeats was a better inhibitor of IgG binding than one with a single A-repeat. A GAS mutant expressing Mrp with an in-frame deletion of DNA encoding the A-repeats had a dramatically reduced ability to bind human IgG and to grow in human blood. Mrp exhibited host specificity in binding IgG; human IgG was the best inhibitor of the binding of IgG followed by pig, horse, monkey, and rabbit IgG. IgG from goat, mouse, rat, cow, donkey, chicken, and guinea pig were poor inhibitors of binding. These findings indicate that Mrp preferentially binds human IgG and that this binding contributes to the ability of GAS to resist phagocytosis and may be a factor in the restriction of GAS infections to the human host.

  14. Retrospective Study of Phospholipase A2 Receptor and IgG Subclasses in Glomerular Deposits in Chinese Patients with Membranous Nephropathy.

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    Hong-Rui Dong

    Full Text Available The research work in the past years showed that detection of phospholipase A2 receptor (PLA2R antigen and its dominant IgG4 autoantibody in glomerular deposits of patients with membranous nephropathy (MN was useful for the differentiation between primary MN (PMN and secondary MN (SMN, but so far such research data from large Chinese patient series is little. Here, we are going to report a research work in a Chinese cohort.This study enrolled 179 patients with PMN, 40 patients with membranous lupus nephritis (LN-MN, 26 patients with hepatitis B virus-associated MN (HBV-MN, 2 patients with malignancy-associated MN (M-MN and one patient with IgG4-related MN (IgG4-MN. PLA2R and IgG subclasses in glomerular deposits of these patients were examined by immunofluorescence and/or immunohistochemical staining, and the potential value of the above examinations for differential diagnosis of PMN and SMN was evaluated.Glomerular PLA2R deposition was present in 92.2% patients with PMN and 7.7% patients with HBV-MN, but none of the patients with LN-MN. Predominant/codominant IgG4 deposition was found in 93.3% patients with PMN and 11.5% patients with HBV-MN, but none of the patients with LN-MN. The two M-MN patients both had glomerular PLA2R and predominant/codominant IgG4 deposition. The one IgG4-MN patient had deeply staining IgG4 but no PLA2R in glomeruli.The glomerular PLA2R and predominant/codominant IgG4 deposition is frequently observed in Chinese patients with PMN. Immunofluorescence and immunohistochemical staining of renal biopsy tissue for detection of glomerular PLA2R and IgG subclasses deposition can help to distinguish PMN from LN-MN and most of HBV-MN.

  15. Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment.

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    Iain W Chalmers

    Full Text Available The heptalaminate-covered, syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term, intravascular residence in definitive hosts. Investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. Recent studies have revealed a number of novel tegumental surface proteins including three (SmCD59a, SmCD59b and Sm29 containing uPAR/Ly6 domains (renamed SmLy6A SmLy6B and SmLy6D in this study. While vaccination with SmLy6A (SmCD59a and SmLy6D (Sm29 induces protective immunity in experimental models, human immunoglobulin responses to representative SmLy6 family members have yet to be thoroughly explored.Using a PSI-BLAST-based search, we present a comprehensive reanalysis of the Schistosoma mansoni Ly6 family (SmLy6A-K. Our examination extends the number of members to eleven (including three novel proteins and provides strong evidence that the previously identified vaccine candidate Sm29 (renamed SmLy6D is a unique double uPAR/Ly6 domain-containing representative. Presence of canonical cysteine residues, signal peptides and GPI-anchor sites strongly suggest that all SmLy6 proteins are cell surface-bound. To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE responses against two surface-bound representatives (SmLy6A and SmLy6B within a cohort of S. mansoni-infected Ugandan males before and after praziquantel treatment. While pre-treatment IgG1 prevalence for SmLy6A and SmLy6B differs amongst the studied population (7.4% and 25.3% of the cohort, respectively, these values are both higher than IgG1 prevalence (2.7% for a sub-surface tegumental antigen, SmTAL1. Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0.001, respectively when compared to rising IgG

  16. Prognostic significance of specific anti-WT1 IgG antibody level in plasma in patients with ovarian carcinoma

    International Nuclear Information System (INIS)

    Ovarian carcinoma (OC) has a poor prognosis and lack early effective screening markers. Wilm's tumor gene 1 (WT1) is overexpressed in OCs. Therefore, it is of great interest to investigate whether WT1-specific antibody (Ab) measurements in plasma can serve as a biomarker of anti-OC response, and is of importance in relation to patient prognosis. Peripheral blood samples were obtained from a total of 103 women with ovarian tumors with median being 1 day (range 0–48 days) before operation. WT1 IgG Ab levels were evaluated using enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis of WT1 protein expression was performed on OC tissue samples. We found that low-WT1 Ab level in plasma was related to improved survival in patients diagnosed at stages III–IV and grade 3 carcinomas. Positive WT1 protein staining on OC tissue samples had a negative impact on survival in the entire cohort, both overall survival (OS) (P = 0.046) and progression-free survival (PFS) (P = 0.006), but not in the serous OC subtype. Combining WT1 IgG Ab levels and WT1 staining, patients with high-WT1 IgG Ab levels in plasma and positive WT1 protein staining in cancer tissues had shorter survival, with a significant association in PFS (P = 0.016). These results indicated that WT1 Ab measurements in plasma and WT1 staining in tissue specimens could be useful as biomarkers for patient outcome in the high-risk subtypes of OCs for postoperative individualized therapy

  17. Goat anti-rabbit IgG conjugated fluorescent dye-doped silica nanoparticles for human breast carcinoma cell recognition.

    Science.gov (United States)

    Chen, Min-Yan; Chen, Ze-Zhong; Wu, Ling-Ling; Tang, Hong-Wu; Pang, Dai-Wen

    2013-11-12

    We report an indirect method for cancer cell recognition using photostable fluorescent silica nanoprobes as biological labels. The dye-doped fluorescent silica nanoparticles were synthesized using the water-in-oil (W/O) reverse microemulsion method. The silica matrix was produced by the controlled hydrolysis of tetraethylorthosilicate (TEOS) in water nanodroplets with the initiation of ammonia (NH3·H2O). Fluorescein isothiocyanate (FITC) or rhodamine B isothiocyanate conjugated with dextran (RBITC-Dextran) was doped in silica nanoparticles (NPs) with a size of 60 ± 5 nm as a fluorescent signal element by covalent bonding and steric hindrance, respectively. The secondary antibody, goat anti-rabbit IgG, was conjugated on the surface of the PEG-terminated modified FITC-doped or RBITC-Dextran-doped silica nanoparticles (PFSiNPs or PBSiNPs) by covalent binding to the PEG linkers using the cyanogen bromide method. The concentrations of goat anti-rabbit IgG covering the nanoprobes were quantified via the Bradford method. In the proof-of-concept experiment, an epithelial cell adhesion molecule (EpCAM) on the human breast cancer SK-Br-3 cell surface was used as the tumor marker, and the nanoparticle functionalized with rabbit anti-EpCAM antibody was employed as the nanoprobe for cancer cell recognition. Compared with fluorescent dye labeled IgG (FITC-IgG and RBITC-IgG), the designed nanoprobes display dramatically increased stability of fluorescence as well as photostability under continuous irradiation. PMID:24179992

  18. IgG variable region and VH CDR3 diversity in unimmunized mice analyzed by massively parallel sequencing.

    Science.gov (United States)

    Lu, Jin; Panavas, Tadas; Thys, Kim; Aerssens, Jeroen; Naso, Michael; Fisher, Jamie; Rycyzyn, Michael; Sweet, Raymond W

    2014-02-01

    Most antigen-specific mouse antibodies have been derived by hybridoma technology, predominantly through use of the Balb/c strain. Much of the Balb/c germline repertoire of variable genes (V regions) is known. However, there is little information about the background expressed repertoire of IgG antibodies in mice, which reflects the baseline against which antigen-specific antibodies are generated through immunization. To assess this baseline repertoire, RNA was isolated from splenic B-cells enriched for expression of IgG from three mice. The RNA was individually amplified with three distinct PCR primer sets for comprehensive recovery of the heavy and light chain variable regions. Each PCR product was independently subjected to deep sequencing using 454 pyro-sequencing technology and analysed for redundancy, open reading frame, germline representation, and CDR3 sequence of the heavy chain variable region (VH CDR3) within and across the primer sets and mice. A highly skewed abundance of heavy and light chain variable gene usage was observed for all three primers in all three mice. While showing considerable overlap, there were differences among these profiles indicative of primer bias and animal-to-animal variation. VH CDR3 sequences were likewise highly skewed indicating that the heavy chain genes profiles substantially reflected individual antibodies. This observation was confirmed through analysis of randomly selected complete heavy chain variable sequences. However, there was very little redundancy in VH CDR3 sequences across the different mice. We conclude that the background IgG repertoire in young, unimmunized mice is highly skewed within individual mice and is diverse among them, a pattern similar to that observed in highly immunized mice.

  19. Structural Basis for Fc[gamma]RIIa Recognition of Human IgG and Formation of Inflammatory Signaling Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Ramsland, Paul A.; Farrugia, William; Bradford, Tessa M.; Sardjono, Caroline Tan; Esparon, Sandra; Trist, Halina M.; Powell, Maree S.; Tan, Peck Szee; Cendron, Angela C.; Wines, Bruce D.; Scott, Andrew M.; Hogarth, P. Mark (Burnet); (Monash); (LICR); (Melbourne)

    2011-09-20

    The interaction of Abs with their specific FcRs is of primary importance in host immune effector systems involved in infection and inflammation, and are the target for immune evasion by pathogens. Fc{gamma}RIIa is a unique and the most widespread activating FcR in humans that through avid binding of immune complexes potently triggers inflammation. Polymorphisms of Fc{gamma}RIIa (high responder/low responder [HR/LR]) are linked to susceptibility to infections, autoimmune diseases, and the efficacy of therapeutic Abs. In this article, we define the three-dimensional structure of the complex between the HR (arginine, R134) allele of Fc{gamma}RIIa (Fc{gamma}RIIa-HR) and the Fc region of a humanized IgG1 Ab, hu3S193. The structure suggests how the HR/LR polymorphism may influence Fc{gamma}RIIa interactions with different IgG subclasses and glycoforms. In addition, mutagenesis defined the basis of the epitopes detected by FcR blocking mAbs specific for Fc{gamma}RIIa (IV.3), Fc{gamma}RIIb (X63-21), and a pan Fc{gamma}RII Ab (8.7). The epitopes detected by these Abs are distinct, but all overlap with residues defined by crystallography to contact IgG. Finally, crystal structures of LR (histidine, H134) allele of Fc{gamma}RIIa and Fc{gamma}RIIa-HR reveal two distinct receptor dimers that may represent quaternary states on the cell surface. A model is presented whereby a dimer of Fc{gamma}RIIa-HR binds Ag-Ab complexes in an arrangement that possibly occurs on the cell membrane as part of a larger signaling assembly.

  20. Community knowledge, health beliefs, practices and experiences related to dengue fever and its association with IgG seropositivity.

