Sample records for characterize polysorbate-containing igg

  1. In vitro functional characterization of feline IgGs. (United States)

    Strietzel, Catherine J; Bergeron, Lisa M; Oliphant, Theodore; Mutchler, Veronica T; Choromanski, Leszek J; Bainbridge, Graeme


    Very little is known about the functional properties of feline IgGs. Here we report the in vitro characterization of cloned feline IgGs. Rapid amplification of cDNA ends (RACE) and full-length PCR of cat splenic cDNA were used to identify feline sequences encoding IgG heavy chain constant regions (IGHC). Two of the sequences are possibly allelic and have been previously reported in the literature as the only feline IgG, IgG1. Although we confirmed these alleles to be highly abundant (∼98%), analysis of numerous amplification products revealed an additional sequence (∼2%). We cloned and characterized chimeric monoclonal antibodies with each of these heavy chains. Using RACE we revealed the sequences for feline Fc gamma receptor I (FcγRI) and feline Fc neonatal receptor (FcRn). We constructed these recombinant receptors as well as fFcγRIII and determined their binding affinities to the chimeras. All of the chimeras bound to Protein A but not to Protein G, and bound tightly to fFcRn (KD=2-5 nM). Both IgG1 alleles have a high affinity for fFcγRI (KD=10-20 nM), they bind to the low-affinity fFcγRIII receptor (2-4 μM), and also bind to human complement C1q. Thus, feline IgG1a and 1b are expected to induce strong effector function in vivo. The additional IgG detected does not bind to recombinant fFcγRI or fFcγRIII and has negligible binding to hC1q. Consequently, although this putative subclass is projected to have a similar serum half-life as the IgG1 alleles based on comparable in vitro affinity to FcRn, it may not elicit the effector responses mediated by fFcγRI or fFcγRIII. Further testing with native receptors and functional cell-based assays would confirm effector function capabilities of feline IgG subclasses; however this is the first report characterizing affinities of feline IgGs to their Fc receptors and helps pave the way for construction of feline-specific IgGs for therapeutic use.

  2. Biophysical and Functional Characterization of Rhesus Macaque IgG Subclasses

    Directory of Open Access Journals (Sweden)

    Austin W. Boesch


    Full Text Available Antibodies raised in Indian rhesus macaques (Macaca mulatta, MM in many preclinical vaccine studies are often evaluated in vitro for titer, antigen-recognition breadth, neutralization potency, and/or effector function, and in vivo for potential associations with protection. However, despite reliance on this key animal model in translation of promising candidate vaccines for evaluation in first in man studies, little is known about the properties of MM IgG subclasses and how they may compare to human IgG subclasses. Here we evaluate the binding of MM IgG1, IgG2, IgG3, and IgG4 to human FcγR and their ability to elicit the effector functions of human FcγR-bearing cells, and unlike in humans, find a notable absence of subclasses with dramatically silent Fc regions. Biophysical, in vitro, and in vivo characterization revealed MM IgG1 exhibited the greatest effector function activity followed by IgG2 and then IgG3/4. These findings in rhesus are in contrast with the canonical understanding that IgG1 and IgG3 dominate effector function in humans, indicating that subclass-switching profiles observed in rhesus studies may not strictly recapitulate those observed in human vaccine studies.

  3. Pemphigus vulgaris is characterized by low IgG reactivities to specific self-antigens along with high IgG reactivity to desmoglein 3. (United States)

    Fattal, Ittai; Rimer, Jacob; Shental, Noam; Molad, Yair; Gabrielli, Armando; Livneh, Avi; Sarig, Ofer; Goldberg, Ilan; Gafter, Uzi; Domany, Eytan; Cohen, Irun R


    Pemphigus vulgaris (PV) is an autoimmune skin disease, which has been characterized by IgG autoantibodies to desmoglein 3. Here we studied the antibody signatures of PV patients compared with healthy subjects and with patients with two other autoimmune diseases with skin manifestations (systemic lupus erythematosus and scleroderma), using an antigen microarray and informatics analysis. We now report a previously unobserved phenomenon--patients with PV, compared with the healthy subjects and the two other diseases, show a significant decrease in IgG autoantibodies to a specific set of self-antigens. This novel finding demonstrates that an autoimmune disease may be associated with a loss of specific, healthy IgG autoantibodies and not only with a gain of specific, pathogenic IgG autoantibodies.

  4. DARPA Antibody Technology Program Standardized Test Bed for Antibody Characterization: Characterization of an MS2 Human IgG Antibody Produced by AnaptysBio, Inc. (United States)


    ECBC-TR-1339 DARPA ANTIBODY TECHNOLOGY PROGRAM STANDARDIZED TEST BED FOR ANTIBODY...CHARACTERIZATION: CHARACTERIZATION OF AN MS2 HUMAN IGG ANTIBODY PRODUCED BY ANAPTYSBIO, INC. DARPA ATP Standardized Test Bed for Antibody...Characterization: Characterization of an MS2 human IgG antibody produced by AnaptysBio DARPA ATP Standardized Test Bed for Antibody

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

    Energy Technology Data Exchange (ETDEWEB)

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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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)


    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.)

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

    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


    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.

  8. Characterization of cysteine related variants in an IgG2 antibody by LC-MS with an automated data analysis approach. (United States)

    Zhang, Yuling; Bailey, Robert; Nightlinger, Nancy; Gillespie, Alison; Balland, Alain; Rogers, Richard


    In this communication, a high-throughput method for automated data analysis of cysteine-related product quality attributes (PQAs) in IgG2 antibodies is reported. This method leverages recent advances in the relative quantification of PQAs to facilitate the characterization of disulfide variants and free sulfhydryls (SHs) in IgG2 antibodies. The method uses samples labeled with a mass tag (N-ethyl maleimide [NEM]) followed by enzymatic digestion under non-reducing conditions to maintain the cysteine connectivity. The digested IgG2 samples are separated and detected by mass spectrometry (MS) and the resulting peptide map is analyzed in an automated fashion using Pinpoint software (Thermo Scientific). Previous knowledge of IgG2 disulfide structures can be fed into the Pinpoint software to create workbooks for various disulfide linkages and hinge disulfide variants. In addition, the NEM mass tag can be added to the workbooks for targeted analysis of labeled cysteine-containing peptides. The established Pinpoint workbooks are a high-throughput approach to quantify relative abundances of unpaired cysteines and disulfide linkages, including complicated hinge disulfide variants. This approach is especially efficient for comparing large sets of similar samples such as those created in comparability and stability studies or chromatographic fractions. Here, the high throughput method is applied to quantify the relative abundance of hinge disulfide variants and unpaired cysteines in the IgG2 fractions from non-reduced reversed-phase high-performance liquid chromatography (nrRP-HPLC). The LC-MS data analyzed by the Pinpoint workbook suggests that the nrRP-HPLC separated peaks contain hinge disulfide isoforms and free cysteine pairs for each major disulfide isoform structure.

  9. Serum levels of IgG and IgG4 in Hashimoto thyroiditis. (United States)

    Kawashima, Sachiko-Tsukamoto; Tagami, Tetsuya; Nakao, Kanako; Nanba, Kazutaka; Tamanaha, Tamiko; Usui, Takeshi; Naruse, Mitsuhide; Minamiguchi, Sachiko; Mori, Yusuke; Tsuji, Jun; Tanaka, Issei; Shimatsu, Akira


    Although IgG4-related disease is characterized by extensive infiltration of IgG4-positive plasma cells and lymphocytes of various organs, the details of this systemic disease are still unclear. We screened serum total IgG levels in the patients with Hashimoto thyroiditis (HT) to illustrate the prevalence of IgG4-related thyroiditis in HT. Twenty-four of 94 patients with HT (25.5%) had elevated serum IgG levels and their serum IgG4 was measured. Five of the 24 cases had more than 135 mg/dL of IgG4, which is the serum criterion of IgG4-related disease. One was a female patient who was initially treated as Graves' disease and rapidly developed a firm goiter and hypothyroidism. The biopsy of her thyroid gland revealed that follicular cells were atrophic with squamous metaplasia, replaced with fibrosis, which was compatible with the fibrous variant of HT. Immunohistochemical examination revealed diffuse infiltration of IgG4-positive plasma cells, and the serum IgG4 level was 179 mg/dL. The levels of IgG and IgG4 were positively correlated with the titers of anti-thyroglobulin antibody or anti-thyroid peroxidase antibody. In conclusion, at least a small portion of patients with HT with high titers of anti-thyroid antibodies may overlap the IgG4-related thyroiditis.

  10. IgG4-Related Disease without Overexpression of IgG4: Pathogenesis Implications

    Directory of Open Access Journals (Sweden)

    Naoshi Nishina


    Full Text Available IgG4-related disease is a new disease group that affects multiple organs. It is characterized by high serum IgG4 and abundant infiltration of IgG4-bearing plasma cells in the affected organ. Here, we describe an intriguing case that suggested that IgG4-related disease might present without IgG4 overexpression or infiltration, at least during a relapse. A 47-year-old man had been diagnosed with systemic lupus erythematosus 15 years. He was admitted due to a pituitary mass, systemic lymphadenopathy, and multiple nodules in the lungs and kidneys. The serum IgG4 level was normal and histopathological examination of the pituitary mass showed abundant lymphocyte and plasma cell infiltration with very few IgG4-positive cells. When we examined specimens preserved from 15 years ago, we found high serum IgG4 levels and IgG4-bearing plasma cell infiltration. This resulted in a diagnosis of IgG4-related disease, and we considered the current episode to be a relapse without IgG4 overexpression. This case indicated that, to clarify the pathogenesis of IgG4-related disease, current cases should repeat specimen evaluations over the course of IgG4-related disease to define diagnostic markers.

  11. Serum IgG subclasses in autoimmune diseases. (United States)

    Zhang, Haoze; Li, Ping; Wu, Di; Xu, Dong; Hou, Yong; Wang, Qian; Li, Mengtao; Li, Yongzhe; Zeng, Xiaofeng; Zhang, Fengchun; Shi, Qun


    To characterize serum IgG subclass levels in several autoimmune diseases, including primary Sjogren syndrome (pSS), systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and primary biliary cirrhosis (PBC). We aimed to analyze serum IgG subclass distribution and to test whether serum IgG4 levels are elevated in these diseases. Serum IgG subclass levels from 102 pSS, 102 SSc, 100 SLE, and 59 PBC patients, as well as 40 healthy controls (HCs), were measured using the immunonephelometric assay. The distribution of IgG subclasses among these autoimmune diseases was analyzed. In this cross-sectional study, serum IgG1 (IgG1/IgG) and/or IgG3 (IgG3/IgG) were significantly increased, compared with those in HCs. Only 6.34% of patients had levels of serum IgG4 >135 mg/dL. There were no significant differences in the frequency of elevated serum IgG4 levels between patients and HC. In pSS, serum IgG1 levels were much higher than those in other disease groups, whereas serum IgG2 and IgG3 levels were most prominently increased in PBC. A strikingly different serum IgG subclass distribution was detected in patients with autoimmune diseases compared with HCs. Serum IgG subclass levels also showed distinct characteristics among different autoimmune diseases. Serum IgG4 levels in these patients were lower or not much higher than those in HCs, which differed from IgG4-related diseases.

  12. Characterization of expression, cytokine regulation, and effector function of the high affinity IgG receptor Fc gamma RI (CD64) expressed on human blood dendritic cells. (United States)

    Fanger, N A; Voigtlaender, D; Liu, C; Swink, S; Wardwell, K; Fisher, J; Graziano, R F; Pfefferkorn, L C; Guyre, P M


    The mechanisms responsible for efficient sequestration of Ag by cells of the dendritic cell (DC) lineage remain incompletely characterized. One pathway, internalization of Ag-IgG complexes via CD32 (the type II IgG FcR, Fc gamma RII) enhances Ag presentation 100-fold over noncomplexed Ag. Blood leukocytes differentially express two additional IgG FcR, Fc gamma RI (CD64) and Fc gamma RIII (CD16), which may also participate in leukocyte functions such as phagocytosis, Ab-dependent cellular cytotoxicity (ADCC), release of oxygen intermediates, and enhancement of Ag presentation. A phagocytically active form of CD64 was recently demonstrated on human blood DC, but complete functional potential of CD64 on the DC lineage remains undefined. Therefore, highly purified human blood DC (CD33(2)+, CD14-, CD11c2+, HLA-DR3+, CD64+ (CD83+ after overnight culture)) and monocytes (CD33(2)+, CD14(3)+, CD11c2+, HLA-DR+, CD64(2)+, CD83-) were compared for cytokine modulation and effector functions of CD64. Both DC and monocyte CD64 expression was increased by IFN-gamma and IL-10, but while monocyte CD64 was decreased by IL-4, DC CD64 remained unchanged. FcR-mediated functional differences were also evident between the DC and the monocytes. Monocytes generated robust Fc gamma R-dependent superoxide anion release and ADCC activity, while DC failed to release reactive oxygen intermediates and demonstrated minimal ADCC activity, despite apparently normal expression of the gamma-chain subunit and the signaling molecule Syk. In contrast, DC were more efficient than monocytes with respect to T cell activation when Ag was targeted specifically to CD64. These new findings suggest a previously unappreciated potential for CD64 to shape the immune response by dramatically increasing the efficiency with which DC sequester Ag prior to achieving full T cell stimulatory potential.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Lv Zhengjian


    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.

  15. IgG4-related sclerosing disease

    Institute of Scientific and Technical Information of China (English)

    Terumi Kamisawa; Atsutake Okamoto


    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.

  16. Large Scale Production and Characterization of Anti-Human IgG Monoclonal Antibody in Peritoneum of Balb/c MICE

    Directory of Open Access Journals (Sweden)

    B. Baradaran


    Full Text Available Monoclonal antibodies are key reagents that are used in biomedical researches, diagnosis of immunodeficiency diseases such as IgG subclasses deficiency and treatment of diseases like infections and cancers .For large scale production of monoclonal antibody, hybridoma cells that produce monoclonal antibody against human IgG were injected into the peritoneum of the Balb/c mice which have previously been primed with 0.5 ml Pristane. After ten days, approximately 3 ml ascitic fluid was harvested from the peritoneum of each mouse. Ascitic fluid was assayed for the titer of monoclonal antibody in reaction with human IgG and its cross reactivity in reaction with IgM & IgA. The titer of mAb was 100,000 and didn't show cross reactivity with IgM & IgA. Immunobloting was done for confirming the ELISA method. In immunobloting, only one sharp band in the heavy chain position of IgG was developed. The subclass of antibody was IgG1 and its light chain was kappa. Ascitic fluid was purified by ion exchange chromatography and the purified monoclonal antibody was conjugated with HRP. The conjugated monoclonal antibody could have application in diagnosis of infectious diseases like Toxoplasmosis, Rubella and IgG class of all other infectious diseases.

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


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


    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 li...

  18. IgG4 Inflammatory Pseudotumor of the Kidney

    Directory of Open Access Journals (Sweden)

    Ahmed N. Alkhasawneh


    Full Text Available Hyper-IgG4 disease is a rare systemic disorder that usually affects middle age males. It is characterized by elevated serum IgG4 levels and infiltration of organs by IgG4 positive plasma cells associated with fibrosis. Patients usually present with mass or masses in the involved organ that mimic neoplasia. While initially described in the pancreas, IgG4-related inflammatory tumors have been now described in many organs. We describe an unusual case of an IgG4-related pseudotumor of the kidney.

  19. Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases. (United States)

    Yamamoto, Motohisa; Tabeya, Tetsuya; Naishiro, Yasuyoshi; Yajima, Hidetaka; Ishigami, Keisuke; Shimizu, Yui; Obara, Mikiko; Suzuki, Chisako; Yamashita, Kentaro; Yamamoto, Hiroyuki; Hayashi, Toshiaki; Sasaki, Shigeru; Sugaya, Toshiaki; Ishida, Tadao; Takano, Ken-Ichi; Himi, Tetsuo; Suzuki, Yasuo; Nishimoto, Norihiro; Honda, Saho; Takahashi, Hiroki; Imai, Kohzoh; Shinomura, Yasuhisa


    IgG4-related disease (IgG4-RD) is a novel disease entity that includes Mikulicz's disease, autoimmune pancreatitis (AIP), and many other conditions. It is characterized by elevated serum IgG4 levels and abundant IgG4-bearing plasmacyte infiltration of involved organs. We postulated that high levels of serum IgG4 would comprise a useful diagnostic tool, but little information is available about IgG4 in conditions other than IgG4-RD, including rheumatic diseases. Several reports have described cutoff values for serum IgG4 when diagnosing IgG4-RD, but these studies mostly used 135 mg/dL in AIP to differentiate from pancreatic cancer instead of rheumatic and other common diseases. There is no evidence for a cutoff serum IgG4 level of 135 mg/dL for rheumatic diseases and common diseases that are often complicated with rheumatic diseases. The aim of this work was to re-evaluate the usual cutoff serum IgG4 value in AIP (135 mg/dL) that is used to diagnose whole IgG4-RD in the setting of a rheumatic clinic by measuring serum IgG4 levels in IgG4-RD and various disorders. We therefore constructed ROC curves of serum IgG4 levels in 418 patients who attended Sapporo Medical University Hospital due to IgG4-RD and various rheumatic and common disorders. The optimal cut-off value of serum IgG4 for a diagnosis of IgG4-RD was 144 mg/dL, and the sensitivity and specificity were 95.10 and 90.76%, respectively. Levels of serum IgG4 were elevated in IgG4-RD, Churg-Strauss syndrome, multicentric Castleman's disease, eosinophilic disorders, and in some patients with rheumatoid arthritis, systemic sclerosis, chronic hepatitis, and liver cirrhosis. The usual cut-off value of 135 mg/dL in AIP is useful for diagnosing whole IgG4-RD, but high levels of serum IgG4 are sometimes observed in not only IgG4-RD but also other rheumatic and common diseases.


    Directory of Open Access Journals (Sweden)

    E. V. Sokol


    Full Text Available IgG4-related disease (IgG4-RD is a fibroinflammatory condition characterized by the occurrence of tumor-like foci in different organs with a unique histological pattern (moirо-like fibrosis, obvious lymphoplasmacytic infiltration with large numbers of IgG4+ plasma cells, and obliterating phlebitis and elevated serum IgG4 levels in the majority of patients. Its first-line therapy is glucocorticoids at a starting dose of 0.6 mg/kg/day (equivalent to prednisolone; however, this treatment entails a great number of adverse events and high recurrence rates. The paper provides a review of today's literature on the treatment of IgG4-RD; particular emphasis is laid on the description of therapy with glucocorticoids and rituximab.

  1. A small subgroup of Hashimoto's thyroiditis is associated with IgG4-related disease. (United States)

    Jokisch, Friedrich; Kleinlein, Irene; Haller, Bernhard; Seehaus, Tanja; Fuerst, Heinrich; Kremer, Marcus


    IgG4-related disease is a newly identified syndrome characterized by high serum IgG4 levels and increased IgG4-positive plasma cells in involved organs. The incidence of IgG4-related thyroiditis in the Caucasian population of Europe is unknown. We investigated formalin-fixed thyroid gland samples of 216 patients (191 Hashimoto's thyroiditis, 5 Riedel's thyroiditis, and 20 goiters, as controls), morphologically, and immunohistochemically. Cases were divided into two groups: IgG4-related Hashimoto's thyroiditis (24 cases) together with Riedel thyroiditis (1 case) and 171 non-IgG4-related thyroiditis. Compared to the non-IgG4-related cases, IgG4-related thyroiditis showed a higher IgG4/IgG ratio (0.6 vs. 0.1, p thyroiditis was diagnosed in 23 of the 24 IgG4-related cases (96 %) and in 13 of 167 (18 %, p > 0.001) non-IgG4-related cases. The single case of IgG4-related Riedel's thyroiditis also showed a higher median IgG4 plasma cell count (56.3 vs. 14.3) and a higher IgG4/IgG ratio (0.5 vs. 0.2) than the four cases of non-IgG4-related Riedel's thyroiditis. Our data suggests the incidence of IgG4-related disease (IgG4-RD) of the thyroid gland in Europe is considerably lower than that observed in other studies. A significant elevation of IgG4-positive plasma cells was only found in a small group of Hashimoto's thyroiditis and then accompanied by intense fibrosis, indicating an association with IgG4-RD. Morphologically, IgG4-RD of the thyroid gland differs from that in other organ systems, exhibiting a dense fibrosis without intense eosinophilia or obliterative phlebitis.

  2. IgG4-Related Perineural Disease

    Directory of Open Access Journals (Sweden)

    Dai Inoue


    Full Text Available Aims. To elucidate characteristics of IgG4-related disease involving the peripheral nervous system. Methods. Retrospective review of 106 patients with IgG4-related disease identified 21 peripheral nerve lesions in 7 patients. Clinicopathological and radiological features were examined. Results. Peripheral nerve lesions were commonly identified in orbital or paravertebral area, involving orbital (=9, optic (=4, spinal (=7, and great auricular nerves (=1. The predominant radiological feature was a distinct perineural soft tissue mass, ranging 8 to 30 mm in diameter. Histologically, the epineurium was preferentially involved by massive lymphoplasmacytic infiltration rich in IgG4+ plasma cells. All lesions were neurologically asymptomatic and steroid-responsive at the first presentation, but one recurrent lesion around the optic nerve caused failing vision. Conclusion. IgG4-related disease of the peripheral nervous system is characterized by orbital or paravertebral localization, perineural mass formation, and rare neurologic symptoms. The term “IgG4-related perineural disease” seems appropriate to describe this entity.

  3. IgG4-associated cholangitis. (United States)

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


    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.

  4. IgG4-Related Disease: A Multispecialty Condition

    Directory of Open Access Journals (Sweden)

    Iuri Usêda Santana


    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.

  5. Overlapping Morphologic and Immunohistochemical Features of Hashimoto Thyroiditis and IgG4-Related Thyroid Disease. (United States)

    Raess, Philipp W; Habashi, Arlette; El Rassi, Edward; Milas, Mira; Sauer, David A; Troxell, Megan L


    Immunoglobulin G4-related disease (IgG4-RD) is an emerging clinicopathologic entity characterized by both IgG4+ plasma cell infiltration and fibrosis in one or more organs, prototypically pancreas or salivary/lacrimal glands. IgG4-RD in the thyroid (IgG4-RTD) is an area of active study, and the relationship between IgG4-RTD and Hashimoto thyroiditis is not fully delineated due to their overlapping histologic features. Retrospective review was performed of all thyroidectomy cases demonstrating lymphocytic inflammation at a single institution over a 4-year period. Approximately half (23/38) of patients had a clinical diagnosis of Hashimoto thyroiditis (HT). Nine of the 38 patients had increased absolute and relative numbers of IgG4+ plasma cells. Patients with a clinical diagnosis of HT had increased lymphoplasmacytic inflammation, but the relative proportion of IgG4+ plasma cells was not increased compared to patients without HT. There was no correlation between IgG4 levels and the amount of fibrosis in patients with or without HT. Patients identified as having the fibrosing variant of HT were not more likely to have increased levels of IgG4+ plasma cells than those without. There is significant morphologic and immunohistochemical overlap between HT and IgG4-RTD. Future studies to identify specific characteristics of IgG4-RTD involving the thyroid are necessary to accurately define this entity.

  6. IgG4-Related Disease in a Urachal Tumor

    Directory of Open Access Journals (Sweden)

    Travis W. Dum


    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.

  7. [Review of ear and nose and throat involvement in IgG4-RD]. (United States)

    Tao, Xiaofeng; Liu, Chang; Song, Bo


    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.

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

    Directory of Open Access Journals (Sweden)

    Kazuichi Okazaki


    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.

  9. 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

    DEFF Research Database (Denmark)

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


    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....

  10. IgG4检测在IgG4相关性疾病的新进展%Value of serum IgG4 in IgG4-related disease

    Institute of Scientific and Technical Information of China (English)

    荆红运; 关秀茹


    Immunoglobulin G4(IgG4)-related disease (IgG4-RD) is a new systemic and chronic autoimmune disease.It is characterized by increased serum levels of IgG 4 and infiltration of abundant IgG 4-positive cells in various organs and tissues .It is needed to distinguish IgG 4-RD and other diseases which will induce high level of serum IgG4 and infiltration of abundant IgG4-positive cells in tissues.This study described the value of serum IgG4 in IgG4-RD.%IgG4相关性疾病( IgG4-RD)是一种新的系统性、慢性自身免疫性疾病。临床表现为IgG4阳性浆细胞及淋巴细胞浸润多种器官和组织,并伴有血清IgG4水平升高。此外,一些其他疾病也会出现血清IgG4升高或组织中IgG4阳性浆细胞浸润,因此需要进行鉴别诊断。本文论述了血清IgG4对IgG4-RD诊断及鉴别诊断的价值。(中华检验医学杂志,2016,39:817-819)

  11. A case of progressively transformed germinal center-type IgG4-related lymphadenopathy. (United States)

    Seki, Nobuhiko; Yamazaki, Norikazu; Koizumi, Jun-ichi; Takano, Ken-ichi; Abe, Ayumi; Ikeda, Tatsuru; Noguchi, Hiroko; Himi, Tetsuo


    Progressively transformed germinal centers (PTGC), a lymph node process unfamiliar to most otolaryngologists, is a morphological variant of reactive lymphofollicular hyperplasia of lymph nodes. Immunoglobulin (Ig)G4-related disease (IgG4-RD) is a newly identified condition, characterized by hyper-IgG4-γ-globulinemia and mass-forming or hypertrophic lesions associated with infiltration of IgG4(+) plasma cells in the affected organs. Recently, a case study of PTGC was reported that fulfilled the diagnostic criteria of IgG4-RD (IgG4(+) PTGC) [1]. A 68-year-old male was referred to our hospital with swelling in the left submandibular region. Palpation revealed swollen lymph nodes, the largest of which measured 5cm in diameter. (18)F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography identified lymphadenopathy with high (18)F-FDG uptake in the left submandibular region. We strongly suspected malignant lymphoma, and excisional biopsy of the submandibular lymph node was performed under general anesthesia. Pathological findings were consistent with IgG4(+) PTGC, and serological examination demonstrated elevated levels of IgG4. These findings were consistent with IgG4-RD. The patient did not have systemic lesions; therefore, he has not undergone corticosteroid therapy. IgG4(+) PTGC should be considered as a differential diagnosis for cervical lymphadenopathy by otolaryngologists as well as pathologists.

  12. Serum total IgG and IgG4 levels in thyroid eye disease

    Directory of Open Access Journals (Sweden)

    Sy A


    Full Text Available Aileen Sy, Rona Z Silkiss Department of Ophthalmology, California Pacific Medical Center, San Francisco, CA, USA Purpose: To investigate the relationship between immunoglobulin G (IgG4-related disease (IgG4-RD and thyroid eye disease (TED with respect to IgG levels. Patients and methods: A retrospective review of total IgG, IgG subclass, and thyroid stimulating immunoglobulin (TSI levels in 24 patients with TED. Results: Five patients (20.8% demonstrated serum IgG4 levels consistent with IgG4-RD without any additional systemic disease. Total IgG and IgG subclass levels were found to be an inadequate proxy for TSI elevation. Conclusion: There may be a subtype of TED patients with elevated IgG4 in the absence of IgG4-RD systemic findings. Keywords: thyroid eye disease, IgG subclass, IgG4, Graves’ disease, Graves’ ophthalmopathy, IgG4-RD

  13. IgG4-associated vasculitis. (United States)

    Perez Alamino, Rodolfo; Martínez, Carlos; Espinoza, Luis R


    Elevated IgG4 is characteristic of cases of IgG4-RD, a newly recognized systemic disease. However, several chronic inflammatory conditions, including rheumatic diseases, can also be associated with increased levels of IgG4. There have also recently been several reports describing an increased IgG4 immune response to some vasculitis syndromes, in particular Churg-Strauss syndrome and granulomatosis with polyangiitis. To avoid misdiagnosis, clinicians must be aware that the clinical manifestations of IgG4-RD and ANCA-associated vasculitis may overlap. The meaning of these observations is not yet understood, and more studies are needed to determine the true significance of the increased IgG4 response to vasculitis syndromes, especially anti-neutrophil cytoplasmatic antibodies (ANCA)-associated vasculitis.

  14. IgG4 Related Sclerosing Cholangitis

    Directory of Open Access Journals (Sweden)

    D. Joshi


    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.

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

    Directory of Open Access Journals (Sweden)

    Yasufumi Masaki


    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.

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

    Directory of Open Access Journals (Sweden)

    D. Eric Ewing, MD


    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.

  17. A case of tubulointerstitial nephritis in IgG4-related systemic disease with markedly enlarged kidneys. (United States)

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Arezou Khosroshahi


    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.

  19. IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy (United States)

    Li, Dujuan; Kan, Yunzhen; Fu, Fangfang; Wang, Shuhuan; Shi, Ligang; Liu, Jie; Kong, Lingfei


    Immunoglobulin G4-related disease (IgG4-RD) is a recently described inflammatory disease involving multiple organs. Prostate involvement with IgG4-RD is very rare. In this report, we describe a case of IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy. This patient was present with urine retention symptoms. MRI and CT examination revealed the prostatic enlargement and the multiple lymphadenopathy. Serum IgG4 levels were elevated. Prostatic tissue samples resected both this time and less than 1 year earlier showed the same histological type of prostatitis with histopathologic and immunohistochemical findings characteristic of IgG4-RD. The right submandibular lymph nodes excised 2 years earlier were eventually proven to be follicular hyperplasia-type IgG4-related lymphadenopathy. This is the first case of IgG4-RD that began as localized IgG4-related lymphadenopathy and progressed into a systemic disease involving prostate and multiple lymph nodes. This patient showed a good response to steroid therapy. This leads us to advocate a novel pathogenesis of prostatitis, and a novel therapeutic approach against prostatitis. Pathologists and urologists should consider this disease entity in the patients with elevated serum IgG4 levels and the symptoms of prostatic hyperplasia to avoid ineffective medical or unnecessary surgical treatment. PMID:26617921

  20. A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis. (United States)

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


    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.

  1. Clinicopathological features of Riedel's thyroiditis associated with IgG4-related disease in Japan. (United States)

    Takeshima, Ken; Inaba, Hidefumi; Ariyasu, Hiroyuki; Furukawa, Yasushi; Doi, Asako; Nishi, Masahiro; Hirokawa, Mitsuyoshi; Yoshida, Akira; Imai, Ryoukichi; Akamizu, Takashi


    Riedel's thyroiditis (RT) is a rare chronic fibrosing disorder characterized by a hard, infiltrative lesion in the thyroid gland, which is often associated with multifocal fibrosclerosis. Immunoglobulin G4-related disease (IgG4-RD) is typified by infiltration of IgG4-positive plasma cells into multiple organs, resulting in tissue fibrosis and organ dysfunction. In order to evaluate the clinicopathological features of RT and its relationship with IgG4-RD, we performed a Japanese literature search using the keywords "Riedel" and "Riedel's thyroiditis." We used the electronic databases Medline and Igaku Chuo Zasshi, the latter of which is the largest medical literature database in Japan. The diagnosis of RT was based on the presence of a fibroinflammatory process with extension into surrounding tissues. Only 10 patients in Japan fulfilled RT diagnostic criteria during the 25-year period between 1988 and 2012. Two patients with confirmed IgG4/IgG immunohistochemical findings demonstrated 43 and 13 IgG4-positive plasma cells per high-power field, respectively, and the IgG4-positive/IgG-positive plasma cell ratios of 20% and less than 5%. Of the 10 patients with RT, two received glucocorticoids, one of whom experienced marked shrinkage of the thyroid lesion. One patient had extra-thyroid involvement in the form of retroperitoneal fibrosis. Although the clinicopathological features of RT suggest that IgG4-RD may be the underlying condition in some cases, further investigation is needed to clarify the etiology of RT in relation to IgG4-RD.

  2. Is IgG4-Related Disease a Cause of Xerostomia? A Cohort Study of 60 Patients

    Directory of Open Access Journals (Sweden)

    M. Hermet


    Full Text Available Objective. Immunoglobulin-G4-(IgG4- related disease (IgG4 RD is a fibrosing process characterized by a significant infiltration of IgG4-secreting plasma cells. IgG4 RD can affect almost all organs including salivary glands. Whether IgG4 RD plays a role in the development of sicca syndrome and particularly dry mouth syndrome remains to be investigated. Methods. We conducted a monocentric cohort study for two years to search for IgG4 RD features in patients with dry mouth syndrome using immunostainings of labial salivary gland specimens with anti-IgG4 antibody. Results. Among 60 patients presenting with dry mouth syndrome who underwent labial salivary gland biopsy, 18 showed positive immunostaining with the anti-IgG4 antibody including 4 patients with typical systemic IgG4 RD. Five also fulfilled criteria for Sjögren's syndrome. Conclusion. These findings suggest that clinical forms of IgG4 RD salivary involvement without salivary swelling may occur. This salivary involvement is probably overlooked in everyday practice and could represent a mild form of IgG4 RD.

  3. IgG4-related disease: a novel lymphoproliferative disorder discovered and established in Japan in the 21st century. (United States)

    Masaki, Yasufumi; Kurose, Nozomu; Umehara, Hisanori


    IgG4-related disease is a novel lymphoproliferative disorder that shows hyper-IgG4-γ-globulinemia and IgG4-producing plasma cell expansion in affected organs with fibrotic or sclerotic changes. Patients show systemic inflammatory conditions and various symptoms depending on the affected organ. Since the first report of patients with elevated serum IgG4 in sclerosing pancreatitis in 2001, various systemic disorders described by many names have been reported. Despite similarities in the organs involved in IgG4-related Mikulicz's disease and Sjögren's syndrome, there are marked clinical and pathological differences between these conditions. Most patients diagnosed with autoimmune pancreatitis in Japan have IgG4-related pancreatitis [Type 1 autoimmune pancreatitis (AIP), lymphoplasmacytic sclerosing pancreatitis (LPSP)], a disease distinct from some of the western type [Type 2 AIP, idiopathic duct-centric chronic pancreatitis (IDCP), autoimmune pancreatitis with granulocytic epithelial lesions (GEL)]. Diagnosis of IgG4-related disease is characterized by both elevated serum IgG4 (>135 mg/dL) and histopathological features including lymphocyte and IgG4(+) plasma cell infiltration (IgG4(+) plasma cells/IgG(+) plasma cells>40%). Differential diagnosis from other distinct disorders, such as sarcoidosis, Castleman's disease, Wegener's granulomatosis, lymphoma, cancer, and other existing conditions associated with high serum IgG4 level or abundant IgG4-bearing plasma cells in tissues is necessary. We have begun a clinical prospective study to establish a treatment strategy (Phase II prospective treatment study for IgG4-multiorgan lymphoproliferative syndrome: UMIN R000002311).

  4. [An IgG4-related pancreatitis mimicking an adenocarcinoma: A case report]. (United States)

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


    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.

  5. Pathologies Associated with Serum IgG4 Elevation

    Directory of Open Access Journals (Sweden)

    Mikael Ebbo


    Full Text Available Statement of Purpose. IgG4-related disease (IgG4-RD is usually associated to an increase of serum IgG4 levels. However other conditions have also been associated to high serum IgG4 levels. Methods. All IgG subclasses analyses performed in our hospital over a one-year period were analyzed. When IgG4 level were over 1.35 g/L, the patient’s clinical observation was analyzed and both final diagnosis and reason leading to IgG subclasses analysis were recorded. Only polyclonal increases of IgG4 were considered. Summary of the Results. On 646 IgG subclass analysis performed, 59 patients had serum IgG4 over 1.35 g/L. The final diagnosis associated to serum IgG4 increase was very variable. Most patients (25% presented with repeated infections, 13.5% with autoimmune diseases, and 10% with IgG4-RD. Other patients presented with cancer, primary immune deficiencies, idiopathic interstitial lung disease, cystic fibrosis, histiocytosis, or systemic vasculitis and 13.5% presented with various pathologies or no diagnosis. Mean IgG4 levels and IgG4/IgG ratio were higher in IgG4-RD than in other pathologies associated to elevated IgG4 levels. Conclusions. Our study confirms that elevation of serum IgG4 is not specific to IgG4-RD. Before retaining IgG4-RD diagnosis in cases of serum IgG4 above 1.35 g/L, several other pathological conditions should be excluded.

  6. IgG4 related sclerosing mastitis: expanding the morphological spectrum of IgG4 related diseases. (United States)

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


    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.

  7. Cholangiocarcinoma with respect to IgG4 Reaction

    Directory of Open Access Journals (Sweden)

    Kenichi Harada


    Full Text Available IgG4 reactions marked by infiltration of IgG4-positive plasma cells in affected organs occur in cancer patients and in patients with IgG4-related diseases. Extrahepatic cholangiocarcinomas including gall bladder cancer are often accompanied by significant IgG4 reactions; these reactions show a negative correlation with CD8-positive cytotoxic T cells, suggesting that the evasion of immune surveillance is associated with cytotoxic T cells. The regulatory cytokine IL-10 may induce IgG4-positive plasma cell differentiation or promote B cell switching to IgG4 in the presence of IL-4. Cholangiocarcinoma cells may function as nonprofessional antigen presenting cells that indirectly induce IgG4 reactions via the IL-10-producing cells and/or these may act as Foxp3-positive and IL-10-producing cells that directly induce IgG4 reactions. Moreover, IgG4-related disease is a high-risk factor for cancer development; IgG4-related sclerosing cholangitis (IgG4-SC cases associated with cholangiocarcinoma or its precursor lesion biliary intraepithelial neoplasia (BilIN have been reported. IgG4-positive cell infiltration is an important finding of IgG4-SC but is not a histological hallmark of IgG4-SC. For the diagnosis of IgG4-SC, its differentiation from cholangiocarcinoma remains important.

  8. Heat sensitivity of porcine IgG. (United States)

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


    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.

  9. Characterization of the promoter of the human gene encoding the high-affinity IgG receptor: Transcriptional induction by. gamma. -interferon is mediated through common DNA response elements

    Energy Technology Data Exchange (ETDEWEB)

    Pearse, R.N.; Feinman, R.; Ravetch, J.V. (DeWitt Wallace Research Lab., New York, NY (United States))


    Expression of the high-affinity receptor for IgG (Fc{sub {gamma}}RI) is restricted to cells of myeloid lineage and is induced by {gamma}-interferon (IFN-{gamma}) but not by IFN-{alpha}/{beta}. The organization of the human Fc{sub {gamma}}RI gene has been determined and the DNA elements governing its cell type-restricted transcription and IFN-{gamma} induction are reported here. A 39-nucleotide sequence (IFN-{gamma} response region, or GRR) is defined that is both necessary and sufficient for IFN-{gamma} inducibility. Sequence analysis of the GRR reveals the presence of promoter elements initially defined for the major histocompatibility complex class 2 genes: i.e., X, H, and {gamma}-IRE sequences. Comparison of a number of genes whose expression is induced selectively by IFN-{gamma} indicated that the presence of these elements is a general feature of IFN-{gamma}-responsive genes. The studies suggest that the combination of X, H, and {gamma}-IRE elements is a common motif in the pathway of transcriptional induction by this lymphokine.

  10. IgG Subclass Staining in Routine Renal Biopsy Material. (United States)

    Hemminger, Jessica; Nadasdy, Gyongyi; Satoskar, Anjali; Brodsky, Sergey V; Nadasdy, Tibor


    Immunofluorescence staining plays a vital role in nephropathology, but the panel of antibodies used has not changed for decades. Further classification of immunoglobulin (Ig)G-containing immune-type deposits with IgG subclass staining (IgG1, IgG2, IgG3, and IgG4) has been shown to be of diagnostic utility in glomerular diseases, but their value in the evaluation of renal biopsies has not been addressed systematically in large renal biopsy material. Between January 2007 and June 2014, using direct immunofluorescence, we stained every renal biopsy for the IgG subclasses if there was moderate to prominent glomerular IgG staining and/or IgG-predominant or IgG-codominant glomerular staining. The total number of biopsies stained was 1084, which included 367 cases of membranous glomerulonephritis, 307 cases of lupus nephritis, 74 cases of fibrillary glomerulonephritis, 53 cases of proliferative glomerulonephritis with monoclonal IgG deposits, and 25 cases of antiglomerular basement membrane disease, among others. We found that monoclonality of IgG deposits cannot always be reliably determined on the basis of kappa and lambda light chain staining alone, particularly if concomitant (frequently nonspecific) IgM staining is present. In IgG heavy and heavy and light chain deposition disease (3 cases), subclass staining is very helpful, and in proliferative glomerulonephritis with monoclonal IgG deposits subclass staining is necessary. IgG subclass staining is useful in differentiating primary from secondary membranous glomerulonephritis. In proliferative glomerulonephritis with polyclonal IgG deposition, IgG1 dominance/codominance with concomitant IgG3 and IgG2 but weak or absent IgG4 staining favors an underlying autoimmune disease. IgG subclass staining is a very useful diagnostic method in a selected cohort of renal biopsies, particularly in biopsies with glomerulonephritis with monoclonal IgG deposits.

  11. Advances in the diagnosis and treatment of IgG4-related sclerosing cholangitis:a review

    Institute of Scientific and Technical Information of China (English)

    Shunda Du; Gang Liu; Yilei Mao


    Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is an IgG4-related disease characterized by bile duct fibroinflammatory wal-thickening and stenosis, resulting in obstruction jaundice, weight loss. Dif-ferent regions of the bile duct can be involved, with the distal region being the most common. IgG4-SC can also have other organ involvement, such as the pancreas, urinary tract, salivary glands and lacrimal glands. In clinical practice, the manifestation of IgG4-SC is very similar to cholangiocarcinoma (CC) and primary sclerosing cholangitis (PSC), as wel as pancreatic malignancies, while the treatment and prognosis are totaly diferent. Japanese researchers ever established the clinical diagnostic criteria in 2012: (1) charac-teristic biliary imaging findings; (2) elevated serum IgG4 concentrations; (3) the coexistence of IgG4-related diseases except those of the biliary tract; and (4) characteristic histopathological features. According to our observations, IgG4-SC can be distinguished from CC with 100% specificity only at a cutof of six times the upper normal limit. Imaging findings have low specificity for diagnosis, with the exception of intraductal ultrasonography, which can reflect the lesion with relatively high specificity. IgG4 plasma cel infiltration can be found in bile duct biopsy tissue, although this procedure is dificult. According to recent studies, the treatment of IgG4-SC relies mainly on corticosteroids. Folowing steroid treatment, most IgG4-SC patients can recover and their symptoms are resolved although a few patients relapse after steroid withdrawal. Maintenance of steroid therapy or alternative drugs is necessary in such cases. There is, however, no strong evidence for malignant transformation in IgG4-SC.

  12. A brief contextualization on IgG4 tubulointerstitial nephritis based on a case report in south Brazil. (United States)

    Pêgas, Karla Lais; Cambruzzi, Eduardo; Lobato, Gisele


    IgG4-related disease (IgG4RD) is a recent inflammatory process of supposed autoimmune etiology, which is characterized by elevated serum IgG4 levels, dense lymphoplasmacytic infiltration rich in IgG4-positive plasma cells and storiform fibrosis. Tubulointerstitial nephritis is the most common renal manifestation, with different degrees of kidney dysfunction and variable clinical findings. Herein, the authors describe a new case of IgG4 tubulointerstitial nephritis (IgG4TN), and discuss clinic and pathologic criteria. Male patient, 72 years-old, was admitted on hospital service with clinical complaint of asthenia, loss of strength, emaciation, and anosmia. Previous history included type 2 diabetes mellitus. Laboratorial data included normochromic anemia, proteinuria, and creatinine elevation. Bilateral kidney ultrassonography/computed tomography revealed a heterogenous parenchyma, with diffuse irregular dense zones, areas of fibrosis on upper poles, and hydronephrosys. Kidney biopsy showed a dense interstitial lymphoplasmacytic infiltrate, with more than 50 plasma cell per high power field, irregular areas of fibroblastic and collagenous fibrosis, focal tubulitis, and normal glomeruli. Immunofluorescence revealed mild granular deposition of C3c and IgG in the tubular basement membrane. Immunohistochemestry was positive for CD138, lambda and Kappa light chains, and IgG4 (around forty five IgG4 positive plasma cells per high power field). IgG4 serum level was increased. The diagnosis of IgG4TN was then established. The patient received corticotherapy and strict control of glycemia with insulin, with marked improvement of symptoms and creatinine levels.

  13. [IgG4-related kidney disease: what the nephrologist needs to know]. (United States)

    Galeano, Dario; Zanoli, Luca; Scarfia, Viviana Rosalia; L'Imperio, Vincenzo; Malatino, Lorenzo; Fatuzzo, Pasquale; Granata, Antonio


    IgG4 related disease is a systemic fibro-inflammatory disorder characterized by multiple organ and multiple tissue lesions. The real pathogenesis is currentlyactually unknown. For these reasons many authors compare IgG4 related disease to sarcoidosis. Lesions are often localized in the pancreas, salivary and lacrimal glands, biliary ducts, retroperitoneum and in many other organs. The diagnosisis difficult because of mild symptoms and the possibility of mimicking other severe diseases. Therefore, histopathology together with clinical and radiological typical findings are mandatory tools for diagnosis. Steroidtherapy usually enables disappearance of tumor like lesions and complete recovery. Kidney has an extensive organ involvement in the contextof IgG4-related disease. Historically, tubule - interstitial nephritis(TIN) is considered the main renal feature of renal lesions, however recent studies extend the spectrum of renal lesions also to glomerular tuft. These findings allow to introduce in the nosography the term of IgG4related kidney disease (IgG4 RKD). This review focuses on renal involvement in IgG4related disease, in order to help nephrologists to improve their clinical, diagnostic and therapeutic approach to this emerging pleiotropic clinical pattern.

  14. 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


    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.