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    Li Ping Wong

    2014-05-01

    Full Text Available BACKGROUND: Demographic, economic and behavioural factors are central features underpinning the successful management and biological control of dengue. This study aimed to examine these factors and their association with the seroprevalence of this disease. METHODOLOGY: We conducted a cross-sectional telephone survey of households in a 3 km radius of the schools where we had conducted serological tests on the student population in a previous study. Households were surveyed about their socio-demographics, knowledge, practices, and Health Belief Model (HBM constructs. The results were then associated with the prevalence rate of dengue in the community, as marked by IgG seropositivity of the students who attended school there. RESULTS: A total of 1,400 complete responses were obtained. The community's IgG seropositivity was significantly positively associated with high household monthly income, high-rise residential building type, high surrounding vegetation density, rural locality, high perceived severity and susceptibility, perceived barriers to prevention, knowing that a neighbour has dengue, frequent fogging and a higher level of knowledge about dengue. In the multivariate analyses, three major correlates of the presence of IgG seropositivity in the community: (1 high-rise residential apartment house type or condominium buildings; (2 the main construct of the HBM, perceived severity and susceptibility; and (3 the additional constructs of the HBM, lack of preventive measures from the community level and having a neighbour with dengue as a cue to action. Weak correlations were found between self-practices to prevent dengue and the level of dengue seropositivity in the community, and between HBM constructs and knowledge (r = 0.09. CONCLUSIONS: The residential environment factor and the constructs of the HBM are useful and important elements in developing interventions to prevent and control dengue. The study also sheds light on the importance

  1. Diphtheria toxin IgG levels in military and civilian blood donors in Rio de Janeiro, Brazil

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    F.A.B. Speranza

    2010-01-01

    Full Text Available Serologic data on diseases that are preventable by vaccines are necessary to evaluate the success of immunization programs and to identify susceptible subgroups. In the present study, we determined serum IgG levels against diphtheria toxin of military and civilian blood donors (N = 75; 69.3% males and 30.7% females aged 18-64 years, from the Brazilian Army Biology Institute, Rio de Janeiro, using a commercial diphtheria kit (Diphtheria IgG ELISA; IBL, Germany. Most (63% unprotected military donors were from the older age group of 41 to 64 years. In contrast, the majority (71% of young military donors (18 to 30 years were fully protected. About half of the military donors aged 31 to 40 years were protected against diphtheria. Among the civilians, about 50% of persons aged 18 to 30 years and 31 to 40 years had protective antibody levels against diphtheria as also did 64% of individuals aged 41 to 64 years. All civilians had a similar antibody response (geometric mean = 0.55 IU/mL independent of age group. Military donors aged 18-30 years had higher IgG levels (geometric mean = 0.82 IU/mL than military donors of 41-64 years (geometric mean = 0.51 IU/mL; P > 0.05. In conclusion, the existence of a considerable proportion of susceptible adults supports the position that reliable data on the immune status of the population should be maintained routinely and emphasizes the importance of adequate immunization during adulthood.

  2. IgG receptor FcγRIIB plays a key role in obesity-induced hypertension.

    Science.gov (United States)

    Sundgren, Nathan C; Vongpatanasin, Wanpen; Boggan, Brigid-Meghan D; Tanigaki, Keiji; Yuhanna, Ivan S; Chambliss, Ken L; Mineo, Chieko; Shaul, Philip W

    2015-02-01

    There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fcγ receptor IIB (FcγRIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and hypertension in humans, in the present study we tested the hypothesis that FcγRIIB plays a role in obesity-induced hypertension in mice. Using radiotelemetry, we first demonstrated that the hypertension observed in transgenic mouse-CRP is mediated by the receptor, indicating that FcγRIIB is capable of modifying blood pressure. We then discovered in a model of diet-induced obesity yielding equal adiposity in all study groups that whereas FcγRIIB(+/+) mice developed obesity-induced hypertension, FcγRIIB(-/-) mice were fully protected. Levels of CRP, the related pentraxin serum amyloid P component which is the CRP-equivalent in mice, and total IgG were unaltered by diet-induced obesity; FcγRIIB expression in endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice had no effect, IgG from high-fat diet-fed mice inhibited endothelial NO synthase in cultured endothelial cells, and this was an FcγRIIB-dependent process. Thus, we have identified a novel role for FcγRIIB in the pathogenesis of obesity-induced hypertension, independent of processes regulating adiposity, and it may entail an IgG-induced attenuation of endothelial NO synthase function. Approaches targeting FcγRIIB may potentially offer new means to treat hypertension in obese individuals.

  3. Seroprevalence of Toxoplasma gondii IgG antibody in HIV/AIDS-infected individuals in Maputo, Mozambique

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    Abílio Domingos

    2013-10-01

    Full Text Available OBJECTIVE To analyze the prevalence of IgG antibodies to Toxoplasma gondii in patients infected with HIV/AIDS and the association of demographic and social variables. METHODS Descriptive cross-sectional study that included the analysis of sociodemographic data and laboratory findings of 200 patients infected with HIV/AIDS treated in a laboratory unit in Maputo, Mozambique, in 2010. Individual data for all participants were collected with a self-administered questionnaire. Plasma samples were tested for IgG testing of anti- T. gondii using hemagglutination for the analysis of antibodies. RESULTS The seroprevalence of IgG anti- T. gondii was 46.0% (95%CI 39.2;52.9, 39.3% (95%CI 29.5;50.0 in men and 50.9% (95%CI 41.9;59.8 in women, with no difference between sex (OR 1.30; 95%CI 0.95;1.77; p = 0.12. Ages ranged from 10 to 60 years, with a higher prevalence of infection in older age groups, but with no significant difference between them. Regularly consuming cattle meat (OR 1.74; 95%CI 1.04;2.89, p = 0.05, breeding cats/dogs (OR 6.18; 95%CI 3.60;10.62, p < 0.000 and having regular contact with soil (OR 3.38; 95%CI 2.19;5.21; p < 0.000 were significantly associated with risk of latent infection. CONCLUSIONS Toxoplasmosis is an infection with high prevalence in Mozambique. Cultural and behavioral aspects increase the risk. Toxoplasmosis can be responsible in our environment by the great burden of morbidity and mortality associated with meningoencephalic injuries in patients with HIV/AIDS.

  4. Multiplex microsphere immunoassays for the detection of IgM and IgG to arboviral diseases.

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    Alison J Basile

    Full Text Available Serodiagnosis of arthropod-borne viruses (arboviruses at the Division of Vector-Borne Diseases, CDC, employs a combination of individual enzyme-linked immunosorbent assays and microsphere immunoassays (MIAs to test for IgM and IgG, followed by confirmatory plaque-reduction neutralization tests. Based upon the geographic origin of a sample, it may be tested concurrently for multiple arboviruses, which can be a cumbersome task. The advent of multiplexing represents an opportunity to streamline these types of assays; however, because serologic cross-reactivity of the arboviral antigens often confounds results, it is of interest to employ data analysis methods that address this issue. Here, we constructed 13-virus multiplexed IgM and IgG MIAs that included internal and external controls, based upon the Luminex platform. Results from samples tested using these methods were analyzed using 8 different statistical schemes to identify the best way to classify the data. Geographic batteries were also devised to serve as a more practical diagnostic format, and further samples were tested using the abbreviated multiplexes. Comparative error rates for the classification schemes identified a specific boosting method based on logistic regression "Logitboost" as the classification method of choice. When the data from all samples tested were combined into one set, error rates from the multiplex IgM and IgG MIAs were <5% for all geographic batteries. This work represents both the most comprehensive, validated multiplexing method for arboviruses to date, and also the most systematic attempt to determine the most useful classification method for use with these types of serologic tests.

  5. A Historical Look at the First Reported Cases of Lassa Fever: IgG Antibodies 40 Years After Acute Infection

    OpenAIRE

    Bond, Nell; John S Schieffelin; Moses, Lina M; Andrew J Bennett; Bausch, Daniel G.

    2013-01-01

    Lassa fever is an acute and sometimes severe viral hemorrhagic illness endemic in West Africa. One important question regarding Lassa fever is the duration of immunoglobulin G (IgG) antibody after infection. We were able to locate three persons who worked in Nigeria dating back to the 1940s, two of whom were integrally involved in the early outbreaks and investigations of Lassa fever in the late 1960s, including the person from whom Lassa virus was first isolated. Two persons had high titers ...

  6. A study on the effects of the estrous cycle on uterine fluid and blood serum immunoglobulin G (IgG content in the cow

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    Sayed Mortaza Alavi-Shoushtari

    2014-06-01

    Full Text Available To investigate the IgG content and its variations in uterine fluid (UF during the estrous cycle of the cow and to compare them with those of the blood serum (S, six pairs of serum and UF samples for each phase of the cycle selected out of 240 bovine genital tracts and blood samples were collected from Urmia abattoir. The UF samples were collected by gentle scraping of the endometrium using a curette after uterine incision and their IgG content and those of the serum were measured by single radial immuno-diffusion (SRID assay. Serum IgG values (Mean ± SEM were generally higher than the UF values throughout the cycle except for di-estrus (S: 38.50 ± 0.90, UF: 51.60 ± 2.10 mg mL-1, in which the highest values were observed in UF samples. In met-estrus the difference was not significant (S: 34.80 ± 1.80mg mL-1, UF: 30.80 ± 5.20 mg mL-1, however, in estrus the mean UF IgG value (12.50 ± 1.10 mg mL-1 was lower than that of the serum (31.30 ± 1.20 mg mL-1. In pro-estrus, the lowest values (S: 27.80 ± 1.30 mg mL-1, UF: 9.10 ± 1.50 mg mL-1 were obtained. The results showed a lower IgG values in the bovine UF than those of the serum in the follicular phase of the cycle, while in di-estrus the UF IgG content was the highest, suggesting some IgG production in the uterus at this phase.

  7. IgG4相关硬化性疾病30例病理特点%Pathological Features of 30 Cases IgG4 Related Sclerosing Disease

    Institute of Scientific and Technical Information of China (English)

    陈志忠; 陈小岩

    2014-01-01

    Objective To explore the IgG4 related to the pathological features of disease, to improve the recognition of clinical and pathologic doctor for this disease. Methods Collect the pathological diagnosis of IgG4 related pathological 30 cases, disease changes to the histological and immunohistochemical characteristics and so on carries on the observation and analysis, and review the relevant literature. Results 30 cases of IgG4 related mean age, 52.0 years, patients with sclerosing disease than for men and women:3:2, af ected organs including nasopharyngeal 4 cases, 5 cases of submandibular gland, sublingual gland in 1 case, 1 cases of parotid gland, tear ducts or surrounding tissue in 3 cases, 1 case of spleen, lung, 4 cases, 2 cases of liver, lymph nodes in 1 case, 1 case of abdominal wall, 1 cases of retroperitoneal, 1 cases of pelvic floor, 2 cases and left temporal maxil ary neoplasm, knee, back the mass in 1 case;Histological changes of the af ected tissue lymphocytic and plasma cell infiltrates in great quantities, part with lymphoid fol icular formation, fibrous tissue hyperplasia, some cases visible inherent gland atrophy, infringement of vascular, hyperplasia of vascular occlusive vasculitis and existence;Immunohistochemical staining showed IgG4 + 30 ~ 100 / HPF plasma cellcounts, IgG4 + / IgG ratio > 40%. Conclusion IgG4 related sclerosing disease is a rare autoimmune disease, etiology is unknown and involving multiple systems, lack of characteristic clinical manifestations, diagnosis combined with clinical manifestation, laboratory examination and histopathology of comprehensive analysis, among them, the laboratory examination, tissue morphological features and immunohistochemical expression is an important diagnostic basis.%目的探讨IgG4相关硬化性疾病的病理特征,提高临床和病理医生对本病的认识。方法收集病理诊断为IgG4相关硬化性疾病的病理30例,对其组织学改变及免疫组化特点等进

  8. An engineered diatom acting like a plasma cell secreting human IgG antibodies with high efficiency

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    Hempel Franziska

    2012-09-01

    Full Text Available Abstract Background Although there are many different expression systems for recombinant production of pharmaceutical proteins, many of these suffer from drawbacks such as yield, cost, complexity of purification, and possible contamination with human pathogens. Microalgae have enormous potential for diverse biotechnological applications and currently attract much attention in the biofuel sector. Still underestimated, though, is the idea of using microalgae as solar-fueled expression system for the production of recombinant proteins. Results In this study, we show for the first time that completely assembled and functional human IgG antibodies can not only be expressed to high levels in algal systems, but also secreted very efficiently into the culture medium. We engineered the diatom Phaeodactylum tricornutum to synthesize and secrete a human IgG antibody against the Hepatitis B Virus surface protein. As the diatom P. tricornutum is not known to naturally secrete many endogenous proteins, the secreted antibodies are already very pure making extensive purification steps redundant and production extremely cost efficient. Conclusions Microalgae combine rapid growth rates with all the advantages of eukaryotic expression systems, and offer great potential for solar-powered, low cost production of pharmaceutical proteins.

  9. Comparative Diagnosis of Serum IgG1 and Coproantigen ELISA for Fasciolosis Detection of Goats in Mexico.

    Science.gov (United States)

    Villa-Mancera, Abel; Molina-Mendoza, Pedro; Hernández-Guzmán, Karina; Olivares-Pérez, Jaime; Sarracent-Pérez, Jorge; Zumaquero-Ríos, José

    2016-01-01

    The objective of present study was to determine the prevalence of natural caprine fasciolosis in the Mixteca region of Mexico using coproantigen and serum IgG1 ELISA tests for comparative purposes. A total of 1070 serum and faecal samples were analyzed for IgG1 antibodies and coproantigens, using ELISA with E/S products as antigen and a monoclonal antibody-based sandwich ELISA. Prevalence of 73.46% was found using the serological ELISA and a percentage of 77.20 was found for coproantigen ELISA. The diagnostic sensitivity and specificity for serum ELISA were 86.7% and 96.4%, and for the coproantigen ELISA they were 93.1% and 97.8%, respectively. The seropositive samples were further categorized as low, medium, or high positivity. Results show a great proportion of low and medium positive goats when the serum ELISA test was used. Correlation coefficients between coproantigens and seropositivity were statistically significant (P < 0.01) for low seropositivity (r = 0.93) and medium seropositivity (r = 0.84). The accuracy of faecal antigen ELISA was higher compared to indirect ELISA serological test. Two ELISAs were shown to be useful for demonstrating the current status of F. hepatica infection in the endemic areas and can be employed in studies on epidemiology as well as anthelmintics treatment for preventing economic loss and the risk of transmission to humans. PMID:27563665

  10. Comparative Diagnosis of Serum IgG1 and Coproantigen ELISA for Fasciolosis Detection of Goats in Mexico.

    Science.gov (United States)

    Villa-Mancera, Abel; Molina-Mendoza, Pedro; Hernández-Guzmán, Karina; Olivares-Pérez, Jaime; Sarracent-Pérez, Jorge; Zumaquero-Ríos, José

    2016-01-01

    The objective of present study was to determine the prevalence of natural caprine fasciolosis in the Mixteca region of Mexico using coproantigen and serum IgG1 ELISA tests for comparative purposes. A total of 1070 serum and faecal samples were analyzed for IgG1 antibodies and coproantigens, using ELISA with E/S products as antigen and a monoclonal antibody-based sandwich ELISA. Prevalence of 73.46% was found using the serological ELISA and a percentage of 77.20 was found for coproantigen ELISA. The diagnostic sensitivity and specificity for serum ELISA were 86.7% and 96.4%, and for the coproantigen ELISA they were 93.1% and 97.8%, respectively. The seropositive samples were further categorized as low, medium, or high positivity. Results show a great proportion of low and medium positive goats when the serum ELISA test was used. Correlation coefficients between coproantigens and seropositivity were statistically significant (P < 0.01) for low seropositivity (r = 0.93) and medium seropositivity (r = 0.84). The accuracy of faecal antigen ELISA was higher compared to indirect ELISA serological test. Two ELISAs were shown to be useful for demonstrating the current status of F. hepatica infection in the endemic areas and can be employed in studies on epidemiology as well as anthelmintics treatment for preventing economic loss and the risk of transmission to humans.

  11. Comparative Diagnosis of Serum IgG1 and Coproantigen ELISA for Fasciolosis Detection of Goats in Mexico

    Directory of Open Access Journals (Sweden)

    Abel Villa-Mancera

    2016-01-01

    Full Text Available The objective of present study was to determine the prevalence of natural caprine fasciolosis in the Mixteca region of Mexico using coproantigen and serum IgG1 ELISA tests for comparative purposes. A total of 1070 serum and faecal samples were analyzed for IgG1 antibodies and coproantigens, using ELISA with E/S products as antigen and a monoclonal antibody-based sandwich ELISA. Prevalence of 73.46% was found using the serological ELISA and a percentage of 77.20 was found for coproantigen ELISA. The diagnostic sensitivity and specificity for serum ELISA were 86.7% and 96.4%, and for the coproantigen ELISA they were 93.1% and 97.8%, respectively. The seropositive samples were further categorized as low, medium, or high positivity. Results show a great proportion of low and medium positive goats when the serum ELISA test was used. Correlation coefficients between coproantigens and seropositivity were statistically significant (P<0.01 for low seropositivity (r=0.93 and medium seropositivity (r=0.84. The accuracy of faecal antigen ELISA was higher compared to indirect ELISA serological test. Two ELISAs were shown to be useful for demonstrating the current status of F. hepatica infection in the endemic areas and can be employed in studies on epidemiology as well as anthelmintics treatment for preventing economic loss and the risk of transmission to humans.

  12. Neuronal Fc gamma receptor I as a novel mediator for IgG immune complex-induced peripheral sensitization

    Institute of Scientific and Technical Information of China (English)

    Lintao Qu

    2012-01-01

    Chronic pain often accompanies immune-related diseases with an elevated level of IgG immune complex (IgG-IC) in the serum and/or the affected tissues though the underlying mechanisms are largely unknown. Fc gamma receptors (FcγRs), known as the receptors for the Fc domain of immunoglobulin G (IgG), are typically expressed on immune cells. A general consensus is that the activation of FcγRs by IgG-IC in such immune cells induces the release of proinflammatory cytokines from the immune cells, which may contribute to the IgG-IC-mediated peripheral sensitization. In addition to the immune cells, recent studies have revealed that FcγRI, but not FcγRII and FcγRIII, is also expressed in a subpopulation of primary sensory neurons. Moreover, IgG-IC directly excites the primary sensory neurons through neuronal FcγRI. These findings indicate that neuronal FcγRI provides a novel direct linkage between immunoglobulin and primary sensory neurons, which may be a novel target for the treatment of pain in the immune-related disorders. In this review, we summarize the expression pattern, functions, and the associated cellular signaling of FcγRs in the primary sensory neurons.

  13. Site-Specific Photolabeling of the IgG Fab Fragment Using a Small Protein G Derived Domain.

    Science.gov (United States)

    Kanje, Sara; von Witting, Emma; Chiang, Samuel C C; Bryceson, Yenan T; Hober, Sophia

    2016-09-21

    Antibodies are widely used reagents for recognition in both clinic and research laboratories all over the world. For many applications, antibodies are labeled through conjugation to different reporter molecules or therapeutic agents. Traditionally, antibodies are covalently conjugated to reporter molecules via primary amines on lysines or thiols on cysteines. While efficient, such labeling is variable and nonstoichiometric and may affect an antibody's binding to its target. Moreover, an emerging field for therapeutics is antibody-drug conjugates, where a toxin or drug is conjugated to an antibody in order to increase or incorporate a therapeutic effect. It has been shown that homogeneity and controlled conjugation are crucial in these therapeutic applications. Here we present two novel protein domains developed from an IgG-binding domain of Streptococcal Protein G. These domains show obligate Fab binding and can be used for site-specific and covalent attachment exclusively to the constant part of the Fab fragment of an antibody. The two different domains can covalently label IgG of mouse and human descent. The labeled antibodies were shown to be functional in both an ELISA and in an NK-cell antibody-dependent cellular cytotoxicity assay. These engineered protein domains provide novel tools for controlled labeling of Fab fragments and full-length IgG.

  14. Comparative Diagnosis of Serum IgG1 and Coproantigen ELISA for Fasciolosis Detection of Goats in Mexico

    Science.gov (United States)

    Molina-Mendoza, Pedro; Hernández-Guzmán, Karina; Olivares-Pérez, Jaime; Sarracent-Pérez, Jorge; Zumaquero-Ríos, José

    2016-01-01

    The objective of present study was to determine the prevalence of natural caprine fasciolosis in the Mixteca region of Mexico using coproantigen and serum IgG1 ELISA tests for comparative purposes. A total of 1070 serum and faecal samples were analyzed for IgG1 antibodies and coproantigens, using ELISA with E/S products as antigen and a monoclonal antibody-based sandwich ELISA. Prevalence of 73.46% was found using the serological ELISA and a percentage of 77.20 was found for coproantigen ELISA. The diagnostic sensitivity and specificity for serum ELISA were 86.7% and 96.4%, and for the coproantigen ELISA they were 93.1% and 97.8%, respectively. The seropositive samples were further categorized as low, medium, or high positivity. Results show a great proportion of low and medium positive goats when the serum ELISA test was used. Correlation coefficients between coproantigens and seropositivity were statistically significant (P < 0.01) for low seropositivity (r = 0.93) and medium seropositivity (r = 0.84). The accuracy of faecal antigen ELISA was higher compared to indirect ELISA serological test. Two ELISAs were shown to be useful for demonstrating the current status of F. hepatica infection in the endemic areas and can be employed in studies on epidemiology as well as anthelmintics treatment for preventing economic loss and the risk of transmission to humans. PMID:27563665

  15. IgE- and IgG mediated severe anaphylactic platelet transfusion reaction in a known case of cerebral malaria

    Directory of Open Access Journals (Sweden)

    B Shanthi

    2013-01-01

    Full Text Available Background: Allergic reactions occur commonly in transfusion practice. However, severe anaphylactic reactions are rare; anti-IgA (IgA: Immunoglobulin A in IgA-deficient patients is one of the well-illustrated and reported causes for such reactions. However, IgE-mediated hypersensitivity reaction through blood component transfusion may be caused in parasitic hyperimmunization for IgG and IgE antibodies. Case Report: We have evaluated here a severe anaphylactic transfusion reaction retrospectively in an 18year-old male, a known case of cerebral malaria, developed after platelet transfusions. The examination and investigations revealed classical signs and symptoms of anaphylaxis along with a significant rise in the serum IgE antibody level and IgG by hemagglutination method. Initial mild allergic reaction was followed by severe anaphylactic reaction after the second transfusion of platelets. Conclusion: Based on these results, screening of patients and donors with mild allergic reactions to IgE antibodies may help in understanding the pathogenesis as well as in planning for preventive desensitization and measures for safe transfusion.

  16. Evaluation of cysticercus-specific IgG (total and subclasses and IgE antibody responses in cerebrospinal fluid samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies Avaliação das respostas de anticorpos anti-cisticercos IgG (total e subclasses e IgE em amostras de líquido cefalorraquidiano de pacientes com neurocisticercose apresentando produção intratecal de anticorpos específicos IgG

    Directory of Open Access Journals (Sweden)

    Lisandra Akemi Suzuki

    2013-01-01

    Full Text Available In the present study, an enzyme-linked immunosorbent assay (ELISA standardized with vesicular fluid of Taenia solium cysticerci was used to screen for IgG (total and subclasses and IgE antibodies in cerebrospinal fluid (CSF samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies and patients with other neurological disorders. The following results were obtained: IgG-ELISA: 100% sensitivity (median of the ELISA absorbances (MEA=1.17 and 100% specificity; IgG1-ELISA: 72.7% sensitivity (MEA=0.49 and 100% specificity; IgG2-ELISA: 81.8% sensitivity (MEA=0.46 and 100% specificity; IgG3-ELISA: 63.6% sensitivity (MEA=0.12 and 100% specificity; IgG4-ELISA: 90.9% sensitivity (MEA=0.85 and 100% specificity; IgE-ELISA 93.8% sensitivity (MEA=0.60 and 100% specificity. There were no significant differences between the sensitivities and specificities in the detection of IgG-ELISA and IgE-ELISA, although in CSF samples from patients with neurocysticercosis the MEA of the IgG-ELISA was significantly higher than that of the IgE-ELISA. The sensitivity and MEA values of the IgG4-ELISA were higher than the corresponding values for the other IgG subclasses. Future studies should address the contribution of IgG4 and IgE antibodies to the physiopathology of neurocysticercosis.No presente estudo, uma reação imunoenzimática (ELISA padronizada com o fluido vesicular de cisticercos de Taenia solium foi utilizada para avaliar as respostas de anticorpos anti-cisticercos IgG (total e subclasses e IgE em amostras de líquido cefalorraquidiano (LCR de pacientes com neurocisticercose apresentando produção intratecal de anticorpos específicos IgG e pacientes com outras desordens neurológicas. Os seguintes resultados foram obtidos: ELISA-IgG: 100% de sensibilidade (mediana das absorbâncias das reações ELISA (MAE=1,17 e especificidade 100%; ELISA-IgG1: sensibilidade 72,7% (MAE=0,49 e especificidade 100%; ELISA-IgG2

  17. IgG subclass and heavy chain domains contribute to binding and protection by mAbs to the poly γ-D-glutamic acid capsular antigen of Bacillus anthracis.