  15. Association between IgG4-related disease and progressively transformed germinal centers of lymph nodes. (United States)

    Sato, Yasuharu; Inoue, Dai; Asano, Naoko; Takata, Katsuyoshi; Asaoku, Hideki; Maeda, Yoshinobu; Morito, Toshiaki; Okumura, Hirokazu; Ishizawa, Shin; Matsui, Shoko; Miyazono, Takayoshi; Takeuchi, Tamotsu; Kuroda, Naoto; Orita, Yorihisa; Takagawa, Kiyoshi; Kojima, Masaru; Yoshino, Tadashi


    Progressively transformed germinal centers is a benign condition of unknown pathogenesis characterized by a distinctive variant form of reactive follicular hyperplasia in lymph nodes. We recently reported Ig G4-related disease in progressively transformed germinal centers. However, no large case series has been reported and clinicopathologic findings remain unclear. Here, we report 40 Japanese patients (28 men, 12 women; median age, 56 years) with progressively transformed germinal centers of the lymph nodes who fulfilled the histological diagnostic criteria for IgG4-related disease (IgG4(+) progressively transformed germinal centers), with asymptomatic localized lymphadenopathy involving the submandibular nodes in 24, submandibular and cervical nodes in 14, cervical nodes only in 1, and cervical and supraclavicular nodes in 1. In all, 16 (52%) of 31 examined patients had allergic disease. Histologically, the lymph nodes demonstrated uniform histological findings, namely marked follicular hyperplasia with progressively transformed germinal centers, and localization of the majority of IgG4(+) plasma cells in the germinal centers. Serum IgG4, serum IgE and peripheral blood eosinophils were elevated in 87%, 92% and 53% of examined patients, respectively. Eighteen patients subsequently developed extranodal lesions (including five who developed systemic disease), which on histological examination were consistent with IgG4-related disease. IgG4(+) progressively transformed germinal centers presents with uniform clinicopathological features of asymptomatic localized submandibular lymphadenopathy, which persists and/or relapses, and sometimes progresses to extranodal lesions or systemic disease. Nine patients were administered steroid therapy when the lesions progressed, to which all responded well. We suggest that IgG4(+) progressively transformed germinal centers should be included in the IgG4-related disease spectrum.

  16. IgG4-Related Nasal Pseudotumor

    Directory of Open Access Journals (Sweden)

    L. K. Døsen


    Full Text Available IgG4-related disease is recognized as one form of autoimmune pancreatitis. During the last ten years, it has also been described in several other organs. We present two patients with lesions showing a histological picture of fibrosis and lymphoplasmacytic infiltrations with abundant IgG4 positive plasma cells at hitherto unreported symmetrical nasal locations. The symmetrical complex consisted of one central lesion in the anterior nasal septum and the two others in each of the lateral nasal walls. The lesions extended from the anterior part of the inferior concha into the vestibulum and caused severe nasal obstruction.

  17. 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


    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.

  18. IgG4 Related Lung Disease

    Directory of Open Access Journals (Sweden)

    Mihir Patel


    Full Text Available IgG4 related disease is a poorly understood immune mediated condition. Lung involvement is rare and difficult to diagnose and can mimic primary lung malignancy on imaging. A patient who was found to have an incidental lung lesion with risk factors for primary pulmonary malignancy is reported.

  19. Isolated Liver Hilar Infiltration by IgG4 Inflammation Mimicking Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Laurent Bochatay


    Full Text Available IgG4-related disease represents a heterogeneous group of disease characterized by infiltration of various tissues by IgG4 plasmocytes. In case of liver infiltration, this condition classically mimics primary sclerosing cholangitis or multifocal cholangiocarcinoma due to inflammation that preferentially affects the intra- and extrahepatic bile duct. Diagnostic criteria have recently been reviewed in order to better define the disease and help physicians make the diagnosis. Herein, we present the case of a patient who died after liver surgery for suspected cholangiocarcinoma that finally turned out to be IgG4-associated liver disease, a condition being out of current consensual criteria. The patient presented with progressive cholestasis identified by MR cholangiography as an isolated hilar mass responsible for dilatation of the left and right intrahepatic bile duct suspicious for a Klatskin tumor. The IgG4 blood level was normal as was biliary cytology. The patient underwent right portal embolization followed by right extended hepatectomy. Pathologic examination found no tumor but intense fibrosclerotic infiltration with a marked inflammatory infiltrate characterized by IgG4-positive plasmocytes. Despite immunosuppressive treatment, cholestasis was never controlled and successive biopsies of the remaining liver showed progressive cholestasis, liver infiltrate and no bile duct regeneration. The patient finally presented an upper gastrointestinal hemorrhage leading to death 4 months after hepatectomy and appropriate immunosuppressive therapy.

  20. Isolated Liver Hilar Infiltration by IgG4 Inflammation Mimicking Cholangiocarcinoma (United States)

    Bochatay, Laurent; Majno, Pietro; Giostra, Emiliano; Frossard, Jean Louis


    IgG4-related disease represents a heterogeneous group of disease characterized by infiltration of various tissues by IgG4 plasmocytes. In case of liver infiltration, this condition classically mimics primary sclerosing cholangitis or multifocal cholangiocarcinoma due to inflammation that preferentially affects the intra- and extrahepatic bile duct. Diagnostic criteria have recently been reviewed in order to better define the disease and help physicians make the diagnosis. Herein, we present the case of a patient who died after liver surgery for suspected cholangiocarcinoma that finally turned out to be IgG4-associated liver disease, a condition being out of current consensual criteria. The patient presented with progressive cholestasis identified by MR cholangiography as an isolated hilar mass responsible for dilatation of the left and right intrahepatic bile duct suspicious for a Klatskin tumor. The IgG4 blood level was normal as was biliary cytology. The patient underwent right portal embolization followed by right extended hepatectomy. Pathologic examination found no tumor but intense fibrosclerotic infiltration with a marked inflammatory infiltrate characterized by IgG4-positive plasmocytes. Despite immunosuppressive treatment, cholestasis was never controlled and successive biopsies of the remaining liver showed progressive cholestasis, liver infiltrate and no bile duct regeneration. The patient finally presented an upper gastrointestinal hemorrhage leading to death 4 months after hepatectomy and appropriate immunosuppressive therapy. PMID:27843427

  1. IgG abnormality in narcolepsy and idiopathic hypersomnia.

    Directory of Open Access Journals (Sweden)

    Susumu Tanaka

    Full Text Available BACKGROUND: A close association between narcolepsy and the Human Leukocyte Antigen (HLA-DQB1*0602 allele suggests the involvement of the immune system, or possibly an autoimmune process. We investigated serum IgG levels in narcolepsy. METHODOLOGY/PRINCIPAL FINDINGS: We measured the serum total IgG levels in 159 Japanese narcolepsy-cataplexy patients positive for the HLA-DQB1*0602 allele, 28 idiopathic hypersomnia patients with long sleep time, and 123 healthy controls (the HLA-DQB1*0602 allele present in 45 subjects. The serum levels of each IgG subclass were subsequently measured. The distribution of serum IgG was significantly different among healthy controls negative for the HLA-DQB1*0602 allele (11.66+/-3.55 mg/ml, healthy controls positive for the HLA-DQB1*0602 allele (11.45+/-3.43, narcolepsy patients (9.67+/-3.38, and idiopathic hypersomnia patients (13.81+/-3.80. None of the following clinical variables, age, disease duration, Epworth Sleepiness Scale, smoking habit and BMI at the time of blood sampling, were associated with IgG levels in narcolepsy or idiopathic hypersomnia. Furthermore we found the decrease in IgG1 and IgG2 levels, stable expression of IgG3, and the increase in the proportion of IgG4 in narcolepsy patients with abnormally low IgG levels. The increase in the proportion of IgG4 levels was also found in narcolepsy patients with normal serum total IgG levels. Idiopathic hypersomnia patients showed a different pattern of IgG subclass distribution with high IgG3 and IgG4 level, low IgG2 level, and IgG1/IgG2 imbalance. CONCLUSIONS/SIGNIFICANCE: Our study is the first to determine IgG abnormalities in narcolepsy and idiopathic hypersomnia by measuring the serum IgG levels in a large number of hypersomnia patients. The observed IgG abnormalities indicate humoral immune alterations in narcolepsy and idiopathic hypersomnia. Different IgG profiles suggest immunological differences between narcolepsy and idiopathic hypersomnia.

  2. Overexpression of Serpinb1 in Chinese hamster ovary cells increases recombinant IgG productivity. (United States)

    Lin, Nan; Brooks, Jeanne; Sealover, Natalie; George, Henry J; Kayser, Kevin J


    We report the discovery and validation of a novel CHO cell engineering target for improving IgG expression, serpin peptidase inhibitor, clade B, member 1 (Serpinb1). Transcriptomic studies using microarrays revealed that Serpinb1 was up-regulated in cultures with IgG heavy and light chain transcription transiently repressed compared with cultures treated with non-targeting siRNA. As proof of concept, a lentiviral vector was employed to overexpress the Chinese Hamster Serpinb1 in a CHOZN(®) Glutamine Synthetase (-/-) recombinant IgG producing CHO line. The lentiviral stable pool demonstrated 4.2-fold SERPINB1 overexpression compared with the non-transduced control. The peak viable cell density (VCD) and peak IgG volumetric productivity of the lentiviral stable pool increased 1.3 and 2.0 fold, respectively, compared with the non-transduced control. For host cell engineering, a plasmid encoding SERPINB1 was transfected into the CHOZN(®) GS (-/-) host cell line to create several stable pools. Single-cell clones isolated from the pools were characterized for their SERPINB1 expression levels and growth. The clone (SERPINB1_OE_27) with the highest SERPINB1 expression had decreased peak viable cell density and exponential phase growth rate. Selected SERPINB1 OE clones were subsequently evaluated for their IgG expression capabilities using GS selection. Clone SERPINB1_OE_42 with moderate SERPINB1 overexpression demonstrated increased IgG productivity in "bulk" selection. We conclude that manipulating Serpinb1 expression can lead to increased recombinant IgG productivity, but the effect in host cell lines may vary by clone and by overexpression level. This work represents the ongoing effort in applying "-omics" findings to novel CHO host cell line engineering.

  3. IgG4-related Disease of the Genitourinary Tract

    Directory of Open Access Journals (Sweden)

    Mukul K. Divatia


    Full Text Available IgG4-related disease (IgG4-RD is a recently established albeit well recognized fibro-inflammatory condition with distinctive features including a characteristic histopathological appearance; a propensity to develop tumefactive lesions in multiple body sites; and oft elevated serum IgG4 levels. The consensus statement on IgG-4 RD equips practicing pathologists with a set of working guidelines for the diagnosis of pathologic lesions identified in a host of different organ system affected with this disease. The diagnosis of IgG4-RD requires the combined presence of the characteristic histopathological appearance and increased numbers of IgG4-positive plasma cells. The essential histopathological features include a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. Tissue IgG4-positive plasma cell counts and IgG4: IgG ratios are significant ancillary aids in establishing the diagnosis. The spectrum of IgG4-RD continues to expand and involve multiple body sites. The genitourinary system comprising of the kidneys, ureters, urinary bladder, urethra, prostate gland, testes and penis is one of the multiple organ systems to be affected by IgG4-RD. This review describes the clinical and histopathologic patterns of involvement of the genitourinary system by IgG4-RD, in association with serologic and radiological features. [J Interdiscipl Histopathol 2014; 2(1.000: 3-18

  4. Asma y deficiencia de subclases de IgG Asthma and IgG subclases deficiency

    Directory of Open Access Journals (Sweden)

    Lucía Santamaría Ortiz


    Full Text Available

    Se estudiaron 45 pacientes asmáticos adultos de difícil manejo, de más de 5 años de evolución, 37 de ellos esteroide dependientes y 8 no dependientes, con asma alérgica o intrínseca y algunos con Infecciones respiratorias recurrentes de predominio viral. Por nefelometría se midieron los niveles séricos de las IgsG, M y A, y por ELISA se determinó la IgE total. Se encontraron 4 pacientes con deficiencia de IgG total, en el grupo de los esteroide dependientes. Mediante ELISA tipo sandwich y con anticuerpos monoclonales específicos para las sub clases de IgG se investigaron los niveles sé ricos de IgG1, 2, 3 y 4. En el 55.6% de los enfermos se encontraron una O más deficiencias de sub clases. No hubo diferencias significativas entre los grupos esteroide y no esteroide dependientes, ni entre los asmáticos alérgicos e intrínsecos, ni entre los con infección recurrente o sin ella. predominó la deficiencia de IgG1; en total el 46.7% de los pacientes tenían deficiencia aislada o combinada de IgG1, el 31.1% de IgG2, el 24.4% de IgG3 y el 17.8% de Igd4. La alta incidencia de deficiencia de sub clases podría deberse a la acción de los esteroides o a una alteración en la regulación de la síntesis de Igs producida por un defecto Inmune primario. Esta deficiencia sería la responsable del comportamiento agresivo de la enfermedad.

    We studied 45 adult asthmatic patients with difficult to care disease and who had more than five years of evolution; they suffered from elther allergic or intrinsic asthma and some had experienced recurrent respiratory tract infections. predominantly of viral etiology. Serum levels of IgA, IgG and IgM were measured by nephelometry and total lgE was determined by an Enzyme-Linked immunosorbent Assay (ELISA. Total lg

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

    Directory of Open Access Journals (Sweden)

    Zhen-qi LI


    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

  6. IgG4-related pleuritis with chylothorax. (United States)

    Kato, Eisuke; Takayanagi, Noboru; Ishiguro, Takashi; Kagiyama, Naho; Shimizu, Yoshihiko; Sugita, Yutaka


    Presently, 6 cases of IgG4-related pleuritis have been reported. We encountered a patient who developed chylothorax due to IgG4-related disease. To our knowledge, such patients have not been reported. This patient developed right-sided chylothorax and left-sided non-chylothorax lymphocyte-predominant pleuritis. Elevated serum and pleural IgG4 concentrations and histopathological analysis of pleural biopsy confirmed the diagnosis of IgG4-related pleuritis. Left-sided pleuritis improved with corticosteroid therapy, but right-sided chylothorax persists. IgG4-related disease can be one cause of chylothorax.

  7. Dissecting the relationships of IgG subclasses and complements in membranous lupus nephritis and idiopathic membranous nephropathy (United States)

    Na, Woong; Yi, Kijong; Park, Moon Hyang


    Membranous lupus nephritis (MLN) and idiopathic membranous nephropathy (IMN) are kidney diseases with similar morphology, but distinct etiologies, both producing glomeruli with immune deposits. Immunoglobulins and complements, the main components of the deposits, can be detected by immunofluorescence (IF) microscopy. Previous researches characterized the immune deposits only individually, but not the interactions between them. To study these relationships we analyzed an IF profile of IgG subclasses and complements (IgG1, IgG2, IgG3, IgG4, C3, C1q, and C4) in 53 and 95 cases of biopsy-confirmed MLNs and IMNs, respectively, mainly using information theory and Bayesian networks. We identified significant entropy differences between MLN and IMN for all markers except C3 and IgG1, but mutual information (a measure of mutual dependence) were not significantly different for all the pairs of markers. The entropy differences between MLN and IMN, therefore, were not attributable to the mutual information. These findings suggest that disease type directly and/or indirectly influences the glomerular deposits of most of IgG subclasses and complements, and that the interactions between any pair of the markers were similar between the two diseases. A Markov chain of IgG subclasses was derived from the mutual information about each pair of IgG subclass. Finally we developed an integrated disease model, consistent with the previous findings, describing the glomerular immune deposits of the IgG subclasses and complements based on a Bayesian network using the Markov chain of IgG subclasses as seed. The relationships between the markers were effectively explored by information theory and Bayesian network. Although deposits of IgG subclasses and complements depended on both disease type and the other markers, the interaction between the markers appears conserved, independent from the disease type. The disease model provided an integrated and intuitive representation of the

  8. IgG4相关性疾病的发病机制及进展%Progress in pathogenesis of IgG4-related disease

    Institute of Scientific and Technical Information of China (English)

    苏玉莹; 王晨琼; 董凌莉


    IgG4-related disease, a newly recognized systemic entity, is characterized by elevated serum levels of IgG4 and a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells in involved tissues. Its complicated clinical manifestation and multidiscipline involvement make it easy to be misdiagnosed or miss diagnosed. In order to better understand this disease, this review elaborated on update in pathogenesis of IgG4-related disease including genetics, infection and molecular mimicry, immunology and so on.%IgG4相关性疾病是一种多器官、多系统受累的新被认识的疾病,其主要特征为:血清IgG4水平升高和病变组织IgG4+浆细胞浸润。IgG4相关性疾病临床表现复杂多样,可涉及多个学科,临床易漏诊和误诊。本篇综述将从基因遗传、感染和分子模拟、免疫学角度等多方面阐述IgG4相关性疾病的发病机制,以加深临床医师对该病的了解。

  9. Detection of serum IgG4 levels in patients with IgG4-related disease and other disorders.

    Directory of Open Access Journals (Sweden)

    Yuying Su

    Full Text Available Elevated serum IgG4 levels are an important hallmark for diagnosing IgG4-related disease (IgG4-RD, but can also be observed in other diseases. This study aimed to compare two different testing methods for IgG4: ELISA and nephelometric assay. Both assays were used to measure serum IgG4 concentrations, and to assess the prevalence of high serum IgG4 levels in both IgG4-RD and non-IgG4-RD diseases.A total of 80 serum samples were tested using the nephelometric assay and ELISA method that we established. Serum IgG4 concentrations were determined by ELISA for 957 patients with distinct diseases, including 12 cases of IgG4-RD and 945 cases of non-IgG4-RD.IgG4 levels from 80 selected serum samples examined by ELISA were in agreement with those detected using the nephelometry assay. Meanwhile, the serum IgG4 concentrations measured by ELISA were also consistent with the clinical diagnoses of patients with IgG4-RD during the course of disease. The Elevated levels of serum IgG4 (>1.35 g/L were detected in all IgG4-RD (12/12 patients, and the prevalence of high IgG4 serum levels was 3.39% in non-IgG4-RD cases. Among them, the positive rates of serum IgG4 were 2.06% in patients with carcinoma and 6.3% in patients with other non-IgG4 autoimmune diseases.Our established ELISA method is a reliable and convenient technique, which could be extensively used in the clinic to measure serum IgG4 levels. High levels of IgG4 were observed in IgG4-RD. However, this phenomenon could also be observed in other diseases, such as carcinomas and other autoimmune diseases. Thus, a diagnosis of IgG4 disease cannot only be dependent on the detection of elevated serum IgG4 levels.

  10. Simultaneous Quantification of Anticardiolipin IgG and IgM by Time Resolved Fluoroimmunoassay (United States)

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


    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

  11. Phase transitions in human IgG solutions. (United States)

    Wang, Ying; Lomakin, Aleksey; Latypov, Ramil F; Laubach, Jacob P; Hideshima, Teru; Richardson, Paul G; Munshi, Nikhil C; Anderson, Kenneth C; Benedek, George B


    Protein condensations, such as crystallization, liquid-liquid phase separation, aggregation, and gelation, have been observed in concentrated antibody solutions under various solution conditions. While most IgG antibodies are quite soluble, a few outliers can undergo condensation under physiological conditions. Condensation of IgGs can cause serious consequences in some human diseases and in biopharmaceutical formulations. The phase transitions underlying protein condensations in concentrated IgG solutions is also of fundamental interest for the understanding of the phase behavior of non-spherical protein molecules. Due to the high solubility of generic IgGs, the phase behavior of IgG solutions has not yet been well studied. In this work, we present an experimental approach to study IgG solutions in which the phase transitions are hidden below the freezing point of the solution. Using this method, we have investigated liquid-liquid phase separation of six human myeloma IgGs and two recombinant pharmaceutical human IgGs. We have also studied the relation between crystallization and liquid-liquid phase separation of two human cryoglobulin IgGs. Our experimental results reveal several important features of the generic phase behavior of IgG solutions: (1) the shape of the coexistence curve is similar for all IgGs but quite different from that of quasi-spherical proteins; (2) all IgGs have critical points located at roughly the same protein concentration at ~100 mg/ml while their critical temperatures vary significantly; and (3) the liquid-liquid phase separation in IgG solutions is metastable with respect to crystallization. These features of phase behavior of IgG solutions reflect the fact that all IgGs have nearly identical molecular geometry but quite diverse net inter-protein interaction energies. This work provides a foundation for further experimental and theoretical studies of the phase behavior of generic IgGs as well as outliers with large propensity to

  12. Development of an IgG4-RD Responder Index

    Directory of Open Access Journals (Sweden)

    Mollie N. Carruthers


    Full Text Available IgG4-related disease (IgG4-RD is a multiorgan inflammatory disease in which diverse organ manifestations are linked by common histopathological and immunohistochemical features. Prospective studies of IgG4-RD patients are required to clarify the natural history, long-term prognosis, and treatment approaches in this recently recognized condition. Patients with IgG4-RD have different organ manifestations and are followed by multiple specialties. Divergent approaches to the assessment of patients can complicate the interpretation of studies, emphasizing the critical need for validated outcome measures, particularly assessments of disease activity and response to treatment. We developed a prototype IgG4-RD Responder Index (IgG4-RD RI based on the approach used in the development of the Birmingham Vasculitis Activity Score for Wegener’s granulomatosis (BVAS/WG. The IgG4-RD RI was refined by members of the International IgG4-RD Symposium Organizing Committee in a paper case exercise. The revised instrument was applied retrospectively to fifteen IgG4-RD patients at our institution. Those scores were compared to physician’s global assessment scale for the same visits. This paper describes the philosophy and goals of the IgG4-RD RI, the steps in the development of this instrument to date, and future plans for validation of this instrument as an outcome measure.

  13. Fractionation of rat IgG subclasses and screening for IgG Fc-binding to bacteria. (United States)

    Nilsson, R; Myhre, E; Kronvall, G; Sjögren, H O


    The four IgG subclasses of the rat, IgGl, IgG2a, IgG2b and IgG2c, were purified from normal serum by a combination of protein A-affinity chromatography and DEAE-cellulose chromatography. Purified, radiolabelled preparations of IgG were tested for binding to Gram-positive bacteria representing five different Fc-receptor (FcR) types. Distinct rat subclass-specific Fc-binding was noted to bacterial species belonging to different Fc-receptor types. Staphylococcus aureus (FcR I) strains bind IgGl and IgG2c as shown by others. Group C and G Streptococci (FcR III) bind all four subclasses of rat IgG. Streptococcus zooepidemicus strains (FcR V) also bind all four subclases but only to a lower degree. Human group A Streptococci (FcR II) and bovine group G Streptococci (FcR IV) do not bind any of the rat IgG subclasses. Elution studies on two strains. Staphylococcus aureus, Cowan I, and human group G Streptococcus, G 148, showed that both thiocyanate and pH-elution might be useful for the fractionation of IgG subclasses bound to bacterial cells. The present work indicates the possible use of bacterial cells as solid-phase absorbents in immunological studies of rat IgG.

  14. Epitope-Specific Suppression of IgG Responses by Passively Administered Specific IgG: Evidence of Epitope Masking (United States)

    Bergström, Joakim J. E.; Xu, Hui; Heyman, Birgitta


    Specific IgG, passively administered together with particulate antigen, can completely prevent induction of antibody responses to this antigen. The ability of IgG to suppress antibody responses to sheep red blood cells (SRBCs) is intact in mice lacking FcγRs, complement factor 1q, C3, or complement receptors 1 and 2, suggesting that Fc-dependent effector functions are not involved. Two of the most widely discussed explanations for the suppressive effect are increased clearance of IgG–antigen complexes and/or that IgG “hides” the antigen from recognition by specific B cells, so-called epitope masking. The majority of data on how IgG induces suppression was obtained through studies of the effects on IgM-secreting single spleen cells during the first week after immunization. Here, we show that IgG also suppresses antigen-specific extrafollicular antibody-secreting cells, germinal center B-cells, long-lived plasma cells, long-term IgG responses, and induction of memory antibody responses. IgG anti-SRBC reduced the amount of SRBC in the spleens of wild-type, but not of FcγR-deficient mice. However, no correlation between suppression and the amount of SRBC in the spleen was observed, suggesting that increased clearance does not explain IgG-mediated suppression. Instead, we found compelling evidence for epitope masking because IgG anti-NP administered with NP-SRBC suppressed the IgG anti-NP, but not the IgG anti-SRBC response. Vice versa, IgG anti-SRBC administered with NP-SRBC, suppressed only the IgG anti-SRBC response. In conclusion, passively transferred IgG suppressed all measured parameters of an antigen-specific antibody/B cell response and an important mechanism of action is likely to be epitope masking.

  15. IgG subclasses in human chronic schistosomiasis: over-production of schistosome-specific and non-specific IgG4. (United States)

    Boctor, F N; Peter, J B


    IgG subclasses were determined quantitatively in sera from 63 Egyptian men who were infected with Schistosoma mansoni. Total and antigen-specific IgG was measured pre- and post-treatment. Total IgG subclass antibodies were determined by immunoradiometric assay (IRMA) using monoclonal antibodies (MoAbs). The anti-worm and anti-egg specific S. mansoni IgG subclass antibodies were quantitatively measured by ELISA using specific MoAbs and standards obtained by affinity chromatography. Our data show that total IgG of the patients was elevated in the range of two to three times above normal. The magnitude of increase differed markedly among the four subclasses of IgG. The IgG1, IgG2 and IgG3 concentrations were approximately two to four times higher than normal, whereas the IgG4 concentrations was 20 times normal (9000 mg/l). IgG1 and IgG4 tended to dominate the IgG subclass distribution of anti-soluble worm antigen preparation (SWAP) antibodies followed by IgG2 and IgG3. On the other hand, IgG1 and IgG2 dominated the IgG subclass distribution of anti-soluble egg antigen (SEA) antibodies. As with IgG1, IgG2 and IgG3, most IgG4 was non-specific. The role of IgG subclasses in the pathogenesis of schistosomiasis is not clear. However, the high concentration of IgG4 might act as IgE blocking antibody, possibly as anti-idiotypes that may play a role in down-regulation of the immune system when it is challenged with an excess of antigen.

  16. Pseudotumors due to IgG4 immune-complex tubulointerstitial nephritis associated with autoimmune pancreatocentric disease. (United States)

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


    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

  17. Interleukin-33 produced by M2 macrophages and other immune cells contributes to Th2 immune reaction of IgG4-related disease (United States)

    Furukawa, Sachiko; Moriyama, Masafumi; Miyake, Kensuke; Nakashima, Hitoshi; Tanaka, Akihiko; Maehara, Takashi; Iizuka-Koga, Mana; Tsuboi, Hiroto; Hayashida, Jun-Nosuke; Ishiguro, Noriko; Yamauchi, Masaki; Sumida, Takayuki; Nakamura, Seiji


    IgG4-related disease (IgG4-RD) is characterized by elevated serum IgG4 and marked infiltration of IgG4-positive cells in multiple organs. Interleukin-33 (IL-33) is a recently described cytokine that is secreted by damaged epithelial cells, macrophages, and dendritic cells, and potently activates helper T type 2 (Th2) immune responses, which have been suggested to play a major role in IgG4 production of IgG4-RD. Here, we assessed the expression of IL-33 and related molecules in the salivary glands (SGs) of patients with IgG4-RD versus that in patients with Sjögren’s syndrome (SS) and controls. Expression of IL-33 and its receptor (ST2) was strongly detected around ectopic germinal centers (GCs) in the SGs from patients with IgG4-RD, whereas IL-33 was expressed only in epithelial cells in patients with SS and controls. Moreover, IL-33 and CD68+/CD163+ macrophages were mainly distributed around ectopic GCs in patients with IgG4-RD. Double immunofluorescence staining showed that IL-33 expression co-localized with CD68+/CD163+ macrophages. Finally, mRNA expression levels of IL-33 showed a positive correlation to those of Th2 cytokines (IL-4 and IL-13) in patients with IgG4-RD. Our data suggest that IL-33 produced by M2 macrophages might contribute to the pathogenesis of IgG4-RD via aberrant activation of Th2 immune responses. PMID:28205524

  18. Group G streptococcal IgG binding molecules FOG and protein G have different impacts on opsonization by C1q. (United States)

    Nitsche-Schmitz, D Patric; Johansson, Helena M; Sastalla, Inka; Reissmann, Silvana; Frick, Inga-Maria; Chhatwal, Gursharan S


    Recent epidemiological data on diseases caused by beta-hemolytic streptococci belonging to Lancefield group C and G (GCS, GGS) underline that they are an emerging threat to human health. Among various virulence factors expressed by GCS and GGS isolates from human infections, M and M-like proteins are considered important because of their anti-phagocytic activity. In addition, protein G has been implicated in the accumulation of IgG on the bacterial surface through non-immune binding. The function of this interaction, however, is still unknown. Using isogenic mutants lacking protein G or the M-like protein FOG (group G streptococci), respectively, we could show that FOG contributes substantially to IgG binding. A detailed characterization of the interaction between IgG and FOG revealed its ability to bind the Fc region of human IgG and its binding to the subclasses IgG1, IgG2, and IgG4. FOG was also found to bind IgG of several animal species. Surface plasmon resonance measurements indicate a high affinity to human IgG with a dissociation constant of 2.4 pm. The binding site was localized in a central motif of FOG. It has long been speculated about anti-opsonic functions of streptococcal Fc-binding proteins. The presented data for the first time provide evidence and, furthermore, indicate functional differences between protein G and FOG. By obstructing the interaction between IgG and C1q, protein G prevented recognition by the classical pathway of the complement system. In contrast, IgG that was bound to FOG remained capable of binding C1q, an effect that may have important consequences in the pathogenesis of GGS infections.

  19. Decreased Expression of Innate Immunity-Related Genes in Peripheral Blood Mononuclear Cells from Patients with IgG4-Related Disease.

    Directory of Open Access Journals (Sweden)

    Akio Nakajima

    Full Text Available IgG4-related disease (IgG4-RD is a new clinical entity of unknown etiology characterized by elevated serum IgG4 and tissue infiltration by IgG4-positive plasma cells. Although aberrancies in acquired immune system functions, including increases in Th2 and Treg cytokines observed in patients with IgG4-RD, its true etiology remains unclear. To investigate the pathogenesis of IgG4-RD, this study compared the expression of genes related to innate immunity in patients with IgG4-RD and healthy controls.Peripheral blood mononuclear cells (PBMCs were obtained from patients with IgG4-RD before and after steroid therapy and from healthy controls. Total RNA was extracted and DNA microarray analysis was performed in two IgG4-RD patients to screen for genes showing changes in expression. Candidate genes were validated by real-time RT-PCR in 27 patients with IgG4-RD and 13 healthy controls.DNA microarray analysis identified 21 genes that showed a greater than 3-fold difference in expression between IgG4-RD patients and healthy controls and 30 genes that showed a greater than 3-fold change in IgG4-RD patients following steroid therapy. Candidate genes related to innate immunity, including those encoding Charcot-Leyden crystal protein (CLC, membrane-spanning 4-domain subfamily A member 3 (MS4A3, defensin alpha (DEFA 3 and 4, and interleukin-8 receptors (IL8R, were validated by real-time RT-PCR. Expression of all genes was significantly lower in IgG4-RD patients than in healthy controls. Steroid therapy significantly increased the expression of DEFA3, DEFA4 and MS4A3, but had no effect on the expression of CLC, IL8RA and IL8RB.The expression of genes related to allergy or innate immunity, including CLC, MS4A3, DEFA3, DEFA4, IL8RA and IL8RB, was lower in PBMCs from patients with IgG4-RD than from healthy controls. Although there is the limitation in the number of patients applied in DNA microarray, impaired expression of genes related to innate immunity may be

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

    Directory of Open Access Journals (Sweden)

    Xinsheng Tian


    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.

  1. IgG4相关唾液腺炎研究热点概述%Research hotspot in IgG4-related sialadenitis

    Institute of Scientific and Technical Information of China (English)

    王琼; 平飞云; 潘恒标


    IgG4相关疾病累及唾液腺称为IgG4相关唾液腺炎,中老年好发,男女性均可发病.IgG4相关唾液腺炎以唾液腺无痛性肿胀、血清IgG4升高、组织内大量特征性IgG4阳性浆细胞浸润伴纤维化为主要特点,糖皮质激素治疗反应良好.通过复习国内外文献,着重于该病近年来的研究热点阐述并分析多种免疫细胞和细胞因子、上皮间质转化参与的致病过程、正确看待血清IgG4浓度升高和组织IgG4阳性浆细胞浸润的临床病理意义及其诊断价值、与唾液腺癌和淋巴瘤的相关性、正电子发射型计算机断层摄影(positron emission tomography,PET)-CT的应用、唇腺活检对病理诊断的意义及治疗预后等问题.%IgG4-related disease is a novel clinical entity which can affect single or multiple organs.IgG4-related sialadenitis is referred to the salivary gland involvement of IgG4-related disease, with or without other organ involvement.IgG4-related sialadenitis is characterized by painless swelling or enlargement of salivary glands, high serum IgG4 level, abundant IgG4+ plasma cells infiltration with fibrosis histologically, and good response to glucocorticoids.With review of related articles, highlight and provide an overview of the most recent and focused findings and concepts of this disease, including the most significant pathogenic process based on kinds of immunocytes, cytokines, as well as participation of epithelial-mesenchymal transition, the clinical value of elevated serum IgG4 concentration and pathological role of infiltrated IgG4+ plasma cells, the potential relationship with salivary gland malignant tumor, the applying and usefulness of positron emission tomography-CT, the diagnostic utility of lip biopsy, treatment, prognosis, and also future perspectives.

  2. Heterogeneity of IgG glycosylation in adult periodontal disease. (United States)

    Novak, J; Tomana, M; Shah, G R; Brown, R; Mestecky, J


    Periodontal disease is a chronic inflammatory disease of bacterial etiology. In many other chronic inflammatory diseases, IgG glycans are galactose-deficient and thus capable of complement activation through the lectin pathway. In this study, we examined whether IgG in serum and gingival crevicular fluid, and IgG locally produced by plasma cells in gingiva of periodontal disease patients, display altered glycosylation. We developed a lectin-ELISA to measure levels of galactose-deficient IgG in the fluids and immunofluorescence staining to detect galactose-deficient IgG-producing cells in gingiva. Our results indicated higher levels of galactose-deficient IgG in sera and gingival crevicular fluid from periodontal disease patients, compared with levels in healthy controls. Furthermore, gingivae from periodontal disease patients exhibited infiltration of IgG-producing plasma cells; many of them contained galactose-deficient IgG in the cytoplasm. Analysis of our data suggests that IgG secreted by B-cells was aberrantly glycosylated, which resulted in the production of pro-inflammatory galactose-deficient IgG.

  3. Clinical study on IgG4-related autoimmune pancreatitis

    Institute of Scientific and Technical Information of China (English)



    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

  4. IgG glycosylation changes and MBL2 polymorphisms

    DEFF Research Database (Denmark)

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


    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)....

  5. IgG4-Seronegative Autoimmune Pancreatitis and Sclerosing Cholangitis

    Directory of Open Access Journals (Sweden)

    Allon Kahn


    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.

  6. IgG4-Related Disease Presenting as Isolated Scleritis

    Directory of Open Access Journals (Sweden)

    Eran Berkowitz


    Full Text Available A rare case of IgG4-related disease (IgG4-RD manifesting as nodular scleritis is presented in a 20-year-old female. Patient complained of left eye pain and redness for one week. Ocular examination together with ancillary testing led to the diagnosis of nodular scleritis. Since the patient did not show apparent improvement after one week of systemic steroidal treatment, she underwent a biopsy of the affected area revealing histopathological characteristics of IgG4-RD. Long-term treatment with corticosteroids and a steroid-sparing agent (methotrexate led to significant improvement in signs and symptoms. This case highlights the significance of IgG4-RD in the differential diagnosis of scleritis and raises the question as to whether various organs affected by IgG4-RD may have different underlying pathophysiological mechanisms in which pathogenic T cells play a role.

  7. IgG4-Related Disease Presenting as Isolated Scleritis (United States)

    Arnon, Ella; Yaakobi, Alona; Cohen, Yuval; Tiosano, Beatrice


    A rare case of IgG4-related disease (IgG4-RD) manifesting as nodular scleritis is presented in a 20-year-old female. Patient complained of left eye pain and redness for one week. Ocular examination together with ancillary testing led to the diagnosis of nodular scleritis. Since the patient did not show apparent improvement after one week of systemic steroidal treatment, she underwent a biopsy of the affected area revealing histopathological characteristics of IgG4-RD. Long-term treatment with corticosteroids and a steroid-sparing agent (methotrexate) led to significant improvement in signs and symptoms. This case highlights the significance of IgG4-RD in the differential diagnosis of scleritis and raises the question as to whether various organs affected by IgG4-RD may have different underlying pathophysiological mechanisms in which pathogenic T cells play a role. PMID:28149653

  8. A Case Report of an Atypical Presentation of IgG4-Related Disease and Idiopathic CD4 Lymphocytopenia

    Directory of Open Access Journals (Sweden)

    Francesco Rapisarda


    Full Text Available The IgG4-related disease is a fibroinflammatory disease characterized by tumefactive lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and, often but not always, elevated serum levels of IgG4. Idiopathic CD4 lymphocytopenia is a heterogenic and rare syndrome characterized by the detection of a persistent absolute CD4 T cells count <300 cells/mm3 (or <20% of total T cells in more than one occasion and no evidence of HIV infection in absence of immunodeficiency or therapy associated with depressed levels of CD4 T cells. We report the case of a 50-year-old man with a multiorgan IgG4-related disease presenting in a temporal association with a profound and symptomatic idiopathic CD4 lymphocytopenia. Both clinical pictures improved after steroid treatment. Idiopathic CD4 lymphocytopenia has been associated with a number of autoimmune conditions but, to the best of our knowledge, this is the first case in which an association with the IgG4-related disease is reported.

  9. A Case Report of an Atypical Presentation of IgG4-Related Disease and Idiopathic CD4 Lymphocytopenia. (United States)

    Rapisarda, Francesco; Zanoli, Luca; Portale, Grazia; Scuto, Salvo; Castellino, Pietro


    The IgG4-related disease is a fibroinflammatory disease characterized by tumefactive lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and, often but not always, elevated serum levels of IgG4. Idiopathic CD4 lymphocytopenia is a heterogenic and rare syndrome characterized by the detection of a persistent absolute CD4 T cells count <300 cells/mm(3) (or <20% of total T cells) in more than one occasion and no evidence of HIV infection in absence of immunodeficiency or therapy associated with depressed levels of CD4 T cells. We report the case of a 50-year-old man with a multiorgan IgG4-related disease presenting in a temporal association with a profound and symptomatic idiopathic CD4 lymphocytopenia. Both clinical pictures improved after steroid treatment. Idiopathic CD4 lymphocytopenia has been associated with a number of autoimmune conditions but, to the best of our knowledge, this is the first case in which an association with the IgG4-related disease is reported.

  10. The blocking activity of birch pollen-specific immunotherapy-induced IgG4 is not qualitatively superior to that of other IgG subclasses

    DEFF Research Database (Denmark)

    Ejrnaes, Anne M; Bødtger, Uffe; Larsen, Jørgen N;


    blocking activity was found in the purified IgG4 fraction. There was no significant difference in the binding avidities (1/K(d)) measured in the two IgG fractions. Thus, it appears that SIT-induced specific IgG4 contributes to the IgG blocking of allergen binding to IgE in a simple quantitative manner...

  11. Successful treatment of pediatric IgG4 related systemic disease with mycophenolate mofetil: case report and a review of the pediatric autoimmune pancreatitis literature

    Directory of Open Access Journals (Sweden)

    Cron Randy Q


    Full Text Available Abstract Autoimmune pancreatitis is frequently associated with elevated serum and tissue IgG4 levels in the adult population, but there are few reports of pediatric autoimmune pancreatitis, and even fewer reports of IgG4 related systemic disease in a pediatric population. The standard of care treatment in adults is systemic corticosteroids with resolution of symptoms in most cases; however, multiple courses of corticosteroids are occasionally required and some patients require long term corticosteroids. In these instances, steroid sparing disease modify treatments are in demand. We describe a 13-year-old girl with IgG4 related systemic disease who presented with chronic recurrent autoimmune pancreatitis resulting in surgical intervention for obstructive hyperbilirubinemia and chronic corticosteroid treatment. In addition, she developed fibrosing medianstinitis as part of her IgG4 related systemic disease. She was eventually successfully treated with mycophenolate mofetil allowing for discontinuation of corticosteroids. This is the first reported use of mycophenolate mofetil for IgG4 related pancreatitis. Although autoimmune pancreatitis as part of IgG4 related systemic disease is rarely reported in pediatrics, autoimmune pancreatitis is also characterized as idiopathic fibrosing pancreatitis. All pediatric autoimmune pancreatitis cases reported in the world medical literature were identified via a PUBMED search and are reviewed herein. Twelve reports of pediatric autoimmune pancreatitis were identified, most of which were treated with corticosteroids or surgical approaches. Most case reports failed to report IgG4 levels, so it remains unclear how commonly IgG4 related autoimmune pancreatitis occurs during childhood. Increased evaluation of IgG4 levels in patients with autoimmune pancreatitis may shed further light on the association of IgG4 with pancreatitis and the underlying pathophysiology.

  12. Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus. (United States)

    Sjöwall, C; Zapf, J; von Löhneysen, S; Magorivska, I; Biermann, M; Janko, C; Winkler, S; Bilyy, R; Schett, G; Herrmann, M; Muñoz, L E


    In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the

  13. [IgG4-related kidney disease. Diagnosis and treatment]. (United States)

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


    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.

  14. Bioavailability of IgG Administered by the Subcutaneous Route


    Berger, Melvin; Jolles, Stephen; Orange, Jordan S.; Sleasman, John W


    Purpose US licensing studies of subcutaneous IgG (SCIG) calculate dose adjustments necessary to achieve area under the curve (AUC) of serum IgG vs. time on SCIG that is non-inferior to that on intravenous IgG (IVIG), within the FDA-set limit of ±20 %. The results are interpreted as showing that different SCIGs differ in bioavailability. We used three approaches to determine if the bioavailabilities were actually different. Methods Dose adjustments and AUCs from published licensing studies wer...

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

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


    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. Analysis of Fcgrt gene polymorphism in indigenous Chinese sheep and its association with colostrum IgG concentration. (United States)

    Tian, Z H; Shi, F; Zhong, F G; Bai, D P; Zhang, X Y


    The neonatal Fc receptor (FcRn) plays an important role in regulating IgG homeostasis in the body and passive protection to the offspring. Changes in FcRn expression levels caused by genetic polymorphisms of Fcgrt, which encodes FcRn, may lead to inter-individual differences in colostrum IgG levels in sheep. In this study, we sequenced the FcRn partial heavy chain from 179 sheep from Xinjiang Province, China, and detected the differences in colostrum IgG levels and Fcgrt genotypes to identify the correlation between the Fcgrt genotype and colostrum IgG levels in 4 sheep breeds. The DNA sequencing of a 680-bp fragment of the Fcgrt gene revealed various patterns depending on the single-strand conformation in the Suffolk breed. Sequencing analysis revealed a total of 3 patterns, AA, BB, AB, in this fragment, among which the absence of AB and BB genotype acted as a marker for breed identification and characterization, while the AA genotype was shared by Suffolk and 3 other breeds. The only allele found in all 4 breeds was allele A, indicating that natural selection may be favoring the AB and BB genotypes in general and B allele in particular, as the colostrum IgG concentration was relatively higher in the Suffolk breed compared to the other 3 breeds.

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

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


    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


    Directory of Open Access Journals (Sweden)

    Vladimir Ivanovich Vasilyev


    Full Text Available IgG4-related diseases are a new nosological entity that encompasses a few previously known diseases. IgG4-related systemic disease is diagnosed if two or more affected organs are detected. This group of diseases has two similar signs: serological (elevated serum IgG4 subclass concentrations and histological (organ and tissue infiltration from plasmo-cytes secreting IgG4, and eosinophils, and the development of fibrosclerosis and phlebitis obliterans. The paper describes two cases. In one case, a multisystemic disease was observed virtually at its onset whereas in the other this lesion was diagnosed several years after the natural course of the disease.

  19. Increased IgG4-Positive Plasma Cells in Granulomatosis with Polyangiitis: A Diagnostic Pitfall of IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Sing Yun Chang


    Full Text Available Granulomatosis with polyangiitis (Wegener’s (GPA may mimic IgG4-related disease (IgG4-RD on histologic examination of some biopsies, especially those from head and neck sites. IgG4 immunostain is often performed in this context for differential diagnosis with IgG4-RD. However, the prevalence of IgG4+ cells in GPA has not been explored. We examined the IgG4+ cells in 26 cases confirmed as GPA by a thorough clinical and pathologic assessment. Twenty-six biopsies consisted of 14 sinonasal/oral cavity/nasopharynx, 7 orbit/periorbital, 3 lung/pleura, 1 iliac fossa/kidney, and 1 dura specimens. Eight of 26 (31% biopsies revealed increased IgG4+ cells (>30/HPF and >40% in IgG4+/IgG+ ratio. The IgG4+ cells and IgG4+/IgG+ ratio ranged 37–137/hpf and 44–83%, respectively. Eight biopsies with increased IgG4+ cells were from sinonasal (n=4 or orbital/periorbital (n=4 sites. In conclusion, increased IgG4+ cells are not uncommonly seen in sinonasal or orbital/periorbital biopsies of GPA, which could pose as a diagnostic pitfall.

  20. Localized IgG4-related Cholecystitis Mimicking Gallbladder Cancer. (United States)

    Inoue, Tadahisa; Okumura, Fumihiro; Mizushima, Takashi; Nishie, Hirotada; Iwasaki, Hiroyasu; Anbe, Kaiki; Ozeki, Takanori; Kachi, Kenta; Fukusada, Shigeki; Suzuki, Yuta; Watanabe, Kazuko; Sano, Hitoshi


    We encountered a case of localized IgG4-cholecystitis mimicking gallbladder cancer with focal/segmental type1 autoimmune pancreatitis (AIP). In this case, we were unable to exclude a diagnosis of gallbladder cancer and thus performed radical cholecystectomy. Type1 AIP is often associated with gallbladder lesions, accompanied by generally diffuse, circumferential thickening of the gallbladder wall. Although localized IgG4-related cholecystitis is extremely rare, differentiating this condition from gallbladder cancer is often very difficult.