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    Maria Hovenden

    Full Text Available Bacterial capsules are common targets for antibody-mediated immunity. The capsule of Bacillus anthracis is unusual among capsules because it is composed of a polymer of poly-γ-d-glutamic acid (γdPGA. We previously generated murine IgG3 monoclonal antibodies (mAbs to γdPGA that were protective in a murine model of pulmonary anthrax. IgG3 antibodies are characteristic of the murine response to polysaccharide antigens. The goal of the present study was to produce subclass switch variants of the γdPGA mAbs (IgG3 → IgG1 → IgG2b → IgG2a and assess the contribution of subclass to antibody affinity and protection. Subclass switch antibodies had identical variable regions but differed in their heavy chains. The results showed that a switch from the protective IgG3 to IgG1, IgG2b or IgG2a was accompanied by i a loss of protective activity ii a change in mAb binding to the capsular matrix, and iii a loss of affinity. These results identify a role for the heavy chain constant region in mAb binding. Hybrid mAbs were constructed in which the CH1, CH2 or CH3 heavy chain constant domains from a non-protective, low binding IgG2b mAb were swapped into the protective IgG3 mAb. The IgG3 mAb that contained the CH1 domain from IgG2b showed no loss of affinity or protection. In contrast, swapping the CH2 or CH3 domains from IgG2b into IgG3 produced a reduction in affinity and a loss of protection. These studies identify a role for the constant region of IgG heavy chains in affinity and protection against an encapsulated bacterial pathogen.

  18. Diagnostic Value of the Serum Anti-Toxocara IgG Titer for Ocular Toxocariasis in Patients with Uveitis at a Tertiary Hospital in Korea

    Science.gov (United States)

    Bae, Ki Woong; Ahn, Seong Joon; Park, Kyu Hyung

    2016-01-01

    Purpose This study evaluated the prevalence of ocular toxocariasis (OT) in patients with uveitis of unknown etiology who visited a tertiary hospital in South Korea and assessed the success of serum anti-Toxocara immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) as a diagnostic test for OT. Methods The records of consecutive patients with intraocular inflammation of unknown etiology were reviewed. All participants underwent clinical and laboratory investigations, including ELISA for serum anti-Toxocara IgG. OT was diagnosed based on typical clinical findings. Clinical characteristics, seropositivity, and IgG titers were compared between patients diagnosed with OT and non-OT uveitis. The seropositivity and the diagnostic value of anti-Toxocara IgG was investigated among patients with different types of uveitis. Results Of 238 patients with uveitis of unknown etiology, 71 (29.8%) were diagnosed with OT, and 80 (33.6%) had positive ELISA results for serum anti-Toxocara IgG. The sensitivity and specificity of the ELISA test were 91.5% (65 / 71) and 91.0% (152 / 167), respectively. The positive predictive value of the serum anti-Toxocara IgG assay was 81.3%. Among patients with anterior, intermediate, posterior, and panuveitis, the prevalence rates of OT were 8.3%, 47.1%, 44.8%, and 7.1%, respectively; the seropositivity percentages were 18.1%, 47.1%, 43.7%, and 17.9%; and the positive predictive values were 38.5%, 95.8%, 92.1%, and 40.0%. The serum anti-Toxocara IgG titer also significantly decreased following albendazole treatment. Conclusions OT is a common cause of intraocular inflammation in the tertiary hospital setting. Considering that OT is more prevalent in intermediate and posterior uveitis, and that the positive predictive value of the anti-Toxocara IgG assay is high, a routine test for anti-Toxocara IgG might be necessary for Korean patients with intermediate and posterior uveitis. PMID:27478352

  19. Molecular modeling and conformational IgG epitope mapping on bovine β-casein

    NARCIS (Netherlands)

    Liu, Fahui; Gao, Jinyan; Li, Xin; Chen, Hongbing

    2016-01-01

    Characterizing conformational B-cell epitopes is a key step for understanding the immunological basis of allergy contributed by β-casein. There is no resolved conformational structure of β-casein in protein data bank, and most of the previous research on epitope identification of β-casein focused

  20. Intrinsic Properties of immunoglobulin IgG1 Isotype-Switched B Cell Receptors Promote Microclustering and the Initiation of Signaling

    Science.gov (United States)

    Liu, Wanli; Meckel, Tobias; Tolar, Pavel; Sohn, Hae Won; Pierce, Susan K.

    2010-01-01

    Summary Memory B cells express high affinity, immunoglobulin B cell receptors (IgG-BCRs) that enhance B cell responses giving rise to the rapid production of high affinity, IgG antibodies. Despite the central role of IgG-BCRs in memory responses, the mechanisms by which the IgG-BCRs function to enhance B cell responses are not fully understood. Using high-resolution live-cell imaging we showed that independent of affinity, IgG1-BCRs dramatically enhanced the earliest BCR-intrinsic events that followed within seconds of B cells’ encounter with membrane bound antigen including BCR oligomerization and BCR microcluster growth, leading to Syk kinase recruitment and calcium responses. The enhancement of these early events was dependent on a membrane proximal region of the IgG1 cytoplasmic tail not previously appreciated to play a role in IgG1-BCR signaling. Thus, intrinsic properties of the IgG1-BCR enhance early antigen-driven events that ultimately translate into heightened signaling. PMID:20620943

  1. Evaluation of four commercial IgG- and IgM-specific enzyme immunoassays for detecting Mycoplasma pneumoniae antibody: comparison with particle agglutination assay.

    Science.gov (United States)

    Yoo, Soo Jin; Oh, Hye-Jeon; Shin, Bo-Moon

    2007-10-01

    Diagnosis of Mycoplasma pneumoniae infection is important due to its variable clinical manifestations and absence of response to beta-lactams. Introduction of enzyme immunoassays (EIAs) for serologic diagnosis of M. pneumoniae has made it possible to separate the analyses of specific IgG and IgM antibodies. We compared four different commercial EIAs, ImmunoWELL IgG, IgM (GenBio), Medac IgG, IgA, IgM (Medac), Platelia IgG, IgM (Sanofi Pasteur), and Ridascreen IgG, IgA, IgM (r-Biopharm) with indirect particle agglutination assay (PA), Serodia-MycoII (Fujirebio). We tested 91 specimens from 73 pediatric patients (2-17 yr) hospitalized at a tertiary-care hospital between December 2005 and January 2006. The measurements of IgM EIAs were correlated with PA titers (Spearman's correlation coefficient, from 0.89 to 0.92) with high concordance rates, ranging from 82.4% to 92.3%. However, some negative IgM-EIA results in PA-positive specimens indicated that serial samplings with convalescent sera would be necessary to confirm M. pneumoniae infection.

  2. Study of chronic hemolytic anaemia patients in Rio de Janeiro: prevalence of anti-human parvovirus B19 IgG antibodies and the developement aplastic crises

    Directory of Open Access Journals (Sweden)

    SANT'ANNA Anadayr L.M.

    2002-01-01

    Full Text Available The prevalence of anti-human parvovirus B19 IgG antibodies was determined in sera from 165 chronic hemolytic anemia patients, receiving medical care at Instituto Estadual de Hematologia (IEHE, Rio de Janeiro, during the year of 1994. This sample represents around 10% of the chronic hemolytic anemia patients attending at IEHE. Most of these patients (140 have sickle cell disease. Anti-B19 IgG antibodies were detected in 32.1% of patients. No statistically significant difference (p > 0.05 was seen between IgG antibody prevalence in male (27.8% and female (35.5% patients. Anti-B19 IgG antibodies were more frequent in older (37.6% than younger (28.2% than 20 years old patients, although this difference had no statistical significance (p > 0.05. Anti-B19 IgG antibody prevalence showed that 67.9% of patients enrolled in the study were susceptible to B19 acute infection. With the aim to detect acute B19 infection, patients follow up continued until February 1996. During this period four patients presented transient aplastic crisis due to human parvovirus B19 as confirmed by the detection of specific IgM antibodies. All four patients were younger than 20 years old, and 3 were younger than 10 years old. Three of them were sickle cell disease patients. Three of the four acute B19 infection occurred during 1994 springtime.

  3. Radioimmunotherapy for hepatocellular carcinoma (HCC) using /sup 131/I-anti HCC isoferritin IgG: preliminary results of experimental and clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Liu, K.D.; Tang, Z.Y.; Bao, Y.M.; Lu, J.Z.; Qian, F.; Yuan, A.N.; Zhao, H.Y.

    1989-02-01

    Based on radioimmunoimaging for HCC using /sup 131/I-anti HCC isoferritin IgG, the experimental and clinical studies on radioimmunotherapy for HCC were reported. Thirty-six nude mice bearing human HCC were used for the study of labeled IgG, pure /sup 131/NaI and pure IgG. In the labeled IgG group, the tumor inhibition rate was significantly higher than that in other groups (81%, 60%, and 18%, respectively, p less than 0.05). The tumor cell DNA analysis showed the tumor cell was inhibited in the S stage of the cell cycle. Twenty pathologically proven unresectable HCC patients were treated by /sup 131/I-antihuman HCC isoferritin IgG 20-55mCi monthly for 1-3 times (via hepatic arterial catheter or intravenously). The short-term response was promising, a decline in AFP level and shrinkage of tumor were observed in 80% (12/15) and 65% (13/20) of patients respectively. Sequence resection was successful in five patients (5/20) after radioimmunotherapy. No marked toxic effects were noted in our limited experience, but some problems remain to be discussed.

  4. Usefulness of a commercial equine IgG test and serum protein concentration as indicators of failure of transfer of passive immunity in hospitalized foals.

    Science.gov (United States)

    Metzger, Nadine; Hinchcliff, Kenneth W; Hardy, Joanne; Schwarzwald, Colin C; Wittum, Thomas

    2006-01-01

    Detection of failure of transfer of passive immunity (FTPI) is important in reducing morbidity and mortality in neonatal foals. We investigated the performance of a commercial equine IgG test (SNAP Foal IgG Test Kit) to diagnose FTPI in hospitalized foals. Furthermore, we evaluated the usefulness of serum total protein (STP) and serum globulin (SG) concentrations as indicators of FTPI. Serum IgG concentration was measured by means of the SNAP test and single radial immunodiffusion, and SG and STP concentrations were determined by means of a clinical chemistry analyzer. Subjects were 67 hospitalized foals .05) by plasma fibrinogen concentration, sepsis score, or bacteremia. Specificity for detection of [IgG] < or = 800 mg/dl was lower (P < .05) in foals with sepsis score < or =11 (50% [31-60%] versus 100% [8-100%]) and bacteremia (25% [5-56%] versus 62% [45-62%]). Sensitivity and specificity of [STP] < or = 5.0 g/dl for [IgG] < or =800 mg/dl was 94% (83-99%) and 47% (30-56%), respectively. Performance of the SNAP test in hospitalized foals is impaired because of low specificity, but can have usefulness provided that the properties of the test and characteristics of the foal being examined are considered when interpreting the results. The STP and SG concentrations are poor sole indicators of FTPI in hospitalized foals, but may be useful adjunctive tests.

  5. Purely cutaneous sclerosing IgG4-related disease of the cephalic region: case report and a mini-review of the clinical and pathological aspects.