  1. Aggregated IgG inhibits the differentiation of human fibrocytes. (United States)

    Pilling, Darrell; Tucker, Nancy M; Gomer, Richard H


    Fibrocytes are fibroblast-like cells, which appear to participate in wound healing and are present in pathological lesions associated with asthma, pulmonary fibrosis, and scleroderma. Fibrocytes differentiate from CD14+ peripheral blood monocytes, and the presence of serum delays this process dramatically. We previously purified the factor in serum, which inhibits fibrocyte differentiation, and identified it as serum amyloid P (SAP). As SAP binds to Fc receptors for immunoglobulin G (IgG; Fc gammaRs), Fc gammaR activation may be an inhibitory signal for fibrocyte differentiation. Fc gammaR are activated by aggregated IgG, and we find aggregated but not monomeric, human IgG inhibits human fibrocyte differentiation. Monoclonal antibodies that bind to Fc gammaRI (CD64) or Fc gammaRII (CD32) also inhibit fibrocyte differentiation. Aggregated IgG lacking Fc domains or aggregated IgA, IgE, or IgM do not inhibit fibrocyte differentiation. Incubation of monocytes with SAP or aggregated IgG inhibited fibrocyte differentiation. Using inhibitors of protein kinase enzymes, we show that Syk- and Src-related tyrosine kinases participate in the inhibition of fibrocyte differentiation. These observations suggest that fibrocyte differentiation can occur in situations where SAP and aggregated IgG levels are low, such as the resolution phase of inflammation.

  2. Results from an inter-laboratory comparison of pneumococcal serotype-specific IgG measurement and critical parameters that affect assay performance. (United States)

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


    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.


    Directory of Open Access Journals (Sweden)

    S. M. Sobolev


    Full Text Available As assessed by decreased response of ConA-induced blasts to IL-2, a staphylococcal protein A was shown to extract IL-2 from cultural medium after its preincubation with IgG, but it did not bind pure IL-2. Normal human immunoglobulin inhibits reaction of DTH effectors to Listeria antigen, which is also IL-2-dependent. An immunomodulating drug Phosprenyl (sodium polyprenylphosphate abolishes the inhibitory ffect of immunoglobulin. Since Phosprenyl (as shown earlier interacts with alpha-chain of rIL-2 and blocks IL-2 activity, the two drugs are in competitive relations. The latter may be explained by identities in prostetic carbohydrate groups of the both glycoproteins (CD25 and immunoglobulin, whereas Phosprenyl and IL-2 would behave like as lectins. These results characterize local conditions and mechanisms of immune regulation under tissue domination of gamma-globulin or antibodies of a given isotype. IgG binds with IL-2, reacting not with an active center but with effector region of IgG molecule, thus blocking IL-2 activity. Since a similar effect is observed under in vivo conditions (in a DTH model, the phenomenon revealed may explein inhibition of immune response after passive injection of antibodies, as well as a feed-back relationship between humoral and cellular immunity. Inhibition of IL-2 biological activity after its interaction with IgG and immune complexes may be considered as a universal mechanism of immune regulation performed by a feedback regulation, which may be influenced by means of Phosprenyl-like immunomodulators. In some infections, malignant growth etc., such mechanism may be of utmost pathogenetic significance. Moreover, such a mechanism cannot be also excluded in some physiological immunogenetic interactions, e.g., in feto-maternal system, where it could promote a positive selection for individuals with broader MHC repertoire, which would be necessary for development of individual and population-based resistance to

  4. IgG+ platelets in the marmoset: their induction, maintenance, and survival

    Energy Technology Data Exchange (ETDEWEB)

    Gengozian, N.; McLaughlin, C.L.


    Immunization of marmosets with platelets from another species of marmoset leads to antibody formation to the donor platelets, deposition of IgG on the host's platelets, and thrombocytopenia. This disease closely resembles posttransfusion purpura of man, which may develop after one or two transfusions of whole blood. The mode of immunization in the marmoset was found to be important: intravenous (i.v.) inoculations were without effect, while intramuscular (i.m.) immunizations led to the disease. Intramuscular inoculations were characterized by formation of 7S antibodies, as measured by indirect immunofluorescent (IF) and complement-dependent platelet cytotoxicity (PC) tests; in contrast, i.v. immunizations, while leading to 7S antibodies by the IF test, yielded only 19S antibodies reactive in the PC assay. The titers were also consistently higher with i.m. immunizations. Antibody was not limited to the donor platelets, but auto- or host-type reactivity was also present; this antibody was in very low titer and could be found only when the animal was thrombocytopenic. A primary finding was the ability to maintain increased deposition of IgG on the host's platelets in the absence of thrombocytopenia by biweekly or monthly inoculations of the donor platelet antigen. The amount of IgG found on platelets of normal and immunized marmosets was comparable to that reported for normal humans and patients with cinical immune thrombocytopenia. Finally, platelet survival studies in animals with IgG+ platelets and normal platelet counts indicated a rapid turnover, suggesting operation of a compensatory mechanism to maintain platelet levels.

  5. Selection of IgG variants with increased FcRn binding using random and directed mutagenesis: impact on effector functions

    Directory of Open Access Journals (Sweden)

    Céline eMonnet


    Full Text Available Despite the reasonably long half-life of IgGs, market pressure for higher patient convenience while conserving efficacy continues to drive IgG half-life improvement. IgG half-life is dependent on the neonatal Fc receptor FcRn, which amongst other functions, protects IgG from catabolism. FcRn binds the Fc domain of IgG at an acidic pH ensuring that endocytosed IgG will not be degraded in lysosomal compartments and will then be released into the bloodstream. Consistent with this mechanism of action, several Fc engineered IgG with increased FcRn affinity and conserved pH-dependency were designed and resulted in longer half-life in vivo in human FcRn transgenic mice (hFcRn, cynomolgus monkeys and recently in healthy humans. These IgG variants were usually obtained by in silico approaches or directed mutagenesis in the FcRn binding site. Using random mutagenesis, combined with a pH-dependent phage display selection process, we isolated IgG variants with improved FcRn-binding which exhibited longer in vivo half-life in hFcRn mice. Interestingly, many mutations enhancing Fc/FcRn interaction were located at a distance from the FcRn binding site validating our random molecular approach. Directed mutagenesis was then applied to generate new variants to further characterize our IgG variants and the effect of the mutations selected. Since these mutations are distributed over the whole Fc sequence, binding to other Fc effectors, such as complement C1q and FcgRs, was dramatically modified, even by mutations distant from these effectors’ binding sites. Hence, we obtained numerous IgG variants with increased FcRn binding and different binding patterns to other Fc effectors, including variants without any effector function, providing distinct fit-for-purpose Fc molecules. We therefore provide evidence that half-life and effector functions should be optimized simultaneously as mutations can have unexpected effects on all Fc receptors that are critical for IgG

  6. IgG4相关性淋巴结病与淋巴瘤%IgG4-related lymphadenopathy and lymphoma

    Institute of Scientific and Technical Information of China (English)



    IgG4在IgG中是最小的亚群,近年来一种并不多见的以淋巴结及一系列结外部位出现硬化性损害伴随受累部位IgG4亚型浆细胞增多、血清IgG4水平升高以及经常出现自身抗体等表现为特征的系统性疾病经常被报道,该病现在一般被称为IgG4相关性疾病(IgG4-RD),对糖皮质激素治疗反应良好;一些研究者认为IgG4-RD有可能最终发展为淋巴瘤。本综述阐述了与IgG4-RD相关的淋巴结病变,探讨了病变淋巴结中 IgG4阳性浆细胞增多的意义,同时结合文献讨论了与IgG4-RD相关的淋巴瘤以及IgG4-RD患者发生淋巴瘤风险。%IgG4 is one of the IgG subtypes, but it is the most uncommon. In recent years an relatively rare systemic disorder characterized by some manifestations that may include the sclerosing lesions in a wide variety of extranodal sites, lymphadenopathy, appearance of increased numbers of plasma cells of IgG4 subtype in affected area, elevated serum IgG4 and autoantibodies may positive has been described. This disease has a good response to steroid therapy and now known as IgG4-related disease (IgG4-RD). Some researchers believe that IgG4-RD may eventually develop to lymphoma. This review described lymphadenopathy associated with the IgG4-RD, discusseed the significance of increased IgG4+ plasma cells in the isolated lymphadenopathy. It also discussed the IgG4-RD related lymphoma and the risk of progression to lymphoma in IgG4-RD patients.

  7. IgG4相关性疾病的研究进展%Immunoglobulin G4-related disease

    Institute of Scientific and Technical Information of China (English)

    张雪英; 乔建军


    IgG4相关性疾病是近年来提出的一种新病种,本病可累及人体任何组织和器官.IgG4相关性疾病的显著特征为血清IgG4水平升高以及多种器官和组织中IgG4阳性浆细胞浸润.近年来发现,IgG4相关性疾病可有皮肤改变,皮损可表现为多种皮肤病的症状,包括Mikulicz病、皮肤浆细胞增多症、假性淋巴瘤、血管淋巴样增生伴嗜酸细胞增多和木村病等.IgG4相关性疾病患者对系统糖皮质激素治疗反应较好.%Immunoglobulin G4 (IgG4)-related disease is a recently proposed entity, and can affect any tissue or organ in the human body.It is characterized by increased serum levels of IgG4 and infiltration of abundant IgG4-positive cells in various organs and tissues.Recent studies have found that IgG4-related disease may present with various skin manifestations, such as Mikulicz's disease, cutaneous plasmacytosis, pseudolymphoma, angiolymphoid hyperplasia with eosinophilia and Kimura's disease.Systemic glucocorticoids are effective for the treatment of IgG4-related disease.

  8. 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


    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.

  9. Immunohistochemical Characteristics of IgG4-Related Tubulointerstitial Nephritis: Detailed Analysis of 20 Japanese Cases

    Directory of Open Access Journals (Sweden)

    Mitsuhiro Kawano


    Full Text Available Although tubulointerstitial nephritis with IgG4+ plasma cell (PC infiltration is a hallmark of IgG4-related kidney disease (IgG4-RKD, only a few studies are available about the minimum number of IgG4+ PC needed for diagnosis along with IgG4+/IgG+ PC ratio in the kidney. In addition, the significance of the deposition of IgG or complement as a reflection of humoral immunity involvement is still uncertain. In this study, we analyzed 20 Japanese patients with IgG4-RKD to evaluate the number of IgG4+ PCs along with IgG4+/IgG+ PC ratio and involvement of humoral immunity. The average number of IgG4+ PCs was 43.8/hpf and the average IgG4+/IgG+ or IgG4+/CD138+ ratio was 53%. IgG and C3 granular deposits on the tubular basement membrane (TBM were detected by immunofluorescence microscopy in 13% and 47% of patients, respectively. Nine patients had a variety of glomerular lesions, and 7 of them had immunoglobulin or complement deposition in the glomerulus. In conclusion, we confirmed that infiltrating IgG4+ PCs > 10/hpf and/or IgG4/IgG (CD138+ PCs > 40% was appropriate as an item of the diagnostic criteria for IgG4-RKD. A relatively high frequency of diverse glomerular lesions with immunoglobulin or complement deposits and deposits in TBM may be evidence of immune complex involvement in IgG4-related disease.

  10. In a SLE mouse model the production of IgG autoantibody requires expression of activation-induced deaminase in early developing B cells (United States)

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


    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

  11. Physiological changes in the peri-partum period and colostral IgG transfer in prolific D'man sheep: effects of parity and litter size. (United States)

    Chniter, Mohamed; Salhi, Imed; Harrabi, Hager; Khorchani, Touhami; Lainé, Anne-Lyse; Nowak, Raymond; Hammadi, Mohamed


    The aim of this work was to assess maternal and neonatal changes in plasma proteins, glucose and cortisol and to quantify the colostral immunoglobulin G (IgG) transfer in the peri-partum period in D'man sheep, a prolific breed, taking into account the parity of the ewe. The concentrations of proteins and glucose were high in the ewes on day 7 and at lambing before decreasing. Likewise, cortisol plasma concentration was maximal during the 6 h following lambing and dropped at 12 h. Protein and glucose concentrations were low in lambs at 1 h of birth after which they increased. By contrast, cortisol level was the highest during the first 12 h of birth and then decreased. The colostral IgG level was high at lambing and dropped by over 87 % from 1 to 48 h post-partum. In the newborn, the plasma IgG concentration was lowest at birth and increased rapidly during the first 24 h of birth. Parity influenced maternal physiology with multiparous ewes having the lowest concentrations of proteins, glucose, IgG and cortisol, but the highest colostrum IgG level. Accordingly, lambs born from primiparous ewes had lower protein, glucose and plasma IgG concentrations than lambs born from multiparous ewes. The main outcome of this study was that lambs born from primiparous ewes are characterized by the lowest physiological indices and this may influence their survival chance.

  12. [PHEMA/PEI]-Cu(II) based immobilized metal affinity chromatography cryogels: Application on the separation of IgG from human plasma. (United States)

    Bakhshpour, Monireh; Derazshamshir, Ali; Bereli, Nilay; Elkak, Assem; Denizli, Adil


    The immobilized metal-affinity chromatography (IMAC) has gained significant interest as a widespread separation and purification tool for therapeutic proteins, nucleic acids and other biological molecules. The enormous potential of IMAC for proteins with natural surface exposed-histidine residues and for recombinant proteins with histidine clusters. Cryogels as monolithic materials have recently been proposed as promising chromatographic adsorbents for the separation of biomolecules in downstream processing. In the present study, IMAC cryogels have been synthesized and utilized for the adsorption and separation of immunoglobulin G (IgG) from IgG solution and whole human plasma. For this purpose, Cu(II)-ions were coupled to poly(hydroxyethyl methacrylate) PHEMA using poly(ethylene imine) (PEI) as the chelating ligand. In this study the cryogels formation optimized by the varied proportion of PEI from 1% to 15% along with different amounts of Cu (II) as chelating metal. The prepared cryogels were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The [PHEMA/PEI]-Cu(II) cryogels were assayed for their capability to bind the human IgG from aqueous solutions. The IMAC cryogels were found to have high affinity toward human IgG. The adsorption of human IgG was investigated onto the PHEMA/PEI cryogels with (10% PEI) and the concentration of Cu (II) varied as 10, 50, 100 and 150 mg/L. The separation of human IgG was achieved in one purification step at pH7.4. The maximum adsorption capacity was observed at the [PHEMA/PEI]-Cu(II) (10% PEI) with 72.28 mg/g of human IgG. The purification efficiency and human IgG purity were investigated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).

  13. IgG red blood cell autoantibodies in autoimmune hemolytic anemia bind to epitopes on red blood cell membrane band 3 glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Victoria, E.J.; Pierce, S.W.; Branks, M.J.; Masouredis, S.P. (Univ. of California, San Diego (USA))


    Red blood cell (RBC) autoantibodies from patients with IgG warm-type autoimmune hemolytic anemia were labeled with iodine 125 and their RBC binding behavior characterized. Epitope-bearing RBC membrane polypeptides were identified after autoantibody immunoprecipitation of labeled membranes and immunoblotting. Immunoaffinity isolation of labeled membrane proteins with 12 different IgG hemolytic autoantibodies with protein A-agarose revealed a major polypeptide at Mr 95 to 110 kd, which coelectrophoresed on sodium dodecylsulfate-polyacrylamide gel electrophoresis with a membrane component isolated with sheep IgG anti-band 3. Immunoprecipitation studies with chymotrypsinized RBCs resulted in the recovery of two labeled membrane polypeptides with molecular weights characteristically resulting from the chymotryptic fragmentation of band 3. Immunoblotting with sheep IgG anti-band 3 of the immunoprecipitated polypeptides confirmed that hemolytic autoantibody binding led to recovery of band 3 or its fragments. Two 125I-labeled IgG hemolytic autoantibodies showed binding behavior consistent with epitope localization on band 3. The labeled RBC autoantibodies bound immunospecifically to all types of human RBC tested, including those of rare Rh type (Rh-null, D--) at a site density of approximately 10(6) per RBC. The 125I-IgG in two labeled autoantibodies was 84% and 92% adsorbable by human and higher nonhuman primate RBCs. Antigen-negative animal RBC bound less than 10%, consistent with immunospecific RBC binding. IgG-1 was the major subclass in five autoantibodies tested; one of six fixed complement; and autoantibody IgG appeared polyclonal by isoelectric focusing. We conclude that IgG eluted from RBCs of patients with autoimmune hemolytic anemia consists predominantly of a single totally RBC-adsorbable antibody population that binds to antigenic determinants on band 3.

  14. Acute Painful Ptosis Secondary to IgG4 Dacryoadenitis

    Directory of Open Access Journals (Sweden)

    Rumana Hussain


    Full Text Available A 48-year-old lorry driver presented with 3 weeks of blurred vision, pain and diplopia. There was a right upper lid ptosis with some restriction of eye movements. A CT revealed an enlarged lacrimal gland and lacrimal gland biopsy showed IgG4-positive plasma cells. The patient responded to oral prednisolone and fully recovered. As a condition which mimics a number of diseases, an IgG4-related disease presents a diagnostic challenge and ought to be considered in both acute and chronic presentations.

  15. Coadsorption of IgG and BSA onto sulfonated polystyrene latex: I. Sequential and competitive coadsorption isotherms. (United States)

    Peula, J M; Hidalgo-Alvarez, R; de las Nieves, F J


    In this work the sequential and competitive coadsorption of IgG and BSA proteins on a sulfonate polystyrene latex with high surface charge density have been studied. For sequential coadsorption the IgG/a-CRP was first adsorbed and then the free surface of the particle was saturated by redispersion of the pellet in a solution with a high concentration of monomeric BSA (m-BSA). The competitive coadsorption experiments were carried out in two separate experiments by changing the initial concentration of one protein when the concentration of other protein was high and constant. During the incubation the pH was 5 or 6, and the ionic strength 2 mM, as in previous studies the adsorption of BSA was very low at neutral or basic pH regardless of the amount of adsorbed IgG. From these coadsorption experiments it was possible to obtain latex-protein complexes with a similar degree of coverage by each protein, high adsorption of IgG and different amounts of BSA, or high adsorption of BSA and a low, but significant, amount of IgG. The latex-protein complexes were electrokinetically characterized by measuring the electrophoretic mobility of each complex vs the pH of redispersion. In that way we can detect the i.e.p. of the complexes and the pH range in which the electrostatic repulsion can make them colloidally stable.

  16. Results of anti-Toxoplasma gondii IgG, IgM, IgA and IgG Avidity testing in pregnant women in Rome, Italy

    Directory of Open Access Journals (Sweden)

    Carla Nisii


    Full Text Available To evaluate the incidence of Toxoplasma gondii infection, the detection of specific IgG, IgM, IgA and IgG avidity was performed on 1424 pregnant women referred to the “L. Spallanzani” Hospital in Rome (Italy. Of the 1424 women screened, 20 (1.40% were likely to have been recently infected (presence of IgM/IgA, and/or low IgG avidity, 29 (2.04% had positive IgM coupled with high IgG avidity, 7 (0.49% had an unspecific result for IgM alone, 1339 (94.0%, were negative for both IgG and IgM, 29 (2.04% showed evidence of past infection (IgG positive, IgM negative, high IgG avidity. In Conclusion our results underscore the importance of efficient antenatal screening and appropriate treatment for Toxoplasma infection in Italy.

  17. Half molecular exchange of IgGs in the blood of healthy humans: chimeric lambda-kappa-immunoglobulins containing HL fragments of antibodies of different subclasses (IgG1-IgG4). (United States)

    Sedykh, Sergey E; Lekchnov, Evgenii A; Prince, Viktor V; Buneva, Valentina N; Nevinsky, Georgy A


    In the classic paradigm, immunoglobulins represent products of clonal B cell populations, each producing antibodies recognizing a single antigen (monospecific). There is a common belief that IgGs in mammalian biological fluids are monospecific molecules having stable structures and two identical antigen-binding sites. But the issue concerning the possibility of exchange by HL-fragments between the antibody molecules in human blood is still unexplored. Different physico-chemical and immunological methods for analysis of half-molecule exchange between human blood IgGs were used. Using eighteen blood samples of healthy humans we have shown unexpected results for the first time: blood antibodies undergo extensive post-transcriptional half-molecule exchange and IgG pools on average consist of 62.4 ± 6.5% IgGs containing kappa light chains (kappa-kappa-IgGs), 29.8.6 ± 5.4% lambda light chains (lambda-lambda-IgGs), and 8.8 ± 2.7% (range 2.6-16.8%) IgGs containing both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained on average (%): IgG1 (36.0 and 32.3), IgG2 (50.9 and 51.4), IgG3 (9.7 and 9.9), and IgG4 (6.5 and 5.7), while chimeric kappa-lambda-IgGs consisted of (%): 25.5 ± 4.2 IgG1, 50.8 ± 3.9 IgG2, 9.1 ± 2.1 IgG3, and 14.5 ± 2.2 IgG4. Our unexpected data are indicative of the possibility of half-molecule exchange between blood IgGs of various subclasses, raised against different antigens. The existence of blood chimeric bifunctional IgGs with different binding sites destroys the classic paradigm. Due to the phenomenon of polyspecificity and cross-reactivity of bifunctional IgGs containing HL-fragments of different types to different antigens, such IgGs may be important in human blood for widening their different biological functions.

  18. Glycation of polyclonal IgGs: Effect of sugar excipients during stability studies. (United States)

    Leblanc, Y; Bihoreau, N; Jube, M; Andre, M-H; Tellier, Z; Chevreux, G


    A number of intravenous immunoglobulin preparations are stabilized with sugar additives that may lead over time to undesirable glycation reactions especially in liquid formulation. This study aimed to evaluate the reactivity of sugar excipients on such preparations in condition of temperature, formulation and concentration commonly used for pharmaceutical products. Through an innovative LC-MS method reported to characterize post-translational modifications of IgGs Fc/2 fragments, a stability study of IVIg formulated with reducing and non-reducing sugars has been undertaken. The rate of polyclonal IgGs glycation was investigated during 6months at 5, 25, 30 and 40°C. High levels of glycation were observed with reducing sugars such as glucose and maltose in the first months of the stability study from 25°C. Non-reducing sugars presented a low reactivity even at the highest tested temperature (40°C). Furthermore, a site by site analysis was performed by MS/MS to determine the glycation sites which were mainly identified at Lys246, Lys248 and Lys324. This work points out the high probability of glycation reactions in some commercialized products and describes a useful method to characterize IVIg glycated products issued from reducing sugar excipients.

  19. IgGs containing light chains of the lambda and kappa type and of all subclasses (IgG1-IgG4) from sera of patients with multiple sclerosis hydrolyze DNA. (United States)

    Parkhomenko, Taisiya A; Legostaeva, Galina A; Doronin, Boris M; Buneva, Valentina N; Nevinsky, Georgy A


    We present the first evidence demonstrating that small fractions of IgGs of all four subclasses (IgG1-IgG4) are catalytically active in the hydrolysis of DNA and on average their relative activity (nM supercoiled DNA/1mg IgG/1 h) increases in the order: IgG1 (0.58) light chains of the lambda-type are severalfold more active in the hydrolysis of DNA than IgGs with light chains of the kappa-type. Using different physicochemical methods of antibody analysis we have shown that the immune system of multiple sclerosis patients generates a variety of anti-DNA abzymes of different type and with different catalytic properties, which can play an important role in multiple sclerosis pathogenesis.

  20. Suitability of bio-based ionic liquids for the extraction and purification of IgG antibodies. (United States)

    Mondal, Dibyendu; Sharma, Mukesh; Quental, Maria V; Tavares, Ana P M; Prasad, Kamalesh; Freire, Mara G


    In the past decade, remarkable advances in the production and use of antibodies as therapeutic drugs and in research/diagnostic fields have led to their recognition as value-added proteins. These biopharmaceuticals have become increasingly important, reinforcing the current demand for the development of more benign, scalable and cost-effective techniques for their purification. Typical polymer-polymer and polymer-salt aqueous biphasic systems (ABS) have been studied for such a goal; yet, the limited polarity range of the coexisting phases and their low selective nature still are their major drawbacks. To overcome this limitation, in this work, ABS formed by bio-based ionic liquids (ILs) and biocompatible polymers were investigated. Bio-based ILs composed of ions derived from natural sources, namely composed of the cholinium cation and anions derived from plants natural acids, have been designed, synthesized, characterized and used for the creation of ABS with polypropyleneglycol (PPG 400). The respective ternary phase diagrams were initially determined at 25 °C to infer on mixture compositions required to form aqueous systems of two phases, further applied in the extraction of pure immunoglobulin G (IgG) to identify the most promising bio-based ILs, and finally employed in the purification of IgG from complex and real matrices of rabbit serum. Remarkably, the complete extraction of IgG to the IL-rich phase was achieved in a single-step. With pure IgG a recovery yield of 100% was obtained, while with rabbit serum this value slightly decreased to ca. 85%. Nevertheless, a 58% enhancement in the IgG purity was achieved when compared with its purity in serum samples. The stability of IgG before and after extraction was also evaluated by size exclusion high-performance liquid chromatography (SE-HPLC), sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and Fourier transform infrared spectroscopy (FTIR). In most ABS formed by bio-based ILs, IgG retained

  1. The changing faces of IgG4-related disease: Clinical manifestations and pathogenesis. (United States)

    Islam, Arshia Duza; Selmi, Carlo; Datta-Mitra, Ananya; Sonu, Rebecca; Chen, Mingyi; Gershwin, M Eric; Raychaudhuri, Siba P


    Since the earliest reports in 2001, immunoglobulin G4 (IgG4)-related disease has been defined as an autoimmune systemic disease characterized by the lymphoplasmacytic infiltration of affected tissues leading to fibrosis and obliterative phlebitis along with elevated serum IgG4 levels. Prior to this unifying hypothesis, a plethora of clinical manifestations were considered as separate entities despite the similar laboratory profile. The pathology can be observed in virtually all organs and may thus be a challenging diagnosis, especially when the adequate clinical suspicion is not present or when obtaining a tissue biopsy is not feasible. Nonetheless, the most frequently involved organs are the pancreas and exocrine glands but these may be spared. Immunosuppressants lead to a prompt clinical response in virtually all cases and prevent histological sequelae and, as a consequence, an early differential diagnosis from other conditions, particularly infections and cancer, as well as an early treatment should be pursued. We describe herein two cases in which atypical disease manifestations were observed, i.e., one with recurrent neck lymph node enlargement and proptosis, and one with jaundice. Our understanding of the pathogenesis of IgG4-related disease is largely incomplete but data support a significant role for Th2 cytokines with the contribution of innate immunity factors such as Toll-like receptors, macrophages and basophils. Further, macrophages activated by IL4 overexpress B cell activating factors and contribute to chronic inflammation and the development of fibrosis. We cannot rule out the possibility that the largely variable disease phenotypes reflect different pathogenetic mechanisms and the tissue microenvironment may then contribute to the organ involvement.

  2. Spectrum of Disorders Associated with Elevated Serum IgG4 Levels Encountered in Clinical Practice

    Directory of Open Access Journals (Sweden)

    Jay H. Ryu


    Full Text Available IgG4-related disease (IgG4-RD is a recently described systemic fibroinflammatory disease associated with elevated circulating levels of IgG4 and manifests a wide spectrum of clinical presentations. Although serum IgG4 level has been described to be the most sensitive and specific laboratory test for the diagnosis of IgG4-RD, it is recognized that an elevated serum IgG4 level can be encountered in other diseases. In this study, we sought to identify the frequency of IgG4-RD and other disease associations in patients with elevated serum IgG4 levels seen in clinical practice. Among 3,300 patients who underwent IgG subclass testing over a 2-year period from January 2009 to December 2010, 158 (4.8% had an elevated serum IgG4 level (>140 mg/dL. IgG4 subclass testing was performed for evaluation of suspected IgG4-RD or immunodeficiency. Twenty-nine patients (18.4% had definite or possible IgG4-RD. Among those patients without IgG4-RD, a broad spectrum of biliary tract, pancreatic, liver, and lung diseases, as well as systemic vasculitis, was diagnosed. We conclude that patients with elevated serum IgG4 levels encountered in clinical practice manifest a wide array of disorders, and only a small minority of them has IgG4-RD.

  3. T Cell Polarization toward TH2/TFH2 and TH17/TFH17 in Patients with IgG4-Related Disease (United States)

    Grados, Aurélie; Ebbo, Mikael; Piperoglou, Christelle; Groh, Matthieu; Regent, Alexis; Samson, Maxime; Terrier, Benjamin; Loundou, Anderson; Morel, Nathalie; Audia, Sylvain; Maurier, François; Graveleau, Julie; Hamidou, Mohamed; Forestier, Amandine; Palat, Sylvain; Bernit, Emmanuelle; Bonotte, Bernard; Farnarier, Catherine; Harlé, Jean-Robert; Costedoat-Chalumeau, Nathalie; Vély, Frédéric; Schleinitz, Nicolas


    IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder involving virtually every organ with a risk of organ dysfunction. Despite recent studies regarding B cell and T cell compartments, the disease’s pathophysiology remains poorly understood. We examined and characterized subsets of circulating lymphocytes in untreated patients with active IgG4-RD. Twenty-eight consecutive patients with biopsy-proven IgG4-RD were included in a prospective, multicentric study. Lymphocytes’ subsets were analyzed by flow cytometry, with analysis of TH1/TH2/TH17, TFH cells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy controls and to patients with primary Sjögren’s syndrome. Patients with IgG4-RD showed an increase of circulating T regulatory, TH2, TH17, and CD4+CXCR5+PD1+ TFH cell subsets. Accordingly, increased levels of IL-10 and IL-4 were measured in IgG-RD patients. TFH increase was characterized by the specific expansion of TFH2 (CCR6−CXCR3−), and to a lesser extent of TFH17 (CCR6+CXCR3−) cells. Interestingly, CD4+CXCR5+PD1+ TFH cells normalized under treatment. IgG4-RD is characterized by a shift of circulating T cells toward a TH2/TFH2 and TH17/TFH17 polarization. This immunological imbalance might be implicated in the disease’s pathophysiology. Treatment regimens targeting such T cells warrant further evaluation. PMID:28348556

  4. Graves' Disease Patients with Persistent Hyperthyroidism and Diffuse Lymphoplasmacytic Infiltration in the Thyroid Show No Histopathological Compatibility with IgG4-Related Disease.

    Directory of Open Access Journals (Sweden)

    Eijun Nishihara

    Full Text Available IgG4-related disease is a novel disease entity characterized by diffuse lymphoplasmacytic infiltration rich in IgG4-positive plasma cells and fibrosis into multiple organs. There is still controversy over whether some thyroid diseases are actually IgG4-related disease. The objective of this study was to elucidate the clinicopathological features of Graves' disease with diffuse lymphoplasmacytic infiltration in the thyroid.Among 1,484 Graves' disease patients who underwent thyroidectomy, we examined their histopathological findings including the degree of lymphoplasmacytic and fibrotic infiltration and levels of IgG4-positive plasma cells in the thyroid. Their clinical pictures were defined by laboratory and ultrasonographic evaluation.A total of 11 patients (0.74% showed diffuse lymphoplasmacytic infiltration in the stroma of the thyroid gland. Meanwhile, other patients showed variable lymphoid infiltration ranging from absent to focally dense but no aggregation of plasma cells in the thyroid gland. Based on the diagnostic criteria of IgG4-related disease, 5 of the 11 subjects had specifically increased levels of IgG4-positive plasma cells in the thyroid. Fibrotic infiltration was present in only 1 patient developing hypothyroidism after anti-thyroid drug treatment for 4 years, but not in the other 10 patients with persistent hyperthyroidism. Obliterative phlebitis was not identified in any of the 11 subjects. Thyroid ultrasound examination showed 1 patient developing hypothyroidism who had diffuse hypoechogenicity, but the other hyperthyroid patients had a coarse echo texture.In our study, Graves' disease patients with persistent hyperthyroidism who had diffuse lymphoplasmacytic infiltration rich in IgG4-positive plasma cells in the thyroid showed no concomitant fibrosis or obliterative phlebitis.

  5. IgG4-related epididymo-orchitis associated with bladder cancer: possible involvement of BAFF/BAFF-R interaction in IgG4-related urogenital disease. (United States)

    Migita, Kiyoshi; Miyashita, Taiichiro; Mizuno, Aya; Jiuchi, Yuka; Ito, Masahiro; Matsuo, Manabu; Izumi, Yasumori; Takeoka, Atsushi; Nishino, Ayako; Hayashi, Mikio


    We describe herein a patient who presented with immunoglobulin G4-related disease (IgG4-RD) involving the testis and prostate as well as the submandibular glands. Massive infiltration of IgG4-expressing plasma cells was observed in testis and prostate tissues. Serum concentrations of B cell activating factor belonging to the tumor necrosis factor family (BAFF) were elevated in parallel with serum IgG4 concentrations, and infiltration of BAFF-receptor (BAFF-R)-expressing B cells and BAFF-expressing lymphoid cells was observed around the ectopic lymphoid foci in the affected urogenital tissues. To date, testicular involvement in a patient diagnosed with IgG4-RD had not been reported, making this the first reported case of IgG4-related epididymo-orchitis. These findings suggest that the immune mechanism underlying ectopic lymphoneogenesis in IgG4-RD may involve enhanced BAFF/BAFF-R interactions among lymphoid cells.

  6. Specific IgG(4) responses during chronic and transient antigen exposure in aspergillosis

    NARCIS (Netherlands)

    Tomee, JFC; Dubois, AEJ; Koeter, GH; Beaumont, F; vanderWerf, TS; Kauffman, HF


    The factors that lead to increased production of specific IgG subclasses are still largely unknown. Recent studies suggest that increased IgG(4) responses may be related to prolonged antigen exposure. We present data showing that increased IgG(4) responses are found under conditions of chronic expos

  7. On the Perplexingly Low Rate of Transport of IgG2 across the Human Placenta

    NARCIS (Netherlands)

    Einarsdottir, Helga K.; Stapleton, Nigel M.; Scherjon, Sicco; Andersen, Jan Terje; Rispens, Theo; van der Schoot, C. Ellen; Vidarsson, Gestur


    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

  8. 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

  9. [Raise awareness of IgG4 relative ocular disease]. (United States)

    Wei, Shihui; Li, Hongyang


    Purpose IgG4-related ocular disease is a chronic systemic disease with lymphocyte abnormal. The lacrimal glands, extraocular muscles and infraorbital nerve were often involved which was often the first symptom of systemic disease. While ophthalmologists did not know this disease well. They usually misdiagnosed it as idiopathic inflammatory pseudotumor, thyroid-associated ophthalmopathy etc, which resulted in delayed treatments. Here pathogenesis, clinical features and treatment methods of IgG4-relative ocular disease were described in order to improve awareness of this ocular disease, reduce clinical misdiagnosis, improve disease prognosis and standardized treatment. As the incidence of this disease increased in recent years, it is very necessary to improve awareness of the disease for ophthalmologists.

  10. Aggregated IgG inhibits the differentiation of human fibrocytes


    Pilling, Darrell; Tucker, Nancy M.; Gomer, Richard H.


    Fibrocytes are fibroblast-like cells, which appear to participate in wound healing and are present in pathological lesions associated with asthma, pulmonary fibrosis, and scleroderma. Fibrocytes differentiate from CD14+ peripheral blood monocytes, and the presence of serum delays this process dramatically. We previously purified the factor in serum, which inhibits fibrocyte differentiation, and identified it as serum amyloid P (SAP). As SAP binds to Fc receptors for immunoglobulin G (IgG; Fcγ...

  11. Serological IgG avidity test for ocular toxoplasmosis

    Directory of Open Access Journals (Sweden)

    Suresh S


    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

  12. IgG and IgG subclass specific antibody responses to diphtheria and tetanus toxoids in newborns and infants given DTP immunization. (United States)

    Dengrove, J; Lee, E J; Heiner, D C; St Geme, J W; Leake, R; Baraff, L J; Ward, J I


    To evaluate immune responses to diphtheria and tetanus toxoids in infants we used enzyme-linked immunosorbent assays to detect total IgG and specific IgG-1, IgG-2, IgG-3, and IgG-4 antibody. One group of infants received a newborn dose and subsequently received the usual three doses of DTP. A second group of infants received only the routine dosage at 2, 4, and 6 months of age. In sera acquired at birth, 6, and 9 months of age, there were no statistically significant differences between the two vaccine groups in IgG antibody responses to diphtheria or tetanus, or in IgG subclass tetanus-specific antibody responses. In individual children, tetanus-specific subclass responses were similar in pattern to that for total IgG tetanus antibody, i.e. each IgG subclass response appeared to be regulated by similar mechanisms in that child, but the regulation differed between children. In contrast to a prior study of pertussis immunity, maternally acquired antibody did not significantly affect immune responses to diphtheria or tetanus toxoid by 9 months of age. There was no discernible tolerance due to early tetanus or diphtheria immunization or to high levels of maternally acquired antibody.

  13. Evaluation of IgG4 and total IgG antibodies against cysticerci and peptide antigens for the diagnosis of human neurocysticercosis by ELISA. (United States)

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


    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.


    Directory of Open Access Journals (Sweden)

    V. G. Levchenko


    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.

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


    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.

  16. Granulocyte-associated IgG in neutropenic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Cines, D.B.; Passero, F.; Guerry, D. IV; Bina, M.; Dusak, B.; Schreiber, A.D


    We applied a radiolabeled antiglobulin test to a study of patients with a variety of neutropenic disorders. After defining the nature of the interaction of radiolabeled anti-IgG with the neutrophil, we studied 16 patients with neutropenia of uncertain etiology and adequate bone marrow granulocyte precursors. Twelve of these 16 patients had increased neutrophil-associated IgG (PMN-IgG). Patients with the highest levels of PMN-IgG had the lowest neutrophil counts. The majority of patients with neutropenia and increased PMN-IgG had an underlying immunologic disorder that included immune thrombocytopenic purpura in 5 patients and autoimmune hemolytic anemia in 1 patient. In some patients, elevated PMN-IgG preceded other evidence for immunologic disease. The direct antiglobulin test helped to distinguish neutropenic patients with increased PMN-IgG both from patients with neutropenia due to a known nonimmune disorder and from noneutropenic patients with rheumatoid arthritis or systemic lupus erythematosis. Each of four patients with increased neutrophil-associated IgG treated with systemic corticosteroids responded clinically with an associated fall in neutrophil IgG and a rise in the circulating neutrophil count. The radiolabeled antiglobulin test appears useful in defining a subpopulation of patients with neutropenia due to an underlying immunologic disorder.

  17. Granulocyte-associated IgG in neutropenic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Cines, D.B.; Passero, F.; Guerry, D.; Bina, M.; Dusak, B.; Schreiber, A.D.


    We applied a radiolabeled antiglobulin test to a study of patients with a variety of neutropenic disorders. After defining the nature of the interaction of radiolabeled anti-IgG with the neutrophil, we studied 16 patients with neutropenia of uncertain etiology and adequate bone marrow granulocyte precursors. Twelve of these 16 patients had increased neutrophil-associated IgG (PMN-IgG). Patients with the highest levels of PMN-IgG had the lowest neutrophil counts. The majority of patients with neutropenia and increased PMN-IgG had an underlying immunologic disorder that included immune thrombocytopenic purpura in 5 patients and autoimmune hemolytic anemia in 1 patient. In some patients, elevated PMN-IgG preceded other evidence for immunologic disease. The direct antiglobulin test helped to distinguish neutropenic patients with increased PMN-IgG both from patients with neutropenia due to a known nonimmune disorder and from nonneutropenic patients with rheumatoid arthritis or systemic lupus erythematosis. Each of four patients with increased neutrophil-associated IgG treated with systemic corticosteroids responded clinically with an associated fall in neutrophil IgG and a rise in the circulating neutrophil count. The radiolabeled antiglobulin test appears useful in defining a subpopulation of patients with neutropenia due to an underlying immunologic disorder.

  18. Highly immunoreactive IgG antibodies directed against a set of twenty human proteins in the sera of patients with amyotrophic lateral sclerosis identified by protein array.

    Directory of Open Access Journals (Sweden)

    Caroline May

    Full Text Available Amyotrophic lateral sclerosis (ALS, the most common adult-onset motor neuron disorder, is characterized by the progressive and selective loss of upper and lower motor neurons. Diagnosis of this disorder is based on clinical assessment, and the average survival time is less than 3 years. Injections of IgG from ALS patients into mice are known to specifically mark motor neurons. Moreover, IgG has been found in upper and lower motor neurons in ALS patients. These results led us to perform a case-control study using human protein microarrays to identify the antibody profiles of serum samples from 20 ALS patients and 20 healthy controls. We demonstrated high levels of 20 IgG antibodies that distinguished the patients from the controls. These findings suggest that a panel of antibodies may serve as a potential diagnostic biomarker for ALS.

  19. The Utility of Serum IgG4 Concentrations as a Biomarker

    Directory of Open Access Journals (Sweden)

    Shigeyuki Kawa


    Full Text Available IgG4-related disease is a new disease entity involving IgG4 in its clinical presentation and having 6 characteristic features: (1 systemic involvement; (2 solitary or multiple lesions showing diffuse or localized swelling, masses, nodules, and/or wall thickening on imaging; (3 high serum IgG4 concentration >135 mg/dL; (4 abundant infiltration of lymphoplasmacytes and IgG4-bearing plasma cells; (5 a positive response to corticosteroid therapy; and (6 complications of other IgG4-related diseases. To date, most IgG4-related diseases have been recognized as extrapancreatic lesions of autoimmune pancreatitis. This paper will discuss the utility of IgG4 as a biomarker of IgG4-related diseases, including in the diagnosis of autoimmune pancreatitis and its differentiation from pancreatic cancer, in the prediction of relapse, in the long-term follow-up of patients with autoimmune pancreatitis and normal or elevated IgG4 concentrations, and in patients with autoimmune pancreatitis and extrapancreatic lesions, as well as the role of IgG4 in the pathogenesis of IgG4-related disease.

  20. Neuron-derived IgG protects neurons from complement-dependent cytotoxicity. (United States)

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


    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.

  1. Responses of IgE, IgG1, and IgG4 to concanavalin A-binding Blomia tropicalis antigens in allergic patients

    Directory of Open Access Journals (Sweden)

    K.C. Almeida


    Full Text Available Blomia tropicalis (Bt and Dermatophagoides pteronyssinus (Dp are the prevalent house dust mites in tropical countries and are associated with allergic diseases. Glycosylated antigens are highly immunogenic and involved in different pathologies. We evaluated the presence of IgE, IgG1, and IgG4 to concanavalin A-binding antigens (Bt-Con-A isolated from Bt-total extract in sera of allergic and non-allergic subjects. Bt-total and Bt-Con-A extracts were evaluated by SDS-PAGE and ELISA for reacting with IgE, IgG1, and IgG4 in sera of 121 patients with allergic rhinitis and 36 non-allergic individuals. All subjects were skin prick tested with Bt-total extract and inhibition tests were performed for IgE, IgG1, and IgG4 using both extracts (Bt-total and Bt-Con-A. Skin prick test showed that 58% of the patients were sensitized to Bt (Bt+, with 52% reactive to both mites (Bt and Dp and 6% to Bt only. A broad spectrum of proteins (14-152 kDa was visualized in Bt-total and components >27 kDa for the Bt-Con-A extract. ELISA showed a similar profile of IgE, IgG1 and IgG4 levels in response to Bt-total and Bt-Con-A extracts in different groups, although Bt+ patients showed a lower IgG4 reactivity to Bt-Con-A extract. Specific IgG1 levels were higher in Bt+ patients than in control subjects, and IgG4 levels showed no significant difference among groups. ELISA inhibition showed a partial IgE and total IgG1 and IgG4 cross-reactivity with Dp extract for Bt-total and Bt-Con-A extracts. We conclude that Con-A-binding components isolated from Bt constitute major allergens and are involved in both allergen sensitization (IgE response and homeostasis maintenance (IgG1 and IgG4 responses.

  2. Orbital Pseudotumor: Uncommon Initial Presentation of IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Teresa Carbone


    Full Text Available IgG4-related disease (IgG4-RD encompasses a group of fibroinflammatory conditions recognized in recent times. The main clinical features include variable degrees of tissue fibrosis, tumorlike expansions, perivascular lymphocytic infiltration rich in IgG4-positive plasma cells, and elevated serum IgG4. A case has been reported of an elderly patient with an unexplained unilateral exophthalmia; biopsy was performed and revealed lymphocytic infiltration, suggesting IgG4-RD. High serum levels of IgG4, in association with a good response to steroid therapy and to the exclusion of other diagnoses, confirmed the hypothesis of orbital pseudotumor by IgG4-RD.

  3. A Case of IgG4-Related Lung Disease Presenting as Interstitial Lung Disease. (United States)

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


    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.

  4. Covariance structures of fat and protein influence the estimation of IgG in bovine colostrum. (United States)

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


    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.

  5. 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


    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

  6. Specific IgE, IgG and IgG4 antibodies against house dust mite in patients with bronchial asthma.

    Directory of Open Access Journals (Sweden)



    Full Text Available Serum levels of total IgE, specific IgE, IgG and IgG4 against house dust mite were measured in mite-sensitive asthma patients receiving immunotherapy with house dust. Serum levels of total IgE, mite specific IgE and IgG did not significantly change during the course of hyposensitization. Increased levels of mite specific IgG4 were observed in patients during immunotherapy. The increase in specific IgG4 was dependent on the total dose of house dust administered in both children (r = 0.636, p less than 0.001 and adults (r = 0.629, p less than 0.01. However, the increase of specific IgG4 in adults was not as apparent as in children. These results might suggest that mite specific IgG4 is a useful immunological marker in the immunotherapy for allergic asthma, and that IgG4 antibody acts as a blocking antibody in atopic bronchial asthma.


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


    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. Radioimmunoassay of IgG and IgM rheumatoid factors reacting with human IgG. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Carson, D.A.; Lawrance, S.; Catalano, M.A.; Vaughan, J.H.; Abraham, G.


    Although IgG rheumatoid factor may play a central role in the pathogenesis of rheumatoid arthritis, previously there have been no precise methods for its specific measurement in serum and synovial fluid. This paper describes a solid phase radioimmunoassay for the independent quantification of IgM and IgG rheumatoid factor reacting with the Fc fragment of human IgG. As measured by this assay, serum IgG rheumatoid factor levels differed significantly between patients with seropositive and seronegative rheumatoid arthritis and normal control subjects. In addition, several sera and joint fluids from patients with seropositive rheumatoid arthritis, even without vasculitis, were shown by gel chromatography to have acid-dissociable complexes of IgG rheumatoid factor suggestive of IgG-IgG dimer or trimer formation.

  9. Increased IgG4 responses to multiple food and animal antigens indicate a polyclonal expansion and differentiation of pre-existing B cells in IgG4-related disease


    Culver, EL; Vermeulen, E.; Makuch, M; Leeuwen, A. van; Sadler, R.; Cargill, T; Klenerman, P; Aalberse, RC; van Ham, SM; Barnes, E; Rispens, T


    Background: IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition, characterised by an elevated serum IgG4 concentration and abundant IgG4-positive plasma cells in the involved organs. An important question is whether the elevated IgG4 response is causal or a reflection of immune-regulatory mechanisms of the disease. Objectives: To investigate if the IgG4 response in IgG4-RD represents a generalised polyclonal amplification by examining the response to common environmental ...

  10. IgG Conformer's Binding to Amyloidogenic Aggregates.

    Directory of Open Access Journals (Sweden)

    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.

  11. IgG Conformer's Binding to Amyloidogenic Aggregates (United States)

    Phay, Monichan; Welzel, Alfred T.; Williams, Angela D.; McWilliams-Koeppen, Helen P.; Blinder, Veronika; O'Malley, Tiernan T.; Solomon, Alan; Walsh, Dominic M.; O'Nuallain, Brian


    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. PMID:26367058

  12. 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


    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.

  13. Severe IgG4-Related Disease in a Young Child: A Diagnosis Challenge

    Directory of Open Access Journals (Sweden)

    Susana Corujeira


    Full Text Available Immunoglobulin G4-related disease (IgG4-RD is an increasingly recognized syndrome that can appear with multiple organ involvement, typically with tumor-like swelling, lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, and elevated serum IgG4 concentrations. We report the case of a 22-month-old female child with failure to thrive and recurrent respiratory tract infections since 8 months of age. Physical examination was normal except for pulmonary auscultation with bilateral crackles and wheezes. Laboratory tests revealed elevated erythrocyte sedimentation rate, and elevated serum IgG and IgG4 with polyclonal hypergammaglobulinemia. Thoracic CT and MRI showed multiple mediastinal lymphadenopathies and a nodular posterior mediastinal mass in right paratracheal location with bronchial compression. Initial fine needle aspiration biopsy was compatible with reactive lymphadenopathy but after clinical worsening a thoracoscopic partial resection of the mass was performed and tissue biopsy revealed lymphoplasmacytic infiltrate and increased number of IgG4-positive plasma cells and a ratio of IgG4/IgG positive cells above 40%. Glucocorticoids therapy was started with symptomatic improvement, reduction in the size of the mass, and decrease of serum IgG4 levels after 6 weeks. There are very few reports of IgG4-RD in children. Long-term follow-up is necessary to monitor relapses and additional organ involvement.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Normal pressure hydrocephalus, a possible complication in IgG4-related disease

    Directory of Open Access Journals (Sweden)

    Hiroshi Kobayashi


    Full Text Available We report a 75-year-old man with glucocorticoid-responsive normal pressure hydrocephalus (NPH complicated with tubulointerstitial renal disease, protein-losing gastroenteropathy (PLG and elevated serum IgG4, which might be a possible subset of IgG4-related disease (IgG4-RD. Although either PLG or NPH, especially in combination, has rarely been reported in IgG4-RD, the glucocorticoid-responsive nature of every abnormality observed in the patient supports the diagnosis of IgG4-RD. Of course, pathological confirmation is essential to fulfill the recently raised diagnostic criteria, however, such invasive procedure might not always be indicated in high-risk patients. Our report illustrates that IgG4-RD might be considered as one of the underlying causes and/or the aggravating factors of NPH before shunt operation.

  16. 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


    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.

  17. Elevated serum IgG4 levels in two cases of paragonimiasis (United States)

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


    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

  18. Isolated Mass-Forming IgG4-Related Cholangitis as an Initial Clinical Presentation of Systemic IgG4-Related Disease. (United States)

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


    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.

  19. Increased IgG4 responses to multiple food and animal antigens indicate a polyclonal expansion and differentiation of pre-existing B cells in IgG4-related disease (United States)

    Culver, Emma L; Vermeulen, Ellen; Makuch, Mateusz; van Leeuwen, Astrid; Sadler, Ross; Cargill, Tamsin; Klenerman, Paul; Aalberse, Rob C; van Ham, S Marieke; Barnes, Eleanor; Rispens, Theo


    Background IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition, characterised by an elevated serum IgG4 concentration and abundant IgG4-positive plasma cells in the involved organs. An important question is whether the elevated IgG4 response is causal or a reflection of immune-regulatory mechanisms of the disease. Objectives To investigate if the IgG4 response in IgG4-RD represents a generalised polyclonal amplification by examining the response to common environmental antigens. Methods Serum from 24 patients with IgG4-RD (14 treatment-naive, 10 treatment-experienced), 9 patients with primary sclerosing cholangitis and an elevated serum IgG4 (PSC-high IgG4), and 18 healthy controls were tested against egg white and yolk, milk, banana, cat, peanut, rice and wheat antigens by radioimmunoassay. Results We demonstrated an elevated polyclonal IgG4 response to multiple antigens in patients with IgG4-RD and in PSC-high IgG4, compared with healthy controls. There was a strong correlation between serum IgG4 and antigen-specific responses. Responses to antigens were higher in treatment-naive compared with treatment-experienced patients with IgG4-RD. Serum electrophoresis and immunofixation demonstrated polyclonality. Conclusions This is the first study to show enhanced levels of polyclonal IgG4 to multiple antigens in IgG4-RD. This supports that elevated IgG4 levels reflect an aberrant immunological regulation of the overall IgG4 response, but does not exclude that causality of disease could be antigen-driven. PMID:25646372

  20. Fibrosing variant of Hashimoto thyroiditis is an IgG4 related disease. (United States)

    Deshpande, Vikram; Huck, Amelia; Ooi, Esther; Stone, John H; Faquin, William C; Nielsen, G Petur


    Hashimoto thyroiditis (HT) and the fibrosing variant of Hashimoto thyroiditis (FVHT) are immune-mediated tumefactive lesions of the thyroid. Immunoglobulin G4-related disease (IgG4-RD) is now a widely recognised multi-organ system disease characterised by elevated serum and tissue concentrations of IgG4. In this study, the authors address several unresolved questions pertaining to the relationship between HT and FVHT, and the association of each of these diseases with IgG4-RD. The authors evaluated 28 consecutive cases of HT and nine cases of FVHT. The clinical, demographic and serological data were recorded. The slides were stained immunohistochemically using antibodies to IgG4 and IgG and the quantitative analysis was recorded. Data on thyroid function tests were available on seven cases of FVHT and 14 cases of HT. Based on the availability of data, hypothyroidism was noted in 62% (9/14) of HT and 86% of FVHT (6/7). FVHT demonstrated an exaggerated lobular pattern with lobules separated by cellular storiform-type fibrosis, resembling fibrosis seen in other forms of IgG-RD. The median IgG4 counts per high power field (×40) in HT and FVHT were 2.3 and 22, respectively. The median IgG4:IgG ratios in HT and FVHT were 0.11 and 0.58, respectively. The authors propose that FVHT belongs to the spectrum of IgG4-RD. Although a proportion of cases of HT show elevated numbers of IgG4 positive plasma cells, these cases lack the histological features typically associated with IgG4-RD, and thus the relationship between HT and IgG4-RD remains unproven.

  1. Bilateral Vision Loss Secondary to Pachymeningitis in a Patient with IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Lucas eRamirez


    Full Text Available IgG4-Related Disease is a recently recognized fibroinflammatory condition associated with disease in nearly every organ, including the meninges. A proportion of Idiopathic Hypertrophic Pachymeningitis cases may involve a component of meningeal IgG4-RD. We present a patient with severe bilateral vision loss found to have thickening of the dura mater on MRI, and subsequently diagnosed with IgG4-RD after dural biopsy.

  2. Mitochondrial-dependent Autoimmunity in Membranous Nephropathy of IgG4-related Disease

    Directory of Open Access Journals (Sweden)

    Simona Buelli


    Full Text Available The pathophysiology of glomerular lesions of membranous nephropathy (MN, including seldom-reported IgG4-related disease, is still elusive. Unlike in idiopathic MN where IgG4 prevails, in this patient IgG3 was predominant in glomerular deposits in the absence of circulating anti-phospholipase A2 receptor antibodies, suggesting a distinct pathologic process. Here we documented that IgG4 retrieved from the serum of our propositus reacted against carbonic anhydrase II (CAII at the podocyte surface. In patient's biopsy, glomerular CAII staining increased and co-localized with subepithelial IgG4 deposits along the capillary walls. Patient's IgG4 caused a drop in cell pH followed by mitochondrial dysfunction, excessive ROS production and cytoskeletal reorganization in cultured podocytes. These events promoted mitochondrial superoxide-dismutase-2 (SOD2 externalization on the plasma membrane, becoming recognizable by complement-binding IgG3 anti-SOD2. Among patients with IgG4-related disease only sera of those with IgG4 anti-CAII antibodies caused low intracellular pH and mitochondrial alterations underlying SOD2 externalization. Circulating IgG4 anti-CAII can cause podocyte injury through processes of intracellular acidification, mitochondrial oxidative stress and neoantigen induction in patients with IgG4 related disease. The onset of MN in a subset of patients could be due to IgG4 antibodies recognizing CAII with consequent exposure of mitochondrial neoantigen in the context of multifactorial pathogenesis of disease.

  3. An IgG4-related sclerosing mediastinitis in posterior mediastinum: CT findings

    Directory of Open Access Journals (Sweden)

    Xiaolong Liu


    Full Text Available Immunoglobulin G4 (IgG4-related sclerosing disease, an uncommon disease entity, is known to involve various organs. To our knowledge, few reports have been presented on IgG4-related sclerosing diseases involving the mediastinum, especially the posterior mediastinum. We present a case of IgG4-related sclerosing disease of the posterior mediastinum with imaging findings on computed tomography (CT.

  4. 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


    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.

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

    Directory of Open Access Journals (Sweden)

    Masayuki Ishida


    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.

  6. Effect of the mass of immunoglobulin (Ig)G intake and age at first colostrum feeding on serum IgG concentration in Holstein calves. (United States)

    Osaka, I; Matsui, Y; Terada, F


    Forty-four Holstein calves (19 male and 25 female) were used in this study of the relationships among age at first colostrum feeding, IgG intake, and apparent efficiency of IgG absorption. Time of birth was recorded for each calf and the calves were fed colostrum ad libitum after birth at either 0930 or 1630 h. Blood samples were collected immediately before and 24h after colostrum feeding. Data from calves were then categorized into 4 groups representing time from birth to colostrum feeding: A=fed within 1h (n=5); B=fed from 1 to 6h (n=10); C=fed from 6 to 12 h (n=21); and D=fed from 12 to 18 h (n=8) after birth. Average total intake of colostrum was 3.6 ± 0.1L. Over 80% of the calves consumed ≥3 L of colostrum. Apparent efficiency of IgG absorption declined remarkably 12 h after birth. Mean apparent efficiency of absorption of IgG in group D (15.8 ± 3.0%) was lower than that in groups A (30.5 ± 3.9%) and B (27.4 ± 2.8%). Serum IgG concentration in calves was positively correlated with IgG intake in all groups. The relationship between mass of IgG consumed and calf serum IgG at 24 h was different for each time of colostrum feeding, with only limited differences observed between groups A and B. We concluded that failure of transfer of passive immunity in newborn calves may be avoided if calves consume ≥3 L of colostrum with IgG concentration >40 mg/mL within 6 h after birth. These findings help define the opportunity to minimize failure of transfer of passive immunity to newborn calves under management programs similar to those used on commercial dairy farms.

  7. 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

  8. Purification of rabbit IgG, obtention of sheep anti rabbit IgG and their use in radioimmunoassay of avian leukosis virus p15

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, Tomoko; Ogata, Hiroe; Veiga, Silvio Sanches; Nogueira, Zelia Maria [Instituto de Quimica, Sao Paulo, SP (Brazil); Souza Felippe, Julia Maria Martins de [Instituto Adolfo Lutz, Sao Paulo, SP (Brazil). Div. de Virus


    Immunoglobulin from rabbit serum was purified by ammonium sulphate precipitation followed by chromatography on DEA-cellulose and gel filtration in Sephadex G-200. The efficiency of all steps was followed by protein determination and profiles in sodium dodecyl-sulphate polyacrylamide gel electrophoresis. Sheeps were immunized with purified IgG. The deep anti-rabbit IgG titre was evaluated by double immuno diffusion gel plates. The system rabbit serum vs sheep anti-rabbit IgG serum was used as precipitating system in radioimmunoassay of the retrovirus immunogens, in this case, p15 of avian leukosis virus. (author). 19 refs., 4 figs., 3 tabs.

  9. Prevalence of IgG4-Related Disease in Japan Based on Nationwide Survey in 2009

    Directory of Open Access Journals (Sweden)

    Kazushige Uchida


    Full Text Available The number of patients with autoimmune pancreatitis who visited hospitals in Japan in 2007 was approximately 2709 (95% confidence interval; range 2540–3040. Because IgG4-related disease is a new clinical entity, there are no data with regard to its prevalence. To estimate the number of patients with IgG4-related disease in Japan, we randomly selected hospitals using stratification and asked them how many patients they had with IgG4-related disease in 2009. The number of patients with Mikulicz’s disease, IgG4-related retroperitoneal fibrosis, IgG4-related renal disease, IgG4-related pulmonary disease, and IgG4-related lymphadenopathy who visited hospitals in Japan in 2009 was approximately 4304 (95% confidence interval; range 3360–5048, 272 (95% confidence interval; range 264–306, 57 (95% confidence interval; range 47–66, 354 (95% confidence interval; range 283–424, and 203 (95% confidence interval; range 187–240, respectively. The total number of patients with IgG4-related disease without autoimmune pancreatitis in Japan was approximately 5190 (95% confidence interval; range 4141–6084. The male : female ratio was 1 : 0.77, and the average of age of disease onset was 58.8 years. The total number of patients with IgG4-related disease in Japan in 2009, including autoimmune pancreatitis, was approximately 8000.

  10. Histologically confirmed isolated IgG4-related hypophysitis: two case reports in young women


    Sosa, Gabriela Alejandra; Bell, Soledad; Christiansen, Silvia Beatriz; Pietrani, Marcelo; Glerean, Mariela; Loto, Monica; Lovazzano,Soledad; Carrizo, Antonio; Ajler, Pablo; Fainstein Day, Patricia


    Summary IgG4-related hypophysitis is a recently described entity belonging to the group of IgG4-related diseases. Many other organs can also be affected, and it is more common in older men. To date, 32 cases of IgG4-related hypophysitis have been reported in the literature, 11 of which included confirmatory tissue biopsy and the majority affecting multiple organs. The aim of this report is to present two cases of biopsy-proven IgG4-related hypophysitis occurring in two young female patients w...

  11. Granuloma faciale: a cutaneous lesion sharing features with IgG4-associated sclerosing diseases. (United States)

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


    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

  12. [Two cases of IgG4-related disease with pleural effusion]. (United States)

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


    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.

  13. 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


    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.


    Directory of Open Access Journals (Sweden)

    Milena Karcheva


    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.

  15. 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


    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...... and Results: Animals were selected from two herds with long-term infection (years) and two herds recently infected (...) was calculated for IgG (IgG-AI), IgG(1) (IgG(1)-AI) and IgG(2) (IgG(2)-AI). The mean IgG-AI for suspected carrier animals with either persistently high (group 1) or persistently high to medium high (group 2) antibody levels was significantly (P = 0.003) higher (32.1% and 38.4%) than for acutely infected animals...

  16. Evidence for shared idiotypy expressed by the IgM, IgG, and IgA serum proteins of a patient with a complex multiple paraprotein disorder

    Energy Technology Data Exchange (ETDEWEB)

    Hopper, J.E.; Haren, J.M.; Kmiecik, T.E.


    The results of a comparative idiotypic analysis of multiple Ig paraproteins isolated from the serum of an individual patient, Ca, with Sjoegren's syndrome and Waldenstroem's macroglobulinemia are reported. At initial presentation, Ca serum was found to contain two major paraproteins, an IgMk and an IgGk, together with a small elevation in the level of IgA protein. The patient's clinical course was characterized by dramatic and opposing changes in the respective serum levels of the IgMk and IgGk paraproteins over an extended time period that coincided in part with received chemotherapy. Idiotypic antigenic analysis of the IgMk and IgGk paraproteins revealed that the two monotypic proteins shared identical idiotypic determinants. The Ca IgA serum fraction, specifically isolated by an immunoabsorbent and free of any IgG and IgM, was shown to possess idiotypic determinants identical to the IgG and IgM proteins. In extensive tests of specificity, the idiotypic determinants shared by Ca IgM, IgG, and IgA proteins were not present in large excesses of heterologous IgM and IgG, nor on Ig molecules contained in a large number of normal and myeloma sera.

  17. Renal manifestations of IgG4-related systemic disease%IgG4相关系统性疾病的肾脏损害

    Institute of Scientific and Technical Information of China (English)



    IgG4相关系统性疾病(IgG4-related systemic disease,IgG4-RSD)是一组最近认识的临床综合征,可累及多个器官,胰腺最常受累,主要表现为血清IgG4升高,受累组织弥漫IgG4阳性浆细胞浸润.本文主要介绍IgG4-RSD累及肾脏时的临床表现、影像学、实验室检查、病理特点及治疗情况.%IgG4-related systemic disease represents a recently recognized group of multi-organ diseases characterized by a high level of serum IgG4 and dense infiltration of IgG4-positive cells into multiple organs. The most commonly involved organ was pancreas. In this article,the relevant literatures about the renal involvements of IgG4-related systemic disease will be reviewed.

  18. Analysis of clinicopathological characters for IgG4-related disease%IgG4相关性疾病临床病理学特征分析

    Institute of Scientific and Technical Information of China (English)

    钟卫祥; 孙柯; 滕晓东


    目的:探讨IgG4相关性疾病的病理学形态、免疫表型特征。方法观察12例IgG4相关性疾病的镜下特点,结合免疫组化EnVision两步法染色检测IgG、IgG4、CD138、CD34的表达,分析IgG4相关性疾病的病理学形态特征。结果 IgG4相关性疾病主要表现为组织弥漫性纤维化;伴大量淋巴细胞、浆细胞浸润,围绕血管神经分布;闭塞性静脉炎形成,免疫组化EnVision两步法染色IgG4阳性浆细胞与IgG阳性浆细胞比例>40%。结论 IgG4相关性疾病临床特点和影像学无特异性,易误诊为肿瘤,术前血清IgG4检测可作为疑似病例的首选方法。%Purpose To study the clinicopathological features and immunohistochemical characteristics of IgG4-related disease. Meth-ods The microscopic characteristics and immunohistochemical staining (EnVision) of IgG, IgG4, CD138 and CD34 have been per-formed on 12 cases of IgG4-related disease. Results IgG4-related disease were characterized by diffuse fibrosis, accompanied with in-filtrating of dense lymphocytes and plasma cells surrounding neurovascular and occlusive phlebitis. Immunohistochemical staining re-sults showed the ratio of IgG4+/IgG+ cells were over 40%. Conclusions IgG4-related disease is absent of characteristic clinical and radiographic features and is easily misdiagnosed as tumor. Preoperative serum IgG4 detection could be used as the prior examina-tion for the suspected cases.

  19. IgG4-Associated Cholangitis--A Mimic of PSC. (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


    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.

  20. [IgM, IgG and IgG subclass antibodies to herpes simplex virus in persons of different ages]. (United States)

    Zazimko, L A; Kuzenkova, A V; Ivanova, I A; Bashukova, S S; Rybakov, V P; Klimovich, V B; Shitikova, G S


    IgM, IgG antibodies to herpes simplex virus and their subclases were investigated in 565 subjects of different age tested at virological laboratories of St. Petersburg in 1996-1997. The majority of these subjects had a history of herpes infection and 21.5% had IgM antibodies to herpes simplex virus (HSV), marker of acute herpetic infection. Besides IgM, IgG1 antibodies can be referred to early antibodies appearing during the acute stage of herpetic infection. The predominant subclass was HSV IgG3 antibodies. As for IgG4, they were completely absent in infants aged under 1 year, were detected in 6.2% children aged under 14 years, and were present in 12.2-12.5% adults.

  1. Comparison of IgM, IgG1 and IgG2 responses to Trichinella spiralis and Trichinella britovi in swine

    Directory of Open Access Journals (Sweden)

    Serrano F.J


    Full Text Available Pigs infected with T. spiralis and T. britovi were followed by double (lgG and triple antibody ELISA (IgG1, lgG 2 and IgM during a 12-week-period. Specific IgG and IgG1 responses were similar and showed a significant relation with the infecting doses and intensity of infection. Response to T. britovi was slightly lower than in groups infected with the same dose of T. spiralis. lgG 2 response was weak and almost undetectable in the lowest infected pigs, but relationship with the intensity of infection was unclear. IgM antibodies showed rapid but transient increases, generally simultaneous to peaks of IgG response.

  2. Histopathologic Overlap between Fibrosing Mediastinitis and IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Tobias Peikert


    Full Text Available Fibrosing mediastinitis (FM and IgG4-related disease (IgG4-RD are two fibroinflammatory disorders with potentially overlapping clinical and radiological features. In this paper, we looked for histopathologic features of IgG4-RD and enumerated infiltrating IgG4-positive plasma cells within mediastinal tissue biopsies from FM patients. We identified 15 consecutive FM surgical mediastinal tissue biopsies between 1985 and 2006. All patients satisfied the clinical and radiological diagnostic criteria for FM. All patients had either serological or radiological evidence of prior histoplasmosis or granulomatous disease, respectively. Formalin-fixed paraffin-embedded tissue sections of all patients were stained for H&E, IgG, and IgG4. Three samples met the predefined diagnostic criteria for IgG4-RD. In addition, characteristic histopathologic changes of IgG4-RD in the absence of diagnostic numbers of tissue infiltrating IgG4-positive plasma cells were seen in a number of additional cases (storiform cell-rich fibrosis in 11 cases, lymphoplasmacytic infiltrate in 7 cases, and obliterative phlebitis/arteritis in 2 cases. We conclude that up to one-third of histoplasmosis or granulomatous-disease-associated FM cases demonstrate histopathological features of IgG4-RD spectrum. Whether these changes occur as the host immune response against Histoplasma or represent a manifestation of IgG4-RD remains to be determined. Studies to prospectively identify these cases and evaluate their therapeutic responses to glucocorticoids and/or other immunosuppressive agents such as rituximab are warranted.

  3. 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


    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.

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

    Directory of Open Access Journals (Sweden)

    María T. Bourlon


    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.

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

    DEFF Research Database (Denmark)

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


    The neonatal Fc receptor (FcRn) directs the transfer of maternal immunoglobulin G (IgG) antibodies across the placenta and thus provides the fetus and newborn with passive protective humoral immunity. Pathogenic maternal IgG antibodies will also be delivered via the placenta and can cause alloimm...

  6. Enhanced HIV-1 neutralization by a CD4-VH3-IgG1 fusion protein

    Energy Technology Data Exchange (ETDEWEB)

    Meyuhas, Ronit; Noy, Hava; Fishman, Sigal [Laboratory of Immunology, MIGAL, P.O. Box 831, Kiryat Shmona 11016 (Israel); Margalit, Alon [Laboratory of Immunology, MIGAL, P.O. Box 831, Kiryat Shmona 11016 (Israel); Department of Biotechnology, Tel-Hai Academic College, Upper Galilee 12210 (Israel); Montefiori, David C. [Department of Surgery, Duke University Medical Center, Durham, NC 27710 (United States); Gross, Gideon, E-mail: [Laboratory of Immunology, MIGAL, P.O. Box 831, Kiryat Shmona 11016 (Israel); Department of Biotechnology, Tel-Hai Academic College, Upper Galilee 12210 (Israel)


    HIV-1 gp120 is an alleged B cell superantigen, binding certain VH3+ human antibodies. We reasoned that a CD4-VH3 fusion protein could possess higher affinity for gp120 and improved HIV-1 inhibitory capacity. To test this we produced several human IgG1 immunoligands harboring VH3. Unlike VH3-IgG1 or VH3-CD4-IgG1, CD4-VH3-IgG1 bound gp120 considerably stronger than CD4-IgG1. CD4-VH3-IgG1 exhibited {approx}1.5-2.5-fold increase in neutralization of two T-cell laboratory-adapted strains when compared to CD4-IgG1. CD4-VH3-IgG1 improved neutralization of 7/10 clade B primary isolates or pseudoviruses, exceeding 20-fold for JR-FL and 13-fold for Ba-L. It enhanced neutralization of 4/8 clade C viruses, and had negligible effect on 1/4 clade A pseudoviruses. We attribute this improvement to possible pairing of VH3 with CD4 D1 and stabilization of an Ig Fv-like structure, rather than to superantigen interactions. These novel findings support the current notion that CD4 fusion proteins can act as better HIV-1 entry inhibitors with potential clinical implications.


    NARCIS (Netherlands)



    IgG(+) cells were detected in the bursa of Fabricius after hatching by immunofluorescence staining of single cells and immunohistologic studies using mAb anti-Ig gamma-heavy chain. The frequency of IgG(+) cells in the bursa increased rapidly immediately after hatching. In histologic studies, most of

  8. Sialylation of IgG Fc domain impairs complement-dependent cytotoxicity. (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


    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.

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

    Directory of Open Access Journals (Sweden)

    Angel Guevara E.


    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.

  10. Bovine IgG subclasses and fertility of Echinococcus granulosus hydatid cysts. (United States)

    Riesle, Silke; García, María Pía; Hidalgo, Christian; Galanti, Norbel; Saenz, Leonardo; Paredes, Rodolfo


    Hydatidosis is an important zoonotic disease of worldwide distribution, causing important health problems to humans and major economical losses in infected livestock. Echinococcus granulosus, the etiological agent of hydatid disease, induces a humoral immune response in the intermediate host (human and herbivorous) against hydatid cyst antigens. Specifically, IgGs are found in the laminar and germinal layers and inside the lumen of fertile and infertile hydatid cysts. In the germinal layer of infertile cysts IgGs are found in an order of magnitude greater than in the germinal layer of fertile cysts; a fraction of those IgGs are associated with high affinity to germinal layer proteins, suggesting their binding to specific parasite antigens. We have previously shown that those immunoglobulins, bound with high affinity to the germinal layer of hydatid cysts, induce apoptosis leading to cyst infertility. In the present work the presence of IgG1 and IgG2 subclasses in the germinal layer of both fertile and infertile hydatid cysts is reported. IgG1 is the most relevant immunoglobulin subclass present in the germinal layer of infertile cysts and bound with high affinity to that parasite structure. Contrarily, though the IgG2 subclass was also found in the germinal and adventitial layers, those immunoglobulins show low affinity to parasite antigens. We propose that the binding of an IgG1 subclass to parasite antigens present in the germinal layer is involved in the mechanism of cyst infertility.

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


    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.

  12. [IgG4-related disease is a rare differential diagnosis of malignant and autoimmune diseases]. (United States)

    Storgaard, Anders; Detlefsen, Sönke


    Immunoglobulin G4-related disease (IgG4-RD) is an inflammatory and fibrotic disease with the potential to produce diffuse enlargement, massforming lesions or stenoses in a wide range of organs. Elevation of serum IgG4 concentration and high levels of IgG4-positive cells in the inflamed tissue are common denominators. Type 1 autoimmune pancreatitis is one of the main manifestations, and its recognition preceded the definition of IgG4-RD as a novel clinical entity. The aetiology, pathophysiology, epidemiology and clinical long-term outcome of IgG4-RD are not fully elucidated. Steroids are effective in most patients, sometimes combined with other antiinflammatory drugs.

  13. Avaliação das subclasses IgG1 e IgG3 na doença hemolítica perinatal Assessment of IgG1 and IgG3 subclasses in perinatal hemolytic disease

    Directory of Open Access Journals (Sweden)

    Maria A. Araújo


    Full Text Available A doença hemolítica perinatal (DHPN ainda é um problema clínico. Nenhum teste isolado prediz, com segurança, a gravidade do quadro hemolítico. O objetivo do presente estudo foi determinar as subclasses de anticorpos IgG1 e IgG3 por citometria de fluxo no soro de 42 gestantes isoimunizadas e correlacionar os dados obtidos com a gravidade da DHPN. A distribuição dos fetos ou neonatos segundo a gravidade do quadro hemolítico evidenciou 13 casos com doença leve, 16 casos com doença moderada e 13 com doença grave. As subclasses foram detectadas em 33/42 (79% amostras. A subclasse IgG1, isoladamente, foi evidenciada em 14/33 (42,4% casos. Na relação entre gravidade da doença e subclasses de IgG, observou-se que IgG1 isolada foi encontrada em todos os grupos, e os valores da mediana de intensidade de fluorescência (MIF foram significativamente mais altos nas formas mais graves da DHPN (pThe hemolytic disease of the newborn (HDN continues to be a clinical problem in spite of prophylaxis. To date, none of the available tests, developed to predict the severity of HDN, has provided complete reliability. The objective of the present study was to determine the IgG1 and IgG3 subclasses in 42 isoimmunized pregnant women, and to correlate them with clinical severity of hemolytic disease. The IgG subclasses were determined employing flow cytometry. According to the clinical severity of HDN, fetuses and newborn babies were classified as 13 mild, 16 moderate and 13 severe cases. The IgG subclasses were detected in 33 of the 42 pregnant women. Of these, IgG1 was predominant in 72.7% of the cases; either isolated (42.4% or in association with IgG3 (30.3%. IgG1 was present in all the three clinical severity categories, however, its values were significantly higher in cases with greater clinical severity of HDN (p<0.01. On the other hand, the distribution of IgG3 values within each group was not statistically significant (p=0.11. IgG3 seems to be more

  14. Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. (United States)

    van der Neut Kolfschoten, Marijn; Schuurman, Janine; Losen, Mario; Bleeker, Wim K; Martínez-Martínez, Pilar; Vermeulen, Ellen; den Bleker, Tamara H; Wiegman, Luus; Vink, Tom; Aarden, Lucien A; De Baets, Marc H; van de Winkel, Jan G J; Aalberse, Rob C; Parren, Paul W H I


    Antibodies play a central role in immunity by forming an interface with the innate immune system and, typically, mediate proinflammatory activity. We describe a novel posttranslational modification that leads to anti-inflammatory activity of antibodies of immunoglobulin G, isotype 4 (IgG4). IgG4 antibodies are dynamic molecules that exchange Fab arms by swapping a heavy chain and attached light chain (half-molecule) with a heavy-light chain pair from another molecule, which results in bispecific antibodies. Mutagenesis studies revealed that the third constant domain is critical for this activity. The impact of IgG4 Fab arm exchange was confirmed in vivo in a rhesus monkey model with experimental autoimmune myasthenia gravis. IgG4 Fab arm exchange is suggested to be an important biological mechanism that provides the basis for the anti-inflammatory activity attributed to IgG4 antibodies.

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

    CERN Document Server

    de Thier, P


    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...

  16. First case of IgG4-related sclerosing cholangitis associated with autoimmune hemolytic anemia. (United States)

    Masutani, Hironori; Okuwaki, Kosuke; Kida, Mitsuhiro; Yamauchi, Hiroshi; Imaizumi, Hiroshi; Miyazawa, Shiro; Iwai, Tomohisa; Takezawa, Miyoko; Koizumi, Wasaburo


    To our knowledge, patients with immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) associated with autoimmune hemolytic anemia (AIHA) have not been reported previously. Many patients with IgG4-SC have autoimmune pancreatitis (AIP) and respond to steroid treatment. However, isolated cases of IgG4-SC are difficult to diagnose. We describe our experience with a patient who had IgG4-SC without AIP in whom the presence of AIHA led to diagnosis. The patient was a 73-year-old man who was being treated for dementia. Liver dysfunction was diagnosed on blood tests at another hospital. Imaging studies suggested the presence of carcinoma of the hepatic hilus and primary sclerosing cholangitis, but a rapidly progressing anemia developed simultaneously. After the diagnosis of AIHA, steroid treatment was begun, and the biliary stricture improved. IgG4-SC without AIP was thus diagnosed.

  17. IgG and IgG2 antibodies from cattle naturally infected with Anaplasma marginale recognize the recombinant vaccine candidate antigens VirB9, VirB10, and elongation factor-Tu

    Directory of Open Access Journals (Sweden)

    Flábio R Araújo


    Full Text Available Anaplasma marginale is an important vector-borne rickettsia of ruminants in tropical and subtropical regions of the world. Immunization with purified outer membranes of this organism induces protection against acute anaplasmosis. Previous studies, with proteomic and genomic approach identified 21 proteins within the outer membrane immunogen in addition to previously characterized major surface protein1a-5 (MSP1a-5. Among the newly described proteins were VirB9, VirB10, and elongation factor-Tu (EF-Tu. VirB9, VirB10 are considered part of the type IV secretion system (TFSS, which mediates secretion or cell-to-cell transfer of macromolecules, proteins, or DNA-protein complexes in Gram-negative bacteria. EF-Tu can be located in the bacterial surface, mediating bacterial attachment to host cells, or in the bacterial cytoplasm for protein synthesis. However, the roles of VirB9, VirB10, and TFSS in A. marginale have not been defined. VirB9, VirB10, and EF-Tu have not been explored as vaccine antigens. In this study, we demonstrate that sera of cattle infected with A. marginale, with homologous or heterologous isolates recognize recombinant VirB9, VirB10, and EF-Tu. IgG2 from naturally infected cattle also reacts with these proteins. Recognition of epitopes by total IgG and by IgG2 from infected cattle with A. marginale support the inclusion of these proteins in recombinant vaccines against this rickettsia.

  18. Progress in diagnosis and treatment of IgG4-related hepatobiliary diseases%lgC4相关肝胆疾病诊疗进展

    Institute of Scientific and Technical Information of China (English)

    李萍; 李永哲


    IgG4相关性疾病是一类以淋巴浆细胞性炎症为主,伴血清和组织中IgG4增多并累及多器官或组织的慢性进行性全身性炎性疾病,累及肝胆胰腺系统时称之为IgG4相关肝胆疾病。简述了IgG4相关自身免疫性胰腺炎、IgG4相关硬化性胆管炎、IgG4相关自身免疫性肝炎的临床表现和实验室检查等方面。准确识别IgG4相关肝胆疾病的各个实验室结果,并正确诊断此类疾病,有助于避免不必要的手术和错误的治疗。%IgG4-related diseases are a class of chronic,progressive,systemic inflammatory disorders that are characterized by lymphoplas-macytic inflammation,as well as elevated IgG4 levels in serum and tissue,and may involve multiple organs or tissues.When involving the pancreas,liver,and biliary tracts,they are called IgG4-related hepatobiliary diseases.IgG4-related autoimmune pancreatitis,IgG4-re-lated sclerosing cholangitis,and IgG4-associated autoimmune hepatitis are reviewed in terms of their clinical manifestations and laboratory findings.Accurate identification of the laboratory results for IgG4-related hepatobiliary diseases and correct diagnosis of these diseases help to avoid unnecessary surgery and wrong treatment.

  19. 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)



    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.

  20. Circulating IgG autoantibodies to IgE in atopic syndromes. (United States)

    Quinti, I; Brozek, C; Wood, N; Geha, R S; Leung, D Y


    Sera from nonatopic healthy donors and patients with hyper-IgE syndrome, allergic respiratory disease, i.e., allergic rhinitis and asthma, and atopic dermatitis were assayed for the presence of IgG and IgM antibodies to IgE. The assay used was based on an ELISA method that measured the binding of IgG or IgM in test sera to myeloma IgE (PS)-coated microtiter wells. The levels of IgG anti-IgE but not of IgM anti-IgE were elevated in patient sera of all three categories tested. The same sera failed to demonstrate increased levels of IgG anti-IgM or IgG anti-IgA. Significant IgG anti-IgE activity remained after absorption of patient sera over pooled human IgG F(ab')2 Sepharose. The IgG anti-IgE activity appeared to be directed toward the Fc portion of IgE because absorption of positive sera over IgE (ADZ) Sepharose but not over myeloma IgG Sepharose completely removed their reactivity with IgE (PS) and because sera from atopic individuals but not from normal subjects contained IgG anti-IgE activity against the protein backbone of the Fc portion of IgE synthesized from a fragment of the cloned gene of human myeloma IgE (ND) heavy chain. Regression analysis demonstrated a weak but significant correlation (r = 0.31; p less than 0.05) between serum IgE levels and IgG anti-IgE activity. Fractionation of sera from the three patient categories by gel filtration over Sepharose 6B revealed that IgG anti-IgE activity was present both as monomeric IgG and in IgE containing immune complexes (IC). Intermediate molecular size IC (between 7S and 19S) were present in all three patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)


    Directory of Open Access Journals (Sweden)

    Fernanda S. NASCIMENTO


    Full Text Available SUMMARY Cerebral toxoplasmosis can be highly debilitating and occasionally fatal in persons with immune system deficiencies. In this study, we evaluated the Toxoplasma gondii-specific IgG subclass antibody response in 19 cerebrospinal fluid (CSF samples from patients with cerebral toxoplasmosis who had a positive IgG anti-T. gondii ELISA standardized with a cyst antigen preparation. There were no significant differences between the rates of positivity and the antibody concentrations (arithmetic means of the ELISA absorbances, MEA for IgG1 and IgG2, but the rates of positivity and MEA values for these two IgG subclasses were significantly higher than those for IgG3 and IgG4. The marked IgG2 response in CSF from patients with cerebral toxoplasmosis merits further investigation.


    Nascimento, Fernanda S; Suzuki, Lisandra A; Branco, Nilson; Franco, Regina M B; Andrade, Paula D; Costa, Sandra C B; Pedro, Marcelo N; Rossi, Cláudio L


    Cerebral toxoplasmosis can be highly debilitating and occasionally fatal in persons with immune system deficiencies. In this study, we evaluated the Toxoplasma gondii-specific IgG subclass antibody response in 19 cerebrospinal fluid (CSF) samples from patients with cerebral toxoplasmosis who had a positive IgG anti-T. gondii ELISA standardized with a cyst antigen preparation. There were no significant differences between the rates of positivity and the antibody concentrations (arithmetic means of the ELISA absorbances, MEA) for IgG1 and IgG2, but the rates of positivity and MEA values for these two IgG subclasses were significantly higher than those for IgG3 and IgG4. The marked IgG2 response in CSF from patients with cerebral toxoplasmosis merits further investigation.

  3. Igg Subclasses Targeting the Flagella of Salmonella enterica Serovar Typhimurium Can Mediate Phagocytosis and Bacterial Killing (United States)

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


    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

  4. 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


    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.

  5. Enhanced FCGR2A and FCGR3A signaling by HIV viremic controller IgG (United States)

    Alvarez, Raymond A.; Maestre, Ana M.; Durham, Natasha D.; Barria, Maria Ines; Ishii-Watabe, Akiko; Tada, Minoru; Hotta, Mathew T.; Rodriguez-Caprio, Gabriela; Fierer, Daniel S.; Fernandez-Sesma, Ana; Simon, Viviana; Chen, Benjamin K.


    HIV-1 viremic controllers (VC) spontaneously control infection without antiretroviral treatment. Several studies indicate that IgG Abs from VCs induce enhanced responses from immune effector cells. Since signaling through Fc-γ receptors (FCGRs) modulate these Ab-driven responses, here we examine if enhanced FCGR activation is a common feature of IgG from VCs. Using an infected cell–based system, we observed that VC IgG stimulated greater FCGR2A and FCGR3A activation as compared with noncontrollers, independent of the magnitude of HIV-specific Ab binding or virus neutralization activities. Multivariate regression analysis showed that enhanced FCGR signaling was a significant predictor of VC status as compared with chronically infected patients (CIP) on highly active antiretroviral therapy (HAART). Unsupervised hierarchical clustering of patient IgG functions primarily grouped VC IgG profiles by enhanced FCGR2A, FCGR3A, or dual signaling activity. Our findings demonstrate that enhanced FCGR signaling is a common and significant predictive feature of VC IgG, with VCs displaying a distinct spectrum of FCGR activation profiles. Thus, profiling FCGR activation may provide a useful method for screening and distinguishing protective anti-HIV IgG responses in HIV-infected patients and in monitoring HIV vaccination regimens.

  6. Concurrent systemic AA amyloidosis can discriminate primary sclerosing cholangitis from IgG4-associated cholangitis. (United States)

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


    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.

  7. Myocarditis in different experimental models infected by Trypanosoma cruzi is correlated with the production of IgG1 isotype. (United States)

    Caldas, Ivo Santana; Diniz, Livia de Figueiredo; Guedes, Paulo Marcos da Matta; Nascimento, Álvaro Fernando da Silva do; Galvão, Lúcia Maria da Cunha; Lima, Wanderson Geraldo de; Caldas, Sérgio; Bahia, Maria Terezinha


    This study was designed to verify the relationship between IgG antibodies isotypes and myocarditis in Trypanosoma cruzi infection using mice and dogs infected with different T. cruzi strains. The animals were infected with benznidazole-susceptible Berenice-78 and benznidazole-resistant AAS and VL-10 strains. The IgG subtypes were measured in serum samples from dogs (IgG, IgG1, and IgG2) and mice (IgG, IgG1, IgG2a, and IgG2b). The infection of dogs with VL-10 strain induced the highest levels of heart inflammation while intermediate and lower levels were detected with Berenice-78 and AAS strains, respectively. Similar results were found in mice infected with VL-10, but not in those infected with AAS or Berenice-78 strains. The AAS strain induced higher levels of heart inflammation in mice, while Berenice-78 strain was not able to induce it. Correlation analysis between myocarditis and antibody reactivity index revealed very interesting results, mainly for IgG and IgG1, the latter being the most exciting. High IgG1 showed a significant correlation with myocarditis in both experimental models, being more significant in dogs (r=0.94, pmyocarditis intensity in Chagas disease.

  8. IgG4-Related Hypophysitis: Case Report and Literature Review. (United States)

    Decker, Lauren; Crawford, Angela M; Lorenzo, Gamaliel; Stippler, Martina; Konstantinov, Konstantin N; SantaCruz, Karen


    IgG4-related hypophysitis is a rare, inflammatory process of the pituitary that mimics more commonly seen pituitary tumors. We report a case of IgG4-related hypophysitis in a 16-year-old female with diabetes insipidus who was found to have IgG4-related hypophysitis based on tissue diagnosis. This entity has not been previously described in a pediatric patient. Recognition of certain inflammatory processes of the pituitary may lead to alternative means of diagnosis and medical management without a biopsy.

  9. Distinct histopathological features of Hashimoto's thyroiditis with respect to IgG4-related disease. (United States)

    Li, Yaqiong; Zhou, Gengyin; Ozaki, Takashi; Nishihara, Eijun; Matsuzuka, Fumio; Bai, Yanhua; Liu, Zhiyan; Taniguchi, Emiko; Miyauchi, Akira; Kakudo, Kennichi


    A form of Hashimoto's thyroiditis with lymphoplasmacytic sclerosing changes and increased numbers of IgG4-positive plasma cells has recently been reported in the literature. These histopathological features suggest that this subtype of Hashimoto's thyroiditis may be closely related to IgG4-related disease. Therefore, this unique form of IgG4-related Hashimoto's thyroiditis, which is referred to as IgG4 thyroiditis, has its own clinical, serological, and sonographic features that are distinct from those associated with non-IgG4 thyroiditis. IgG4 thyroiditis shares similarities with the well-known fibrous variant of Hashimoto's thyroiditis; however, the detailed histopathological features of IgG4 thyroiditis have not been well established. Based on immunostaining results, 105 patients with Hashimoto's thyroiditis were divided into an IgG4 thyroiditis group (n=28) and a non-IgG4 thyroiditis group (n=77). As in our previous reports, IgG4 thyroiditis was associated with a patient population of a younger age, a lower female-to-male ratio, rapid progression, higher levels of thyroid autoantibodies, subclinical hypothyroidism, and diffuse sonographic echogenicity. Histopathologically, this group revealed severe lymphoplasmacytic infiltration, dense stromal fibrosis, marked follicular cell degeneration, numerous micro-follicles, and notable giant cell/histiocyte infiltration. Importantly, the IgG4-related group did not completely overlap with fibrous variant of Hashimoto's thyroiditis. Four cases (14%) in the IgG4 thyroiditis group presented only mild fibrosis in the stroma, whereas 29 cases (38%) in the non-IgG4 thyroiditis group met the diagnostic criteria for fibrous variant of Hashimoto's thyroiditis. Furthermore, we observed three patterns of stromal fibrosis in Hashimoto's thyroiditis: interfollicular fibrosis, interlobular fibrosis, and scar fibrosis. The IgG4 thyroiditis group was significantly associated with the presence of predominant interfollicular fibrosis. In

  10. Development time of IgG antibodies to West Nile virus. (United States)

    Papa, Anna; Danis, Kostas; Tsergouli, Katerina; Tsioka, Katerina; Gavana, Elpida


    Following an outbreak of West Nile virus (WNV) infections in Greece during summer/autumn 2010, a study was conducted to investigate the patterns of WNV IgG reactivity in 255 patients with respect to the day of illness and the type of clinical syndrome. IgG antibodies were detectable after a mean of 8.1 ± 4.9 and 12.6 ± 11.3 days after onset of illness in neuroinvasive and non-neuroinvasive cases, respectively (p < 0.001), suggesting that a delay in the development of WNV IgG antibodies is seen in non-neuroinvasive cases.

  11. Immunoglobulin G4-related cholangitis: a variant of IgG4-related systemic disease. (United States)

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


    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

  12. A circulating complex between ASAT and IgG in serum in an apparently healthy woman. (United States)

    Fex, G; Berntorp, K


    An elevated level of serum aspartate aminotransferase (ASAT) activity in a subjectively healthy woman was shown to be due to circulating ASAT:IgG complexes. The complexes were demonstrated by taking advantage of the specific interaction between protein A and IgG. Thus, greater than 90% of the patient's ASAT activity in serum could be bound to protein A-Sepharose demonstrating that nearly all the patient's serum ASAT was complexed to IgG. The ASAT-binding capacity of patient serum was calculated as approximately 850 micrograms ASAT/l which corresponds to about 0.01% of patient's IgG.