    Science.gov (United States)

    Muscardin, Luca; Paolino, Giovanni; Panetta, Chiara; Donati, Pietro

    2016-06-01

    IgG4-related disease is a recently defined emerging entity. Many different organs may be affected by this disease: pancreas, salivary and lacrimal glands, liver, peritoneum and lung. Also the skin may be affected, as secondary localization, while as primary cutaneous localization it has been rarely described. A male patient presented at our Institute with a two-year history of sclerosing erythematous nodules of the scalp. Histological examination showed a T-lymphocyte (CD3+) infiltrate with interspersed plasmacytoid cells and the interposition of a fibrosclerotic tissue. We found numerous IgG4+ cells at the periphery of the nodular structures, while the serum levels of IgG4 and the remaining blood chemistry analysis were normal. Only a few cases of primitive cutaneous pseudo-lymphomatous IgG4-related disease have been described in the literature. Our case showed the same clinical and histologic features of those previously described; the etiology of IgG4-related diseases remains to be elucidated. PMID:26340764

  6. Competitive Enzymatic Fluorescence Immunoassay for Human IgG by Using a Temperature-Sensitive Phase Separating Polymer with Regulated Phase Transition Temperature

    Institute of Scientific and Technical Information of China (English)

    LIN Peng; WANG Yi-Lei; FENG Jian-Jun; ZOU Zhi-Hua; YANG Qian

    2008-01-01

    A new enzymatic fluorescence immunoassay for human IgG was developed using a temperature-sensitive polymer, poly(N-isopropylacrylamide-co-acrylamide) [P(NIP-AA)], as a carrier. The lower critical solution temperature of the P(NIP-AA) containing molar fraction of 8% for AA was 37 ℃. In a competitive immunoassay, immobilized IgG and the standard IgG (or sample) competed for binding to a horseradish peroxidase labeled antibody at 33 ℃ in homogeneous format. After changing the temperature to separate the polymer-immune complex, the complex precipitate was re-dissolved and determined by coupling with the fluorescence reaction of hydrogen peroxide and p-hydroxyphenylacetic acid. The calibration graph for human IgG was linear over the range of 100-1000 ng/mL with a detection limit of 2.0 ng/mL. The method is rapid, sensitive and simple. The immune reaction efficiency was improved. In addition, the sensitivity of this method was close to that using traditional microtitration plates as carriers. However, the assay was much faster (the assay time decreased from 100-120 to 30 min). The method has been applied to the determination of the human IgG levels in human sera with satisfactory results.

  7. Murine germinal center B cells require functional Fms-like tyrosine kinase 3 signaling for IgG1 class-switch recombination.

    Science.gov (United States)

    Svensson, Mattias N D; Andersson, Karin M E; Wasén, Caroline; Erlandsson, Malin C; Nurkkala-Karlsson, Merja; Jonsson, Ing-Marie; Brisslert, Mikael; Bemark, Mats; Bokarewa, Maria I

    2015-12-01

    Switched antibody classes are important for efficient immune responses. Aberrant antibody production to otherwise harmless antigens may result in autoimmunity. The protein kinase fms-like tyrosine kinase 3 receptor (Flt3) has an important role during early B-cell development, but the role of Flt3 in peripheral B cells has not been assessed before. Herein we describe a previously unappreciated role for Flt3 in IgG1 class-switch recombination (CSR) and production. We show that Flt3 is reexpressed on B-cell lymphoma 6(+) germinal center B cells in vivo and following LPS activation of peripheral B cells in vitro. Absence of Flt3 signaling in Flt3 ligand-deficient mice results in impaired IgG1 CSR and accumulation of IgM-secreting plasma cells. On activated B cells, Flt3 is coexpressed and functions in synergy with the common-gamma chain receptor family. B cells from Flt3 ligand-deficient mice have impaired IL-4R signaling, with reduced phosphorylation of signal transducer and activator of transcription (Stat) 6, and demonstrate a failure to initiate CSR to IgG1 with low expression of γ1 germ-line transcripts, resulting in impaired IgG1 production. Thus, functional synergy between Flt3 and IL-4R signaling is critical for Stat-mediated regulation of sterile γ1 germ-line transcripts and CSR to IgG1. PMID:26627255

  8. A nylon ball solid-phase radioimmunoassay for specific antibodies in human sera. Application to measurement of IgG antibodies to pollen allergens

    International Nuclear Information System (INIS)

    The principle of the radioallergosorbent test (RAST) has been used to measure IgG antibodies to timothy grass pollen allergens in sera from desensitized allergic subjects. 125I-labeled goat anti-human IgG was used as detector protein. Non-specific binding was eliminated by use of a non-porous nylon ball an antigen carrier and by use of a special buffer with high ionic strength and pH, containing 1% bovine gamma globulin and 5% normal rabbit serum as 'balance proteins'. At dilution 1:80 non-specific binding was only 0.28% and the binding ratio for a high-titer serum was about 10. By inhibition experiments the assay was demonstrated to be specific for IgG antibodies to timothy grass pollen. The results obtained with this assay correlated statistically significantly with those found with a double-antibody method. Serum dilution curves were parallel, indicating that the assay is in allergen excess. The within-assay coefficient of variation ranged from 3.9 to 7.6%; the between-assay coefficient of variation from 8.4 to 19.5%. The assay is very simple to perform, requiring no centrifugation. The allergen-coated balls are stable for at least 3 months. The assay should be applicable to measurement of IgG antibodies and IgG subclass antibodies to any protein antigen of interest. (Auth.)

  9. ELISA indireto para detecção de IgG antivírus da doença de Newcastle em soro de codorna Indirect ELISA for the detection of IgG specific to Newcastle disease virus in quail serum

    Directory of Open Access Journals (Sweden)

    D.D. Oliveira

    2007-10-01

    Full Text Available An indirect ELISA for the detection of japanese quail IgG specific to Newcastle disease virus (NDV was developed. The secondary anti-quail IgG was produced in Balb/c mice, by inoculating Freund's complete adjuvant emulsified japanese quail-IgG extract. The purification of IgG was achieved using the caprilic acid method. The ELISA was compared to the haemagglutination-inhibition (HI test for antibodies to NDV. ELISA cut-off point was established through TG-ROC analysis. Total correlation was observed between the ELISA and the HI, being the ELISA efficient in the identification of positive and negative sera, with high sensitivity and specificity (100%. These results validate the use of the indirect ELISA as an alternative for the detection of NDV-specific IgG in japanese quail sera, with the advantage of high sensitivity and automation.

  10. Interaction of human IgG chimeric antibodies with the human FcRI and FcRII receptors: requirements for antibody-mediated host cell-target cell interaction.

    Science.gov (United States)

    Walker, M R; Woof, J M; Brüggemann, M; Jefferis, R; Burton, D R

    1989-04-01

    Chimeric monoclonal antibodies (McAb), specific for the hapten 5-iodo-4-hydroxy-3-nitrophenacetyl (NIP), expressing human IgG1, IgG2, IgG3 and IgG4 subclass constant domains, have been examined for their ability to interact with the human FcRII receptor. Human red blood cells (RBC) sensitized by each of these McAbs have been assayed for their ability to form rosettes with the human histiocytic lymphoma U937 cell line, human B cell line Daudi and erythroblastoid K562 cell line. IgG1 and IgG3 sensitized RBC formed significant rosettes with the FcR- and FcRII+ Daudi and K562 cell lines, the percentage of cells forming rosettes being directly proportional to the degree of sensitization of the RBC. Bromelin treating Daudi cells did not alter this pattern of reactivity, whereas bromelin treated FcRI+ and FcRII+ U937 cells formed significant resettes with IgG1, IgG3 and IgG4 sensitized RBC, demonstrating a difference in the IgG subclass specificity between human FcRI and FcRII. Murine IgG2b anti-NIP sensitized RBC did not form rosettes with any cell line tested; however, RBC sensitized by some members of a panel of murine IgG1 McAb, specific for the glycophorin A molecule, were able to form rosettes with Daudi, U937 and K562 cells. This interaction was enhanced by bromelin treating the Daudi or U937 cells and can be correlated to the disposition of the epitopes recognized, relative to the target cell membrane, those McAbs recognizing epitopes furthest from the RBC surface being most effective in interacting with FcRII. The data are interpreted in terms of a simple model for antibody-mediated cell--cell interaction. PMID:2716734

  11. The Developmental History of IgE and IgG4 Antibodies in Relation to Atopy, Eosinophilic Esophagitis, and the Modified TH2 Response.

    Science.gov (United States)

    Aalberse, Rob C; Platts-Mills, Thomas A; Rispens, Theo

    2016-06-01

    A common reaction from anyone confronted with allergy is the question: what prevents universal allergy? We will discuss recent findings in the mouse system that have provided us with clues on why allergy is not more common. We will also address one crucial aspect of atopic allergy in humans, which is absent in most mouse model systems, an IgG/IgE ratio response to be more closely related to the "modified TH2" response in humans. We will discuss the similarities and differences between the IgE and IgG4 response to allergens and an update on the IgG4 B cell, partly derived from studies on eosinophilic esophagitis and IgG4-related diseases. PMID:27221343

  12. Strong IgG antibody responses to Borrelia burgdorferi glycolipids in patients with Lyme arthritis, a late manifestation of the infection.

    Science.gov (United States)

    Jones, Kathryn L; Seward, Robert J; Ben-Menachem, Gil; Glickstein, Lisa J; Costello, Catherine E; Steere, Allen C

    2009-07-01

    In this study, the membrane lipids of B. burgdorferi were separated into 16 fractions; the components in each fraction were identified, and the immunogenicity of each fraction was determined by ELISA using sera from Lyme disease patients. Only the 2 glycolipids, acylated cholesteryl galactoside (ACG, BbGL-I) and monogalactosyl diacylglycerol (MgalD, BbGL-II), were immunogenic. Early in the infection, 24 of 84 patients (29%) who were convalescent from erythema migrans and 19 of the 35 patients (54%) with neuroborreliosis had weak IgG responses to purified MgalD, and a smaller percentage of patients had early responses to synthetic ACG. However, almost all of 75 patients with Lyme arthritis, a late disease manifestation, had strong IgG reactivity with both glycolipids. Thus, almost all patients with Lyme arthritis have strong IgG antibody responses to B. burgdorferi glycolipid antigens.

  13. Comparison of the Hemagglutination Inhibition Test and IgG ELISA in Categorizing Primary and Secondary Dengue Infections Based on the Plaque Reduction Neutralization Test

    Science.gov (United States)

    Lukman, Nurhayati; Susanto, Nugroho Harry; Parwati, Ida; Fitri, Silvita; Alisjahbana, Bachti; Widjaja, Susana; Williams, Maya

    2016-01-01

    Secondary dengue infection by heterotypic serotypes is associated with severe manifestations of disease, that is, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The World Health Organization (WHO) has recommended criteria based on the hemagglutination inhibition (HI) test to distinguish between primary and secondary dengue infections. Since the HI test has practical limitations and disadvantages, we evaluated the accuracy of WHO HI criteria and compared it with criteria based on an IgG enzyme-linked immunosorbent assay (ELISA) using a plaque reduction neutralization test (PRNT) as the gold standard. Both WHO HI criteria and IgG ELISA criteria performed strongly (16/16) in determining primary infection. However, to determine secondary infection, the IgG ELISA criteria performed better (72/73) compared to the WHO HI criteria (23/73). PMID:27446953

  14. MyD88-dependent pro-inflammatory activity in Vi polysaccharide vaccine against typhoid promotes Ab switching to IgG.

    Science.gov (United States)

    Garg, Rohini; Akhade, Ajay Suresh; Yadav, Jitender; Qadri, Ayub

    2015-10-01

    Vi capsular polysaccharide is currently in use as a vaccine against human typhoid caused by Salmonella Typhi. The vaccine efficacy correlates with IgG anti-Vi Abs. We have recently reported that Vi can generate inflammatory responses through activation of the TLR2/TLR1 complex. In the present study, we show that immunization with Vi produces IgM as well as IgG Abs in wild type mice. This ability is not compromised in mice deficient in T cells. However, immunization of mice lacking the TLR adaptor protein, MyD88, with Vi elicits only IgM Abs. These results suggest that MyD88-dependent pro-inflammatory ability of the Vi vaccine might be vital in generating IgG Abs with this T-independent Ag.

  15. Comparison of the Hemagglutination Inhibition Test and IgG ELISA in Categorizing Primary and Secondary Dengue Infections Based on the Plaque Reduction Neutralization Test.

    Science.gov (United States)

    Lukman, Nurhayati; Salim, Gustiani; Kosasih, Herman; Susanto, Nugroho Harry; Parwati, Ida; Fitri, Silvita; Alisjahbana, Bachti; Widjaja, Susana; Williams, Maya

    2016-01-01

    Secondary dengue infection by heterotypic serotypes is associated with severe manifestations of disease, that is, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The World Health Organization (WHO) has recommended criteria based on the hemagglutination inhibition (HI) test to distinguish between primary and secondary dengue infections. Since the HI test has practical limitations and disadvantages, we evaluated the accuracy of WHO HI criteria and compared it with criteria based on an IgG enzyme-linked immunosorbent assay (ELISA) using a plaque reduction neutralization test (PRNT) as the gold standard. Both WHO HI criteria and IgG ELISA criteria performed strongly (16/16) in determining primary infection. However, to determine secondary infection, the IgG ELISA criteria performed better (72/73) compared to the WHO HI criteria (23/73). PMID:27446953

  16. Relationship between Antibody Levels, IgG Binding to Plasmodium falciparum-Infected Erythrocytes, and Disease Outcome in Hospitalized Urban Malaria Patients from Dakar, Sénégal.