  13. Colovesical fistula caused by glucocorticoid therapy for IgG4-related intrapelvic mass



    IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that can occur in almost all systemic organs and generally responds to corticosteroid treatment. We report a rare case of an IgG4-related intrapelvic mass lesion that responded to steroid therapy but caused a fistula between the sigmoid colon and bladder. A 71-year-old man was followed after treatment for hepatocellular carcinoma. Follow-up computed tomography (CT) incidentally depicted left hydronephrosis with an...

  14. Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease. (United States)

    Beltrame, Rafael Coimbra Ferreira; Friderichs, Maurício; Fior, Bárbara Rayanne; Schaefer, Pedro Guilherme; Thomé, Gustavo Gomes; Silva, Dirceu Reis da; Barros, Elvino José Guardão; Seligman, Renato; Veronese, Francisco Veríssimo


    The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients. Resumo A doença relacionada à IgG4 tem um espectro clínico amplo em que múltiplos órgãos podem ser afetados, e o diagnóstico depende de achados histopatológicos típicos e elevada expressão de IgG4 em plasmócitos no tecido afetado. Descrevemos o quadro clínico e a evolução de um paciente com nefrite túbulo-intersticial aguda, insuficiência renal grave e manifestações sistêmicas como linfoadenomegalias e pancreatite crônica. O diagnóstico foi confirmado pelas características clínicas e pela histopatologia renal e de linfonodo, na qual a imunohistoquímica mostrou tecido linfoide com policlonalidade e expressão aumentada de IgG4, com uma relação IgG4/IgG total > 80%. O paciente foi tratado com prednisona na dose de 60 mg/dia, seguido de micofenolato mofetil, e apresentou melhora clínica e da função renal depois de 6 meses de tratamento. O alto índice de suspeição da doença relacionada ao IgG4 com comprometimento multissist

  15. Antigen binding of human IgG Fabs mediate ERK-associated proliferation of human breast cancer cells. (United States)

    Wen, Yue-Jin; Mancino, Anne; Pashov, Anastas; Whitehead, Tracy; Stanley, Joseph; Kieber-Emmons, Thomas


    Serum-circulating antibody can be linked to poor outcomes in some cancer patients. To investigate the role of human antibodies in regulating tumor cell growth, we constructed a recombinant cDNA expression library of human IgG Fab from a patient with breast cancer. Clones were screened from the library with breast tumor cell lysate. Sequence analysis of the clones showed somatic hypermutations when compared to their closest VH/VL germ-line genes. Initial characterizations focused on five clones. All tested clones displayed stronger binding to antigen derived from primary breast cancers and established breast cancer cell lines than to normal breast tissues. In vitro functional studies showed that four out of five tested clones could stimulate the growth of MDA-MB-231 breast cancer cell lines, and one out of five was able to promote MCF-7 cell growth as well. Involvement of ERK2 pathway was observed. By 1H-NMR spectra and Western blot analysis, it was evident that two tested antibody Fabs are capable of interacting with sialic acid. Our study suggests a possible role for human antibody in promoting tumor cell growth by direct binding of IgG Fab to breast tumor antigen. Such studies prompt speculation regarding the role of serum antibodies in mediating tumor growth as well as their contribution to disease progression.

  16. Extracellular polysaccharides do not inhibit the reaction between Streptococcus mutans and its specific immunoglobulin G (IgG) or penetration of the IgG through S. mutans biofilm. (United States)

    Zhu, M; Takenaka, S; Sato, M; Hoshino, E


    The present study investigated whether extracellular polysaccharides inhibit reaction between Streptococcus mutans and its specific immunoglobulin G (IgG) and penetration of the IgG through S. mutans biofilm. The planktonic organisms with or without extracellular polysaccharides were prepared, incubated with rabbit IgG against whole cell of S. mutans and fluorescein isothiocyanate (FITC)-conjugated goat affinity purified antibody to rabbit IgG. Biofilms with or without extracellular polysaccharides were formed on cover glasses and incubated with rabbit IgG against S. mutans and FITC-conjugated goat antibody to rabbit IgG. Then, biofilms were stained with propidium iodide. The amount of specific IgG binding on S. mutans was determined by FITC intensity with a fluorescence microplate reader. The penetration of IgG through biofilms was determined by confocal laser scanning microscopy. The results showed that the fluorescence intensity of FITC in planktonic organisms with extracellular polysaccharides was similar to that in planktonic organisms without extracellular polysaccharides, indicating that extracellular polysaccharides did not inhibit the reaction between S. mutans and its specific IgG. Although biofilms of S. mutans with extracellular polysaccharides were much thicker and denser than those without extracellular polysaccharides, the speed with which IgG penetrated through both of the biofilms did not differ significantly, suggesting that penetration of IgG through S. mutans biofilm was not affected by extracellular polysaccharides.

  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:;; Reis, Bernardo S.; Goes, Alfredo M. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia]. E-mail:;


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

    Directory of Open Access Journals (Sweden)

    S. Monti


    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.

  19. IgG4-related cholecystitis presenting as biliary malignancy: report of three cases. (United States)

    Feely, Michael M; Gonzalo, David H; Corbera, Montserrat; Hughes, Steven J; Trevino, Jose G


    An increased awareness of IgG4-related diseases has led to an escalation in the number of sites known to be involved by this fibroinflammatory disease. We report three cases of IgG4-related cholecystitis which were thought to represent biliary malignancies both clinically and radiographically. All three cases underwent surgery tailored towards presumed malignant neoplasms. Only following pathologic examination was the true nature of the disease identified. Recognition of the clinical, radiographic, and pathologic presentation of IgG4-related cholecystitis is essential for the consideration of this disease process prior to surgical management for suspected gallbladder malignancies. However, the pre-operative diagnosis remains challenging and extensive surgical intervention is often necessary given the distressing presentation of IgG4-related cholecystitis.

  20. Interactions between DMPC liposomes and the serum blood proteins HSA and IgG. (United States)

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


    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.

  1. The Emerging Importance of IgG Fab Glycosylation in Immunity. (United States)

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


    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


    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. IgG1 variations in the colostrum of Holstein dairy cows. (United States)

    Le Cozler, Y; Guatteo, R; Le Dréan, E; Turban, H; Leboeuf, F; Pecceu, K; Guinard-Flament, J


    High-immune quality colostrum (IgG1 concentration ⩾50 g/l) is crucial for the health and development of the young calf. Studies on colostrum quality tend to focus on external factors such as breed, parity or dry period length, but few have focused on within-cow variations. Here we ran experiments to gain a deeper insight into within-cow variation in IgG1 concentrations in dairy cow colostrum. Trials were performed in an experimental farm, located in the Western part of France. Colostrum from each quarter and a composite sample (mix of four quarters) were concomitantly collected on 77 Holstein dairy cows just after calving to assess the influence of sample type on IgG1 concentrations. Variation in IgG1 concentrations during the first milking was studied on samples from nine cows collected every minute from the start of milking. Repeatability of colostral IgG1 concentration was estimated from 2009 and 2010 data on 16 healthy cows. IgG1 concentrations were tested using a radial immunodiffusion method. Sensitivity and specificity were similar regardless of sample type tested (individual quarter or composite milk). Mean average IgG1 concentration was 54.1 g/l in composite colostrum, and was significantly higher in hind quarter teats (56.2 g/l) than front quarter teats (53.1 g/l). Average IgG1 concentration did not change significantly during colostrum milking, and the variations observed (15% or less) were likely due to the laboratory method (CV 15%). IgG1 concentrations in dam colostrum increased slightly from 2009 to 2010 due to BW and parity effects. In 56% of cases, colostrum quality could have been assessed on either individual or composite colostrum samples collected at any time during the first milking without affecting the reliability of the measurement. However, in other cases, differences were significant enough to mean that estimates of average IgG1 concentration in colostrum from any one quarter would not be reliable. It is concluded that colostrum quality

  4. Idiopathic granulomatous orchitis: morphology and evaluation of its relationship to IgG4 related disease. (United States)

    Karram, Sarah; Kao, Chia-Sui; Osunkoya, Adeboye O; Ulbright, Thomas M; Epstein, Jonathan I


    Idiopathic granulomatous orchitis (IGO) is rare, thought to result from an autoimmune reaction to spermatogenic elements. Its relationship to IgG4-related disease (IgG4-RD) has not been evaluated. Sixteen orchiectomy specimens (1984-2012) with a prominent intratubular granulomatous reaction were reviewed: IGO (n = 6); intratubular germ cell neoplasia unclassified (IGCNU) with a granulomatous reaction and associated seminoma (GS, n = 6); and unclassified intratubular granulomatous orchitis not fitting into a specific entity (UGO, n = 4). Men with IGO were 32 to 86 years old, presenting with a mass suspicious for malignancy. Only one patient had a history of an inflammatory disease. Clinical follow-up was available for 2 patients with IGO, and both had no evidence of systemic IgG4-RD. All IGO cases had an epithelioid granulomatous reaction confined to seminiferous tubules, an extensive interstitial lymphoplasmacytic inflammation, 3 of 6 had prominent interstitial fibrosis, and 3 of 6 cases had plasma cells with an IgG4+/IgG+ ratio >40%. In GS, 10% to 100% of tubules with IGCNU had a granulomatous reaction, which in 3 cases replaced IGCNU cells. In contrast to IGO, GS had more intratubular multinucleated giant cells, more peritubular sclerosis, fewer interstitial plasma cells, and no interstitial fibrosis. Of the 4 UGO cases, most had predominantly interstitial with less intratubular granulomatous inflammation. Only 1 non-IGO case had elevated tissue IgG4 (GS case). It is critical and sometimes difficult to distinguish GS from IGO. IGO shares some features with IgG4-RD, yet current evidence does not support its classification as a localized manifestation of IgG4-RD occurring in the testis.

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

    Institute of Scientific and Technical Information of China (English)


    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.

  6. Oxidative Stress and IgG Antibody Modify Periodontitis-CRP Association. (United States)

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


    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. IgG4-related disease and other causes of inflammatory meningeal disease. (United States)

    Carruthers, Robert; Carruthers, Mollie; Della-Torre, Emanuel


    Immunoglobulin-4 (IgG4-) related disease is a newly described treatable condition that has recently expanded the differential diagnosis of inflammatory meningeal disorders. This review will discuss the main clinical and pathophysiological features of IgG4-related meningeal disease in the context of meningeal inflammatory disorders in general. Particular attention will be dedicated to the differential diagnosis and the different therapeutic approaches.

  8. Acute tubulointerstitial nephritis with severe renal impairment associated with multisystem IgG4-related disease

    Directory of Open Access Journals (Sweden)

    Rafael Coimbra Ferreira Beltrame

    Full Text Available Abstract The IgG4-related disease has a wide clinical spectrum where multiple organs can be affected, and the diagnosis depends on typical histopathological findings and an elevated IgG4 expression in plasma cells in the affected tissue. We describe the clinical presentation and evolution of a patient with acute tubulointerstitial nephritis, severe kidney failure and systemic manifestations such as lymphadenomegaly and chronic pancreatitis. The diagnosis was confirmed by the clinical picture and kidney and lymph node histopathology, in which immunohistochemistry of the lymphoid tissue showed policlonality and increased expression of IgG4, with a IgG4/total IgG ratio > 80%. The patient was treated with prednisone at a dose of 60 mg/day, followed by mycophenolate mofetil, and showed clinical and renal function improvement at 6 months of follow-up. The high index of suspicion of IgG4-related disease with multisystem involvement and the early treatment of this condition are essential to improve the prognosis of affected patients.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nakatani, K., E-mail: [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)


    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.


    Directory of Open Access Journals (Sweden)

    Saeed Jamshidi Far


    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.

  11. Colovesical fistula caused by glucocorticoid therapy for IgG4-related intrapelvic mass. (United States)

    Yabuuchi, Yohei; Matsubayashi, Hiroyuki; Matsuzaki, Masato; Shiomi, Akio; Moriguchi, Michihisa; Kawamura, Ichiro; Ito, Ichiro; Ono, Hiroyuki


    IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disorder that can occur in almost all systemic organs and generally responds to corticosteroid treatment. We report a rare case of an IgG4-related intrapelvic mass lesion that responded to steroid therapy but caused a fistula between the sigmoid colon and bladder. A 71-year-old man was followed after treatment for hepatocellular carcinoma. Follow-up computed tomography (CT) incidentally depicted left hydronephrosis with an ill-demarcated intrapelvic mass lesion. This lesion was histologically diagnosed as IgG4-RD by open biopsy, and peroral steroid therapy was initiated. One month after starting steroids, a colovesical fistula was detected by follow-up CT. A colostomy and urethral catheterization were emergently performed. The patient recovered and the mass lesion was drastically minimized by the initiation of glucocorticoids; however, he still needs urethral catheterization. IgG4-RD develops in various systemic organs and generally responds well to steroids. Clinicians must be watchful for the complications of responses to corticosteroids, such as fistulization, when the mass lesion of IgG4-RD is adjacent to multiple luminal organs.

  12. Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease. (United States)

    Okazaki, Kazuichi; Uchida, Kazushige; Koyabu, Masanori; Miyoshi, Hideaki; Takaoka, Makoto


    Recent studies have suggested the existence of two subtypes of autoimmune pancreatitis (AIP): type 1 AIP, related to IgG4 (lymphoplasmacytic sclerosing pancreatitis); and type 2 AIP, related to a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis). Compared with type 2 AIP, the clinicopathological features of type 1 AIP, with increased serum IgG4/IgE levels, abundant infiltration of IgG4 + plasmacytes and lymphocytes, autoantibodies, and steroid responsiveness, are more suggestive of abnormal immunity such as allergy or autoimmunity. Moreover, patients with type 1 AIP often have extrapancreatic lesions, such as sclerosing cholangitis, sclerosing sialadenitis, or retroperitoneal fibrosis, showing pathological features similar to those of the pancreatic lesions. Based on these findings, an international concept of and diagnostic criteria for AIP have been proposed recently. Of interest, many synonyms have been proposed for the conditions of AIP and extrapancreatic lesions associated with IgG4, such as "multifocal idiopathic fibrosclerosis," "IgG4-related autoimmune disease," "IgG4-related sclerosing disease," "systemic IgG4-related plasmacytic syndrome (SIPS)," and "IgG4-related multiorgan lymphoproliferative syndrome," all of which may refer to the same conditions. Therefore, the Japanese Research Committee for "Systemic IgG4-Related Sclerosing Disease" proposed a disease concept and clinical diagnostic criteria based on the concept of multifocal fibrosclerosing disease, in 2009, in which the term "IgG4-related disease" was agreed upon as a minimal consensus to cover these conditions. Although the significance of IgG4 in the development of "IgG4-related disease" remains unclear, we have proposed a hypothesis for the development of type 1 AIP, one of the IgG4-related diseases. The concept and diagnostic criteria of "IgG4-related disease" will be changed in accordance with future studies.

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

  14. 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)



    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.

  15. Non-apical membrane antigen 1 (AMA1 IgGs from Malian children interfere with functional activity of AMA1 IgGs as judged by growth inhibition assay.

    Directory of Open Access Journals (Sweden)

    Kazutoyo Miura

    Full Text Available BACKGROUND: Apical membrane antigen 1 (AMA1 is one of the best-studied blood-stage malaria vaccine candidates. When an AMA1 vaccine was tested in a malaria naïve population, it induced functionally active antibodies judged by Growth Inhibition Assay (GIA. However, the same vaccine failed to induce higher growth-inhibitory activity in adults living in a malaria endemic area. Vaccination did induce functionally active antibodies in malaria-exposed children with less than 20% inhibition in GIA at baseline, but not in children with more than that level of baseline inhibition. METHODS: Total IgGs were purified from plasmas collected from the pediatric trial before and after immunization and pools of total IgGs were made. Another set of total IgGs was purified from U.S. adults immunized with AMA1 (US-total IgG. From these total IgGs, AMA1-specific and non-AMA1 IgGs were affinity purified and the functional activity of these IgGs was evaluated by GIA. Competition ELISA was performed with the U.S.-total IgG and non-AMA1 IgGs from malaria-exposed children. RESULTS: AMA1-specific IgGs from malaria-exposed children and U.S. vaccinees showed similar growth-inhibitory activity at the same concentrations. When mixed with U.S.-total IgG, non-AMA1 IgGs from children showed an interference effect in GIA. Interestingly, the interference effect was higher with non-AMA1 IgGs from higher titer pools. The non-AMA1 IgGs did not compete with anti-AMA1 antibody in U.S.-total IgG in the competition ELISA. CONCLUSION: Children living in a malaria endemic area have a fraction of IgGs that interferes with the biological activity of anti-AMA1 antibody as judged by GIA. While the mechanism of interference is not resolved in this study, these results suggest it is not caused by direct competition between non-AMA1 IgG and AMA1 protein. This study indicates that anti-malaria IgGs induced by natural exposure may interfere with the biological effect of antibody induced by an AMA1

  16. 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


    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


    NARCIS (Netherlands)

    BROUWER, E.; Tervaert, J.W.C.; HUITEMA, M.G.; VANDERGIESSEN, M.; Limburg, Piet; Kallenberg, Cees; Horst, G.


    In view of the supposed hypersensitivity, the elevated levels of IgE, and the occurrence of eosinophilia reported in Wegener's granulomatosis and related conditions, we studied the IgG subclass distribution of ANCA directed against a 29-kD serine protease and and myeloperoxidase (MPO) in 41 untreate

  18. Novel human IgG1 and IgG4 Fc-engineered antibodies with completely abolished immune effector functions. (United States)

    Schlothauer, Tilman; Herter, Sylvia; Koller, Claudia Ferrara; Grau-Richards, Sandra; Steinhart, Virginie; Spick, Christian; Kubbies, Manfred; Klein, Christian; Umaña, Pablo; Mössner, Ekkehard


    Recombinant human IgG antibodies (hIgGs) completely devoid of binding to Fcγ receptors (FcγRs) and complement protein C1q, and thus with abolished immune effector functions, are of use for various therapeutic applications in order to reduce FcγR activation and Fc-mediated toxicity. Fc engineering approaches described to date only partially achieve this goal or employ a large number of mutations, which may increase the risk of anti-drug antibody generation. We describe here two new, engineered hIgG Fc domains, hIgG1-P329G LALA and hIgG4-P329G SPLE, with completely abolished FcγR and C1q interactions, containing a limited number of mutations and with unaffected FcRn interactions and Fc stability. Both 'effector-silent' Fc variants are based on a novel Fc mutation, P329G that disrupts the formation of a proline sandwich motif with the FcγRs. As this motif is present in the interface of all IgG Fc/FcγR complexes, its disruption can be applied to all human and most of the other mammalian IgG subclasses in order to create effector silent IgG molecules.

  19. IL-21 promotes the production of anti-DNA IgG but is dispensable for kidney damage in lyn-/- mice. (United States)

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


    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.

  20. Epicoccum allergy: skin reaction patterns and spore/mycelium disparities recognized by IgG and IgE ELISA inhibition. (United States)

    Portnoy, J; Chapman, J; Burge, H; Muilenberg, M; Solomon, W


    Comparable degrees of skin reactivity were observed towards spore and mycelium extracts from two isolates of Epicoccum and to one preparation of Alternaria in 35 rural and 120 university patients. The best experimental extracts detected Epicoccum sensitivity in 70% of the group tested while the commercial extract detected sensitivity in only 6%. Skin reaction correlations were greatest within isolates (eg, spore-A/mycelium-A), then for specific fungus parts (eg, spore-A/spore-B), then between isolates and parts (spore-A/mycelium-B). High correlations were found between individual IgG and IgE ELISA values for all antigens using serum from Epicoccum skin-reactive patients. ELISA inhibition results suggested that significant cross-reactivity exists between Epicoccum and Alternaria antigens recognized by IgG but not by IgE. ELISA inhibition cross-reaction patterns among Epicoccum antigens were comparable to skin reactions while IgG patterns showed little variability. Further characterization of spore/mycelium and interstrain recognition patterns among different immunoglobulin isotypes will be necessary before complete standardization of extracts from different parts of fungi will be possible. The use of spore material for skin testing and treatment of Epicoccum sensitivity appears to be both premature and unnecessary at this time.

  1. 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


    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.

  2. Differential evolution of anti-VAR2CSA- IgG3 in primigravidae and multigravidae pregnant women infected by Plasmodium falciparum

    DEFF Research Database (Denmark)

    Guitard, Juliette; Cottrell, Gilles; Magnouha, Nellie Moulopo;


    BACKGROUND: Pregnant women develop protective anti-VSA IgG1 and IgG3 when infected by Plasmodium falciparum. The major target of IgG from serum of infected pregnant women is VAR2CSA. METHODS: In this study, ELISA was used to compare the level of VAR2CSA DBL5epsilon- specific IgG subclasses...

  3. Human placenta: relative content of antibodies of different classes and subclasses (IgG1-IgG4) containing lambda- and kappa-light chains and chimeric lambda-kappa-immunoglobulins. (United States)

    Lekchnov, Evgenii A; Sedykh, Sergey E; Dmitrenok, Pavel S; Buneva, Valentina N; Nevinsky, Georgy A


    The specific organ placenta is much more than a filter: it is an organ that protects, feeds and regulates the growth of the embryo. Affinity chromatography, ELISA, SDS-PAGE and matrix-assisted laser desorption ionization mass spectrometry were used. Using 10 intact human placentas deprived of blood, a quantitative analysis of average relative content [% of total immunoglobulins (Igs)] was carried out for the first time: (92.7), IgA (2.4), IgM (2.5), kappa-antibodies (51.4), lambda-antibodies (48.6), IgG1 (47.0), IgG2 (39.5), IgG3 (8.8) and IgG4 (4.3). It was shown for the first time that placenta contains sIgA (2.5%). In the classic paradigm, Igs represent products of clonal B-cell populations, each producing antibodies recognizing a single antigen. There is a common belief that IgGs in mammalian biological fluids are monovalent molecules having stable structures and two identical antigen-binding sites. However, similarly to human milk Igs, placenta antibodies undergo extensive half-molecule exchange and the IgG pool consists of 43.5 ± 15.0% kappa-kappa-IgGs and 41.6 ± 17.0% lambda-lambda-IgGs, while 15.0 ± 4.0% of the IgGs contained both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained, respectively (%): IgG1 (47.7 and 34.4), IgG2 (36.3 and 44.5), IgG3 (7.4 and 11.8) and IgG4 (7.5 and 9.1), while chimeric kappa-lambda-IgGs consisted of (%): 43.5 IgG1, 41.0 IgG2, 5.6 IgG3 and 7.9 IgG4. Our data are indicative of the possibility of half-molecule exchange between placenta IgGs of various subclasses, raised against different antigens, which explains a very well-known polyspecificity and cross-reactivity of different human IgGs.

  4. Prohibitin Is Involved in Patients with IgG4 Related Disease.

    Directory of Open Access Journals (Sweden)

    Hongwu Du

    Full Text Available IgG4-related disease (IgG4-RD is a chronic systemic disease involved in many organs and tissues. As only limited autoantigens have been found since the beginning of this century, the aim of this study was to reveal new candidate autoantigens of IgG4-RD.Multiple cell lines including HT-29, EA.hy926, HEK 293 and HepG2 were used to test the binding ability of circulating autoantibodies from IgG4-RD sera. The amino-acid sequence was then analyzed by matrix-assisted laser desorption/ionization time-of-flight tandem (MALDI-TOF/TOF mass spectrometry. After the cloning and expression of recombinant putative autoantigen in a bacterial expression system, the corresponding immuno assay was set up and utilized to observe the prevalence of serum autoantibodies in a large set of confirmed clinical samples.One positive autoantigen was identified as prohibitin. ELISA analysis showed that a majority of patients with IgG4-RD have antibodies against prohibitin. Anti-prohibitin antibodies were present in the sera of patients with definite autoimmune pancreatitis (25/34; 73.5%, Mikulicz's disease (8/15; 53.3%, retroperitoneal fibrosis (6/11; 54.5%, other probable IgG4-RD (26/29; 89.7% and Sjögren's syndrome (4/30; 13.3% but not in apparently healthy donors (1/70; 1.4%.An association between prohibitin and patients with some IgG4-RD was observed, although the results were quite heterogeneous among different individuals within autoimmune pancreatitis, Mikulicz's disease and retroperitoneal fibrosis.

  5. IgG4-related disease: current challenges and future prospects

    Directory of Open Access Journals (Sweden)

    Lang D


    Full Text Available David Lang,1 Jochen Zwerina,2 Herwig Pieringer1,3 1Second Department of Internal Medicine, Kepler University Clinic, Linz, 2First Department of Internal Medicine, Ludwig Boltzmann-Institute of Osteology, Hanusch Hospital, Vienna, 3Paracelsus Private Medical University, Salzburg, Austria Abstract: Immunoglobulin G4-related disease (IgG4-RD represents an immune-mediated fibroinflammatory condition with a characteristic histopathological appearance that can affect various organs. Although numerous single-organ manifestations have been described more than a century ago, its systemic nature and unique features were only discovered in the last 2 decades, when IgG4-RD emerged as a new entity of disease. IgG4-RD is usually considered a rare disease, but its true epidemiology has not yet been fully clarified. Also, despite recent advances in the identification of the underlying immunological processes, its pathophysiology is only incompletely understood till now. The diagnostic workup of IgG4-RD is complex and usually requires a combination of clinical examination, imaging, histological, and serological analyses. However, no finding alone is specific for IgG4-RD. Therefore, its diagnosis requires careful interpretation of examination results in context with the patient’s clinical appearance as well as the exclusion of a broad variety of differential diagnoses. The past years brought rapid advances concerning this novel disease entity: diagnostic criteria, further insights into the underlying immunological processes, new biomarkers, and novel therapeutic approaches were proposed and widened the knowledge in the field of IgG4-RD. Still, a greater number of questions remain unanswered, and many recent developments require further discussion and proof from clinical trials. This review should give an overview on current knowledge and future perspectives in epidemiology, pathophysiology, diagnosis, and therapy of IgG4-RD. Keywords: PET/CT, autoimmune

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

    Directory of Open Access Journals (Sweden)

    S Kaur


    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.

  7. Indeterminate/moderate IgG avidity during HCMV infection: comparison of methods

    Directory of Open Access Journals (Sweden)

    Massimo De Paschale


    Full Text Available Background. The IgG avidity test is usually used for differentiating between primary and non-primary HCMV infection within 3 months. Weak avidity is highly suggestive of a primary infection, while high avidity tends to exclude it.An indeterminate or moderate avidity, however, does not allow a clear dating. Since there are several avidity tests with different performances, those tests that are able to minimize the results with indeterminate/moderate avidity are particularly useful. Objectives. The aim of our work was to evaluate the results obtained with two IgG avidity tests in IgG and IgM anti-HCMV positive patients. Study Design. 113 anti-HCMV IgG and IgM positive samples were tested with Enzime Linked Fluorescent Assay (ELFA and Chemiluminescence Immuno Assay (CLIA IgG avidity test. Results. 21 samples (18.6%, 50 (44.2% and 42 (37.2% with ELFA and 53 samples (46.9%, 10 (8.8% and 50 (44.2% with CLIA were found to have respectively low, indeterminate/moderate and high avidity. Of the 50 ELFA indeterminate avidity samples, 32 (64%, 10 (20% and 8 (16% were found to have respectively low, moderate and high CLIA.avidity. For 11 cases of the 32 ELFA indeterminate avidity and CLIA low avidity, there were previous data showing a seroconversion within three months. In a case of the 8 ELFA indeterminate avidity and CLIA high avidity, there were, instead, previous data of IgG and IgM positivity already four months earlier. Conclusions. It appears that the CLIA test for IgG avidity is more effective than ELFA for dating HCMV infection.

  8. The role of IgG4 (+) plasma cells in the association of Hashimoto's thyroiditis with papillary carcinoma. (United States)

    Taşli, Funda; Ozkök, Güliz; Argon, Asuman; Ersöz, Didem; Yağci, Ayşe; Uslu, Adam; Erkan, Nazif; Salman, Tarik; Vardar, Enver


    Hashimoto's thyroiditis (HT) is considered to be a risk factor for the formation of papillary carcinoma. The association of IgG4-related sclerosing disease with tumor is reported to be as sporadic cases in many organs. In this study, it was intended to re-classify the HT diagnosed cases on the basis of the existence of IgG4 (+) plasma cells; to investigate the clinicopathologic and histopathologic features of the both groups; and in addition, to evaluate the papillary carcinoma prevalence in IgG4 (+) and IgG4 (-) HT cases as well as the prognostic parameters between these groups. Totally 59 cases between the years 2008-2013, 29 of which contain Hashimoto thyroiditis diagnosis in total thyroidectomy materials, and 30 of which contain the diagnosis of HT+papillary carcinoma, were included in the study. The materials were immunohistochemically applied IgG and IgG4; and the cases were classified in two groups as IgG4-positive HT and IgG4-negative HT containing cases, on the basis of IgG4/IgG rate. All histopathologic and clinicopathologic parameters between these two groups, as well as their association with papillary carcinoma were investigated. Thirty eight (64.4%) of total 59 cases were NonIgG4 thyroiditis, and 21 (35.5%) were IgG4 thyroiditis. Tumors were detected in 14 (36.8%) of the NonIgG4 thyroiditis cases, and in 16 (76.1%) of the IgG4 thyroiditis cases. The association of IgG4 thyroiditis with tumor is statistically significant (p thyroiditis cases. Perithyroidal extension was detected in six of the cases with tumor, and five of the six cases were IgG4 thyroiditis cases. The association of IgG4 (+) HT cases with increased papillary carcinoma prevalence is suggestive of that IgG4 (+) plasma cells can play a role in carcinogenesis in papillary carcinomas developed in HTs, without a chronic sclerosing ground. In addition, although the number of cases is limited, the high-association of IgG4 (+) plasma cells with adverse prognostic parameters such as

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




    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 flui...

  10. 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.;


    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...

  11. IgG4相关性腹膜后纤维化CT诊断%Diagnosis of IgG4-related retroperitoneal fibrosis

    Institute of Scientific and Technical Information of China (English)

    田芳; 朴雪梅; 周自明; 常时新; 丁永生


    Objective: To study and summarize the clinical features and the imaging manifestations of IgG4-related retroperitoneal fibrosis and to improve the understanding of IgG4-related sclerosing disease. Methods: A case of IgG4-related retroperitoneal fibrosis was reported,including clinical features,laboratory reports,imaging manifestations and pathological results,and relative literatures were reviewed. Results: The disease had no distinctive clinical features. Symptoms include vague pain in the lower back or abdomen,anorexia,fatigue,fever and weight loss. The imaging manifestation was soft tissue mass. The level of serum IgG (especially IgG4) was strikingly high. The histological manifestation in the involved organs showed diffuse infiltration of lymphoplasma cells and fibrosis. Abundant IgG4-positive plasma cells could be found and the treatment with glucocorticoid was effective. Conclusion:IgG4-related retroperitoneal fibrosis lacks specifity. It is essential to improve its understanding to avoid misdiagnosis.%目的:总结IgG4相关腹膜后纤维化的临床表现及影像特点,提高时IgG4相关的硬化性疾病的认识.方法:报告1例IgC4相关腹膜后纤维化的临床表现、实验室检查、影像学资料、病理结果等,并复习相关文献.结果:该病临床症状无明显特异性,可有腹痛、背痛、疲乏、食欲下降等,影像表现为腹膜后肿块,该病与自身免疫性胰腺炎关系密切,血清IgG尤其是IgG4显著升高;受累脏器组织学表现为弥漫性淋巴浆细胞漫润和纤维化,大量IgG4阳性浆细胞;糖皮质激素治疗有效.结论:IgG4相关腹膜后纤维化临床症状缺乏特异性,极易误诊或漏诊,需提高对该病的认识.

  12. Rabbit IgG distribution in skin, spinal cord and DRG following systemic injection in rat. (United States)

    Tonra, J R; Mendell, L M


    In order to determine the distribution of antibodies such as anti-NGF following systemic injection in neonates, immunocytochemical techniques were used to examine the localization of rabbit IgG in rat skin, DRG, and spinal cord after treatments with normal rabbit serum or purified rabbit IgG. Daily subcutaneous injections beginning on postnatal day 2 or on day 15 were given for three days. On the fourth day the animals were sacrificed and tissues were processed for rabbit IgG-IR. In the dorsal and ventral spinal cord, staining intensities suggest a substantial increase in the blood-brain barrier during the first two weeks after birth. Staining intensity in the epidermis of the glabrous skin from the hindpaw was substantially lower than in the adjacent dermis. In addition, IgG infrequently accumulated intracellularly in intensely stained patches in the epidermis. IgG was also able to reach relatively high intracellular concentrations in a small number of sensory neurons. The IgG staining pattern in the skin was similar when anti-NGF itself was administered to the animals. The results are discussed in the context of the effects of anti-NGF on the development of nociceptive afferents.

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

    Directory of Open Access Journals (Sweden)

    April L. Barnado MD


    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. Activation of complement by an IgG molecule without a genetic hinge. (United States)

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


    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.

  15. Clinical evaluation of the Roche Elecsys CMV IgG Avidity assay. (United States)

    Vauloup-Fellous, C; Lazzarotto, T; Revello, M G; Grangeot-Keros, L


    Congenital cytomegalovirus (CMV) infection has potentially severe consequences in newborns. The testing of pregnant women for CMV-specific antibodies may be useful for the identification of women at risk of transmitting the infection to the fetus. The determination of CMV IgG avidity helps to establish the timing of infection as IgG avidity matures during the course of infection. This study examines the performance of the Elecsys CMV IgG Avidity assay using preselected samples from patients at different phases of CMV infection. The Elecsys CMV IgG Avidity assay was tested at three sites using sequential samples from patients with recent primary CMV infection, as well as single samples from patients with recent primary or past CMV infection. The Elecsys assay discriminated well between early (low avidity) and late (high avidity) phases of infection in sequential serum samples. Overall, 98.8% of low-avidity samples corresponded to infection onset 90 days before sampling. The assay's sensitivity was 90-97%, with specificity ranging from 89 to 100%, depending on the consideration of gray-zone avidity values. Single samples from recent primary or past infection showed similar distributions of avidity results. The Elecsys CMV IgG Avidity assay results are in agreement with preselected samples from patients with primary or past CMV infection, showing that the test is an adequate predictor of the phase of infection.

  16. A Glycoform of Immunoglobulin G (IgG) as an Early Biomarker of Exposure to Nonhuman Substances (United States)


    all of which were under-galactosylated IgG (G0 and G1) with core fucose on its constant region N-glycan. We hypothesized that the immunoglobulin...follows its denaturation, presumably because the fucose on the IgG is normally inaccessible to the lectin (1). Heating, or the use of denaturation...reagents such as urea, can fully denature the IgG protein and expose the fucose moieties. In addition, glycosidase treatment or solid-surface

  17. Repertoire of Epitopes Recognized by Serum IgG from Humans Vaccinated with Herpes Simplex Virus 2 Glycoprotein D (United States)

    Huang, Zhen-Yu; Cairns, Tina M.; Gallagher, John R.; Lou, Huan; Ponce-de-Leon, Manuel; Belshe, Robert B.; Eisenberg, Roselyn J.; Cohen, Gary H.


    ABSTRACT The results of a clinical trial of a subunit vaccine against genital herpes were recently reported (R. B. Belshe, P. A. Leone, D. I. Bernstein, A. Wald, M. J. Levin, J. T. Stapleton, I. Gorfinkel, R. L. Morrow, M. G. Ewell, A. Stokes-Riner, G. Dubin, T. C. Heineman, J. M. Schulte, C. D. Deal, N. Engl. J. Med. 366:34–43, 2012, doi:10.1056/NEJMoa1103151). The vaccine consisted of a soluble form of herpes simplex virus 2 (HSV-2) glycoprotein D (gD2) with adjuvant. The goal of the current study was to examine the composition of the humoral response to gD2 within a selected subset of vaccinated individuals. Serum samples from 30 vaccine recipients were selected based upon relative enzyme-linked immunosorbent assay (ELISA) titers against gD2; 10 samples had high titers, 10 had medium titers, and the remaining 10 had low ELISA titers. We employed a novel, biosensor-based monoclonal antibody (MAb)-blocking assay to determine whether gD2 vaccination elicited IgG responses against epitopes overlapping those of well-characterized MAbs. Importantly, IgGs from the majority of gD2-immunized subjects competed for gD binding with four antigenically distinct virus-neutralizing MAbs (MC2, MC5, MC23, and DL11). Screening of patient IgGs against overlapping peptides spanning the gD2 ectodomain revealed that about half of the samples contained antibodies against linear epitopes within the N and C termini of gD2. We found that the virus-neutralizing abilities of the 10 most potent samples correlated with overall gD-binding activity and to an even greater extent with the combined content of IgGs against the epitopes of MAbs MC2, MC5, MC23, and DL11. This suggests that optimal virus-neutralizing activity is achieved by strong and balanced responses to the four major discontinuous neutralizing epitopes of gD2. IMPORTANCE Several herpes simplex virus 2 (HSV-2) subunit vaccine studies have been conducted in human subjects using a recombinant form of HSV-2 glycoprotein D (gD2

  18. Significance of specific IgG against sensitizing antigens in extrinsic allergic alveolitis: serological methods in EAA. (United States)

    Sterclova, M; Vasakova, M; Metlicka, M


    The aim of our study is to find differences in IgG in sera of potentially exposed and nonexposed individuals and to detect differences in concentrations of specific serum IgG among subjects with and without EAA. Seventy-two patients being followed for suspected interstitial lung disease were included. Specific IgG in sera were established by ImmunoCAP. Serum concentrations of Aspergillus fumigatus, Candida albicans IgG and mixture of moulds IgG were higher in subjects with exposure to relevant inhalation antigens (p<0.05). Patients exposed to parrot and mammal hair mixture had higher serum concentration of specific IgG (p<0.05). Subjects without exposure to mites had lower serum IgG to Dermatophagoides pteronyssinus, Dermatophagoides farinae, Dermatophagoides microceras and Glycophagus domesticus (p<0.05). Higher concentration of serum specific IgG may show previous exposure to this antigen. Even though mite specific IgG are not commonly tested in EAA patients, we suggest their immunomodulatory activity may influence susceptibility to other inhalation antigens.

  19. Dectin-1 agonist selectively induces IgG1 class switching by LPS-activated mouse B cells. (United States)

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


    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.

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

    DEFF Research Database (Denmark)

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


    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...

  1. Isolation and Purification of Bovine Colostrum sIgA and IgG

    Institute of Scientific and Technical Information of China (English)

    YAO Yonghao; GAO Xuejun; LIU Xiaofei


    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.

  2. Topiramate-induced maculopathy in IgG4-related disease

    Directory of Open Access Journals (Sweden)

    DaCosta J


    Full Text Available Joanna DaCosta,1,2 Saad Younis1 1Ophthalmology Department, Imperial College Healthcare NHS Trust, Western Eye Hospital, 2Barts Health NHS Trust, Whipps Cross University Hospital, London, UK Abstract: This report describes a case of reversible topiramate-induced maculopathy in a 32-year-old female patient with IgG4-related disease. The patient presented with decreased vision associated with anterior uveitis and cystoid macula edema, which was unresponsive to oral and topical steroids. Following topiramate cessation, both cystoid macula edema and vision improved. The ocular side effects of topiramate and putative pharmacological mechanisms for topiramate-induced maculopathy in the context of IgG4-related disease are discussed. This report highlights that neurologists and ophthalmologists should be aware that patients presenting with topiramate-associated maculopathy should be advised to discontinue topiramate promptly to prevent irreversible loss of vision. Keywords: IgG4 disease, maculopathy, topiramate

  3. IgG4-related intraocular inflammation masquerading as ciliary body melanoma in a young girl

    Directory of Open Access Journals (Sweden)

    Dipankar Das


    Full Text Available Immunoglobulin G4 (IgG4-related diseases affects various tissues and organs of the human body. Orbital, adnexal, and scleral inflammations were already reported in the medical literature. To the best of our knowledge, we report the first case of intraocular IgG4-associated inflammatory mass in the ciliary body mimicking as a melanoma in a 23-year-old female from Northeast India. Characteristic histopathology, immunohistochemistry in the tissue, protein chemistry, and raised serum IgG4 were supportive for the diagnosis. As this newly diagnosed disease has multi-organ affection and little is known about its pathogenesis particularly in eye and adnexa, the present case will open many challenges in clinico-pathological diagnosis and research in the future.

  4. Homogeneous Detection of Human IgG by Gold Nanoparticle Probes

    Institute of Scientific and Technical Information of China (English)

    CAO Qihua; YUAN Hong; CAI Ruxiu


    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.

  5. Recurrent meningitis in a child with IgG3 subclass deficiency. (United States)

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


    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.

  6. Proliferative glomerulonephritis with monoclonal IgG deposits in a patient with autoimmune hemolytic anemia. (United States)

    Fujiwara, Takashi; Komatsuda, Atsushi; Ohtani, Hiroshi; Togashi, Masaru; Sawada, Ken-Ichi; Wakui, Hideki


    A 25-year-old woman was admitted because of proteinuria. A renal biopsy showed mesangial/endocapillary proliferative glomerulonephritis with IgG2-κ deposits. Electron microscopy showed immune complex-type deposits. She also had Coombs-positive hemolytic anemia, anticardiolipin antibodies, and antinuclear antibodies. Middle-dose steroid therapy led to improvement of proteinuria and hemolytic anemia. Six years later, she developed crescentic glomerulonephritis with IgG2-κ deposits during pregnancy. Middle-dose steroid therapy improved renal dysfunction. This is an exceptional case of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a recently described rare dysproteinemia-related glomerulonephritis, associated with autoimmune disease. This case also suggests that crescentic glomerulonephritis can be superimposed on PGNMID.

  7. Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia. (United States)

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


    A Spanish group recently reported that four patients with chronic inflammatory demyelinating polyneuropathy carrying IgG4 autoantibodies against contactin 1 showed aggressive symptom onset and poor response to intravenous immunoglobulin. We aimed to describe the clinical and serological features of Japanese chronic inflammatory demyelinating polyneuropathy patients displaying the anti-contactin 1 antibodies. Thirteen of 533 (2.4%) patients with chronic inflammatory demyelinating polyneuropathy had anti-contactin 1 IgG4 whereas neither patients from disease or normal control subjects did (P = 0.02). Three of 13 (23%) patients showed subacute symptom onset, but all of the patients presented with sensory ataxia. Six of 10 (60%) anti-contactin 1 antibody-positive patients had poor response to intravenous immunoglobulin, whereas 8 of 11 (73%) antibody-positive patients had good response to corticosteroids. Anti-contactin 1 IgG4 antibodies are a possible biomarker to guide treatment option.

  8. Treatment of IgG4-related disease with assistant of corticosteroid:one case report%肾上腺皮质激素助减剂治疗 IgG4相关性疾病一例

    Institute of Scientific and Technical Information of China (English)

    杨彩红; 李雪; 吴恒莲; 杨岫岩


    IgG4-related disease is a newly recognized clinicopathological entity characterized by in-creased serum IgG4 and abundant IgG4-bearing plasma cell infiltration involving a variety of organs and tissues. The most commonly involved organs or tissues include the pancreas,lacrimal gland,salivary glands,retroper-itoneal space,biliary tract,kidney,thyroid and pituitary,etc,presenting with diffuse swelling induced by chronic inflammation accompanied with progressive fibrosis.In this article,we reported the diagnosis and treatment of one case of IgG4-related disease that was effectively treated with disease-modifying anti-rheumatic drugs (DMARDs),providing physicians with deep understanding and clinical evidence of IgG4-related dis-ease.%IgG4相关性疾病(IgG4-RD)是新近被认识和关注的一类疾病。该类疾病以血清IgG4水平升高以及 IgG4阳性浆细胞浸润多种器官和组织为特征,常见受累器官包括胰腺、泪腺、唾液腺、后腹膜、胆道、肾脏、甲状腺及垂体等,累及的器官或组织由于慢性炎症及纤维化进程可导致弥漫性肿大。IgG4-RD 作为一种新的临床疾病逐渐被广泛认识,但国内报道仍较少。该文报道1例IgG4-RD 患者的诊治经过,为临床医生认识、诊治该疾病提供参考。

  9. 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)


    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.

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

    Directory of Open Access Journals (Sweden)

    Anna Popławska-Kita


    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.

  11. Extraction of monoclonal antibodies (IgG1) using anionic and anionic/nonionic reverse micelles. (United States)

    George, Daliya A; Stuckey, David C


    Purification schemes for antibody production based on affinity chromatography are trying to keep pace with increases in cell culture expression levels and many current research initiatives are focused on finding alternatives to chromatography for the purification of Monoclonal antibodies (MAbs). In this article, we have investigated an alternative separation technique based on liquid-liquid extraction called the reverse micellar extraction. We extracted MAb (IgG1) using reverse micelles of an anionic surfactant, sodium bis 2-ethyl-hexyl sulfosuccinate (AOT) and a combination of anionic (AOT) and nonionic surfactants (Brij-30, Tween-85, Span-85) using isooctane as the solvent system. The extraction efficiency of IgG1 was studied by varying parameters, such as pH of the aqueous phase, cation concentration, and type and surfactant concentration. Using the AOT/Isooctane reverse micellar system, we could achieve good overall extraction of IgG1 (between 80 and 90%), but only 30% of the bioactivity of IgG1 could be recovered at the end of the extraction by using its binding to affinity chromatography columns as a surrogate measure of activity. As anionic surfactants were suspected as being one of the reasons for the reduced activity, we decided to combine a nonionic surfactant with an anionic surfactant and then study its effect on the extraction efficiency and bioactivity. The best results were obtained using an AOT/Brij-30/Isooctane reverse micellar system, which gave an overall extraction above 90 and 59% overall activity recovery. An AOT/Tween-85/Isooctane reverse micellar system gave an overall extraction of between 75 and 80% and overall activity recovery of around 40-45%. The results showed that the activity recovery of IgG1 can be significantly enhanced using different surfactant combination systems, and if the recovery of IgG1 can be further enhanced, the technique shows considerable promise for the downstream purification of MAbs.

  12. Actively induced platelet-bound IgG associated with thrombocytopenia in the marmoset

    Energy Technology Data Exchange (ETDEWEB)

    Gengozian, N.; McLaughlin, C.L.


    Interspecies platelet immunizations among marmosets lead to antibody formation to the donor platelets and a profound thrombocytopenia, which when associated with anemia may result in death of the animal. This actively induced immonologic thrombocytopenia closely resembles two clinical disease entities manifesting autoimmune thrombocytopenia, posttransfusion purpura and idiopathic thrombocytopenic purpura. Although antibody to donor-type platelets could be demonstrated readily, antihost activity was most often nondetectable or, when present, was in very low titer. A consistent finding was the appearance of IgG on the host's platelets shortly after immunization and concomitant with the appearance of antidonor platelet antibody. In 3 of 13 immunized animals thromoocytopenia did not occur even though antibody was formed and the host's platelets became IgG positive. In those animals that recovered from the induced thrombocytopenia IgG-positive platelets were found for periods ranging from 30 to greater than 100 days. Splenectomy before or after immunization did not alter the sequential development of antibody formation, appearance of IgG-positive platelets, and thrombocytopenia. Eluates prepared from IgG-positive platelets contained IgG and platelet antigens; the eluted IgG could attach nonspecifically to platelets of host or donor (immunizing) type, in contrast to the species specificity demonstrated for IgG eluted from platelets that had been reacted in vitro with specific antibody. Platelets in a few normal, nonimmunized marmosets were found to have signficant amounts of IgG on their surface, comparable to that observed in the immunized animal; interestingly, such IgG-positive platelets were found among imported but not laboratory-bred marmosets.

  13. 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


    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

  14. 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...

  15. 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


    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.

  16. 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


    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.

  17. Human milk IgGs contain various combinations of different antigen-binding sites resulting in multiple variants of their bispecificity.

    Directory of Open Access Journals (Sweden)

    Sergey E Sedykh

    Full Text Available In the classic paradigm, immunoglobulins represent products of clonal B cell populations, each producing antibodies (Abs recognizing a single antigen. There is a common belief that IgGs in mammalian biological fluids are monovalent molecules having stable structures and two identical antigen-binding sites. However, human milk IgGs to different antigens undergo extensive half-molecule exchange. In the IgGs pool, only 33 ± 5% and 13 ± 5% of Abs contained light chains exclusively of kappa- or lambda-type, respectively, while 54 ± 10% of the IgGs contained both kappa- and lambda- light chains. All Ab preparations contained different amounts of IgGs of all four subclasses. Interestingly, lambda-IgGs contained an increased amount of IgG2 (87% and only 3-6% of each of IgG1, IgG3, and IgG4, while kappa-IgGs consisted of comparable (17-32% amounts of all IgG subtypes. Chimeric kappa-lambda-IgGs consisted of ~74% IgG1, ~16% IgG2, ~5% IgG3 and ~5% IgG4. As the result of the exchange, all IgG fractions eluted from several specific affinity sorbents under the conditions destroying strong immunocomplexes demonstrated high catalytic activities in hydrolysis of ATP, DNA, oligosaccharides, phosphorylation of proteins, lipids, and oligosaccharides. In vitro, an addition of reduced glutathione and milk plasma to two IgG fractions with different affinity for DNA-cellulose led to a transition of 25-60% of Ab of one fraction to the other fraction. Our data are indicative of the possibility of half-molecule exchange between milk IgGs of various subclasses, raised against different antigens (including abzymes, which explains the polyspecificity and cross-reactivity of these IgGs.

  18. [Serum IgG antibodies to GD1a and GM1 gangliosides in elderly people]. (United States)

    Kolyovska, V


    Nowadays, the percentage of elderly people in society grows. Good nutrition and medical care help older people to have a normal life over 80 to 90 years. In the last ten years it is of critical importance to establish the clinical significance of serum IgG anti-GD1a and anti-GM1 ganglioside antibodies as potential biomarkers for neuronal damage in neurodegenerative diseases and immune-mediated neuropathies and demyelination. In the current study, the diagnostic values of IgG anti-GD1a and anti-GM1 antibodies were determined by the ELISA method in serum samples of 18 elderly patients (71-91 years). Significantly elevated serum IgG anti-GD1a and anti-GM1 antibodies titers were detected only in patients over 80 years. These data suggest that the immune-mediated neuropathies, neurodegeneration and demyelination in healthy elderly occur after 80 years old. Therefore, IgG anti-GD1a and anti-GM1 antibodies can serve as biomarkers, showing the nervous system dysfunction.

  19. Relationship between chronic sclerosing dacryoadenitis with high level of IgG4 and Castleman disease

    Directory of Open Access Journals (Sweden)

    Toshiyuki Oshitari


    Full Text Available Toshiyuki Oshitari1, Jiro Yotsukura1, Kaoru Asahagi1, Takayuki Baba1, Takashi Kishimoto2, Shuichi Yamamoto11Department of Ophthalmology and Visual Science, 2Department of Molecular Pathology, Chiba University Graduate School of Medicine, Chiba, JapanAbstract: The purpose of this study is to present a case of chronic sclerosing dacryoadenitis with high level of IgG4 in a patient diagnosed earlier with Castleman disease. A 79-year-old man noticed a swelling of his lower left jaw that was first seen 8 years earlier. He was diagnosed with Castleman disease from the histopathological examination of a biopsy of the submandibular gland. Since then, the size of the gland had not changed, and he had no systemic inflammatory signs or symptoms. He developed diplopia a year earlier, and CT scans showed bilateral swelling of the lacrimal glands. He was referred to our hospital for further examinations. The patient underwent partial dacryoadenectomy. From the histopathological examinations, he was diagnosed with chronic sclerosing dacryoadenitis with high level of the serum IgG4. He underwent oral steroid therapy and the swollen lacrimal glands were significantly improved. The results suggest that there may be pathological links between IgG4-related dacryoadenitis and Castleman disease.Keywords: IgG4, dacryoadenitis, Castleman disease, steroid

  20. Isolated IgG4-related cholecystitis mimicking gallbladder cancer: a case report. (United States)

    Shin, Sang-Wook; Kim, Yongsoo; Jeong, Woo Kyoung; Kim, Jinoo; Kim, Min Yeong; Oh, Young Ha; Pyo, Ju Yeon


    A 58-year-old man with right upper quadrant pain was referred to the radiology department. The patient underwent computed tomography and magnetic resonance imaging, which suggested the diagnosis of gallbladder cancer invading the liver. After surgical removal of the gallbladder, and the adjacent liver parenchyma was performed, the histologic diagnosis of IgG4-related cholecystitis was made.

  1. 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)


    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.

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

    Directory of Open Access Journals (Sweden)

    Heath A. Smith


    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.

  3. A novel chemiluminescent immunoassay for detection of Toxoplasma gondii IgG in human sera. (United States)

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


    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.

  4. Regulatory effects of intrinsic IL-10 in IgG immune complex-induced lung injury

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P;


    injury. In the current study, we sought to determine whether endogenous IL-10 is playing a regulatory role in the lung inflammatory response. On the basis of lung mRNA and ELISA measurements, IL-10 induction was found during development of inflammation in the IgG immune complex model of lung injury...

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

    DEFF Research Database (Denmark)

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


    Tumor cells can express so-called onconeural antigens, which are normally restricted to mature neurons and glial cells in the CNS.1 The detection of neural-reactive immunoglobulin G (IgG) aids the diagnosis of paraneoplastic neurologic syndromes (PNS)1; however, the diagnostic utility and potenti...

  6. Increased RP105-Negative B Cells in IgG4-Related Disease. (United States)

    Koarada, S; Tashiro, S; Nagao, N; Suematsu, R; Ohta, A; Tada, Y


    Four patients with IgG4-related disease (IgG4-RD) showed increased percentages of RP105-negative B cells in the peripheral blood. Case 1: A 66-year-old man having retroperitoneal fibrosis had 18.8% of RP105-negative B cells. Oral prednisolone improved the affected lesions and the percentage of RP105-negative B cells decreased (3.2%) after the treatment. Case 2: A 53-year-old man with retroperitoneal fibrosis had 27.9% of RP105-negative B cells. Case 3: A 38-year-old man with follicular hyperplasia showed increased percentage of RP105-negative B cells (8.3%). Case 4: A 60-year-old man with interstitial nephritis had 27.5% of RP105-negative B cells. The treatment decreased the numbers of RP105-negative B cells. Increased numbers of RP105-negatvie B cells is possibly associated with disease activity of IgG4-RD. Analysis of expression of RP105 on B cells may be helpful in evaluation of disease activity of IgG4-RD.

  7. Anti-amyloidogenic Activity of IgGs Contained in Normal Plasma (United States)

    Williams, Angela D.; McWilliams-Koeppen, Helen P.; Acero, Luis; Weber, Alfred; Ehrlich, Hartmut; Schwarz, Hans P.; Solomon, Alan


    Introduction We have previously shown that a subpopulation of naturally occurring human IgGs has therapeutic potential for the amyloid-associated disorders. These molecules cross-react with conformational epitopes on amyloidogenic assemblies, including amyloid beta (Aβ) protein fibrils that are a pathological hallmark of Alzheimer’s disease. Materials and Methods Using our europium-linked immunosorbant assay, we established that ∼95% of 260 screened donor plasma samples had amyloid fibril-reactive IgGs and Aβ conformer-reactive IgGs with minimal binding to Aβ monomers. Anti-amyloidogenic reactivity was diverse and attributed to Aβ targeting multiple fibril-related binding sites and/or variations in multidentate binding. Results and Discussion There was no correlation between anti-fibril and anti-oligomer reactivity and donor age (19 to 60 years old) or gender. These findings demonstrate the inherent but diverse anti-amyloidogenic activity of natural IgGs contained in normal plasma. Conclusion Our studies provide support for investigating the clinical significance and physiological function of this novel class of antibodies. PMID:20405179

  8. Autoimmune hemolytic anemia, as part of Evans' syndrome, caused by cold reactive IgG autoantibodies

    NARCIS (Netherlands)

    Jaarsma, AS; Muis, N; DeGraaf, SSN


    We describe a boy with Evans' syndrome, consisting of immune thrombocytopenic purpura at age 2 and autoimmune hemolytic anemia (AIHA) at age 4. AIHA was caused by cold Ige autoantibodies. This is unusual because AIHA is generally associated with either warm IgG antibodies or cold IgM antibodies. Tre

  9. IgG antibodies in patients with pemphigus vulgaris before and after diagnosing with immunofluorescence. (United States)

    Azimi, Hamideh; Majidi, Jafar; Estakhri, Rasul; Goldust, Mohamad


    Pemphigus is defined as a group of chronic self-immune vesicular diseases histologically recognized by inter-epidermic vesicles resulting from acantholysis. The aim of this study was to evaluate the precipitant and circulative IgG antibodies in patients with pemphigus vulgaris before and after treating with immunofluorescence. Sixty-two patients (34 females and 28 males) with clinically and pathologically confirmed P.V. were studied prospectively over a one year period of time during which direct and indirect immunofluorescent tests were performed before and after treatment. They had mild or moderate forms of disease. All patients received prednisolon 1-2 mg/kg/day and Azathioprine 2-3 mg/kg/day or methylpredisolon (1 g day(-1) for 4 days) and cyclophosphamide (500 mg/first day) pulse therapy due to general condition. Thirty- four females and 28 males enrolled, the mean age were 39.5 years (SD = 12.7). Before treatment, 10 and 52 cases were positive for skin depositing + or ++) and circulatory IgG (1/20 -1/60), respectively. Two to 3 month later, 37 were IgG positive with titers 1/20 to 1/160. The correlation between circulatory IgG before and after treatment was weakly positive (p = 0.05, r = 0.415). In the present study, treatment methods used for patients suffering from pemphigus vulgaris were not successful in significantly decreasing the circulative autoantibodies levels.

  10. Functionalization of SU-8 Photoresist Surfaces with IgG Proteins

    DEFF Research Database (Denmark)

    Blagoi, Gabriela; Keller, Stephan Urs; Johansson, Alicia;


    The negative epoxy-based photoresist SU-8 has a variety of applications within microelectromechanical systems (MEMS) and lab-on-a-chip systems. Here, several methods to functionalize SU-8 surfaces with IgG proteins were investigated. Fluorescent labeled proteins and fluorescent sandwich immunoass...

  11. 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


    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....

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

    Directory of Open Access Journals (Sweden)

    Jesse W. Williams


    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.

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


    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.

  14. Inhibition of murine fibrocyte differentiation by cross-linked IgG is dependent on FcγRI. (United States)

    Pilling, Darrell; Crawford, Jeffrey R; Verbeek, J Sjef; Gomer, Richard H


    Monocyte-derived, fibroblast-like cells, called fibrocytes, participate in wound-healing and the formation of fibrotic lesions. Aggregated or cross-linked IgG are key effectors in infections, autoimmune diseases, anaphylaxis, and immunotherapy. Cells, including monocytes and fibrocytes, bind IgG using FcγRs, and aggregated or cross-linked IgG inhibits fibrocyte differentiation. Mice have four different FcγRs, and which of these, if any, mediate the cross-linked IgG effect on fibrocyte differentiation is unknown. We find that in mice, deletion of FcγRI or the common signaling protein FcRγ significantly reduces the ability of cross-linked IgG or IgG2a to inhibit fibrocyte differentiation. Cells from FcγRIIb/III/IV KO mice are still sensitive to cross-linked IgG, whereas cells from FcγRI/IIb/III/IV KO mice are insensitive to cross-linked IgG. These observations suggest that IgG-mediated inhibition of fibrocyte differentiation is mediated by FcγRs, with FcγRI mediating most of the signaling.

  15. 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. (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


    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.

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Berrin Uzun


    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

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


    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.

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

    Directory of Open Access Journals (Sweden)

    M Pedram


    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.

  20. IgG, IgA, and lysozyme in Martina Franca donkey jennies and their foals. (United States)

    Veronesi, Maria C; Dall'Ara, Paola; Gloria, Alessia; Servida, Francesco; Sala, Elisabetta; Robbe, Domenico


    Because immune transfer from jenny to donkey foal is mostly unknown, the aim of the present study was to evaluate, from 5 days before to 10 days after foaling, immunoglobulin (Ig)G, IgA, and lysozyme peripartal concentrations in serum and mammary secretions of 10 healthy, spontaneously foaling Martina Franca jennies and in serum of their mature, viable, healthy foals, in the first 10 days after birth. The results showed that, in jennies, mammary secretion of IgG levels (ranging between 16 and 75 mg/mL) and IgA (0.9-2 mg/mL), and IgG (6.8-13.5 mg/mL) and IgA (0.5-2.4 mg/mL) serum concentrations were not different along the time of study. Also, IgG concentrations in serum of foals did not show significant differences although a high level was observed at 12 hours after birth (8 mg/mL), and IgA concentrations in serum of foals did not show any significant difference, although a high level was observed at 12 hours after birth (1.2 mg/mL). Lysozyme increased significantly at Day 2 after parturition in mammary secretions of jennies (551.9 μg/mL) and at 12 hours in serum of foals (25.9 μg/mL). The study demonstrated that the pattern of passive immune transfer in donkey foals seems to be similar to that reported for the horse foal, with IgG predominating IgA in serum and mammary secretions of the jenny and also in serum of foals. The most significant early increase in foals' serum concerns lysozyme, which probably plays an important role in the innate immunity of the donkey foal in the first challenging hours after birth.

  1. Recent advances in the concept and pathogenesis of IgG4-related disease in the hepato-bilio-pancreatic system. (United States)

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


    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.

  2. Concomitant occurrence of IgG4-related pleuritis and periaortitis: a case report with review of the literature. (United States)

    Ishida, Mitsuaki; Hodohara, Keiko; Furuya, Aya; Fujishiro, Aya; Okuno, Hiroko; Yoshii, Miyuki; Horinouchi, Akiko; Shirakawa, Ayaka; Harada, Ayumi; Iwai, Muneo; Yoshida, Keiko; Kagotani, Akiko; Yoshida, Takashi; Okabe, Hidetoshi


    IgG4-related sclerosing disease is an established disease entity with characteristic clinicopathological features. Some recent reports have demonstrated that this disease can occur in the respiratory system including the pleura. Herein, we describe the first documented case of concomitant occurrence of IgG4-related pleuritis and periaortitis. A 71-year-old Japanese female with a history of essential thrombocythemia presented with persistent cough and difficulty in breathing. Computed tomography demonstrated thickening of the right parietal pleura, pericardium, and periaortic tissue and pleural and cardiac effusions. Histopathological study of the surgical biopsy specimen of the parietal pleura revealed marked fibrous thickening with lymphoplasmacytic infiltration. Phlebitis was noted, however, only a few eosinophils had infiltrated. Immunohistochemical study revealed abundant IgG4-positive plasma cell infiltration and high ratio of IgG4-/IgG-positive plasma cells (84%). Therefore, a diagnosis of IgG4-related pleuritis was made with consideration of the elevated serum IgG4 level (684 mg/dL). Recently, the spectrum of IgG4-related sclerosing disease has expanded, and this disease can occur in the pleura, pericardium, and periaortic tissue. Although histopathological analysis of the pericardium and periaortic tissue was not performed in the present case, it was suspected that thickening of the pericardium and periaortic tissue was clinically due to IgG4-related sclerosing disease. Our clinicopathological analyses of IgG4-related pleuritis and pericarditis reveal that this disease can present as dyspnea and pleural and pericardial effusion as seen in the present case, therefore, it is important to recognize that IgG4-related sclerosing disease can occur in these organs for accurate diagnosis and treatment.

  3. 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


    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

  4. Study of IgG subclass profiles of anti-HBs in populations with different HBV infection status. (United States)

    Tsai, Tzu-Hsin; Huang, Chien-Fu; Wei, James Cheng-Chung; Ho, Mei-Shang; Wang, Lina; Tsai, Wei-Yu; Lin, Chien-Chou; Xu, Fang-Ling; Yang, Chi-Chiang


    To study IgG-specific subclasses of hepatitis B virus (HBV) surface antigen (anti-HBs), in different populations in Taiwan, a comparison was made between 104 chronic carriers (60 male and 44 female) and 439 recovered individuals (247 male and 192 female). Biochemical analyses of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also performed. Among the 104 chronic carriers, 21 patients had abnormal ALT and AST levels (> 25 IU/ml). When comparing the patients with abnormal ALT and AST levels to chronic carriers with normal ALT and AST levels, no statistical difference was observed for anti-HBs levels (p > 0.05). The IgG subclass pattern of the relative anti-HBs IgG subclass titers was IgG1 > IgG3 = IgG4 in both chronic carriers and recovered individuals (p anti-HBs antibody after HBV infection, in either chronic carriers or in HBV-cured individuals. This finding is partly inconsistent with data reported from other group who suggested in individuals naturally infected, the anti-HBs IgG consists mainly of IgG3 and IgG1. In contrast to that of our previous studies of anti-HBe and anti-HBc, the mean OD values of anti-HBs total IgG, and all IgG subclasses except for IgG2, of either males or females, were significantly higher in recovered individuals than in chronic carriers, while the mean OD values of anti-HBe and anti-HBc were significantly higher in chronic carriers than in recovered individuals (P anti-HBs in chronic carriers was not changed with liver inflammation and was independent of sex and age, except in individuals with abnormal ALT and AST for whom anti-HBs IgG1 was not significantly higher than IgG3 (p > 0.05), in spite of that whose mean O.D. value is higher.

  5. 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. (United States)

    Suzuki, Lisandra Akemi; Rossi, Cláudio Lúcio


    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.

  6. 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

    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.

  7. Production and Purification of a Polyclonal Antibody Against Purified Mouse IgG2b in Rabbits Towards Designing Mouse Monoclonal Isotyping Kits

    Directory of Open Access Journals (Sweden)

    Sadeq Eivazi


    Full Text Available Purpose: Mouse IgG subclasses containing IgG1, IgG2a, IgG2b and IgG3 have been defined and described both physiochemically and immunologically. Methods: Sepharose beads conjugated with protein A affinity chromatography was used for purification of mouse IgG2b. Sodium citrate buffer (0.1 M, pH: 3.5 was used for separation of mouse IgG2b. Verification of the purified fractions was monitored by SDS-PAGE (polyacrylamide gel electrophoresis in reducing condition. Immunized rabbit serum was collected and precipitated at the final concentration of 50% ammonium sulfate. After dialysis against tris-phosphate buffer (pH: 8.1 ion exchange chromatography column was used for purification of rabbit anti-mouse IgG2b. The periodate method was performed for conjugation with some variations. After conjugation, direct ELISA was used to determine the titer of HRP conjugated rabbit IgG against mouse IgG2b. Results: The titer of rabbit anti-mouse IgG2b that determined by ELISA was 32000. The purity of rabbit anti-mouse IgG2b was about 95%. The optimum dilution of prepared HRP conjugated IgG was 1:10000. This study showed that ion-exchange chromatography and affinity chromatography could be appropriate techniques for purification of mouse IgG and IgG subclasses respectively. Conclusion: This study showed that affinity chromatography could be an appropriate method for purification of IgG2b antibodies.

  8. 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)



    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.

  9. The IgG avidity value for the prediction of Toxoplasma gondii infection in the amniotic fluid. (United States)

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


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bohyun; Kim, Jin Hee, E-mail:; Byun, Jae Ho; Kim, Hyoung Jung; Lee, Seung Soo; Kim, So Yeon; Lee, Moon-Gyu


    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.

  11. 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.

  12. Persistent Low Toxoplasma IgG Avidity Is Common in Pregnancy: Experience from Antenatal Testing in Norway.

    Directory of Open Access Journals (Sweden)

    Gry Findal

    Full Text Available The parasite Toxoplasma gondii might harm the fetus if a woman is infected during pregnancy. IgG seroconversion and significant increase in IgG antibody amount in pregnancy indicates maternal infection. Presence of toxoplasma immunoglobulin M (IgM, immunoglobulin G (IgG and low IgG avidity in a single serum sample indicates possible maternal infection, but positive toxoplasma IgM and low IgG avidity may persist for months and even years. We aimed to evaluate avidity development during pregnancy in a retrospective study. Serial blood samples from 176 pregnant women admitted to Oslo University Hospital 1993-2013 for amniocentesis because of suspected toxoplasma infection were included. Data were obtained from journals and laboratory records. The avidity method used was based on Platelia Toxo IgG assay. Mean maternal age at first serology was 29.9 years (SD 5.2, range 18-42. In 37 (21% women only the avidity increased from low to high in < 3 months. In 139 (79% the IgG avidity remained below the high threshold ≥ 3 months and within this group 74 (42% women had stable low IgG avidity during the observation period. Median gestational age at first test was 10.6 weeks (range 4.6-28.7. Fetal infection was detected in four children, but none among children whose mother had stable low IgG avidity. The first antenatal toxoplasma serology should ideally be collected in early pregnancy and if stable values of toxoplasma IgM and low IgG-avidity are detected in a second sample after three to four weeks, the need for amniocentesis can be questioned.

  13. Decreased HHV-6 IgG in Alzheimer’s Disease (United States)

    Westman, Gabriel; Blomberg, Jonas; Yun, Zhibing; Lannfelt, Lars; Ingelsson, Martin; Eriksson, Britt-Marie


    Human herpesviruses have previously been implicated in the pathogenesis of Alzheimer’s disease (AD) but whether they are causal, facilitating, or confounding factors is yet to be established. A total of 50 AD subjects and 52 non-demented (ND) controls were analyzed in a multiplex assay for IgG reactivity toward herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6). The HHV-6 IgG reactivity was significantly lower in AD subjects compared to ND controls, whereas there were no differences in HSV, VZV, or CMV antibody levels between the groups. Analysis of peripheral blood mononuclear cells with a subtype-specific HHV-6 PCR revealed no signs of reactivation, as AD and ND subjects presented with comparable HHV-6 DNA levels in PBMCs, and all positive samples were of subtype B. Whether HHV-6 is a factor in AD remains to be elucidated in future studies. PMID:28265256

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

    Directory of Open Access Journals (Sweden)



    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.

  15. IgG platelet antibodies in EDTA-dependent pseudothrombocytopenia bind to platelet membrane glycoprotein IIb. (United States)

    Fiorin, F; Steffan, A; Pradella, P; Bizzaro, N; Potenza, R; De Angelis, V


    EDTA-dependent pseudothrombocytopenia (PTCP) consists of an inappropriate low platelet count caused by autoantibodies present in the serum samples reacting with platelets only in EDTA-anticoagulated blood. By using immunoprecipitation and Western blot techniques, we studied the immunochemical specificity of platelet agglutinating autoantibodies in the serum samples of 10 patients with PTCP. Furthermore, to evaluate a possible role of PTCP-associated IgG autoantibodies in increased platelet turnover, we assayed the plasma glycocalicin (GC) level and calculated the GC index for every patient. Our results provide direct evidence that an epitope located on platelet membrane glycoprotein IIb is recognized by PTCP-associated IgG antibodies; moreover GC levels in patients with EDTA-dependent PTCP were similar to control levels, thus excluding an increased platelet turnover. We conclude that antiplatelet antibodies directed against platelet cryptantigens are unlikely to have a major role in the increased removal of cells from circulation.

  16. Steroid-responsive IgG4-related disease with isolated prostatic involvement: An unusual presentation with elevated serum PSA

    Directory of Open Access Journals (Sweden)

    Vikas Jain


    Full Text Available Autoimmune prostatitis is known to occur as a part of multisystem fibro-inflammatory disorder known as IgG4 related disease (IgG4 RD. The usual presentation is with symptoms of gastro-intestinal disease with prostatic involvement presenting as lower urinary tract symptoms. The disease responds to corticosteroids. We report an asymptomatic young man who was diagnosed to have IgG4 related prostatitis on TRUS-guided prostate biopsy done for elevated serum PSA, in the absence of any other systemic involvement. The treatment with steroid resulted in normalization of S PSA levels.

  17. Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. (United States)

    Cross, Shelley A; Salomao, Diva R; Parisi, Joseph E; Kryzer, Thomas J; Bradley, Elizabeth A; Mines, Jonathan A; Lam, Byron L; Lennon, Vanda A


    Autoantibodies have defined two paraneoplastic visual disorders related to small-cell lung carcinoma: retinopathy ("CAR"-IgG [23kDa, recoverin]) and optic neuritis collapsin response-mediated protein 5 (CRMP-5-IgG [62kDa]). Among 16 patients with CRMP-5-IgG and optic neuritis (aged 52-74 years; all smokers, 9 women), we documented coexisting retinitis in 5. None had CAR-IgG. Fifteen had subacute vision loss, swollen optic discs, and field defects. Vascular leakage was evident at and remote from the disc; 5/5 tested had abnormal electroretinograms. Nine had striking vitreous cells. Vitrectomy showed reactive lymphocytosis (4/4), predominantly CD4(+) (1/1). Most patients had multifocal neurological accompaniments. Cerebrospinal fluid contained lymphocytes (7-32), elevated protein, multiple oligoclonal immunoglobulin bands, and CRMP-5-IgG. Three patients superficially resembled Devic's disease at presentation. One autopsied patient had predominantly CD8(+) T lymphocytes infiltrating optic nerve and spinal cord. Eleven patients had confirmed small-cell carcinoma; 1 had imaging evidence of lung cancer; 3 had renal or thyroid carcinoma. Full-length CRMP-5 protein was identified in normal retina and optic nerve by Western blot analyses. Photoreceptor cells, retinal ganglion cells, and nerve fibers exhibited CRMP-5-specific immunoreactivity. In summary, CRMP-5-IgG defines a paraneoplastic ophthalmological entity of combined optic neuritis and retinitis with vitreous inflammatory cells. Positive serology obviates the need for vitreous biopsy and expedites the search for cancer.

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


    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.

  19. Comparison of chemiluminescent immunoassay and ELISA for measles IgG and IgM. (United States)

    de Ory, Fernando; Minguito, Teodora; Balfagón, Pilar; Sanz, Juan C


    In the context of measles elimination, the identification of recent infections is important for clinical laboratories. Serological diagnosis is achieved by detecting specific IgG and IgM. Recently an automated chemiluminescent immunoassay (CLIA) (Liaison, DiaSorin, Italy) has been used to quantify the measles antibody. The aim of this study was to compare this assay with Enzygnost ELISA (Siemens, Germany), with final classification of discrepancies by indirect immunofluorescence (Euroimmun, Germany). For measles IgM, 204 sera were analyzed: 50 IgM-positive, 104 IgM-negative/IgG-positive, and 50 from other viral infections (B19V, rubella, mumps, CMV, and EBV). For the measles IgG assay, 162 samples were tested: 106 were positive and 56 were negative. For measles IgM, the sensitivity and specificity of CLIA against ELISA were 94% (95% CI: 83.2-98.6) and 100% (95% CI: 97.1-100), respectively; the corrected figures after the final classification of discrepancies were 100% (95% CI: 91.0-100) and 99.4% (95% CI: 96.1-100), respectively. In relation to IgG, the sensitivity and specificity of CLIA against ELISA were, respectively, 97.2% (95% CI: 91.7-99.4) and 92.9% (95% CI: 82.5-97.7), and 95.5% (95% CI: 89.5-98.3) and 100% (95% CI: 91.8-100) after the final classification. CLIA showed excellent sensitivity and specificity in detecting measles IgG and IgM antibodies, eliminating the need to aliquot specimens before carrying out the assay.

  20. 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.

  1. IgG4-related Sclerosing Mesenteritis in a 7-year-old Saudi Girl


    Hasosah, Mohammed Y.; Satti, Mohamed B.; Yousef, Yasmin A.; Alzahrani, Daifullah M.; Almutairi, Sajdi A.; Ashraf F Alsahafi; Sukkar, Ghassan A.; Alzaben, Abdullah A.


    Sclerosing mesenteritis (SM) is a rare, benign inflammatory disorder of unknown etiology, affecting the membranes of the digestive tract that involves lymphoplasmacytic inflammation, fat necrosis, and fibrosis of the mesentery. We report a child patient with a history of recurrent abdominal pain and fever who was found to have an intra-abdominal mass suspicious for malignancy. A tissue biopsy revealed the diagnosis of SM associated with IgG4-related systemic disease. The patient is currently ...

  2. 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.


    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.

  3. Immunogenicity of Isogenic IgG in Aggregates and Immune Complexes (United States)

    St. Clair, J. Benjamin; Detanico, Thiago; Aviszus, Katja; Kirchenbaum, Greg A.; Christie, Merry; Carpenter, John F.


    A paradox in monoclonal antibody (mAb) therapy is that despite the well-documented tolerogenic properties of deaggregated IgG, most therapeutic IgG mAb induce anti-mAb responses. To analyze CD4 T cell reactions against IgG in various physical states, we developed an adoptive transfer model using CD4+ T cells specific for a Vκ region-derived peptide in the hapten-specific IgG mAb 36–71. We found that heat-aggregated or immune complexes (IC) of mAb 36–71 elicited anti-idiotypic (anti-Id) antibodies, while the deaggregated form was tolerogenic. All 3 forms of mAb 36–71 induced proliferation of cognate CD4+ T cells, but the aggregated and immune complex forms drove more division cycles and induced T follicular helper cells (TFH) development more effectively than did the deaggregated form. These responses occurred despite no adjuvant and no or only trace levels of endotoxin in the preparations. Physical analyses revealed large differences in micron- and nanometer-sized particles between the aggregated and IC forms. These differences may be functionally relevant, as CD4+ T cell proliferation to aggregated, but not IC mAb 36–71, was nearly ablated upon peritoneal injection of B cell-depleting antibody. Our results imply that, in addition to denatured aggregates, immune complexes formed in vivo between therapeutic mAb and their intended targets can be immunogenic. PMID:28114383

  4. Elevated Serum IgG4 Defines Specific Clinical Phenotype of Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Le-Feng Chen


    Full Text Available Objectives. To explore the correlation of serum IgG4 (sIgG4 with clinical manifestations or therapeutic response in rheumatoid arthritis (RA. Methods. Consecutive 136 RA patients were recruited and followed up at regular interval. SIgG4 was detected by immunonephelometry. Serial synovial tissue sections from 46 RA patients were stained immunohistochemically for IgG4. Results. Forty-six percent of 136 RA patients had elevated sIgG4. Patients with elevated sIgG4 had higher sIgG4/sIgG ratio, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and anticyclic citrullinated peptide antibodies than those with normal sIgG4 (all P<0.05. Among 45 patients who received methotrexate and leflunomide therapy, 50% (9/18 of patients with elevated sIgG4 and 85% (23/27 of patients with normal sIgG4 reached therapeutic target (disease activity score of 28 joints < 3.2 at 6-month visit (χ2=6.508, P=0.011. IgG4-positive plasma cell count correlated positively with sIgG4, total synovitis score, and CD3-, CD20-, and CD38-positive cell counts (all P<0.05. Conclusions. Our results showed that elevated sIgG4 in RA is common and disproportional to total IgG and RA with elevated sIgG4 may be a specific clinical phenotype with higher disease activity, higher level of autoantibodies, and poor response to methotrexate and leflunomide therapy.

  5. Toxocara Canis IgG Seropositivity in Patients with Chronic Urticaria

    Directory of Open Access Journals (Sweden)

    Mehmet Burak-Selek


    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. 

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


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


    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...

  7. Evaluation of an on-farm method to assess colostrum IgG content in sows. (United States)

    Balzani, A; Cordell, H J; Edwards, S A


    The objective of this work was to investigate the evaluation of swine colostrum immunoglobulin G (IgG) concentration using the Brix refractometer. Colostrum samples were collected across all teats, from 124 sows of mixed parities. According to sampling time, three categories were created: samples available from 9 h before the onset of parturition until the first piglet was born were classified as before farrowing; samples collected after the first birth until 4 h later were classified as during farrowing; and finally samples collected from this point until 14 h after parturition, were classified as after farrowing. Samples were drawn and divided into three portions; one was immediately analyzed, a second was refrigerated and the third was frozen at -20°C. Fresh and refrigerated colostrum samples were analyzed at the farm with a Brix refractometer. IgG content of frozen samples was analyzed using a Brix refractometer, with a subset of 42 samples also tested with a commercially available radial immune diffusion (RID) kit. The Brix percentage ranged from 18.3% to 33.2%. Brix percentage repeatability, assessed by the intraclass correlation coefficient (ICC), was very strong (fresh ICC=0.98, refrigerated ICC=0.88 and frozen ICC=0.99). One-way repeated-measures ANOVA showed that storage temperature did not affect BRIX percentage of colostrum IgG (P>0.05). ANOVA results show a significant effect of sampling time on colostrum immunoglobulin concentration, measured with both Brix and RID (Brix: Pcolostrum IgG in sows.

  8. Toxocara Canis IgG Seropositivity in Patients with Chronic Urticaria. (United States)

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


    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.

  9. Plasma IgG autoantibody against actin-related protein 3 in liver fluke Opisthorchis viverrini infection. (United States)

    Rucksaken, R; Haonon, O; Pinlaor, P; Pairojkul, C; Roytrakul, S; Yongvanit, P; Selmi, C; Pinlaor, S


    Opisthorchiasis secondary to Opisthorchis viverrini infection leads to cholangiocellular carcinoma through chronic inflammation of the bile ducts and possibly inducing autoimmunity. It was hypothesized that plasma autoantibodies directed against self-proteins are biomarkers for opisthorchiasis. Plasma from patients with opisthorchiasis was tested using proteins derived from immortalized cholangiocyte cell lines, and spots reacting with plasma were excised and subjected to LC-MS/MS. Seven protein spots were recognized by IgG autoantibodies, and the highest matching scored protein was actin-related protein 3 (ARP3). The antibody against ARP3 was tested in plasma from 55 O. viverrini-infected patients, 24 patients with others endemic parasitic infections and 17 healthy controls using Western blot and ELISA. Immunoreactivity against recombinant ARP3 was significantly more prevalent in opisthorchiasis compared to healthy controls at Western blotting and ELISA (P < 0.05). Plasma ARP3 autoantibody titres were also higher in opisthorchiasis compared to healthy individuals (P < 0.01) and other parasitic infections including Strongyloides stercoralis (P < 0.001), echinostome (P < 0.05), hookworms (P < 0.001) and Taenia spp. (P < 0.05). It was further characterized in that the ARP3 autoantibody titre had a sensitivity of 78.18% and specificity of 100% for opisthorchiasis. In conclusion, it may be suggested that plasma anti-ARP3 might represent a new diagnostic antibody for opisthorchiasis.

  10. Detection of IgG Anti-Leishmania Antigen by Flow Cytometry as a Diagnostic Test for Cutaneous Leishmaniasis (United States)

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


    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

  11. Immunoglobulin clases IgG, IgM, IgA and complement component C3 in dental periapical lesions of patients with rheumatoid disease. (United States)

    Malmström, M


    To identify the immunoglobulin classes present in dental periapical lesions and to determine how, if at all, the distribution of immunoglobulin classes IgG. IgM and IgA differ in the dental periapical lesions of rheumatoid and control patients, paraffin-embedded and frozen tissues from the dental periapical lesions of 36 rheumatoid and 22 control patients were examined by the direct immunofluorescence technique. In addition, both rheumatoid and control tissues were examined for the presence of complement component C3, albumin and fibrinogen. Neither the greater frequency and abundancy with which IgG and to a lesser degree, IgA occurred in the dental periapical lesions of rheumatoid patients than in the corresponding lesions of control patients, nor the more frequent occurrence of complement component C3 in these same lesions, was statistically significant. No difference in the distribution of the various immunoglobulin classed could be discerned between the rheumatoid and control group. Albumin was distributed almost equally between the two patient groups. The greater abundance of fibrinogen among control patients was, however, statistically significant. These results do not provide evidence that an immunologic reaction takes place in the dental periapical lesions of patients with rheumatoid disease similar to that which characterizes rheumatoid inflammation. However, the presence of such a reaction cannot be excluded without more extensive investigation.

  12. Interactions of IgG1 CH2 and CH3 domains with FcRn

    Directory of Open Access Journals (Sweden)

    Tianlei eYing


    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.

  13. Saliva and sera IgA and IgG in Egyptian Giardia-infected children. (United States)

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


    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.

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

    LENUS (Irish Health Repository)

    Coss, K P


    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.

  15. Use of IgG Avidity test in case definitions of toxoplasmosis in pregnancy. (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


    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.

  16. [IgG4- and MPO-ANCA-associated hypertrophic pachymeningitis]. (United States)

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


    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.

  17. Positive IgG Western Blot for Borrelia burgdorferi in Colombia

    Directory of Open Access Journals (Sweden)

    Palacios Ricardo


    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.

  18. [Central nervous system in IgG4-related disease: case report and literature review]. (United States)

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


    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.

  19. Atractylodis macrocephalae Koidz. polysaccharides enhance both serum IgG response and gut mucosal immunity. (United States)

    Xie, Feng; Sakwiwatkul, Kedsirin; Zhang, Cenrong; Wang, Yueming; Zhai, Lijuan; Hu, Songhua


    Fifty-six mice were randomly divided into four groups with 14 mice in each. Two groups were subcutaneously injected twice with a foot-and-mouth disease vaccine with 2-week intervals; each of them had been orally administered 0.89% saline or Atractylodis macrocephalae Koidz. polysaccharides (RAMPS) 0.05 g for 4 days before immunization. The rest were not immunized but treated in the same way. One-week after the primary and two weeks after the booster immunization, half in each group were sacrificed to measure serum IgG and the parameters for the intestinal mucosal immunity. Results indicated that oral administration of RAMPS increased both serum specific IgG response and intestinal mucosal immunity as shown by elevated total sIgA, mRNA expression of TGF-β, IL-6, TNF-α, IgA(+) cells and intestinal intraepithelial lymphocytes in duodenum. It is suggested that increased serum IgG response may be associated with enhanced local mucosal immunity by oral administration of RAMPS.

  20. IgG glycan hydrolysis by EndoS inhibits experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Benkhoucha Mahdia


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

    Directory of Open Access Journals (Sweden)

    Latha G


    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.

  2. Wuchereria bancrofti filariasis in French Polynesia: age-specific patterns of microfilaremia, circulating antigen, and specific IgG and IgG4 responses according to transmission level. (United States)

    Chanteau, S; Glaziou, P; Plichart, C; Luquiaud, P; Moulia-Pelat, J P; N'Guyen, L; Cartel, J L


    The age-specific patterns of microfilaremia, Og4C3 antigenemia, anti-Brugia malayi IgG and IgG4 were assessed in 3 villages of low, medium and high transmission level for Wuchereria bancrofti filariasis. The prevalence rates for each of the 4 markers were clearly age dependent and their patterns strongly associated with the transmission level. The antigenemia prevalence rate was consistently higher than the microfilaremia prevalence rate, in all age groups. The prevalences of anti-B. malayi IgG and IgG4 responses were very similar and much higher than those of microfilaremia or antigenemia. Antibody responses reached the plateau at an earlier age and at a higher prevalence with increased intensity of transmission. For all the markers, the prevalence rates were significantly higher in males than in females.

  3. Avidez de anticorpos IgG específicos como marcadores de infecção primária recente pelo Toxoplasma gondii Avidity of specific IgG antibody as a marker of recent and old toxoplasma infections

    Directory of Open Access Journals (Sweden)

    Mário E. Camargo


    Full Text Available A caracterização de infecção primária recente pelo Toxoplasma gondii se apoia principalmente na presença, no soro, de anticorpos específicos IgM. Para fins diagnósticos de toxoplasmose aguda, ou de contágio recente, a possibilidade de outros marcadores é altamente desejável. Um marcador de infecção recente atualmente referido é a baixa afinidade ou avidez de anticorpos específicos IgG. Para avaliação do novo marcador, titularam-se os soros contra poliantígenos do T. gondii pelo teste imunoenzimático (ELISA, antes e após tratamento dos complexos antígeno-anticorpo formados, com solução de ureia 6 M como agente dissociante. O deslocamento de anticorpos de baixa avidez foi indicado por uma queda de títulos, calculada em porcentagem em relação aos títulos iniciais. Foram estudados 69 soros, 23 de cada um dos 3 perfis sorológicos sucessivos, observados na infecção, e que a caracterizam respectivamente como recente, em fase de transição e crônica. Os perfis foram determinados segundo os resultados de uma bateria de testes, incluindo os de imunofluorescência IgG e IgM, de captura de anticorpos IgM e de hemaglutinação. Para os soros de infecção crônica a queda observada foi de 3% ± 3%, de 34% ± 12% para toxoplasmose recente e de 12% ± 9% para a fase de transição. Conclue-se que a determinação da avidez de anticorpos IgG pode ser utilizada como marcador de infecção primária recente pelo T. gondii.For serologically characterizing a recent primary toxoplasma infection, the low avidity of IgG specific antibodies was studied. Avidity was evaluated as the decrease of IgG antibody titers in ELISA after treating plates with 6 M urea, as a dissociating solution of low avidity antigen-antibody complexes. Sixty nine serum samples were studied, presenting characteristic patterns of recent, transitional or chronic toxoplasmosis. Serological patterns were determined according to results of IgG and Ig

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


    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.

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

    Directory of Open Access Journals (Sweden)

    Tsukuru Minamiki


    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.

  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


    . 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......Therapeutic monoclonal antibodies (mAbs) are mainly produced by heterogonous expression in Chinese hamster ovary (CHO) cells. The glycosylation profile of the mAbs has major impact on the efficacy and safety of the drug and is therefore an important parameter to control during production...... heterogeneity and glycosylation patterns of IgG. None of the eight feed additives caused statistically significant changes to cell growth or IgG productivity, compared to controls. However, the addition of 20 mM galactose did result in a reproducible increase of galactosylated IgG from 14% to 25%. On the other...

  7. 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


    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

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

    Directory of Open Access Journals (Sweden)

    Karasuyama Hajime


    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

  9. Low positive predictive value of anti-Brugia malayi IgG and IgG4 serology for the diagnosis of Wuchereria bancrofti. (United States)

    Chanteau, S; Glaziou, P; Moulia-Pelat, J P; Plichart, C; Luquiaud, P; Cartel, J L


    Enzyme-linked immunosorbent assays (ELISAs) for anti-Brugia malayi immunoglobulin (Ig) G and IgG4 were evaluated on sera from 1561 subjects in French Polynesia for the serodiagnosis of Wuchereria bancrofti filariasis, compared with the test for Onchocerca gibsoni circulating antigen (Og4C3) as a 'gold standard'. The sensitivity of the ELISA-IgG and ELISA-IgG4 assays was 90.8% and 94.5%, and the specificity was 45.9% and 50.7%. The positive predictive values were 41% and 45% respectively for an antigen prevalence rate of 30%. Thus antibody prevalences exceeded by two-fold the antigen prevalence, which itself exceeded by two-fold the prevalence of microfilaraemia.

  10. Agglutinating mouse IgG3 compares favourably with IgMs in typing of the blood group B antigen: Functionality and stability studies. (United States)

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


    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.

  11. Agglutinating mouse IgG3 compares favourably with IgMs in typing of the blood group B antigen: Functionality and stability studies (United States)

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


    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

  12. Decreased levels of bisecting GlcNAc glycoforms of IgG are associated with human longevity.

    Directory of Open Access Journals (Sweden)

    L Renee Ruhaak

    Full Text Available BACKGROUND: Markers for longevity that reflect the health condition and predict healthy aging are extremely scarce. Such markers are, however, valuable in aging research. It has been shown previously that the N-glycosylation pattern of human immunoglobulin G (IgG is age-dependent. Here we investigate whether N-linked glycans reflect early features of human longevity. METHODOLOGY/PRINCIPAL FINDINGS: The Leiden Longevity Study (LLS consists of nonagenarian sibling pairs, their offspring, and partners of the offspring serving as control. IgG subclass specific glycosylation patterns were obtained from 1967 participants in the LLS by MALDI-TOF-MS analysis of tryptic IgG Fc glycopeptides. Several regression strategies were applied to evaluate the association of IgG glycosylation with age, sex, and longevity. The degree of galactosylation of IgG decreased with increasing age. For the galactosylated glycoforms the incidence of bisecting GlcNAc increased as a function of age. Sex-related differences were observed at ages below 60 years. Compared to males, younger females had higher galactosylation, which decreased stronger with increasing age, resulting in similar galactosylation for both sexes from 60 onwards. In younger participants (60 years, decreased levels of non-galactosylated glycoforms containing a bisecting GlcNAc reflected early features of longevity. CONCLUSIONS/SIGNIFICANCE: We here describe IgG glycoforms associated with calendar age at all ages and the propensity for longevity before middle age. As modulation of IgG effector functions has been described for various IgG glycosylation features, a modulatory effect may be expected for the longevity marker described in this study.