    Science.gov (United States)

    Mbengue, Babacar; Fall, Mouhamadou Mansour; Sylla Niang, Maguette; Niang, Birahim; Varela, Marie Louise; Diatta, Antoine Marie; Mbow, Moustapha; Ndiaye, Kantome; Ndiaye Diallo, Rokhaya; Dieye, Alioune; Perraut, Ronald

    2016-01-01

    Background. Management of clinical malaria requires the development of reliable diagnostic methods and efficient biomarkers for follow-up of patients. Protection is partly based on IgG responses to parasite antigens exposed at the surface of infected erythrocytes (iRBCs). These IgG responses appeared low during clinical infection, particularly in severe disease. Methods. We analyzed the IgG binding capacity to the surface of live erythrocytes infected by knob positive FCR3 strain. Sera from 69 cerebral malaria (CM) and 72 mild malaria (MM) cases were analyzed by ELISA for IgG responses to five antigens from iRBC and by flow cytometry for IgG binding as expressed in labeling index ratio (LIR). The relationship between IgG levels, LIR, parasitemia, age, and the clinical outcomes was evaluated. Results. We found a significant decrease of LIR in adult CM fatal cases compared to surviving patients (p = 0.019). In MM, LIRs were correlated to IgG anti-iRBC and anti-PfEMP3/5 levels. In CM, no correlation was found between LIR, IgG levels, and parasitemia. Conclusion. The IgG binding assay was able to discriminate outcome of cerebral malaria cases and it deserves further development as a potential functional-associated assay for symptomatic malaria analysis. PMID:27563669

  17. Reaction of rheumatoid factors with IgG3 monoclonal anti-Rh(D) antibodies: more frequent reactivity to a monoclonal antibody of the Gm allotype G3m(5) in rheumatoid patients negative for G3m(5).

    OpenAIRE

    Puttick, A H; Williamson, E.A.; Merry, A.H.; Kumpel, B M; Thompson, K. M.; Jones, V E

    1988-01-01

    Human monoclonal anti-Rh(D) antibodies of known IgG isotype and Gm allotype were bound to erythrocytes and then used as the target IgG antigens for rheumatoid factors (RFs) in a direct haemagglutination test. When serum samples from patients with rheumatoid arthritis (RA) were tested for RF specificity towards these IgG monoclonal anti-D antibodies the incidence and titre of reactivity towards an IgG3 monoclonal anti-D antibody was considerably greater than for a polyclonal anti-D antibody of...

  18. Preterm and term neonates transplacentally acquire IgG antibodies specific to LPS from Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa.

    Science.gov (United States)

    Silveira Lessa, Ana Lúcia; Krebs, Vera Lúcia Jornada; Brasil, Tatiana Braga; Pontes, Gerlândia Neres; Carneiro-Sampaio, Magda; Palmeira, Patricia

    2011-07-01

    High incidences of Gram-negative bacteria are found in neonatal nosocomial infections. Our aim was to investigate placental transmission of immunoglobulin G (IgG) reactive with lipopolysaccharide from Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli O111, O6 and O26. The total and lipopolysaccharide-specific IgM and IgG were determined in 11 maternal/umbilical-cord sera aged ≤33 weeks (GI); 21 aged >33 and <37 weeks (GII); and 32 term newborns (GIII). The total and lipopolysaccharide-specific IgM concentrations were equivalent in maternal sera. The total IgG concentrations were equivalent in maternal and newborn sera, with the exception of GIII newborns as compared with their mothers (P<0.0001) and with neonates from GI and GII (P<0.05). Lipopolysaccharide-specific IgG concentrations were lower in GI neonates than in their mothers (P<0.01) and lower in GII (P<0.05). Lower lipopolysaccharide-specific IgG levels were observed among neonates only for O111 in GI (P<0.05) and for O26 and Pseudomonas in GII, both as compared with GIII (P<0.05). The anti-lipopolysaccharide IgG transfer ratios were lower in GI (except for O26) and in GII (except for Klebsiella and O111) as compared with GIII (P<0.05). Our results suggest that the greater susceptibility to infections in preterm infants is influenced (besides the humoral response) by factors intrinsic and extrinsic to the condition of prematurity. PMID:21481015

  19. Levels of diphtheria and tetanus specific IgG of Portuguese adult women, before and after vaccination with adult type Td. Duration of immunity following vaccination

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    Santos Maria

    2007-06-01

    Full Text Available Abstract Background The need for tetanus toxoid decennial booster doses has been questioned by some experts. Several counter arguments have been presented, supporting the maintenance of decennial adult booster doses with tetanus and diphtheria toxoids (adult formulation of the vaccine: Td. This study aimed to evaluate the use of Td in Portuguese adult women under routine conditions. For that purpose we selected a group of women 30+ years of age to which vaccination was recommended. We intended to know if pre-vaccination antibody concentrations were associated with factors as age at first and last vaccination, number of doses and time since last revaccination. We also intended to assess the serological efficacy of Td booster. Methods Following the Portuguese guidelines 100 women were vaccinated with Td. Antitetanus toxin IgG (ATT IgG and antidiphtheria toxin IgG (ADT IgG levels were measured (mIU/ml in 100 pre-vaccination and 91 post-vaccination sera. Detailed vaccination records were available from 88 participants. Results Twenty-two women (Group A began vaccination with DPT/DT in their early childhood and their pre-vaccination ATT IgG levels increased with the number of doses received (p = 0.022 and decreased with time since last vaccination (p = 0.016. Among the 66 women who began vaccination in adolescence and adulthood (Group B, with monovalent TT, ATT IgG levels decreased with age at first dose (p Conclusion Our study suggests that, to protect against tetanus, there is no need to administer decennial boosters to the Portuguese adults who have complied with the childhood/adolescent schedule (6 doses of tetanus toxoid. The adult booster intervals could be wider, probably of 20 years. This also seems to apply to protection against diphtheria, but issues on the herd immunity and on the circulation of toxigenic strains need to be better understood.

  20. Pan-HSV-2 IgG antibody in vaccinated mice and guinea pigs correlates with protection against herpes simplex virus 2.

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    William P Halford

    Full Text Available We lack a correlate of immunity to herpes simplex virus 2 (HSV-2 that may be used to differentiate whether a HSV-2 vaccine elicits robust or anemic protection against genital herpes. This gap in knowledge is often attributed to a failure to measure the correct component of the adaptive immune response to HSV-2. However, efforts to identify a correlate of immunity have focused on subunit vaccines that contain less than 3% of HSV-2's 40,000-amino-acid proteome. We were interested to determine if a correlate of immunity might be more readily identified if 1. animals were immunized with a polyvalent immunogen such as a live virus and/or 2. the magnitude of the vaccine-induced immune response was gauged in terms of the IgG antibody response to all of HSV-2's antigens (pan-HSV-2 IgG. Pre-challenge pan-HSV-2 IgG levels and protection against HSV-2 were compared in mice and/or guinea pigs immunized with a gD-2 subunit vaccine, wild-type HSV-2, or one of several attenuated HSV-2 ICP0 (- viruses (0Δ254, 0Δ810, 0ΔRING, or 0ΔNLS. These six HSV-2 immunogens elicited a wide range of pan-HSV-2 IgG levels spanning an ∼500-fold range. For 5 of the 6 immunogens tested, pre-challenge levels of pan-HSV-2 IgG quantitatively correlated with reductions in HSV-2 challenge virus shedding and increased survival frequency following HSV-2 challenge. Collectively, the results suggest that pan-HSV-2 IgG levels may provide a simple and useful screening tool for evaluating the potential of a HSV-2 vaccine candidate to elicit protection against HSV-2 genital herpes.

  1. Determination of human IgG by solid substrate room temperature phosphorescence immunoassay based on an antibody labeled with nanoparticles containing Rhodamine 6G luminescent molecules

    Science.gov (United States)

    Jia-Ming, Liu; hui, Zhu Guo; Aihong, Wu; Pingping, Li; Huanhuan, Xu; Li, Long-Di; Liu, Zhen-bo

    2005-03-01

    Luminescent silicon dioxide nanoparticles (R-SiO 2) with size of 50 nm containing Rhodamine 6G (R) were synthesized by sol-gel method. In the presence of Pb(Ac) 2 as a heavy atom perturber, the particle can emit intense and stable room temperature phosphorescence signal of R, respectively, on polyamide membrane, with the λexmax/λemmax=470/635 nm for R. Our research indicates that the specific immune reaction between goat-anti-human IgG antibody labeled with R-SiO 2 and human IgG can be carried on polyamide membrane quantitatively, and the phosphorescence intensity was enhanced after the immunoreactions. Thus, a new method of solid substrate room temperature phosphorescence immunoassay (SS-RTP-IA) for the determination of human IgG was established basing on antibody labeled with the nanoparticles containing binary luminescent molecules. The linear range of this method is 0.0624-20.0 pg spot -1 of human IgG (corresponding concentration, 0.156-50.0 ng mL -1; sample volume, 0.40 μL spot -1). The regression equations of working curves are Δ Ip = 88.16. + 16.79m IgG (pg spot -1) (485/646 nm, r = 0.9997). Detection limits calculated by 3Sb/k are 0.017 pg spot -1. For samples containing 0.156 and 50.0 ng mL -1 of IgG, we measured repeatedly for 11 times, RSDs are 3.9 and 2.8%, respectively. This method is sensitive, accurate and of high precision.

  2. Immunopathological events initiated and maintained by pathogenic IgG autoantibodies in an experimental autoimmune kidney disease.

    Science.gov (United States)

    Barabas, Arpad Zsigmond; Cole, Chad Douglas; Lafreniere, Rene; Weir, Donald Mackay

    2012-11-01

    The experimental models of Heymann nephritis (HN) and slowly progressive Heymann nephritis (SPHN) give us rare opportunities to investigate the etiologies and pathogenesis of two immunopathological processes in rats leading to: (1) autoimmune disease, where the autoimmune disease HN and SPHN is initiated and maintained by cross-reactive pathogenic IgG autoantibodies (aabs) directed against the renal proximal convoluted tubules' brush border (BB) cells - where the nephritogenic antigen (ag) is produced and localized - damaging and releasing BB associated nephritogenic ag into the circulation which in turn contributes to continuation of the autoimmune disease; and (2) immune complex glomerulonephritis, where the glomerular injury is initiated, proceeding into a chronic progressive disease by depositing immune complexes (ICs) - made up of a glomerular epithelial cell produced endogenous nephritogenic ag and the developing pathogenic IgG aab directed against the nephritogenic ag, and complement components - on the epithelial side of the glomerular basement membrane. We also observed how the normally functioning immune system is able to avert autoimmune disease developments by circulating specific non-pathogenic IgM aabs clearing the system of intracytoplasmic ags released from cells at the end of their life spans or following damage by toxic agents. We also described how an autoimmune disease SPHN can be prevented and when present terminated by the implementation of a new vaccination technique we have developed and call modified vaccination technique. By increasing the specific IgM aab production against the native nephritogenic ag - by injecting ICs made up of: [nephritogenic ag X homologous anti-nephritogenic ag IgM ab] in slight ag excess into SPHN rats - pathogenic IgG aab producing native and modified nephritogenic ags were removed from the circulation and termination of the autoimmune disease causing immune events was achieved. Even though HN and SPHN are not

  3. Analysis of IgG with specificity for variant surface antigens expressed by placental Plasmodium falciparum isolates

    Directory of Open Access Journals (Sweden)

    Kremsner Peter G

    2004-07-01

    Full Text Available Abstract Background Pregnancy-associated malaria (PAM is caused by Plasmodium falciparum-infected erythrocytes that can sequester in placental intervillous space by expressing particular variant surface antigens (VSA that can mediate adhesion to chondroitin sulfate A (CSA in vitro. IgG antibodies with specificity for the VSA expressed by these parasites (VSAPAM are associated with protection from maternal anaemia, prematurity and low birth weight, which is the greatest risk factor for death in the first month of life. Methods In this study, the development of anti-VSAPAM antibodies in a group of 151 women who presented to the maternity ward of Albert Schweitzer Hospital in Lambaréné, Gabon for delivery was analysed using flow cytometry assays. Plasma samples from placenta infected primiparous women were also investigated for their capacity to inhibit parasite binding to CSA in vitro. Results In the study cohort, primiparous as well as secundiparous women had the greatest risk of infection at delivery as well as during pregnancy. Primiparous women with infected placentas at delivery showed higher levels of VSAPAM-specific IgG compared to women who had no malaria infections at delivery. Placental isolates of Gabonese and Senegalese origin tested on plasma samples from Gabon showed parity dependency and gender specificity patterns. There was a significant correlation of plasma reactivity as measured by flow cytometry between different placental isolates. In the plasma of infected primiparous women, VSAPAM-specific IgG measured by flow cytometry could be correlated with anti-adhesion antibodies measured by the inhibition of CSA binding. Conclusion Recognition of placental parasites shows a parity- and sex- dependent pattern, like that previously observed in laboratory strains selected to bind to CSA. Placental infections at delivery in primiparous women appear to be sufficient to induce functional antibodies which can both recognize the surface of

  4. IgG4-related systemic disease of the pancreas with involvement of the lung: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Hurley JR

    2013-08-01

    Full Text Available IgG-related systemic disease (ISD remains exceedingly rare and unfamiliar, particularly extrapancreatic disease. We report a patient with separate presentations of IgG4 pulmonary disease and recurring IgG4 related biliary sclerosis and pancreatitis. Because of the intricate and perplexing pathogenesis, overlapping organ systems and wide variation in disease presentation, ISD in its entirety remains undefined. Accurate identification of ISD is critical to avoid permanent organ damage especially since treatment is nearly always successful with corticosteroids. As recognition and awareness of this disease grows, development of standard diagnostic criteria and treatment plans are needed.

  5. IgG responses to Anopheles gambiae salivary antigen gSG6 detect variation in exposure to malaria vectors and disease risk

    DEFF Research Database (Denmark)

    Stone, Will; Bousema, Teun; Jones, Sophie;

    2012-01-01

    , IgG responses to gSG6 in individual children showed a strong positive association with household level mosquito exposure. IgG levels for all antigens except AMA-1 were associated with the frequency of malaria episodes following sampling. gSG6 seropositivity was strongly positively associated...... with subsequent malaria incidence (test for trend p¿=¿0.004), comparable to malaria antigens MSP-1 and GLURP R2. Our results show that the gSG6 assay is sensitive to micro-epidemiological variations in exposure to Anopheles mosquitoes, and provides a correlate of malaria risk that is unrelated to immune...

  6. Assessing drivers of the IgG4 antibody reactivity to recombinant antigen Bm14 in Wuchereria bancrofti endemic populations in East Africa

    DEFF Research Database (Denmark)

    Hansen, Johanne Damgaard; Meyrowitsch, Dan W.; Rwegoshora, Rwehumbiza T.;

    2016-01-01

    ). The antibodies are commonly regarded as markers of infection and/or exposure to filarial larvae, but a direct association between the antibodies and these indices has not been well documented. The present study assessed the role and relative effect of potential drivers of the human IgG4 antibody reactivity...... antibodies had been induced but where CFA was not (yet?) measurable. Although the study indicated that IgG4 reactivity to Bm14 is a marker of filarial infection, assessment of this reactivity, especially in children, will still be useful for indirect monitoring of changes in transmission intensity, including...

  7. Production and characterization of monoclonal antibodies against dog immunoglobulin isotypes.

    Science.gov (United States)

    Arce, C; Moreno, A; Millán, Y; Martín de las Mulas, J; Llanes, D

    2002-09-01

    A panel of six monoclonal antibodies (mAbs) recognizing antigenic determinants on canine immunoglobulin (Ig) heavy or light chains was produced and characterized. All monoclonals recognized the IgG(2) subclass, although only two were subclass-specific (CA3H1 and CA4F1). The CA3B8 mAb was found to be specific for an epitope on canine immunoglobulin G heavy chain, (IgG(1) and IgG(2) subclasses). Two mAbs (CA2E9 and CA5B2) reacted with an epitope on the heavy chain of canine IgG and IgM and another, CA4E7, bound to canine IgA, IgG and IgM isotypes; CA4E7 recognized an epitope on canine immunoglobulin light chain. CA4E7, CA4F1 and CA5B2 recognized an epitope in the Fab region. Three mAbs, CA3B8, CA4E7 and CA5B2, showed much lower reactivity with canine IgG by ELISA when IgG was periodate-treated, suggesting that they recognized a carbohydrate determinant. Cross-reactivity analysis of these mAbs with sera from horse, goat, cow, sheep, pig, cat, rabbit, hamster, rat, mouse and human indicated that two mAbs, CA3B8 and CA5B2, recognized a canine IgG-specific epitope; two others, CA3H1 and CA4E7, recognized an epitope also present in rabbit and sheep immunoglobulin respectively; and the remaining two (CA2E9 and CA4F1) recognized an epitope broadly present on the Igs of the species analyzed. This panel of antibodies will be a useful tool for future canine immunodiagnosis tests. With the exception of CA2E9, all mAbs were able to recognize plasma cells on paraffin-embedded tissues, and will thus be useful for immunohistochemical assays. PMID:12088642

  8. Evolution of IgG antibody response against Toxoplasma gondii tissue cyst in acute and chronic human infections

    Directory of Open Access Journals (Sweden)

    Margarita VILLAVEDRA

    1998-03-01

    Full Text Available The recognition profile of the tissue cysts antigens by IgG antibodies was studied during acute and chronic human toxoplasmic infection. Thus the IgG response against Toxoplasma gondii was investigated by immunoblotting in two patients accidentally infected with the RH strain as well as in group of naturally infected patients at acute and chronic phase. There was an overall coincidence of molecular mass among antigens of tachyzoites and tissue cysts recognized by these sera, however, they appear not to be the same molecules. The response against tissue cysts starts early during acute infection, and the reactivity of antibodies is strong against a wide range of antigens. Six bands (between 82 and 151 kDa were exclusively recognized by chronic phase sera but only the 132 kDa band was positive in more than 50% of the sera analysed. A mixture of these antigens could be used to discriminate between the two infection phases. The most important antigens recognized by the acute and the chronic phase sera were 4 clusters in the ranges 20-24 kDa, 34-39 kDa, 58-80 kDa and 105-130 kDa as well as two additional antigens of 18 and 29 kDa. Both accidentally infected patients and some of the naturally infected patients showed a weak specific response against tissue cyst antigens.O reconhecimento do perfil dos antígenos de cistos tissulares pelos anticorpos IgG foi estudado durante a infecção toxoplasmótica aguda e crônica. Assim a resposta de IgG contra Toxoplasma gondii foi investigada pelo "immunoblotting" em dois pacientes acidentalmente infectados com a variedade RH bem como em grupos de pacientes naturalmente infectados nas fases aguda e crônica. Houve uma coincidência global da massa molecular entre antígenos de taquizoitas e cistos tissulares reconhecidos por estes soros, todavia, eles parecem não ser as mesmas moléculas. A resposta contra cistos tissulares começa precocemente durante a infecção aguda e a reatividade de anticorpos é forte

  9. Detection of the acute phase of abdominal angiostrongyliasis with a parasite-specific IgG enzyme linked immunosorbent assay

    Directory of Open Access Journals (Sweden)

    Geiger Stefan Michael

    2001-01-01

    Full Text Available Angiostrongylus costaricensis may cause intestinal lesions of varied severity when it accidentally infects man in Central and South America. First-stage larvae have never been detected in stools. Therefore, a parasite-specific IgG ELISA was evaluated for the determination of the acute phase of infection. The specificity and the sensitivity of the immunoassay was shown to be 76.2% and 91.1%, respectively. Eight serum samples taken from patients with histopathological diagnosis, at different time points (3 to 15 months after surgical treatment, showed a sharp and early decline in antibody reactivity. The titration of anti-A. costaricensis antibodies has proved to be a useful method for the diagnosis of acute abdominal angiostrongyliasis.

  10. Development and application of ELISA for the detection of IgG antibodies to lymphocytic choriomeningitis virus.

    Science.gov (United States)

    Lapošová, K; Lukáčiková, Ľ; Ovečková, I; Pastoreková, S; Rosocha, J; Kuba, D; Beňa, Ľ; Tomášková, J

    2016-06-01

    Lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen, which can cause severe illnesses in humans. The most vulnerable are the human foetus and immunosuppressed individuals. Since there is no commercially available enzyme-linked immunosorbent assay (ELISA) for the diagnosis of anti-LCMV antibodies in human sera, we developed a sandwich ELISA method detecting anti-nucleoprotein IgG antibodies, using a specific monoclonal anti-nucleoprotein antibody and cells persistently infected with LCMV strain MX as antigen. In the present study we show standardization of this ELISA protocol, determination of its clinical specificity and sensitivity and its application on 30 clinical samples from multiorgan donors. Comparison of these results to the indirect immunofluorescence antibody test (IFA) demonstrates that ELISA is more sensitive. The developed ELISA assay provides a fast, simple and efficient tool for the clinical detection of anti-nucleoprotein antibodies in human sera. PMID:27265463

  11. Solid-phase radioimmunoassay for IgG gliadin antibodies using /sup 125/I-labelled staphylococcal protein A

    Energy Technology Data Exchange (ETDEWEB)

    Troncone, R.; Pignata, C.; Farris, E.; Ciccimarra, F. (Naples Univ. (Italy). II Facolta di Medicina)

    1983-10-14

    A sensitive radioimmunoassay for IgG gliadin antibodies is described. Serum specimens were added to wells of plastic microtitre plates coated with gliadin. After removal of the unbound material, gliadin antibodies were detected by adding /sup 125/I-labelled staphylococcal protein A (/sup 125/I-SpA). Serum specimens from coeliac patients on a normal diet or on a gluten-free diet were tested, as well as sera from an age-matched control group. Measurements to obtain precise quantitative values were made with gliadin antibody-rich serum as reference standard. High titres of gliadin antibodies were found in 18 out of 19 coeliac patients on a normal diet (95%); in patients on a strict gluten-free diet serum values did not exceed 2 S.D. of the control mean. Due to the high sensitivity of the method a low but detectable amount of gliadin antibody was present in the sera of all controls.

  12. Glycyrrhizic acid prevents astrocyte death by neuromyelitis optica-specific IgG via inhibition of C1q binding.

    Science.gov (United States)

    Kim, Ji-Sun; Cheon, Soyoung; Kim, Seung Woo; Kim, Boram; Kim, Heejaung; Park, Ki Duk; Kim, Sung-Min

    2016-09-16

    Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system and is mediated by complement-dependent cytotoxicity (CDC) of NMO-specific immunoglobulin G (IgG) antibodies (NMO-IgG). Glycyrrhizic acid (GA) has numerous pharmacological effects including inhibition of the complement pathway. We aimed to study the influence of GA on NMO-IgG-induced CDC. NMO-IgG samples from 7 patients with NMO, together with human complement, induced CDC in an aquaporin 4 M23-overexpressing glial cell line, an in vitro NMO model. GA attenuated NMO-IgG-induced CDC in a dose-dependent manner. The mechanism of the GA-related CDC inhibition was sequentially dissected and found to involve inhibition of C1q binding to NMO-IgG. Consequently, GA attenuates NMO-IgG-induced CDC and may be a promising novel therapeutic agent against NMO. PMID:27462020

  13. Localization of the binding site for the human high-affinity Fc receptor on IgG.

    Science.gov (United States)

    Duncan, A R; Woof, J M; Partridge, L J; Burton, D R; Winter, G

    1988-04-01

    A major pathway in the clearance of pathogens involves the coating of the pathogen with specific antibodies, and the binding of the antibody Fc region to cell receptors. This can trigger engulfment of the pathogen by phagocytes or lysis by killer cells. By oligonucleotide site-directed mutagenesis we have engineered a single amino acid change in a mouse IgG2b antibody (Glu 235----Leu) which now enables the antibody to bind to the FcRI (high affinity) receptor on human monocytes with a 100-fold improvement in affinity. This indicates that Leu 235 is a major determinant in the binding of antibody to FcRI and that the receptor may interact directly with the region linking the CH2 domain to the hinge. Tailoring the affinity of antibodies for cell receptors could help dissect their role in clearing pathogen. PMID:2965792

  14. Association of beta2-glycoprotein I IgG and IgM antibodies with thrombosis and thrombocytopenia

    DEFF Research Database (Denmark)

    Voss, Anne-Sofie Boertmann; Jacobsen, Søren; Heegaard, Niels Henrik Helweg

    2001-01-01

    Antiphospholipid antibodies (APA) have been known for decades. Their relation to clinical manifestations, primarily thromboses and thrombocytopenia, was recognised in the 1980s. In this clinical study two cohorts of patients, a population-based (84 patients with systemic lupus erythematosus (SLE......)) and a hospital-based (87 patients with SLE and 53 with other connective tissue diseases) were investigated for APA and associated clinical manifestations. Anticardiolipin antibodies (ACA) of IgG and IgM classes were found in 13 and 38% of the population-based patients and in 29 and 58% of the hospital......-based patients, respectively. The corresponding figures for antibodies against beta2-glycoprotein I (anti-beta2GPI) were 15 and 10% in the population-based patients and 14 and 8% in the hospital-based cohort. Anti-beta2GPI antibodies were always found in association with the corresponding immunoglobulin class...