  13. 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


    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.

  14. The human IgG anti-carbohydrate repertoire exhibits a universal architecture and contains specificity for microbial attachment sites


    Schneider, Christoph; Smith, David F; Cummings, Richard D.; Boligan, Kayluz Frias; Hamilton, Robert G.; Bochner, Bruce S; Miescher, Sylvia; Simon, Hans-Uwe; Pashov, Anastas; Vassilev, Tchavdar; von Gunten, Stephan


    Despite the paradigm that carbohydrates are T cell-independent antigens, isotype-switched glycan-specific IgG antibodies and polysaccharide-specific T cells are found in humans. We employed a systems level approach combined with glycan array technology to decipher the repertoire of carbohydrate-specific IgG antibodies in intravenous and subcutaneous immunoglobulin (IVIG/SCIG) preparations. A strikingly universal architecture of this repertoire with modular organization among different donor p...

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

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


    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.

  16. Detection of Bovine IgG Isotypes in a PPA-ELISA for Johne's Disease Diagnosis in Infected Herds

    Directory of Open Access Journals (Sweden)

    Bárbara Fernández


    Full Text Available Johne's Disease or Paratuberculosis is a chronic granulomatous enteritis disease affecting ruminants. Detection of subclinically infected animals is difficult, hampering the control of this disease. The aim of this work was to evaluate the performance of detection of IgG isotypes in a PPA-ELISA to improve the recognition of cattle naturally infected with Map in different stages. A total of 108 animals from Tuberculosis-free herds were grouped as follows: exposed (n=30, subclinically infected (n=26, clinically infected (n=14, and healthy controls (n=38. Receiver-operating characteristic (ROC curves of isotypes/PPA-ELISAs were constructed and areas under the curves were compared to evaluate the performance of each test. Our study demonstrated that the conventional PPA-ELISA (detecting IgG is the best to identify clinically infected animals with high sensitivity (92.9% and specificity (100%. Meanwhile, IgG2/PPA-ELISA improved the number of subclinically infected cattle detected as compared with conventional IgG/PPA-ELISA (53.8 versus 23.1%. In addition, it had the maximum sensitivity (65.0%, taking into account all Map-infected cattle. In conclusion, the combination of IgG and IgG2/PPA-ELISAs may improve the identification of Map-infected cattle in different stages of disease. The usefulness of IgG2 detection in serological tests for Johne's Disease diagnosis should be further evaluated.

  17. Time-dependent solubilization of IgG in AOT-brine-isooctane microemulsions: role of cluster formation. (United States)

    Gerhardt, N I; Dungan, S R


    The stability and structure of protein-containing water-in-oil (w/o) microemulsions were investigated by using the large protein immunoglobulin G (IgG, MW 155,000) in a mixture comprised of brine, sulfosuccinic acid bis [2-ethylhexyl]ester (sodium salt), and isooctane. We explored factors affecting the initial uptake of IgG into the w/o microemulsion and its subsequent release to a solid (precipitate) phase, and the kinetics of the latter process. Influences of such parameters as pH, ionic strength, and protein concentration on the solubilization and precipitation of bovine IgG in the organic phase are described. The structure and dynamics in microemulsions containing bovine IgG were probed by using dynamic light scattering, and it was found that the presence of IgG in the microemulsion induced strong attractive forces between the droplets. Based on results obtained by using these various experimental approaches, a model for protein solubilization and release is proposed. In this model, we propose the formation of clusters within which bovine IgG resides and which substantially slow the kinetics of protein release from the droplets to the precipitate phase.

  18. Nano-visualization of oriented-immobilized IgGs on immunosensors by high-speed atomic force microscopy (United States)

    Iijima, Masumi; Somiya, Masaharu; Yoshimoto, Nobuo; Niimi, Tomoaki; Kuroda, Shun'ichi


    Oriented immobilization of sensing molecules on solid phases is an important issue in biosensing. In case of immunosensors, it is essential to scrutinize not only the direction and shape of immunoglobulin G (IgG) in solution but also the real-time movement of IgGs, which cannot be achieved by conventional techniques. Recently, we developed bio-nanocapsules (BNCs) displaying a tandem form of the IgG Fc-binding Z domain derived from Staphylococcus aureus protein A (ZZ-BNC) to enhance the sensitivity and antigen-binding capacity of IgG via oriented-immobilization. Here, we used high-speed atomic force microscopy (HS-AFM) to reveal the fine surface structure of ZZ-BNC and observe the movement of mouse IgG3 molecules tethered onto ZZ-BNC in solution. ZZ-BNC was shown to act as a scaffold for oriented immobilization of IgG, enabling its Fv regions to undergo rotational Brownian motion. Thus, HS-AFM could decipher real-time movement of sensing molecules on biosensors at the single molecule level.

  19. Recurrent membranous nephropathy in an allograft caused by IgG3κ targeting the PLA2 receptor. (United States)

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


    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.

  20. Serum or breast milk immunoglobulins mask the self-reactivity of human natural IgG antibodies. (United States)

    Djoumerska-Alexieva, Iglika; Manoylov, Iliyan; Dimitrov, Jordan D; Tchorbanov, Andrey


    B cells producing IgG antibodies specific to a variety of self- or foreign antigens are a normal constituent of the immune system of all healthy individuals. These naturally occurring IgG antibodies are found in the serum, external secretions, and pooled human immunoglobulin preparations. They bind with low affinity to antigens, which can also be targets for pathologic autoantibodies. An enhancement of naturally occurring IgG autoantibody activity was observed after treatment of human IgG molecules with protein-destabilizing agents. We have investigated the interactions of human immunoglobulins that were obtained from serum or from breast milk of healthy individuals or IVIg with human liver antigens. Proteins from an individual serum or milk were isolated by two methods, one of which included exposure to low pH and the other did not. Purified serum, mucosal IgM, IgA, and the fraction containing immunoglobulin G F(ab')2 fragments each inhibited the binding of a single donor or pooled IgG to human liver antigens. Our study presents findings regarding the role of the breast milk or serum antibodies in blocking the self-reactivity of IgG antibodies. It supports the suggestion that not IVIg only, but also the pooled human IgM and IgA might possess a potent beneficial immunomodulatory activity in autoimmune patients.

  1. Binding of fusion protein FLSC IgG1 to CCR5 is enhanced by CCR5 antagonist Maraviroc. (United States)

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


    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.


    Directory of Open Access Journals (Sweden)

    L. A. Burova


    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

  3. Galactosylation of IgG1 modulates FcγRIIB-mediated inhibition of murine autoimmune hemolytic anemia. (United States)

    Yamada, Kazunori; Ito, Kiyoaki; Furukawa, Jun-Ichi; Nakata, Junichiro; Alvarez, Montserrat; Verbeek, J Sjef; Shinohara, Yasuro; Izui, Shozo


    Murine immune effector cells express three different stimulatory FcγRs (FcγRI, FcγRIII and FcγRIV) and one inhibitory receptor, FcγRIIB. Competitive engagement of stimulatory and inhibitory FcγRs has been shown to be critical for the development of immune complex-mediated inflammatory disorders. Because of the previous demonstration that FcγRIIB was unable to inhibit FcγRIII-mediated autoimmune hemolytic anemia induced by 105-2H IgG1 anti-RBC mAb, we reevaluated the regulatory role of FcγRIIB on the development of anemia using two additional IgG1 anti-RBC mAbs (34-3C and 3H5G1) and different 34-3C IgG subclass-switch variants. We were able to induce a more severe anemia in FcγRIIB-deficient mice than in FcγRIIB-sufficient mice after injection of 34-3C and 3H5G1 IgG1, but not 105-2H IgG1. Structural analysis of N-linked oligosaccharides attached to the CH2 domain revealed that 105-2H was poorly galactosylated as compared with the other mAbs, while the extent of sialylation was comparable between all mAbs. In addition, we observed that a more galactosylated 105-2H variant provoked more severe anemia in FcγRIIB-deficient mice than FcγRIIB-sufficient mice. In contrast, the development of anemia induced by three non-IgG1 subclass variants of the 34-3C mAb was not down-regulated by FcγRIIB, although they were more galactosylated than its IgG1 variant. These data indicate that FcγRIIB-mediated inhibition of autoimmune hemolytic anemia is restricted to the IgG1 subclass and that galactosylation, but not sialylation, of IgG1 (but not other IgG subclasses) is critical for the interaction with FcγR, thereby determining the pathogenic potential of IgG1 autoantibodies.

  4. Specificity and Effector Functions of Human RSV-Specific IgG from Bovine Milk.

    Directory of Open Access Journals (Sweden)

    Gerco den Hartog

    Full Text Available BACKGROUND: Respiratory syncytial virus (RSV infection is the second most important cause of death in the first year of life, and early RSV infections are associated with the development of asthma. Breastfeeding and serum IgG have been shown to protect against RSV infection. Yet, many infants depend on bovine milk-based nutrition, which at present lacks intact immunoglobulins. OBJECTIVE: To investigate whether IgG purified from bovine milk (bIgG can modulate immune responses against human RSV. METHODS: ELISAs were performed to analyse binding of bIgG to human respiratory pathogens. bIgG or hRSV was coated to plates to assess dose-dependent binding of bIgG to human Fcγ receptors (FcγR or bIgG-mediated binding of myeloid cells to hRSV respectively. S. Epidermidis and RSV were used to test bIgG-mediated binding and internalisation of pathogens by myeloid cells. Finally, the ability of bIgG to neutralise infection of HEp2 cells by hRSV was evaluated. RESULTS: bIgG recognised human RSV, influenza haemagglutinin and Haemophilus influenza. bIgG bound to FcγRII on neutrophils, monocytes and macrophages, but not to FcγRI and FcγRIII, and could bind simultaneously to hRSV and human FcγRII on neutrophils. In addition, human neutrophils and dendritic cells internalised pathogens that were opsonised with bIgG. Finally, bIgG could prevent infection of HEp2 cells by hRSV. CONCLUSIONS: The data presented here show that bIgG binds to hRSV and other human respiratory pathogens and induces effector functions through binding to human FcγRII on phagocytes. Thus bovine IgG may contribute to immune protection against RSV.

  5. 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: [Department of Molecular Genetics, Institute of Biomedical Science, and JST CREST, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010 (Japan)


    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.

  6. Toxoplasmosis serology: an efficient hemagglutination procedure to detect IgG and IgM antibodies

    Directory of Open Access Journals (Sweden)

    M.E. Camargo


    Full Text Available In search of an efficient but simple, low cost procedure for the serodiagnosis of Toxoplasmosis, especially suited for routine laboratories facing technical and budget limitations as in less developed countries, the diagnostic capability of Hematoxo® , an hemagglutination test for toxoplasmosis, was evaluated in relation to a battery of tests including IgG- and IgM-immunofluorescence tests, hemagglutination and an IgM-capture enzymatic assay. Detecting a little as 5 I.U. of IgG antitoxoplasma antibodies, Hematoxo® showed a straight agreement as to reactivity and non-reactivity for the 443 non-reactive and the 387 reactive serum samples, included in this study. In 23 cases presenting a serological pattern of acute toxoplasmosis and showing IgM antibodies, Hematoxo® could detect IgM antibodies in 18, indicated by negativation or a significant decrease in titers as a result of treating samples with 2-mercapto-ethanol. However, a neat increase in sensitivity for IgM specific antibodies could be achieved by previously removing IgG from the sample, as demonstrated in a series of acute toxoplasmosis sera. A simple procedure was developed for this purpose, by reconstituting a lyophilized suspension of Protein A - rich Staphylococcus with the lowest serum dilution to be tested. Of low cost and easy to perform, Hematoxo® affords not only a practical qualitative procedure for screening reactors and non-reactors, as in prenatal services, but also quantitative assays that permit to titrate antibodies as well as to identify IgM antibodies.

  7. 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.

  8. IgG4相关性疾病的临床及病理学表现%Clinical and Pathologic Characteristics of Immunoglobulin G4 Related Disease

    Institute of Scientific and Technical Information of China (English)

    王咏梅; 杨庆婵(综述); 章明放(审校)


    IgG4相关性疾病( IgG4-RD)是一种新被认识的系统性、纤维炎症性疾病,该病以多位点形成肿瘤样脱髓鞘病变、大量IgG4阳性淋巴细胞和浆细胞浸润以及纤维化为特征,常累及胰腺、胆管、唾液腺、眶周组织、淋巴结及腹膜后间隙等。各器官的病理特征相似,诊断该病时,需结合临床表现、实验室、组织病理及影像学等检查结果,并积极排除其他疾病如肿瘤后作出诊断。该病对激素等免疫抑制剂治疗反应良好,预后较好。%IgG4-related disease(IgG4-RD) is a newly recognized systemic fibro-inflammatory disorder characterized with a tendency to form tumefactive lesions in multiple sites ,massive IgG4-bearing lymphocyte and plasma cell infiltration and fibrosis.The most commonly involved the pancreas,the biliary tree,salivary glands,periorbital tissues,lymph nodes,retroperitoneal space and so on.The histopathological features are similar across the involved organs.Combination of the clinical manifestations,laboratory examination,patholog-ic and imaging findings is recommended for diagnosis of IgG4-RD,while other disorders such as malignancy should be excluded to make a final diagnosis.Treatments with corticosteroid and other immunosuppressive drugs are effective and the prognosis is favorable.

  9. 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


    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.

  10. Heavy chain-only IgG2b llama antibody effects near-pan HIV-1 neutralization by recognizing a CD4-induced epitope that includes elements of coreceptor- and CD4-binding sites. (United States)

    Acharya, Priyamvada; Luongo, Timothy S; Georgiev, Ivelin S; Matz, Julie; Schmidt, Stephen D; Louder, Mark K; Kessler, Pascal; Yang, Yongping; McKee, Krisha; O'Dell, Sijy; Chen, Lei; Baty, Daniel; Chames, Patrick; Martin, Loïc; Mascola, John R; Kwong, Peter D


    The conserved HIV-1 site of coreceptor binding is protected from antibody-directed neutralization by conformational and steric restrictions. While inaccessible to most human antibodies, the coreceptor site has been shown to be accessed by antibody fragments. In this study, we used X-ray crystallography, surface plasmon resonance, and pseudovirus neutralization to characterize the gp120-envelope glycoprotein recognition and HIV-1 neutralization of a heavy chain-only llama antibody, named JM4. We describe full-length IgG2b and IgG3 versions of JM4 that target the coreceptor-binding site and potently neutralize over 95% of circulating HIV-1 isolates. Contrary to established trends that show improved access to the coreceptor-binding region by smaller antibody fragments, the single-domain (VHH) version of JM4 neutralized less well than the full-length IgG2b version of JM4. The crystal structure at 2.1-Å resolution of VHH JM4 bound to HIV-1 YU2 gp120 stabilized in the CD4-bound state by the CD4-mimetic miniprotein, M48U1, revealed a JM4 epitope that combined regions of coreceptor recognition (including the gp120 bridging sheet, V3 loop, and β19 strand) with gp120 structural elements involved in recognition of CD4 such as the CD4-binding loop. The structure of JM4 with gp120 thus defines a novel CD4-induced site of vulnerability involving elements of both coreceptor- and CD4-binding sites. The potently neutralizing JM4 IgG2b antibody that targets this newly defined site of vulnerability adds to the expanding repertoire of broadly neutralizing antibodies that effectively neutralize HIV-1 and thereby potentially provides a new template for vaccine development and target for HIV-1 therapy.

  11. 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


    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...

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

    Directory of Open Access Journals (Sweden)



    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

  13. Application of perturbed angular correlation spectroscopy in IgG immunoglobulins

    Energy Technology Data Exchange (ETDEWEB)

    Silva, A.S.; Amaral, A.A.; Lapolli, A.L.; Carbonari, A.W. [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil)], e-mail:


    In the present work, the technique of perturbed angular correlation (PAC) spectroscopy was used to measure the electric hyperfine field at IgG immunoglobulins using {sup 111}In {yields}{sup 111}Cd and {sup 181}Hf {yields} {sup 181}Ta probe nuclei. The biological materials studied in this work were originating from the immunological response of different mice lineages infected by the Y strain of T. cruzi. The samples were measured at room temperature (295K) and at liquid nitrogen temperature (77K). The PAC results showed that, samples measured with {sup 111}In obtained better results when they were compared with samples measured with {sup 181}Hf. (author)

  14. 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

  15. IgG4-Related Tubulointerstitial Nephritis Pattern in 18F-FDG PET/CT. (United States)

    Bélissant, Ophélie; Guernou, Mohamed; Rouvier, Philippe; Compain, Caroline; Bonardel, Gérald


    A 17-year-old adolescent girl was admitted with chronic arthralgia, Raynaud phenomenon, pericarditis, and evidences of chronic diffuse inflammation. F-FDG PET/CT scan was performed to search systemic vasculitis and showed diffuse moderate uptake in the kidneys. We suggested the existence of a nephritis, but the ultrasonography result was normal, and no treatment was introduced. Another F-FDG PET/CT scan was performed 7 months later to explore abdominal pain. It showed again diffuse intense uptake in both kidneys. A proteinuria was highlighted, and renal biopsy allowed to diagnose IgG4-related disease.

  16. Antigen recognition by IgG4 antibodies in human trichinellosis

    Directory of Open Access Journals (Sweden)

    Pinelli E.


    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.

  17. Hepatic nodular lymphoid lesion with increased IgG4-positive plasma cells associated with primary biliary cirrhosis: a report of two cases. (United States)

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


    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.

  18. 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


    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.

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

    Directory of Open Access Journals (Sweden)

    Christoph Fickentscher


    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.

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


    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

  1. Highly sensitive detection of human IgG using a novel bio-barcode assay combined with DNA chip technology (United States)

    Liu, Zhenbao; Zhou, Bo; Wang, Haiqing; Lu, Feng; Liu, Tianjun; Song, Cunxian; Leng, Xigang


    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.

  2. 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: [The Affiliated Zhongda Hospital of Southeast University, Department of Gerontology (China); Wang, Haiqing; Lu, Feng; Liu, Tianjun; Song, Cunxian; Leng, Xigang, E-mail: [Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College (China)


    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.

  3. Anti-human herpesvirus 6A/B IgG correlates with relapses and progression in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Isabel Ortega-Madueño

    Full Text Available To analyze the titers of the IgG and IgM antibodies against human herpesvirus 6A/B (HHV-6A/B in multiple sclerosis (MS patients treated with different disease modified therapies (DMTs along two-years of follow-up.We collected 2163 serum samples from 596 MS; for 301 MS patients a 2-years follow-up was performed. Serum samples of 337 healthy controls were also analyzed. Anti-HHV-6A/B IgG and IgM were analyzed by ELISA (Panbio.We found that 129/187 (69.0% MS patients with a decrease of the anti-HHV-6A/B IgG titers after 2-years with DMTs were free of relapses and progression vs. 46/113 (40.7% of MS patients with an increase of the anti-HHV-6A/B IgG titers (p = 0.0000015; the higher significance was found for natalizumab. Furthermore, we found that anti-HHV-6A/B IgG titers reached their highest value two weeks before the relapse (p = 0.0142, while the anti-HHV-6A/B IgM titers reached their highest value one month before the relapse (p = 0.0344.The measurement of the anti-HHV-6A/B IgG titers could be a good biomarker of clinical response to the different DMTs. The increase of the anti-HHV-6A/B IgG and IgM titers predicts the upcoming clinical relapses. However, further longitudinal studies are needed to validate these results.

  4. Specific IgG Antibodies React to Mimotopes of BK Polyomavirus, a Small DNA Tumor Virus, in Healthy Adult Sera (United States)

    Pietrobon, Silvia; Bononi, Ilaria; Mazzoni, Elisa; Lotito, Francesca; Manfrini, Marco; Puozzo, Andrea; Destro, Federica; Guerra, Giovanni; Nocini, Pier Francesco; Martini, Fernanda; Tognon, Mauro G.


    BK polyomavirus (BKPyV) was isolated in 1971 from the urine of a kidney transplant patient. Soon after its identification, BKPyV was characterized as a kidney-tropic virus, which is responsible of a significant fraction of the rejection of transplant kidney in the host. Moreover, in experimental conditions, BKPyV is able to transform different types of animal and human cells and to induce tumors of different histotypes in experimental animals. BKPyV DNA sequences have been detected in healthy individuals and cancer patients using polymerase chain reaction/Shouthern blot hybridization methods. Serum antibodies against this polyomavirus were revealed using immunological techniques, which, however, cross-react with other polyomaviruses such as JC (JCPyV) and Simian Virus 40. These non-specific data indicate the need of novel immunological methods and new investigations to check in a specific manner, BKPyV spread in humans. To this aim, mimotopes from BKPyV structural capsid protein 1 (VP1) were employed for specific immunological reactions to IgG antibodies of human serum samples. An indirect enzyme-linked immunosorbent assay with synthetic peptides mimicking immunogenic epitopes of BKPyV VP1 was set up and employed to test sera of healthy adult subjects. Data from this innovative immunological assay indicate that serum antibodies against BKPyV VP1 mimotopes are detectable in healthy subjects ranging from 18 to 90 years old. The overall prevalence of serum samples that reacted to BKPyV VP1 mimotopes was 72%. The strong points from this investigation are the novelty of the immunological method, its simplicity of the approach, and the specificity of BKPyV antibody reaction to VP1 mimotopes. PMID:28321224

  5. Megalin/cubilin-mediated uptake of FITC-labeled IgG by OK kidney epithelial cells. (United States)

    Nagai, Junya; Sato, Koya; Yumoto, Ryoko; Takano, Mikihisa


    In this paper, we characterize the uptake mechanism of fluorescein isothiocyanate-labeled human immunoglobulin G (FITC-hIgG) in opossum kidney (OK) epithelial cells, which have been shown to express megalin and cubilin. Confocal immunofluorescence microscopy showed the punctate expression of the neonatal Fc receptor FcRn in the cytoplasm, but not on the cell surface membrane. Temperature- and energy-dependent uptake of FITC-hIgG was observed at pH 7.4 but not at pH 6.0, indicating that the internalization of FITC-hIgG might not be due to FcRn, which has a binding affinity for IgG under acidic conditions. Under physiological pH conditions, human and bovine serum γ-globulin decreased FITC-hIgG uptake in a concentration-dependent manner. In addition, FITC-hIgG uptake was inhibited by various megalin and/or cubilin ligands including albumin, cytochrome c, transferrin and gentamicin. Endosomal acidification inhibitors (bafilomycin A(1) and chloroquine) significantly decreased the uptake of FITC-hIgG. Clathrin-dependent endocytosis inhibitors (phenylarsine oxide and chlorpromazine) decreased FITC-hIgG uptake. Potassium depletion and hypertonicity, conditions known to inhibit clathrin-dependent endocytosis, also decreased FITC-hIgG uptake. In contrast, caveolin-dependent endocytosis inhibitors (nystatin and methyl-β-cyclodextrin) did not decrease, but rather increased the uptake of FITC-hIgG. These observations suggest that the internalization of FITC-hIgG in OK cells might be, at least in part, due to megalin/cubilin-mediated, clathrin-dependent endocytosis.

  6. [Expression of human IL-35-IgG4 (Fc) fusion protein in CHO/DG44 cells]. (United States)

    Tang, Jing; Gao, Wenda; Zhang, Qing; Zhang, Dawei; Chen, Yang; He, Bo; Liu, Quansheng


    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.

  7. A Case of Adenomyosis with a High Titer of IgG Autoantibody to Calreticulin

    Directory of Open Access Journals (Sweden)

    Neil M. Gude BSc, MSc, PhD


    Full Text Available Background. High prevalence of autoantibodies to the calcium-binding, endoplasmic reticulum chaperone protein calreticulin has been reported in various autoimmune and parasitic diseases. It has been reported that adenomyosis is associated with the presence of autoantibodies, in particular to phospholipids; however, it is not known whether it is associated with autoimmunity to calreticulin. Results. A 35-year-old gravida 4 para 4 woman presented with a history of many years of intractable menorrhagia. Histopathological examination of a subsequent hysterectomy specimen revealed a bulky uterus, a poorly developed secretory endometrium with decidualization of the stroma and chronic endometritis, as well as the presence of adenomyosis uteri. IgG autoantibodies to calreticulin were measured in the plasma of this and 234 other patients. Nine (3.8% patients tested positive. The titer of anticalreticulin IgG autoantibody in the sole case with adenomyosis was approximately 8 times the average of other positive-testing samples. Conclusions. The etiology of adenomyosis is unclear. The presence of a high titer, blocking anticalreticulin autoantibody may directly increase the risk that adenomyosis might develop. It is also possible that the expansion of endometrial glandular tissue, as well as elevated estrogens, during adenomyosis may lead to elevated calreticulin, which induces an autoimmune reaction to it. Further study is required to determine whether there is a significant association between adenomyosis and the prevalence of calreticulin autoantibodies.

  8. Detection of IgG against Toxocara in Sera of Employees of Meat Industry (United States)

    Alvarado-Esquivel, Cosme; Hernández-Tinoco, Jesús; Sánchez-Anguiano, Luis Francisco; Ramos-Nevárez, Agar; Cerrillo-Soto, Sandra Margarita; Guido-Arreola, Carlos Alberto; Saenz-Soto, Leandro


    Contact with raw meat could represent a risk for Toxocara infection. We assessed the association of Toxocara infection with an occupation of meat worker though a case-control seroprevalence study of 124 meat workers and 248 subjects without this occupation. Sera of participants was analyzed for the presence of anti-Toxocara IgG antibodies. One (0.8%) of the 124 meat workers, and 5 (2.0%) of the 248 controls were positive for anti-Toxocara IgG antibodies (OR=0.39; 95% CI: 0.04-3.41; P=0.66). The seropositive meat worker was a male aged 28 years old, without vision impairment. None of the work characteristics i.e. frequency of contact with raw meat, use of safety practices, history of splashes at face with blood or raw meat, and injuries with sharp material at work was associated with Toxocara exposure. Seroprevalence of Toxocara infection was significantly higher (P=0.04) in meat workers with consumption of boar meat (1/6: 16.7%) than in those without this consumption (0/117: 0%). We conclude that meat workers do not have a higher risk for Toxocara infection than subjects without this occupation do. The 2% seroprevalence of Toxocara infection found in control subjects might suggest a low seroprevalence of this infection among people with other occupations in Durango City. However, additional case-control studies with larger sample sizes to confirm our results are needed. PMID:26508909

  9. Direct electrical control of IgG conformation and functional activity at surfaces (United States)

    Ghisellini, Paola; Caiazzo, Marialuisa; Alessandrini, Andrea; Eggenhöffner, Roberto; Vassalli, Massimo; Facci, Paolo


    We have devised a supramolecular edifice involving His-tagged protein A and antibodies to yield surface immobilized, uniformly oriented, IgG-type, antibody layers with Fab fragments exposed off an electrode surface. We demonstrate here that we can affect the conformation of IgGs, likely pushing/pulling electrostatically Fab fragments towards/from the electrode surface. A potential difference between electrode and solution acts on IgGs’ charged aminoacids modulating the accessibility of the specific recognition regions of Fab fragments by antigens in solution. Consequently, antibody-antigen affinity is affected by the sign of the applied potential: a positive potential enables an effective capture of antigens; a negative one pulls the fragments towards the electrode, where steric hindrance caused by neighboring molecules largely hampers the capture of antigens. Different experimental techniques (electrochemical quartz crystal microbalance, electrochemical impedance spectroscopy, fluorescence confocal microscopy and electrochemical atomic force spectroscopy) were used to evaluate binding kinetics, surface coverage, effect of the applied electric field on IgGs, and role of charged residues on the phenomenon described. These findings expand the concept of electrical control of biological reactions and can be used to gate electrically specific recognition reactions with impact in biosensors, bioactuators, smart biodevices, nanomedicine, and fundamental studies related to chemical reaction kinetics.

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

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Khan


    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.

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

    Directory of Open Access Journals (Sweden)

    Chun-Xia Yi


    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.

  12. [Hashimoto's thyroiditis(chronic thyroiditis), IgG4-related thyroiditis]. (United States)

    Itoh, Mitsuyasu


    Hashimoto's thyroiditis emerges in patients who have genetic preponderance such as SNPs of CTLA-4 and risk factors such as excess intake of iodine, pregnancy or postpartum period, and smoking. Such risk factors also affect the entire clinical course. One of the major outcomes in Hashimoto's thyroiditis appears to be increased in cardio-vascular risks through subclinical hypothyroidism and concomitant metabolic syndrome, but in most cases, treatment with L-T4 has little effects on cardio-vascular benefit or quality of life. The pregnant women also have risks for obstetric complications and postpartum thyroid dysfunction. The women who have anti-TPO antibodies, type 1 diabetes, or previous history of post-partum thyroid dysfunction are recommended to be measured their TSH. It is noteworthy that Hashimoto's thyroiditis is sometimes complicated with encephalopathy, papillary carcinoma, or IgG4-related thyroiditis. IgG4-related thyroiditis is partly similar but partly discerned from a variant of Hashimoto's thyroiditis. The pathogenetic roles of this variant on autoimmune-based thyroiditis remain unclear.

  13. Engineering upper hinge improves stability and effector function of a human IgG1. (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


    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.

  14. Monoclonal gammopathy of undeterminated significance and endoneurial IgG deposition (United States)

    Mathis, Stéphane; Franques, Jérôme; Richard, Laurence; Vallat, Jean-Michel


    Abstract Background: Monoclonal gammopathy of undeterminated significance is the most common form of plasma cell dyscrasia, usually considered as benign. In rare cases it may have a malignant course, sometimes limited to an organ such as peripheral nerves. Methods: We describe clinical, electrophysiological and pathological findings in a patient presenting a immunoglobulin G (IgG) paraproteinemic polyneuropathy clinically mimicking a chronic inflammatory demyelinating polyneuropathy. Results: Immuno-electron microscopy (immune-EM) demonstrated that the widenings of the myelin lamellae resulted from the infiltration of IgG between a significant number of myelin lamellae (with absence of inflammatory cells in the epineurium, endoneurium, and perineurium, and the lack signs of vasculitis). This patient was finally treated successfully with lenalidomide then mycophenolate mofetil. Conclusions: In polyneuropathies associated to a monoclonal gammopathy, a nerve biopsy may clinch the diagnosis. Immuno-EM may be required to determine the role of the pathological immunoglobulin in the destruction of the peripheral nerve parenchyma. Diagnosis of such a direct involvement of peripheral nerve can endorse more aggressive treatment of real efficiency. PMID:27603395

  15. Gestational toxoplasmosis in Paraná State, Brazil: prevalence of IgG antibodies and associated risk factors

    Directory of Open Access Journals (Sweden)

    Fabiana Maria Ruiz Lopes-Mori


    Full Text Available The aim of the present study was to verify the association between seropositivity for IgG anti-Toxoplasma gondii antibodies and social, economic and environmental variables of pregnant women attending the public health centers of Paraná, Brazil. From January 2007 to July 2010, 2226 pregnant women were interviewed and detection of anti-T. gondii specific IgG and IgM antibodies was performed by chemiluminescence test. Seropositivity for anti-T. gondii IgG was observed in 1151 (51.7% pregnant women, 29 of which (1.3% presented IgM reagent with IgG of high avidity. The variables associated with the presence of IgG were residency in the rural area, more than one pregnancy, less than or equal to eight years schooling, low per capita income, age group, raw or poorly cooked meat ingestion, and contact with the soil. There was neither association with raw fruit and vegetable ingestion nor with the presence of cats in the residencies.

  16. IgG4-related sclerosing diseases%IgG4相关的硬化性疾病

    Institute of Scientific and Technical Information of China (English)

    孙希印; 燕丽; 刘萍; 李新功


    IgG4-related sclerosing diseases are newly recognized, which are considered to be related to au-toimmunity, including cellular and humoral immune abnormity. IgG4 levels in serum are higher than normal. Histopathological findings include fibrosis with significant inflammatory cells, mainly IgG4(+) plasma cells. Lesions can involve many internal organs. Skin lesions are mostly found in head and neck, presenting with erythema, patches or subcutaneous nodules accompanying itching. Glucocorticoid is effective in the treatment of IgG4-related skin diseases.%IgG4相关硬化性疾病是近年被认识的一种疾病,被认为与自身细胞、体液免疫反应异常有关。患者血清IgG4水平升高,病变器官纤维化,并有显著IgG4阳性浆细胞浸润。病变可以累及许多器官,部分病例伴有皮肤的病变。皮肤病变以头颈部多见,可为红斑、斑片或皮下结节,有痒感。 IgG4相关皮肤疾病糖皮质激素治疗有效。

  17. 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.

  18. Resonance scattering spectral detection of ultratrace IgG using immunonanogold-HAuCl4-NH2OH catalytic reaction

    Institute of Scientific and Technical Information of China (English)


    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.

  19. Natural Mosquito-Pathogen Hybrid IgG4 Antibodies in Vector-Borne Diseases: A Hypothesis (United States)

    Londono-Renteria, Berlin; Cardenas, Jenny C.; Troupin, Andrea; Colpitts, Tonya M.


    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

  20. Molecular Dynamics Simulation of the Crystallizable Fragment of IgG1—Insights for the Design of Fcabs

    Directory of Open Access Journals (Sweden)

    Balder Lai


    Full Text Available An interesting format in the development of therapeutic monoclonal antibodies uses the crystallizable fragment of IgG1 as starting scaffold. Engineering of its structural loops allows generation of an antigen binding site. However, this might impair the molecule’s conformational stability, which can be overcome by introducing stabilizing point mutations in the CH3 domains. These point mutations often affect the stability and unfolding behavior of both the CH2 and CH3 domains. In order to understand this cross-talk, molecular dynamics simulations of the domains of the Fc fragment of human IgG1 are reported. The structure of human IgG1-Fc obtained from X-ray crystallography is used as a starting point for simulations of the wild-type protein at two different pH values. The stabilizing effect of a single point mutation in the CH3 domain as well as the impact of the hinge region and the glycan tree structure connected to the CH2 domains is investigated. Regions of high local flexibility were identified as potential sites for engineering antigen binding sites. Obtained data are discussed with respect to the available X-ray structure of IgG1-Fc, directed evolution approaches that screen for stability and use of the scaffold IgG1-Fc in the design of antigen binding Fc proteins.

  1. Comparative study of number and distribution of IgG+ cells in oral lichen planus and oral lichenoid lesions

    Directory of Open Access Journals (Sweden)

    Parichehr Ghalayani


    Full Text Available Background: Oral lichen planus is a common mucocutaneous disorder with unknown etiology. While current data suggest that oral lichen planus is a cell-mediated disease, differential diagnosis of this disease and oral lichenoid lesions is very problematic, both clinically and histopathologically. This study aimed to compare immunohistochemical features of these similar diseases. Methods: This was a descriptive-analytic study in which formalin-fixed and paraffin-embedded tis-sue sections of 30 oral lichen planus and 30 oral lichenoid lesions were immunohistochemically ana-lyzed for number and distribution of IgG + cells. A standard biotin-streptavidin procedure after anti-gen retrieval was used. Data were analyzed in SPSS software using Mann-Whitney U test. Results: There were some significant differences in distribution of IgG + cells among different loca-tions in oral lichen planus and also in oral lichenoid lesions separately; but the differences between distribution of IgG + cells between the two groups of oral lichen planus and oral lichenoid lesions were not significant. Conclusion: There was no significant difference in number and distribution of IgG + cells between the two groups. So, this study can suggest that location of IgG is similar in samples of oral lichen planus and oral lichenoid lesions and consequently, this marker cannot help us differentiate them from each other. Other markers can be analyzed in further studies in order to find an appropriate distinguisher between the two lesions.

  2. 肺受累的IgG4相关硬化性疾病1例%A case report of IgG4-related sclerosing disease with lung involvement

    Institute of Scientific and Technical Information of China (English)

    张颖健; 赵金霞; 刘蕊; 刘湘源


    IgG4-related sclerosing disease ( IgG4-RSD) is a kind of lymphoplasmacytic disease with multi-organ involvement and is characterized by serum IgG4 elevation and tissue IgG4 positive plasma cell infiltration. Autoimmune pancreatitis, sclerosing cholangitis, sclerosing sialadenitis, retroperitoneal fibrosis and lymphadenopathy make up its main clinical manifestations. This difficult case was a middle-aged female with onset as muiltiple lymph nodes and glands enlargement, including lacrimal gland, salivary glands and pancreas. Meanwhile, repeated examinations of auto-antibodies and serum IgG4 were all negative. The patient didn' t respond well to glucocorticoid therapy, and further progressed to rare lung involvement presenting as lung nodule. This complex entity was eventually diagnosed as IgG4-RSD by the support of histopathology evidence of IgG4 immunohistochemistry stain. Though IgG4-RSD has been known for years, it is still underappreciated in China and case reports are scarce. The case report here with literature review is just to enhance the recognition of this disease regarding its pathogenesis, various clinical manifestations, diagnosis and therapy.%IgG4相关硬化性疾病(IgG4 related sclerosing disease,IgG4-RSD)是一种累及多器官、以血清IgG4升高、组织IgG4阳性浆细胞浸润为特点的淋巴浆细胞病,主要表现为自身免疫性胰腺炎、硬化性胆管炎、硬化性涎腺炎、腹膜后纤维化和淋巴结病.本例患者以泪腺、唾液腺、淋巴结肿大起病,多种自身抗体阴性,外院应用激素效果不佳,多次查血清IgG4阴性,为诊断带来困难,患者在此基础上出现以肺内结节为主要表现的肺受累更为罕见,最终通过组织活检IgG4免疫组织化学染色确诊.IgG4-RSD作为一种新的临床疾病逐渐被广泛认识,但国内报道仍较少.报道这一病例并进行相关文献复习旨在提高对IgG4-RSD多种临床表现的认识并对其诊疗及发病机制进行探讨.

  3. Seroprevalencia y detección de infección primaria por citomegalovirus mediante prueba de avidez IgG en el primer trimestre de embarazo

    Directory of Open Access Journals (Sweden)

    Conne L González-García


    Full Text Available Objective. To determine the seroprevalence and detection of primary infection by cytomegalovirus (CMV with immunoglobulin G (IgG avidity test during the first quarter of pregnancy in the General Hospital in Morelia, Michoacan. Materials and methods. A total of 177 patients were studied employing a modified Elisa test using a chemiluminescent microparticle immunoassay (CMIA for the detection of CMV antibodies (IgG and immunoglobulin M [IgM], and IgG avidity. Results. 90.4% were positive for IgG, and of these, 2.3% were also reactive for IgM, and in this group the IgG avidity test reported low avidity for 1.1% and higher avidity in the same percentage. 9.6% were seronegative. Conclusions. Similarity was found with published studies in Mexico. Health professionals should know the clinical algorithms for diagnosis and proper management of CMV infection using the IgG avidity test.

  4. Repression of the transcription factor Bach2 contributes to predisposition of IgG1 memory B cells toward plasma cell differentiation. (United States)

    Kometani, Kohei; Nakagawa, Rinako; Shinnakasu, Ryo; Kaji, Tomohiro; Rybouchkin, Andrei; Moriyama, Saya; Furukawa, Koji; Koseki, Haruhiko; Takemori, Toshitada; Kurosaki, Tomohiro


    Memory B cells are essential for generating rapid and robust secondary antibody responses. It has been thought that the unique cytoplasmic domain of IgG causes the prompt activation of antigen-experienced IgG memory B cells. To assess this model, we have generated a mouse containing IgG1 B cells that have never encountered antigen. We found that, upon challenge, antigen-experienced IgG1 memory B cells rapidly differentiated into plasma cells, whereas nonexperienced IgG1 B cells did not, suggesting the importance of the stimulation history. In addition, our results suggest that repression of the Bach2 transcription factor, which results from antigen experience, contributes to predisposition of IgG1 memory B cells to differentiate into plasma cells.

  5. Og4C3 circulating antigen, anti-Brugia malayi IgG and IgG4 titers in Wuchereria bancrofti infected patients, according to their parasitological status. (United States)

    Chanteau, S; Glaziou, P; Luquiaud, P; Plichart, C; Moulia-Pelat, J P; Cartel, J L


    This study involved 221 microfilaremic (Mf+), 302 amicrofilaremic (Mf-) antigen positive (AG+) and 1454 Mf-antigen negative (AG-) individuals living in endemic villages. Whatever the group considered, antigen and antibody titers were widely distributed. Og4C3 antigen, detected both in Mf- and Mf+ patients, was significantly higher in Mf+ patients. The Mf parasitological status did not significantly influence the antifilarial antibodies levels in the infected AG+ individuals, although IgG4 was more discriminant. In the supposedly uninfected individuals (Mf-AG-), anti-filarial IgG and IgG4 could be detected in a large proportion of the group. Og4C3 circulating antigen test was confirmed to be a good marker of active Wuchereria bancrofti infection.

  6. Correlation of monocyte-monolayer assay results, number of erythrocyte-bound IgG molecules, and IgG subclass composition in the study of red cell alloantibodies other than D. (United States)

    Zupańska, B; Brojer, E; McIntosh, J; Seyfried, H; Howell, P


    Comparisons have been made between the serological and immunological characteristics of 42 blood group alloantibodies (other than D) covering twelve systems using a monocyte-monolayer assay (MMA), a radiometric antiglobulin test for antibody binding and IgG subclass determinations. The results of the MMA correlated well with the level of IgG molecules bound on incompatible cells, and the highest levels in both cases were associated with the presence of the IgG3 subclass. However, limited clinical data shows that, while in general the MMA clearly identifies the clinically significant antibodies, the correlation with the degree of clinical outcome is less well defined, and in some instances other factors may be operating to ameliorate the in vivo effect of the antibody.

  7. The clinicopathological analysis of 4 cases of IgG4-related nonspecific interstitial pneumonia%IgG4相关非特异性间质性肺炎四例临床病理分析

    Institute of Scientific and Technical Information of China (English)

    张卉; 施举红; 冯瑞娥; 田欣伦; 徐作军; 许文兵; 刘鸿瑞; 刘彤华


    Objectives To observe the immunohistochemical staining of IgG4 in nonspecific interstitial pneumonia (NSIP) and to study the clinicopathological features of IgG4-related NSIP.Methods Retrospective analysis was carried out for 32 patients with NSIP who had been admitted into Peking Union Medical College Hospital from November 2002 to October 2010.The diagnosis of NSIP was established by surgical lung biopsy and all specimens were fixed in neutral formalin and embedded in paraffin.Sections were cut for HE and immunohistochemical stain.According to the diagnostic criteria for IgG4-related disease,4 cases were confirmed to be IgG4-related NSIP.The clinicopathological features including clinical history,laboratory examination,and pathologic evaluation were studied.Results The 4 patients with IgG4-related NSIP included 1 man and 3 women,with a median age of 48 years (range,44-56 years).The presenting symptoms were dry cough or shortness of breath.One patient (1/4,25.0%)was found to have a positive autoantibody but no cases showed positive RF in serum.The histological finding of the 4 cases was characterized by inflammatory cell infiltration in interstitium with fibrosis,and 1 case showed obliterative arteritis.The numbers of IgG4-positive plasma cells in the 4 cases were 42/hpf,22/hpf,11/hpf,and 33/hpf respectively,while the percentages of IgG4-positive to IgG-positive plasma cells were 70%,71%,57%,43% respectively.Conclusions IgG4-related interstitial pulmonary disease can be characterized as the NSIP pattern.The pathological features of IgG4-related NSIP include infiltration of lymphoplasmacytes and eosinophils in interstitium with fibrosis,and lymphoid follicles are frequently identified in the area of lymphocyte aggregation,but obliterative arteritis is infrequently identified in the lesion.Immunohistochemical staining of IgG and IgG4 is very helpful for a definite diagnosis of IgG4-related disease.%目的 观察非特异性间质性

  8. Prevalence estimation of tick-borne encephalitis virus (TBEV) antibodies in dogs from Finland using novel dog anti-TBEV IgG MAb-capture and IgG immunofluorescence assays based on recombinant TBEV subviral particles. (United States)

    Levanov, Lev; Vera, Cristina Pérez; Vapalahti, Olli


    Tick-borne encephalitis (TBE) is one of the most dangerous human neurological infections occurring in Europe and Northern parts of Asia with thousands of cases and millions vaccinated against it. The risk of TBE might be assessed through analyses of the samples taken from wildlife or from animals which are in close contact with humans. Dogs have been shown to be a good sentinel species for these studies. Serological assays for diagnosis of TBE in dogs are mainly based on purified and inactivated TBEV antigens. Here we describe novel dog anti-TBEV IgG monoclonal antibody (MAb)-capture assay which is based on TBEV prME subviral particles expressed in mammalian cells from Semliki Forest virus (SFV) replicon as well as IgG immunofluorescence assay (IFA) which is based on Vero E6 cells transfected with the same SFV replicon. We further demonstrate their use in a small-scale TBEV seroprevalence study of dogs representing different regions of Finland. Altogether, 148 dog serum samples were tested by novel assays and results were compared to those obtained with a commercial IgG enzyme immunoassay (EIA), hemagglutination inhibition test and IgG IFA with TBEV infected cells. Compared to reference tests, the sensitivities of the developed assays were 90-100% and the specificities of the two assays were 100%. Analysis of the dog serum samples showed a seroprevalence of 40% on Åland Islands and 6% on Southwestern archipelago of Finland. In conclusion, a specific and sensitive EIA and IFA for the detection of IgG antibodies in canine sera were developed. Based on these assays the seroprevalence of IgG antibodies in dogs from different regions of Finland was assessed and was shown to parallel the known human disease burden as the Southwestern archipelago and Åland Islands in particular had considerable dog TBEV antibody prevalence and represent areas with high risk of TBE for humans.

  9. 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;


    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, ...

  10. 自身免疫性肝病患者血清IgG4水平分析%Serum IgG4 levels in patients with autoimmune liver diseases

    Institute of Scientific and Technical Information of China (English)

    张敏; 朱争艳; 韩涛; 聂彩云; 王伟; 杜卫杰; 周淑芬; 王棕覃; 孙扬; 丁贤


    To study the differences of serum IgG4 levels in various autoimmune liver diseases and to analyze the clinical characterization of patients with high serum IgG4 levels. Methods 65 patients with autoimmune liver diseases were enrolled for this study including 11 patients with autoimmune hepatitis (AIH),47 patients with primary biliary cirrhosis (PBC) and 7 patients with overlap syndrome of AIH and PBC. The serum IgG4 levels was detected by immuno-scatter turbidmetry. The differences of serum IgG4 levels in the three groups were studied. The clinical features of patients with autoimmune liver disease were analyzed according to their serum IgG4 levels. The significance of inter-group differences of measurement data was assessed by Student’s t-test or Mann-Whitney U test and enumeration data by Fisher’s exact test. Results The serum IgG4 levels in patients with AIH was 642.2 mg/L(97.7 mg/L~1687.0 mg/L),a little higher than in patients with PBC [153.9 mg/L(78.9 mg/L~400.3 mg/L),P=0.076] and in with overlap syndrome [229.9 mg/L(154.9 mg/L ~417.9 mg/L),P=0.388];Three patients with AIH had high serum IgG4 levels (≥1350 mg/L) out of 11 patients with AIH. The ratio of IgG4/IgG was higher in the three patients with higher as compared to 8 with relatively low serum IgG4 levels (P﹤0.05);The three patients with elevated IgG4 levels had diabetes mellitus type 2 and one of them was also complicated with rheumatoid arthritis,whereas the other 8 patients with low serum IgG4 levels were not;14 patients with PBC with higher serum IgG4 levels (≥200 mg/L) had higher total serum bilirubin levels as com-pared to those in 33 patients with relatively low serum IgG4 levels [(45.09 ±74.85)μmol/L vs.(26.38 ±23.03)μmol/L,P=0.05)]. Conclusion Compared with patients with PBC or overlap syndrome of AIH and PBC,the pa-tients with AIH have a higher serum IgG4 levels. The patients with AIH with high serum IgG4 levels might be complicated with other autoimmune or metabolic diseases.%探

  11. 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


    Zeman David; Hradílek Pavel; Švagera Zdeněk; Mojžíšková Eva; Woznicová Ivana; Zapletalová Olga


    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...

  12. Purification of IgG from serum with caprylic acid and ammonium sulphate precipitation is not superior to ammonium sulphate precipitation alone. (United States)

    Mohanty, J G; Elazhary, Y


    Immunoglobulin G (IgG) from bovine serum raised against Aeromonas Salmonicida was purified by ammonium sulphate precipitation (ASP) or caprylic acid treatment followed by ammonium sulphate precipitation (CAAS). Purity of IgG samples prepared by both methods were examined by High Performance Gel Permeation Chromatography, electrophoresis and antibody activity assay. Results suggest that IgG prepared by ASP is better than that obtained by CAAS method in terms of the yield of the IgG monomers and the recovery of the antibody activity.

  13. [IgG4-related disease and clonal B-cell lymphoid proliferation: Description of two clinical cases and a review of literature]. (United States)

    Sokol, E V; Vasilyev, V I; Kovrigina, A M; Safonova, T N; Nasonov, E L


    IgG4-related disease (IgG4-RD) is a systemic immune-related disease that may involve the pancreas, liver, retroperitoneal space, biliary tract, salivary and lacrimal glands, eye socket, lung, and kidney. In term of pathomorphogenesis, it is a fibroinflammatory disease manifesting as a tumor-like lesion of organs, elevated serum IgG4 levels, and a morphofunctional substrate - the development of marked fibrosis and lymphoplasmacytic infiltration in the tissues with the high content of IgG4-positive plasma cells. The detection of a tumor-like nodule frequently leads to that the patients with IgG4-RD undergo major traumatic surgery for presumed cancer. At the same time, a number of investigations show the association of IgG4-RD with the development of cancer and lymphoproliferative diseases. The paper describes two clinical cases: Russia's first diagnosis of MALT lymphoma of the lacrimal gland, IgG4-positive and IgG4-RD with a rare onset with a destruction focus in the cervical vertebrae, multiple organ dysfunction, B-cell clonality in salivary gland tissue and PIgMκ secretion. It also reviews world literature on the development of lymphoproliferative diseases in the presence of IgG4-RD.

  14. 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


    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.

  15. Perspective: hypothesis: serum IgG antibody is sufficient to confer protection against infectious diseases by inactivating the inoculum. (United States)

    Robbins, J B; Schneerson, R; Szu, S C


    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.

  16. Structure of full-length human anti-PD1 therapeutic IgG4 antibody pembrolizumab. (United States)

    Scapin, Giovanna; Yang, Xiaoyu; Prosise, Winifred W; McCoy, Mark; Reichert, Paul; Johnston, Jennifer M; Kashi, Ramesh S; Strickland, Corey


    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.

  17. Adsorption of human serum proteins onto TREN-agarose: purification of human IgG by negative chromatography. (United States)

    Bresolin, Igor Tadeu Lazzarotto; Borsoi-Ribeiro, Mariana; Caro, Juliana Rodrigues; dos Santos, Francine Petit; de Castro, Marina Polesi; Bueno, Sonia Maria Alves


    Tris(2-aminoethyl)amine (TREN) - a chelating agent used in IMAC - immobilized onto agarose gel was evaluated for the purification of IgG from human serum by negative chromatography. A one-step purification process allowed the recovery of 73.3% of the loaded IgG in the nonretained fractions with purity of 90-95% (based on total protein concentration and nephelometric analysis of albumin, transferrin, and immunoglobulins A, G, and M). The binding capacity was relatively high (66.63 mg of human serum protein/mL). These results suggest that this negative chromatography is a potential technique for purification of IgG from human serum.

  18. IgG particle formation during filling pump operation: a case study of heterogeneous nucleation on stainless steel nanoparticles. (United States)

    Tyagi, Anil K; Randolph, Theodore W; Dong, Aichun; Maloney, Kevin M; Hitscherich, Carl; Carpenter, John F


    This study investigated factors associated with vial filling with a positive displacement piston pump leading to formation of protein particles in a formulation of an IgG. We hypothesized that nanoparticles shed from the pump's solution-contact surfaces nucleated protein aggregation and particle formation. Vials of IgG formulation filled at a clinical manufacturing site contained a few visible particles and about 100,000 particles (1.5-3 microm) per mL. In laboratory studies with the same model (National Instruments FUS-10) of pump, pumping of 20 mg/mL IgG formulation resulted in about 300,000 particles (1.5-3 microm) per mL. Pumping of protein-free formulation resulted in 13,000 particles (1.5-15 microm) per mL. More than 99% of the particles were 0.25-0.95 microm in size. Mixing of protein-free pumped solution with an equal volume of 40 mg/mL IgG resulted in 300,000 particles (1.5-15 microm) per mL. Also, mixing IgG formulation with 30,000/mL stainless steel nanoparticles resulted in formation of 30,000 protein microparticles (1.5-15 microm) per mL. Infrared spectroscopy showed that secondary structure of IgG in microparticles formed by pumping or mixing with steel nanoparticles was minimally perturbed. Our results document that nanoparticles of foreign materials shed by pumps can serve as heterogeneous nuclei for formation of protein microparticles.

  19. 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.

  20. Anti-aquaporin-4 IgG in patients presenting with unilateral optic neuritis: A cohort study

    Directory of Open Access Journals (Sweden)

    Masoud Etemadifar


    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. Characterization of antibodies against ferret immunoglobulins, cytokines and CD markers

    DEFF Research Database (Denmark)

    Martel, Cyril Jean-Marie; Aasted, Bent


    immunoglobulins, we identified and characterized polyclonal antibodies towards ferret IgG, IgM and IgA. We also identified 22 monoclonal antibodies (mAbs) raised mostly against human CD markers which cross-reacted with ferret leukocytes. These antibodies were originally specific against human CD8, CD9, CD14, CD18...

  2. IgG accumulates in inhibitory hippocampal neurons of experimental antiphospholipid syndrome. (United States)

    Katzav, Aviva; Menachem, Assaf; Maggio, Nicola; Pollak, Lea; Pick, Chaim G; Chapman, Joab


    Mice immunized with β2-glycoprotein I (β2GPI) are an experimental model of the antiphospholipid syndrome (eAPS) displaying elevated titers of antiphospholipid antibodies (aPL). We presently studied whether the behavioral hyperactivity in eAPS mice is associated with in vivo binding and accumulation of IgG in the brain. At 6 weeks post immunization eAPS mice had significantly higher levels of aPL (1.32 ± 0.28 and 0.02 ± 0.01 AU, p < 0.001 by t-test) compared to adjuvant immunized controls, as measured by ELISA. Significant hyperactivity in a staircase test in the eAPS mice compared to controls was found in stair-climbing (18.4 ± 0.9 and 12.0 ± 1.7, respectively) and rearing measures (23.5 ± 2.1 and 12.5 ± 1.9, p < 0.01 by t-test). Immunofluorescence staining in eAPS mice revealed significant in vivo accumulation of IgG in cortical and hippocampal neurons which was not seen in controls. Staining for IgG was markedly intense in inhibitory interneurons co-stained for GAD67 in the hippocampus of eAPS mice. The integrity of the blood brain barrier (BBB) evaluated by injection of Evans blue (EB) was impaired in eAPS and adjuvant immunized mice compared to naïve mice. Electrophysiological recordings in hippocampal brain slices showed altered response to paired pulse stimulation as well as dysregulation of carbachol-induced γ- oscillations in eAPS mice compared to control. Penetration into the brain and direct interaction of aPL with inhibitory interneurons in the hippocampus may explain the hyperactive behavior of the eAPS mice. A direct role of aPL in causing CNS dysfunction points to these antibodies as an important therapeutic target in APS.

  3. Listeria monocytogenes Meningitis in an Immunosuppressed Patient with Autoimmune Hepatitis and IgG4 Subclass Deficiency

    DEFF Research Database (Denmark)

    Gaini, Shahin


    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. Maternal autism-associated IgG antibodies delay development and produce anxiety in a mouse gestational transfer model. (United States)

    Braunschweig, Daniel; Golub, Mari S; Koenig, Claire M; Qi, Lihong; Pessah, Isaac N; Van de Water, Judy; Berman, Robert F


    A murine passive transfer model system was employed to ascertain the effects of gestational exposure to a single, intravenous dose of purified, brain-reactive IgG antibodies from individual mothers of children with autism (MAU) or mothers with typically developing children (MTD). Growth and behavioral outcomes in offspring were measured from postnatal days 8 to 65 in each group. Comparisons revealed alterations in early growth trajectories, significantly impaired motor and sensory development, and increased anxiety. This report demonstrates for the first time the effects of a single, low dose gestational exposure of IgG derived from individual MAU on their offspring's physical and social development.

  5. Myeloma with xanthoderma due to an IgG lambdamonoclonal anti-flavin antibody. (United States)

    Farhangi, M; Osserman, E F


    When yellow skin and yellow hair developed in an elderly patient with multiple myeloma, we ruled out the usual causes of such pigmentation but identified a monoclonal IgGlambda (lgGGar) with anti-flavin antibody activity. Purified IgGGar was bright yellow, and the acid-dissociated chromophore was identified as riboflavin by chromatography and absorption spectroscopy. Native IgGGar contained 1.45 moles of flavin per mole of IgG, and increased to 2 moles with addition of riboflavin to saturation. The flavin was localized to the Fab fragment and was bound to IgGGar with high affinity. IgGGar showed strongest affinities for riboflavin, flavin mononucleotide and flavin adenine dinucleotide, and lower affinities for dinitrophenyl derivatives and naphthoquinone. The demonstration of hapten bound to the circulating monoclonal immunoglobulin in this case suggests the possibility of bound but colorless haptens on other myeloma proteins as well as on normal immunoglobulins.

  6. IgG4相关性疾病%IgG4-related Disease

    Institute of Scientific and Technical Information of China (English)

    林玮; 张文



  7. Serum Immunoglobulin Free Light Chain Assessment in IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Aurélie Grados


    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.

  8. IgG4-related sclerosing mesenteritis in a 7-year-old Saudi Girl

    Directory of Open Access Journals (Sweden)

    Mohammed Y Hasosah


    Full Text Available Sclerosing mesenteritis (SM is a rare, benign inflammatory disorder of unknown etiology, affecting the membranes of the digestive tract that involves lymphoplasmacytic inflammation, fat necrosis, and fibrosis of the mesentery. We report a child patient with a history of recurrent abdominal pain and fever who was found to have an intra-abdominal mass suspicious for malignancy. A tissue biopsy revealed the diagnosis of SM associated with IgG4-related systemic disease. The patient is currently maintained on 5 mg prednisone daily and no recurrence of symptoms was noted during the 24-month follow-up period. We emphasize, therefore, that SM can present clinical challenges and the presence of SM should cue clinicians to search for other coexisting autoimmune disorders that can have various outcomes.

  9. IgG4-related sclerosing mesenteritis in a 7-year-old Saudi girl. (United States)

    Hasosah, Mohammed Y; Satti, Mohamed B; Yousef, Yasmin A; Alzahrani, Daifullah M; Almutairi, Sajdi A; Alsahafi, Ashraf F; Sukkar, Ghassan A; Alzaben, Abdullah A


    Sclerosing mesenteritis (SM) is a rare, benign inflammatory disorder of unknown etiology, affecting the membranes of the digestive tract that involves lymphoplasmacytic inflammation, fat necrosis, and fibrosis of the mesentery. We report a child patient with a history of recurrent abdominal pain and fever who was found to have an intra-abdominal mass suspicious for malignancy. A tissue biopsy revealed the diagnosis of SM associated with IgG4-related systemic disease. The patient is currently maintained on 5 mg prednisone daily and no recurrence of symptoms was noted during the 24-month follow-up period. We emphasize, therefore, that SM can present clinical challenges and the presence of SM should cue clinicians to search for other coexisting autoimmune disorders that can have various outcomes.

  10. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children (United States)

    Chong, Sze Yee; Coleman, Lee; MacGregor, Duncan; Hardikar, Winita; Oliver, Mark R.


    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

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

    DEFF Research Database (Denmark)

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


    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...... 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. (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


    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. IgG Binding Characteristics of Rhesus Macaque FcγR. (United States)

    Chan, Ying N; Boesch, Austin W; Osei-Owusu, Nana Y; Emileh, Ali; Crowley, Andrew R; Cocklin, Sarah L; Finstad, Samantha L; Linde, Caitlyn H; Howell, Rebecca A; Zentner, Isaac; Cocklin, Simon; Miles, Adam R; Eckman, Joshua W; Alter, Galit; Schmitz, Joern E; Ackerman, Margaret E


    Indian rhesus macaques (Macaca mulatta) are routinely used in preclinical studies to evaluate therapeutic Abs and candidate vaccines. The efficacy of these interventions in many cases is known to rely heavily on the ability of Abs to interact with a set of Ab FcγR expressed on innate immune cells. Yet, despite their presumed functional importance, M. mulatta Ab receptors are largely uncharacterized, posing a fundamental limit to ensuring accurate interpretation and translation of results from studies in this model. In this article, we describe the binding characteristics of the most prevalent allotypic variants of M. mulatta FcγR for binding to both human and M. mulatta IgG of varying subclasses. The resulting determination of the affinity, specificity, and glycan sensitivity of these receptors promises to be useful in designing and evaluating studies of candidate vaccines and therapeutic Abs in this key animal model and exposes significant evolutionary divergence between humans and macaques.

  14. Evolution of the IGG concept at IGF from 2004 to 2007

    CERN Document Server

    Modanese, G


    IGG is the acronym for Impulse Gravity Generator, a device developed by E. Podkletnov in 1997-2003 for generating high-voltage discharges through YBCO electrodes. According to Podkletnov, an anomalous force beam is generated at the discharge, which acts on distant material target of any composition with a small repulsive force proportional to the target mass. An independent replication of this device was started in 2004 at IGF, Germany (Institut fuer Gravitationsforschung, Goede Foundation). The author was involved as theoretical consultant and his first assignment was to study a possible scaled-down version of the device. This required a thorough analysis of the physical working principles of the apparatus, which was documented in several internal reports from 2004 to 2009. The whole content of those from 2004 to 2007 is given here. Several parts are outdated, but useful for an understanding of the phenomenon. In particular, the discharge mechanism was eventually found to be different, namely a vacuum spark ...

  15. Anthrax vaccination induced anti-lethal factor IgG: fine specificity and neutralizing capacity. (United States)

    Crowe, Sherry R; Garman, Lori; Engler, Renata J M; Farris, A Darise; Ballard, Jimmy D; Harley, John B; James, Judith A


    The efficacy biomarker of the currently licensed anthrax vaccine (AVA) is based on quantity and neutralizing capacity of anti-protective antigen (anti-PA) antibodies. However, animal studies have demonstrated that antibodies to lethal factor (LF) can provide protection against in vivo bacterial spore challenges. Improved understanding of the fine specificities of humoral immune responses that provide optimum neutralization capacity may enhance the efficacy of future passive immune globulin preparations to treat and prevent inhalation anthrax morbidity and mortality. This study (n=1000) was designed to identify AVA vaccinated individuals who generate neutralizing antibodies and to determine what specificities correlate with protection. The number of vaccine doses, years post vaccination, and PA titer were associated with in vitro neutralization, reinforcing previous reports. In addition, African American individuals had lower serologic neutralizing activity than European Americans, suggesting a genetic role in the generation of these neutralizing antibodies. Of the vaccinated individuals, only 69 (6.9%) had moderate levels of anti-LF IgG compared to 244 (24.4%) with low and 687 (68.7%) with extremely low levels of IgG antibodies to LF. Using overlapping decapeptide analysis, we identified six common LF antigenic regions targeted by those individuals with moderate levels of antibodies to LF and high in vitro toxin neutralizing activity. Affinity purified antibodies directed against antigenic epitopes within the PA binding and ADP-ribotransferase-like domains of LF were able to protect mice against lethal toxin challenge. Findings from these studies have important implications for vaccine design and immunotherapeutic development.

  16. Coadsorption of IgG and BSA onto sulfonated polystyrene latex: II. Colloidal stability and immunoreactivity. (United States)

    Peula, J M; Hidalgo-Alvarez, R; de las Nieves, F J


    The present work deals with the study of the colloidal stability and immunoreactivity of sulfonated polystyrene latex particles covered by different amounts of m-BSA and IgG/a-CRP. These proteins have been previously adsorbed onto a sulfonated latex by sequential and competitive coadsorption experiments and it was possible to obtain latex-protein particles with different degrees of coverage by each protein. The latex particles, fully or partially covered by each protein (termed latex-protein complexes), were resuspended under several conditions (different pH and ionic strength values) and their colloidal stability, vs the addition of the electrolyte was studied using turbidity measurements. This stability appeared at a high degree of coverage by BSA and at a pH in which the BSA was negatively charged. At a high degree of coverage by IgG, the latex particles were unstable at all pHs. As a final part of this work, the immunoreactivity of several complexes was studied following the changes in the turbidity after the addition of CRP antigen. Only the complexes which were colloidally stable gave detectable reactivity. However, the complexes with a relatively low degree of coverage by IgG/a-CRP gave good immunoreactivity. Therefore, the latex-protein complex properties depended on the percentage of BSA or IgG adsorbed and on the electric state of the proteins at the redispersion pH. Under specific incubation conditions, sulfonated latex covered by significant IgG/BSA percentages was obtained, which showed a high colloidal stability and good immunoreactivity.

  17. Depigmented Allergoids Reveal New Epitopes with Capacity to Induce IgG Blocking Antibodies

    Directory of Open Access Journals (Sweden)

    M. Angeles López-Matas


    Full Text Available Background. The synthesis of allergen-specific blocking IgGs that interact with IgE after allergen immunotherapy (SIT has been related to clinical efficacy. The objectives were to investigate the epitope specificity of IgG-antibodies induced by depigmented-polymerized (Dpg-Pol allergoids and unmodified allergen extracts, and examine IgE-blocking activity of induced IgG-antibodies. Methods. Rabbits were immunized with native and Dpg-Pol extracts of birch pollen, and serum samples were obtained. Recognition of linear IgG-epitopes of Bet v 1 and Bet v 2 and the capacity of these IgG-antibodies to block binding of human-IgE was determined. Results. Serum from rabbits immunized with native extracts recognised 11 linear epitopes from Bet v 1, while that from Dpg-Pol-immunized animals recognised 8. For Bet v 2, 8 epitopes were recognized by IgG from native immunized animals, and 9 from Dpg-Pol immunized one. Dpg-Pol and native immunized serum did not always recognise the same epitopes, but specific-IgG from both could block human-IgE binding sites for native extract. Conclusions. Depigmented-polymerized birch extract stimulates the synthesis of specific IgG-antibodies which recognize common but also novel epitopes compared with native extracts. IgG-antibodies induced by Dpg-Pol effectively inhibit human-IgE binding to allergens which may be part of the mechanism of action of SIT.

  18. The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria (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.


    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

  19. The role of IgG subclass of mouse monoclonal antibodies in antibody-dependent enhancement of feline infectious peritonitis virus infection of feline macrophages. (United States)

    Hohdatsu, T; Tokunaga, J; Koyama, H


    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.

  20. 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


    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.

  1. 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 (United States)

    Akin, Evren; McHugh, Gail L.; Flavell, Richard A.; Fikrig, Erol; Steere, Allen C.


    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

  2. 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


    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

  3. A Retrospectively Diagnosed Case of IgG4-Related Tubulointerstitial Nephritis Showing Good Renal Outcome and Pathological Progress

    Directory of Open Access Journals (Sweden)

    Qiong Wu


    Full Text Available A 74-year-old man was hospitalized for diabetic nephropathy evaluation and assessment of the effect of treatment on his tubulointerstitial nephritis (TIN. When he was 62 years old, he developed polyarthralgia and had superficial lymph node swelling, mildly increased serum creatinine concentration, hypergammaglobulinemia, hypocomplementemia, high serum IL-2R level, and positive titer of antinuclear antibody. Several tissues were biopsied. Mild chronic sialadenitis and reactive lymphadenitis were identified. Renal specimen showed mild glomerular ischemia, extensive storiform fibrosis, and abundant infiltrating monocytes and plasma cells. He was treated with oral prednisolone and cyclophosphamide. After the treatment, most of his clinical parameters quickly returned to within the reference range. However, he developed diabetes mellitus soon after steroid therapy. At the time of rebiopsy, a high level of serum IgG4 was detected. The second renal biopsy showed diabetic nephropathy without any tubulointerstitial damage. The first biopsied tissues were retrospectively investigated. Large numbers of IgG4-positive plasma cells were detected in the kidneys and lymph nodes. A retrospective diagnosis of IgG4-related TIN with lymph node involvement was made. In conclusion, this paper describes a retrospectively diagnosed case of IgG4-related TIN with lymph node involvement, showing good clinical and pathological prognosis.

  4. Role of IgG4 in histamine release from human basophil leucocytes. I. Sensitization of cells from normal donors

    DEFF Research Database (Denmark)

    Poulsen, L K; Stahl Skov, P; Mosbech, H


    Several conflicting reports on the ability of IgG4 to mediate type I allergic reactions have appeared lately. We have developed a model system for testing this possibility, using passive sensitization of basophil leucocytes from normal individuals. At first, the system was optimized with regard...

  5. Effect of delayed anthrax vaccine dose on Bacillus anthracis protective antigen IgG response and lethal toxin neutralization activity. (United States)

    Pittman, Phillip R; Fisher, Diana; Quinn, Xiaofei; Schmader, Trevor; Barrera-Oro, Julio G


    We describe the Bacillus anthracis protective antigen IgG antibody response and the B. anthracis lethal toxin neutralization activity to a delayed dose of anthrax vaccine adsorbed (AVA, BioThrax(®)) using validated assays. 373 individuals received 1, 2, or 3 priming doses, 18-24 months afterward, they received a delayed dose of AVA. Overall, 23.6% of subjects showed detectable anti-PA IgG before the boost, compared to 99.2% (P<0.0001) 28 days after the boost. Geometric mean anti-PA IgG concentration (GMC) was 1.66 μg/mL before and 887.82 μg/mL after the boost (P<0.0001). The proportion of individuals with four-fold increase in GMC following the boost ranged from 93.8% to 100%. Robust anti-PA IgG levels and B. anthracis lethal toxin neutralization activity are induced when an AVA dose is delayed as long as two years. These data support continuing with the vaccination schedule when a dose is delayed as long as two years rather than restarting the series.

  6. Effect of pollen exposure on serum IgE and IgG antibody responses in Japanese cedar pollinosis patients

    Directory of Open Access Journals (Sweden)

    Koichi Imaoka


    Full Text Available We examined the IgE and IgG antibody responses in Japanese cedar pollinosis patients before and after the pollination season for 2 years. The sera from 90 patients in 1990 and 87 in 1991, living in five regions in the Tokyo area, were obtained before and after the pollination season. In all patients, changes (increase then decrease in specific IgE levels were detected after natural pollen exposure. Total IgE and specific IgG concentrations also changed. However, the degree of change in specific IgE was greater than those in total IgE and specific IgG. Then, the geometric means of specific and total IgE levels were compared among the five regions. These levels were found to be highest in the region where the pollen count was the highest. These findings suggest that IgE antibody production is more stimulated after natural pollen exposure compared to IgG antibody production, and is dependent on the amount of allergens.

  7. Maternal and neonatal anti-cytomegalovirus IgG level and risk of postnatal cytomegalovirus transmission in preterm infants

    NARCIS (Netherlands)

    Nijman, Joppe; van Loon, Anton M.; Krediet, Tannette G.; Verboon-Maciolek, Malgorzata A.


    Immunological mechanisms influencing the risk of mother-to-child cytomegalovirus (CMV) transmission in preterm infants have not been studied sufficiently. In this study, the correlation between maternal and neonatal serum anti-CMV IgG levels and risk of postnatal CMV transmission in preterm infants

  8. 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


    /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...

  9. Salivary IgA and IgG in oral lichen planus and oral lichenoid reactions diseases

    Directory of Open Access Journals (Sweden)

    Parichehr Ghaleyani


    Conclusions: Our results showed that the level of salivary IgA and IgG in OLP and OLR patients is higher than healthy controls, but they cannot be used as diagnostic factors to the differential diagnosis of OLP and OLR.

  10. Survival and digestibility of orally-administered immunoglobulin preparations containing IgG through the gastrointestinal tract in humans. (United States)

    Jasion, Victoria S; Burnett, Bruce P


    Oral immunoglobulin (Ig) preparations are prime examples of medicinal nutrition from natural sources. Plasma products containing Ig have been used for decades in animal feed for intestinal disorders to mitigate the damaging effects of early weaning. These preparations reduce overall mortality and increase feed utilization in various animal species leading to improved growth. Oral administration of Ig preparations from human serum as well as bovine colostrum and serum have been tested and proven to be safe as well as effective in human clinical trials for a variety of enteric microbial infections and other conditions which cause diarrhea. In infants, children, and adults, the amount of intact IgG recovered in stool ranges from trace amounts up to 25% of the original amount ingested. It is generally understood that IgG can only bind to antigens within the GI tract if the Fab structure is intact and has not been completely denatured through acidic pH or digestive proteolytic enzymes. This is a comprehensive review of human studies regarding the survivability of orally-administered Ig preparations, with a focus on IgG. This review also highlights various biochemical studies on IgG which potentially explain which structural elements are responsible for increased stability against digestion.

  11. IgG1 adsorption to siliconized glass vials-influence of pH, ionic strength, and nonionic surfactants. (United States)

    Höger, Kerstin; Mathes, Johannes; Frieß, Wolfgang


    In this study, the adsorption of an IgG1 antibody to siliconized vials was investigated with focus on the formulation parameters pH, ionic strength, and nonionic surfactants. Electrophoretic mobility measurements were performed to investigate the charge characteristics of protein and siliconized glass particles at different pH values. Calculation of the electrokinetic charge density allowed further insight into the energetic conditions in the protein-sorbent interface. Maximum adsorption of IgG1 was found at acidic pH values and could be correlated with energetically favorable minimal ion incorporation into the interface. The importance of electrostatic interactions for IgG1 adsorption at acidic pH values was also confirmed by the efficient adsorption reduction at decreased solution ionic strength. A second adsorption maximum around the pI of the protein was assigned to hydrophobic interactions with the siliconized surface. Addition of the nonionic surfactants poloxamer 188 or polysorbate 80 resulted in almost complete suppression of adsorption at pH 7.2, and a strong but less efficient effect at pH 4 on siliconized glass vials. This adsorption suppression was much less pronounced on borosilicate glass vials. From these results, it can be concluded that electrostatic interactions contribute substantially to IgG1 adsorption to siliconized glass vials especially at acidic formulation pH.

  12. Increased blood levels of IgG reactive with secreted Streptococcus pyogenes proteins in chronic plaque psoriasis. (United States)

    El-Rachkidy, Rana G; Hales, Jonathan M; Freestone, Primrose P E; Young, Helen S; Griffiths, Christopher E M; Camp, Richard D R


    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.

  13. pH-dependent binding engineering reveals an FcRn affinity threshold that governs IgG recycling. (United States)

    Borrok, M Jack; Wu, Yanli; Beyaz, Nurten; Yu, Xiang-Qing; Oganesyan, Vaheh; Dall'Acqua, William F; Tsui, Ping


    The Fc domain of IgG has been the target of multiple mutational studies aimed at altering the pH-dependent IgG/FcRn interaction to modulate IgG pharmacokinetics. These studies have yielded antibody variants with disparate pharmacokinetic characteristics, ranging from extended in vivo half-life to those exhibiting extremely rapid clearance. To better understand pH-dependent binding parameters that govern these outcomes and limit FcRn-mediated half-life extension, we generated a panel of novel Fc variants with high affinity binding at acidic pH that vary in pH 7.4 affinities and assessed pharmacokinetic outcomes. Pharmacokinetic studies in human FcRn transgenic mice and cynomolgus monkeys showed that multiple variants with increased FcRn affinities at acidic pH exhibited extended serum half-lives relative to the parental IgG. Importantly, the results reveal an underappreciated affinity threshold of neutral pH binding that determines IgG recycling efficiency. Variants with pH 7.4 FcRn affinities below this threshold recycle efficiently and can exhibit increased serum persistence. Increasing neutral pH FcRn affinity beyond this threshold reduced serum persistence by offsetting the benefits of increased pH 6.0 binding. Ultra-high affinity binding to FcRn at both acidic and neutral pH leads to rapid serum clearance.

  14. Comprehensive Analysis of the Therapeutic IgG4 Antibody Pembrolizumab: Hinge Modification Blocks Half Molecule Exchange In Vitro and In Vivo. (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


    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.

  15. 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.


    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 epito...

  16. Neuron-derived IgG protects dopaminergic neurons from insult by 6-OHDA and activates microglia through the FcγR I and TLR4 pathways. (United States)

    Zhang, Jie; Niu, Na; Wang, Mingyu; McNutt, Michael A; Zhang, Donghong; Zhang, Baogang; Lu, Shijun; Liu, Yuqing; Liu, Zhihui


    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.

  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.;


    Human IgG is produced with C-terminal lysines that are cleaved off in circulation. The function of this modification was unknown and generally thought not to affect antibody function. We recently reported that efficient C1q binding and complement-dependent cytotoxicity (CDC) requires IgG hexameri...

  18. Measurement of allergen-specific IgG in serum is of limited value for the management of dogs diagnosed with cutaneous adverse food reactions

    NARCIS (Netherlands)

    Hagen-Plantinga, E.A.; Leistra, M.H.G.; Sinke, J.D.; Vroom, M.W.; Savelkoul, H.F.J.; Hendriks, W.H.


    Conflicting results have been reported in the literature in terms of the usefulness of serological testing for IgG against food allergens in dogs with cutaneous adverse food reaction (CAFR). The aim of the present study was to evaluate the suitability of a commercially available IgG ELISA for identi

  19. 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; Ejlertsen, Tove; Hilden, Jørgen


    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 ra...

  20. Association of Helicobacter pylori IgG antibody with various demographic and biochemical parameters in kidney transplant recipients

    Directory of Open Access Journals (Sweden)

    Azar Baradaran


    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

  1. Characterization of IgG monoclonal antibody targeted to both tissue cyst and sporocyst walls of Toxoplasma gondii (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. IgG4-related pleural disease diagnosed by a re-evaluation of chronic bilateral pleuritis in a patient who experienced occasional acute left bacterial pleuritis. (United States)

    Yamamoto, Hiroshi; Suzuki, Toshiro; Yasuo, Masanori; Kobayashi, Orie; Tsushima, Kenji; Ito, Michiko; Urushihata, Kazuhisa; Yamazaki, Yoshitaka; Hanaoka, Masayuki; Koizumi, Tomonobu; Uehara, Takeshi; Kawakami, Satoshi; Hamano, Hideaki; Kawa, Shigeyuki; Kubo, Keishi


    A 78-year-old man with cryptogenic chronic bilateral lymphoplasmacytic pleuritis, diagnosed based on left parietal pleural biopsy specimens obtained by pleuroscopy, developed acute left bacterial pleuritis. The left pleural effusion was neutrophil dominant, however, the right pleural effusion showed lymphoplasmacytic infiltration. Laboratory examinations revealed that his serum IgG4 concentration was increased, with a higher level of IgG4 in the right pleural effusion. Re-evaluation of the previous biopsy specimens using an immunostaining method revealed numerous IgG4-positive plasma cell infiltrations with IgG4-positive/IgG-positive plasma cells at 85.4%. Accordingly, the new diagnosis of this patient was considered to be chronic bilateral IgG4-related pleuritis.

  3. Distinct patterns of blood-stage parasite antigens detected by plasma IgG subclasses from individuals with different level of exposure to Plasmodium falciparum infections

    DEFF Research Database (Denmark)

    Olesen, Cathrine Holm; Brahimi, Karima; Vandahl, Brian;


    ABSTRACT: BACKGROUND: In endemic regions naturally acquired immunity against Plasmodium falciparum develops as a function of age and exposure to parasite infections and is known to be mediated by IgG. The targets of protective antibodies remain to be fully defined. Several immunoepidemiological...... then gradually develop into protective response dominated by cytophilic IgG1 and IgG3 antibodies. METHODS: Naturally occurring IgG antibodies against P. falciparum blood-stage antigens were analysed from plasma samples collected from four groups of individuals differing in age and level of exposure to P....... falciparum infections. Western Blot profiling of blood-stage parasite antigens displaying reactivity with individual plasma samples in terms of their subclass specificities was conducted. Parasite antigens detected by IgG were grouped based on their apparent molecular sizes resolved by SDS-PAGE as high...

  4. Plasmodium falciparum infection and age influence parasite growth inhibition mediated by IgG in Beninese infants. (United States)

    Adamou, Rafiou; Chénou, Francine; Sadissou, Ibrahim; Sonon, Paulin; Dechavanne, Célia; Djilali-Saïah, Abdelkader; Cottrell, Gilles; Le Port, Agnès; Massougbodji, Achille; Remarque, Edmond J; Luty, Adrian J F; Sanni, Ambaliou; Garcia, André; Migot-Nabias, Florence; Milet, Jacqueline; Courtin, David


    Antibodies that impede the invasion of Plasmodium falciparum (P. falciparum) merozoites into erythrocytes play a critical role in anti-malarial immunity. The Growth Inhibition Assay (GIA) is an in vitro measure of the functional capacity of such antibodies to limit erythrocyte invasion and/or parasite growth. Up to now, it is unclear whether growth-inhibitory activity correlates with protection from clinical disease and there are inconsistent results from studies performed with GIA. Studies that have focused on the relationship between IgGs and their in vitro parasite Growth Inhibition Activity (GIAc) in infants aged less than two years old are rare. Here, we used clinical and parasitological data to precisely define symptomatic or asymptomatic infection with P. falciparum in groups of infants followed-up actively for 18 months post-natally. We quantified the levels of IgG1 and IgG3 directed to a panel of candidate P. falciparum vaccine antigens (AMA-1, MSP1, 2, 3 and GLURP) using ELISA and the functional activity of IgG was quantified using GIA. Data were then correlated with individuals' infection status. At 18 months of age, infants harbouring infections at the time of blood sampling had an average 19% less GIAc than those not infected (p=0.004, multivariate linear regression). GIAc decreased from 12 to 18 months of age (p=0.003, Wilcoxon matched pairs test). Antibody levels quantified at 18 months in infants were strongly correlated with their exposure to malarial infection, however GIAc was not correlated with malaria infectious status (asymptomatic and symptomatic groups). In conclusion, both infection status at blood draw and age influence parasite growth inhibition mediated by IgG in the GIA. Both factors must be taken into account when correlations between GIAc and anti-malarial protection or vaccine efficacy have to be made.

  5. Impaired clearance of early apoptotic cells mediated by inhibitory IgG antibodies in patients with primary Sjogren's syndrome.

    Directory of Open Access Journals (Sweden)

    Menelaos N Manoussakis

    Full Text Available OBJECTIVES: Deficient efferocytosis (i.e. phagocytic clearance of apoptotic cells has been frequently reported in systemic lupus erythematosus (SLE. Todate, patients with primary Sjögren's syndrome (SS have not been assessed for phagocytosis of apoptotic cells (ApoCell-phagocytosis and of particulate targets (microbeads, MB-phagocytosis. DESIGN: ApoCell-phagocytosis and MB-phagocytosis were comparatively assessed by flow cytometry in peripheral blood specimens and monocyte-derived macrophage (MDM preparations from healthy blood donors (HBD and consecutive SS, SLE and rheumatoid arthritis (RA patients. Cross-admixture ApoCell-phagocytosis experiments were also performed using phagocytes from HBD or patients, and apoptotic cells pretreated with whole sera or purified serum IgG derived from patients or HBD. RESULTS: Compared to HBD, approximately half of SS and SLE patients studied (but not RA manifested significantly reduced ApoCell-phagocytosis (p<0.001 and MB-phagocytosis (p<0.003 by blood-borne phagocytes that correlated inversely with disease activity (p≤0.004. In cross-admixture assays, healthy monocytes showed significantly reduced ApoCell-phagocytosis when fed with apoptotic cells that were pretreated with sera or purified serum IgG preparations from SS and SLE patients (p<0.0001, compared to those from HBD or RA. Such aberrant effect of the SS and SLE sera and IgG preparations correlated linearly with their content of IgG antibodies against apoptotic cells (p≤0.0001. Phagocytic dysfunction maybe also present in certain SS and SLE patients, as supported by deficient capacity of MDM for ApoCell-phagocytosis and MB-phagocytosis under patients' serum-free conditions. CONCLUSION: Similarly to SLE, efferocytosis is frequently impaired in SS and is primarily due to the presence of inhibitory IgG anti-ApoCell antibodies and secondarily to phagocytes' dysfunction.

  6. [Hypertrophic pachymeningitis secondary to IgG4-related disease: case report and review of the literature]. (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


    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.

  7. 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.

  8. IgG from patients with systemic sclerosis bind to DNA antitopoisomerase 1 in normal human fibroblasts extracts

    Directory of Open Access Journals (Sweden)

    Mathieu C Tamby


    Full Text Available Mathieu C Tamby1, Amélie Servettaz1, Nicolas Tamas1, Joseph Reinbolt2, Frédéric Caux3, Olivier Meyer4, Yannick Allanore5, André Kahan5, Loïc Guillevin6, Luc Mouthon1,61Paris-Descartes University, Faculty of Medicine, UPRES-EA 4058, Paris, France; 2UPR 9002, Centre National de la Recherche Scientifique, Strasbourg, France; 3UPRES EA 2436, Paris-Nord University, Bobigny, France; 4Rheumatology Department, Bichat Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP, Paris, France; 5Rheumatology A Department, Cochin Hospital, AP-HP; 6Paris-Descartes University, Faculty of Medicine, Department of Internal Medicine and French Reference Center for Necrotizing Vasculitides and Systemic Sclerosis, Cochin Hospital, AP-HP, Paris, FranceAbstract: By using a semi-quantitative immunoblotting technique, we have analyzed serum immunoglobulin G (IgG reactivities of patients with limited cutaneous systemic sclerosis and anticentromere antibodies, patients with diffuse systemic sclerosis and antitopoisomerase 1 antibodies, patients with diffuse systemic sclerosis without antitopoisomerase 1 or anticentromere antibodies and age- and gender-matched healthy controls with normal human skin fibroblasts and HEp-2 cells antigens. Serum IgG reactivities of patients with diffuse systemic sclerosis and antitopoisomerase 1 antibodies differed significantly from those of healthy controls or systemic sclerosis patients in other groups for reactivity with fibroblast proteins. IgG from patients with antitopoisomerase 1 antibodies bound to a 90 kDa fibroblast band and to a 100 kDa protein band in a HEp-2 cell protein extract. These two bands were further identified as DNA topoisomerase 1. Our results indicate that IgG from patients with diffuse systemic sclerosis bind DNA topoisomerase 1 in normal human fibroblasts extracts.Keywords: systemic sclerosis, autoantibodies, IgG, fibroblast, DNA topoisomerase 1

  9. Influence of IgG Subclass on Human Antimannan Antibody-Mediated Resistance to Hematogenously Disseminated Candidiasis in Mice. (United States)

    Nishiya, Casey T; Boxx, Gayle M; Robison, Kerry; Itatani, Carol; Kozel, Thomas R; Zhang, Mason X


    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.

  10. Human IgG1 monoclonal antibody against human collagen 17 noncollagenous 16A domain induces blisters via complement activation in experimental bullous pemphigoid model. (United States)

    Li, Qiang; Ujiie, Hideyuki; Shibaki, Akihiko; Wang, Gang; Moriuchi, Reine; Qiao, Hong-jiang; Morioka, Hiroshi; Shinkuma, Satoru; Natsuga, Ken; Long, Heather A; Nishie, Wataru; Shimizu, Hiroshi


    Bullous pemphigoid (BP) is an autoimmune blistering disease caused by IgG autoantibodies targeting the noncollagenous 16A (NC16A) domain of human collagen 17 (hCOL17), which triggers blister formation via complement activation. Previous in vitro analysis demonstrated that IgG1 autoantibodies showed much stronger pathogenic activity than IgG4 autoantibodies; however, the exact pathogenic role of IgG1 autoantibodies has not been fully demonstrated in vivo. We constructed a recombinant IgG1 mAb against hCOL17 NC16A from BP patients. In COL17-humanized mice, this mAb effectively reproduced a BP phenotype that included subepidermal blisters, deposition of IgG1, C1q and C3, neutrophil infiltration, and mast cell degranulation. Subsequently, alanine substitutions at various C1q binding sites were separately introduced to the Fc region of the IgG1 mAb. Among these mutated mAbs, the one that was mutated at the P331 residue completely failed to activate the complement in vitro and drastically lost pathogenic activity in COL17-humanized mice. These findings indicate that P331 is a key residue required for complement activation and that IgG1-dependent complement activation is essential for blister formation in BP. This study is, to our knowledge, the first direct evidence that IgG1 Abs to hCOL17 NC16A can induce blister formation in vivo, and it raises the possibility that IgG1 mAbs with Fc modification may be used to block pathogenic epitopes in autoimmune diseases.

  11. 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


    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

  12. NRT Atmospheric Water Vapour Retrieval on the Area of Poland at IGG WUELS AC (United States)

    Kaplon, Jan; Bosy, Jaroslaw; Sierny, Jan; Hadas, Tomasz; Rohm, Witold; Wilgan, Karina; Ryczywolski, Marcin; Oruba, Artur; Kroszczynski, Krzysztof


    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 ( This system was established in year 2008 by the Head Office of Geodesy and Cartography in the frame of the EUPOS project ( 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

  13. 18F-fluoro-deoxyglucose positron emission tomography/computed tomography scan findings in Rosai-Dorfman disease with IgG4-positive plasma cell infiltration mimicking breast malignancy: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Fu Liping


    Full Text Available Abstract Introduction Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy, is a rare benign disorder characterized histologically by lymphatic sinus dilatation due to histiocyte proliferation. Rosai-Dorfman disease accompanied by IgG4+ plasma cell infiltration is an even rarer situation. To the best of our knowledge, no imaging report of fluoro-deoxyglucose positron emission tomography/computed tomography findings of Rosai-Dorfman disease with IgG4+ plasma cell infiltration has been published, although a series of pathological research has focused on this phenomenon. Case presentation We reviewed the 18F-fluoro-deoxyglucose positron emission tomography/computed tomography scan of a 78-year-old Chinese woman with a solid mass that was found in her right breast during a health checkup. 18F-fluoro-deoxyglucose positron emission tomography/computed tomography showed a hypermetabolic nodule in her right breast and slightly heterogeneous increased fluoro-deoxyglucose uptake of the pulmonary nodules, which were histologically proven to be mammary Rosai-Dorfman disease with IgG4+ plasma cell infiltration and pulmonary amyloidosis, respectively. A literature review was performed to gather information on this rare disease process. Conclusions Although distinguishing benign lymphoplasmacytic proliferation from malignancy may be difficult with 18F-fluoro-deoxyglucose positron emission tomography/computed tomography in light of the pattern and intensity of fluoro-deoxyglucose uptake, our case highlights that whole-body positron emission tomography/computed tomography imaging not only can display the extent of the disease to help complete staging but also can provide functional information about disease activity to guide biopsy.

  14. Monitoring of Anti-Hepatitis E Virus Antibody Seroconversion in Asymptomatically Infected Blood Donors: Systematic Comparison of Nine Commercial Anti-HEV IgM and IgG Assays (United States)

    Vollmer, Tanja; Diekmann, Juergen; Eberhardt, Matthias; Knabbe, Cornelius; Dreier, Jens


    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

  15. Shift in epitope dominance of IgM and IgG responses to Plasmodium falciparum MSP1 block 4

    Directory of Open Access Journals (Sweden)

    Leke Rose GF


    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 consi