  15. Membranous-like glomerulopathy with masked IgG kappa deposits.

    Science.gov (United States)

    Larsen, Christopher P; Ambuzs, Josephine M; Bonsib, Stephen M; Boils, Christie L; Cossey, L Nicholas; Messias, Nidia C; Silva, Fred G; Wang, Yihan H; Gokden, Neriman; Walker, Patrick D

    2014-07-01

    The diagnostic classification of glomerulonephritis is determined by the interplay of changes seen using light, immunofluorescence, and electron microscopy of the renal biopsy. Routine direct immunofluorescence on fresh tissue is currently considered the gold standard for the detection and characterization of immune deposits. We recently found a peculiar form of glomerular immune complex deposition in which masked deposits required an antigen-retrieval step to be visualized. Over a 2-year period, 14 cases were characterized by numerous, large subepithelial deposits visualized by electron microscopy and C3-predominant staining by routine immunofluorescence on fresh tissue with weak to negative immunoglobulin staining. Repeat immunofluorescence after digestion of the formalin-fixed paraffin-embedded tissue with pronase elicited strong IgG-κ staining restricted within the deposits. The patients were often young with a mean age of 26 years and commonly had clinical evidence of vague autoimmune phenomenon. The clinicopathologic findings in this unusual form of glomerulopathy do not fit neatly into any currently existing diagnostic category. We have termed this unique form of glomerulopathy membranous-like glomerulopathy with masked IgG-κ deposits. PMID:24429395

  16. Autoimmune pancreatitis with IgG4-positive plasma cell infiltration in salivary glands and biliary tract

    Institute of Scientific and Technical Information of China (English)

    Masashi Taguchi; Gentaro Aridome; Shintaro Abe; Keiichiro Kume; Mitsuo Tashiro; Mitsuyoshi Yamamoto; Yasuyuki Kihara; Hayato Nakamura; Makoto Otsuki

    2005-01-01

    A 62-year-old male was referred to our hospital because of liver dysfunction, diffuse pancreatic swelling, and trachelophyma. At admission, the patient was free of pain.Physical examination showed enlarged and palpable bilateral submandibular masses, but no palpable mass or organomegaly in the abdomen. Laboratory findings were as follows: total protein 90 g/L with γ-globulin of 37.3% (33 g/L), total bilirubin 4 mg/L, aspartate aminotransferase 39 IU/L, alanine aminotransferase 67 IU/L, γ-glutamyl transpeptidase 1 647 IU/L, and amylase 135 IU/L. Autoantibodies were negative, and tumor markers were within the normal range. Serum IgG4 level was markedly elevated (18 900 mg/L). Computed tomography (CT) showed diffuse swelling of the pancreas and dilatation of both common and intra-hepatic bile ducts. Endoscopic retrograde pancreatography (ERP) revealed diffuse irregular and narrow main pancreatic duct and stenosis of the lower common bile duct. Biopsy specimens from the pancreas, salivary gland and liver showed marked periductal IgG4-positive plasma cell infiltration with fibrosis. We considered this patient to be autoimmune pancreatitis (AIP) with fibrosclerosis of the salivary gland and biliary tract, prescribed prednisolone at an initial dose of 40 mg/d. Three months later, the laboratory data improved almost to normal. Abdominal CT reflected prominent improvement in the pancreatic lesion. Swelling of the salivary gland also improved. At present, the patient is on 10 mg/d of prednisolone without recurrence of the pancreatitis. We present here a case of AIP with fibrosclerosis of salivary gland and biliary tract.

  17. Seroprevalence of IgG and IgM anti-Toxoplasma antibodies in HIV/AIDS patients, northern Iran

    Institute of Scientific and Technical Information of China (English)

    Ahmad Daryani; Mehdi Sharif; Masoumeh Meigouni

    2011-01-01

    Objective:To determine the seroprevalence of anti-Toxoplasma gondii(T. gondii) IgG and IgM antibodies inHIV/AIDS patients and uninfected subjects.Methods: This cross sectional survey was carried out on78 healthy and62 HIV+/AIDS individuals in northern Iran between September 2007 and October2008. Five mL of blood samples were collected from each person in case and control groups. Determination ofCD4+ counts was performed by flow cytometry. The serum separated from blood samples was evaluated by conventionalELISA technique to determine the presence of antibodies toT. gondii.Results: Forty eight out of62 (77.4%) HIV/AIDS serum samples were found positive for anti-T. gondii IgG antibody, compared with59 among78 (75.6%) HIV negative samples from the same area (P>0.05). Six out of62 (9.7%) HIV+/AIDS patients showed anti-T. gondiiIgM antibody in their serum samples, compared with 7 among78 (9%) HIV negative samples(P>0.05). The mean ofCD4+ counts inHIV+/AIDS was(430.8±182.3)cells/μL and in control group was(871.0±243.3)% cells/μL (P<0.01).CD4+ estimation in5 (11.1%)ofHIV+/AIDS patients was<200 cells/μL (P<0.000 1).Conclusions: Seroprevalence of latent toxoplasmosis inHIV patients is high, therefore the prevention of toxoplasmic encephalitis, administration of primary prophylaxis with co-trimoxazole to allHIV+/AIDS patients are necessary.

  18. [Lymphocytic hypophysitis and hypertrophic pachymeningitis: description of a possible case associated to IgG4 pathologies].

    Science.gov (United States)

    Blanco-Cantó, M Empar; Dávila-González, Pablo; López de Silanes, Carlos; Cuadrado-Pérez, M Luz; Ortega, Gloria; Porta-Etessam, Jesús

    2015-06-01

    Introduccion. Las patologias relacionadas con la infiltracion de linfocitos y celulas inflamatorias se clasifican, segun su topografia, en patologia orbitaria idiopatica, paquimeningitis hipertrofica idiopatica, sindrome de Tolosa-Hunt e hipofisitis linfocitaria. Presentamos a una paciente que comenzo con una hipofisitis linfocitaria hace ocho años y ha presentado varios episodios de paquimeningitis hipertrofica variables en su localizacion. Caso clinico. Mujer de 55 años, en seguimiento por cefalea de dos meses de evolucion, que ingreso por empeoramiento clinico con paralisis del III par derecho completo, lagrimeo y rinorrea. Se realizo una resonancia magnetica cerebral que demostro la presencia de una lesion sellar compatible con hipofisitis linfocitaria. Se inicio tratamiento con corticoides con mejoria inicial, pero, tras dos años, la paciente presento empeoramiento clinico con cefalea y parestesias perioculares derechas. Se repitio la resonancia, donde se observaron varias lesiones extraaxiales, siendo el resto de estudios normales, por lo que se diagnostico paquimeningitis hipertrofica idiopatica y se inicio tratamiento de nuevo con corticoides. En el seguimiento posterior, la paciente presento nuevas lesiones en diferentes localizaciones y mal control algico, por lo que se añadio tratamiento inmunomodulador. Ante la asociacion de hipofisitis linfocitaria y paquimeningitis hipertrofica, se completo el estudio con determinacion de la IgG4 en el suero, que resulto negativa. Conclusiones. La asociacion de hipofisitis linfocitaria y paquimeningitis hipertrofica con las patologias relacionadas con la IgG4 se ha descrito recientemente. A pesar de que en nuestra paciente no se ha confirmado el diagnostico, se debe considerar esta relacion en aquellos casos idiopaticos y, sobre todo, si se asocian otras manifestaciones sistemicas.

  19. Measles IgG antibody index correlates with T2 lesion load on MRI in patients with early multiple sclerosis.

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    Berit Rosche

    Full Text Available BACKGROUND: B cells and humoral immune responses play an important role in the pathogenesis and diagnosis of multiple sclerosis (MS. A characteristic finding in patients with MS is a polyspecific intrathecal B cell response against neurotropic viruses, specifically against measles virus, rubella virus, and varicella zoster virus, also known as an MRZ reaction (MRZR. Here, we correlated from the routine clinical diagnostics individual IgG antibody indices (AIs of MRZR with magnetic resonance imaging (MRI findings in patients with first MS diagnosis. METHODS/RESULTS: MRZR was determined in 68 patients with a clinically isolated syndrome (CIS or early relapsing-remitting MS (RRMS. Absolute AI values for measles virus, rubella virus, and varicella zoster virus were correlated with T2 lesion load and gadolinium enhancing lesions on cerebral MRI (cMRI and cMRI combined with spinal MRI (sMRI. Measles virus AI correlated significantly with T2 lesion load on cMRI (p = 0.0312, Mann-Whitney U test and the sum of lesions on cMRI and sMRI (p = 0.0413. Varicella zoster virus AI also showed a correlation with T2 lesion load on cMRI but did not reach statistical significance (p = 0.2893. CONCLUSION: The results confirm MRZR as part of the polyspecific immune reaction in MS with possible prognostic impact on MRI and clinical parameters. Furthermore, the data indicate that intrathecal measles virus IgG production correlates with disease activity on cMRI and sMRI in patients with early MS.

  20. An Enhanced Pre- and Postnatal Development Study in Cynomolgus Monkeys with Tabalumab: A Human IgG4 Monoclonal Antibody.

    Science.gov (United States)

    Breslin, William J; Hilbish, Kim G; Martin, Jennifer A; Halstead, Carolyn A; Newcomb, Deanna L; Chellman, Gary J

    2015-06-01

    Tabalumab, a human IgG4 monoclonal antibody (mAb) with neutralizing activity against both soluble and membrane B-cell activating factor (BAFF), has been under development for the treatment of autoimmune diseases. The purpose of this study was to determine the potential adverse effects of maternal tabalumab exposure on pregnancy, parturition, and lactation of the mothers and on the growth, viability, and development of the offspring through postnatal day (PND) 204. Tabalumab was administered by subcutaneous injection to presumed pregnant cynomolgus monkeys (16-19 per group) every 2 weeks from gestation day (GD) 20 to 22 until parturition at doses of 0, 0.3, or 30 mg/kg. Evaluations in mothers and infants included clinical signs, body weight, toxicokinetics, blood lymphocyte phenotyping, T-cell-dependent antibody response (infants only), antitherapeutic antibody (ATA), organ weights (infants only), and gross and microscopic histopathology. Infants were also examined for external and visceral morphologic and neurobehavioral development. There were no adverse tabalumab-related effects on maternal or infant endpoints. An expected pharmacological decrease in peripheral blood B-lymphocytes occurred in adults and infants; however, B-cell recovery was evident by PND154 in adults and infants at 0.3 mg/kg and by PND204 in infants at 30 mg/kg. At 30 mg/kg, a reduced IgM antibody response to T-cell-dependent antigen keyhole limpet hemocyanin (KLH) was observed following primary immunization. Following secondary KLH immunization, all infants in both dose groups mounted anti-KLH IgM and IgG antibody responses similar to control. Placental and mammary transfer of tabalumab was demonstrated. In conclusion, the no-observed-adverse-effect level for maternal and developmental toxicity was 30 mg/kg, the highest dose tested. Exposures at 30 mg/kg provide a margin of safety of 16× the anticipated clinical exposure. PMID:26195230