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Sample records for anti-ley igg reversal

  1. Extraction of monoclonal antibodies (IgG1) using anionic and anionic/nonionic reverse micelles.

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    George, Daliya A; Stuckey, David C

    2010-01-01

    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.

  2. Prediction of reversible IgG1 aggregation occurring in a size exclusion chromatography column is enabled through a model based approach.

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    Ojala, Frida; Sellberg, Anton; Hansen, Thomas Budde; Hansen, Ernst Broberg; Nilsson, Bernt

    2015-09-01

    One important aspect of antibody separation being studied today is aggregation, as this not only leads to a loss in yield, but aggregates can also be hazardous if injected into the body. The aim of this study was to determine whether the methodology applied in the previous study could be used to predict the aggregation of a different batch of IgG1, and to model the aggregation occurring in a SEC column. Aggregation was found to be reversible. The equilibrium parameter was found to be 272 M(-1) and the reaction kinetic parameter 1.33 × 10(-5) s(-1) , both within the 95% confidence interval of the results obtained in the previous work. The effective diffusivities were estimated to be 1.45 × 10(-13) and 1.90 10(-14) m(2) /s for the monomers and dimers, respectively. Good agreement was found between the new model and the chromatograms obtained in the SEC experiments. The model was also able to predict the decrease of dimers due to the dilution and separation in the SEC column during long retention times.

  3. Enhancement of retroviral infection in vitro by anti-Le(y) IgG: reversal by humanization of monoclonal mouse antibody

    DEFF Research Database (Denmark)

    Hansen, J E; Sørensen, A M; Arendrup, M;

    1993-01-01

    Monoclonal mouse IgG3 antibody (ABL 364) against the carbohydrate Le(y) antigen enhanced infection in vitro with HTLV-1 and with HIV-1 when propagated in both transformed and normal lymphocytes. Enhancement was independent of complement, occurred with both lymphocytes and monocytes as target cell...

  4. Enhancement of retroviral infection in vitro by anti-Le(y) IgG: reversal by humanization of monoclonal mouse antibody

    DEFF Research Database (Denmark)

    Hansen, J E; Sørensen, A M; Arendrup, M

    1993-01-01

    Monoclonal mouse IgG3 antibody (ABL 364) against the carbohydrate Le(y) antigen enhanced infection in vitro with HTLV-1 and with HIV-1 when propagated in both transformed and normal lymphocytes. Enhancement was independent of complement, occurred with both lymphocytes and monocytes as target cells...... with no indication of any alternative pathway of infection, as evidenced by abrogation of enhancement by anti-CD4 MAb or soluble recombinant CD4, and also the inability of anti-Le(y) MAb to mediate HIV infection of HSB-2 cells in which HTLV-1/HIV pseudovirus infection was enhanced. While F(ab)2 fragments of ABL 364...

  5. Enhancement of retroviral infection in vitro by anti-Le(y) IgG: reversal by humanization of monoclonal mouse antibody

    DEFF Research Database (Denmark)

    Hansen, J E; Sørensen, A M; Arendrup, M

    1993-01-01

    also enhanced infection, a human/mouse chimeric antibody and a fully humanized antibody had no enhancing effect on free virus infection. We suggest that binding of anti-Le(y) ABL 364 or its F(ab)2 fragment induced a conformational change in the gp120 oligomers facilitating the process of infection...... with no indication of any alternative pathway of infection, as evidenced by abrogation of enhancement by anti-CD4 MAb or soluble recombinant CD4, and also the inability of anti-Le(y) MAb to mediate HIV infection of HSB-2 cells in which HTLV-1/HIV pseudovirus infection was enhanced. While F(ab)2 fragments of ABL 364......Monoclonal mouse IgG3 antibody (ABL 364) against the carbohydrate Le(y) antigen enhanced infection in vitro with HTLV-1 and with HIV-1 when propagated in both transformed and normal lymphocytes. Enhancement was independent of complement, occurred with both lymphocytes and monocytes as target cells...

  6. IgG4-associated cholangitis.

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

    2014-12-01

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

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

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

    2013-12-01

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

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

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    Sy A

    2016-10-01

    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

  9. IgG4 Related Sclerosing Cholangitis

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    D. Joshi

    2014-01-01

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

  10. IgG4-associated vasculitis.

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

    2013-08-01

    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.

  11. Serum levels of IgG and IgG4 in Hashimoto thyroiditis.

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    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

    2014-03-01

    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.

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

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    Naoshi Nishina

    2012-01-01

    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.

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

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    Yasufumi Masaki

    2012-01-01

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

  14. IgG4-related sclerosing disease

    Institute of Scientific and Technical Information of China (English)

    Terumi Kamisawa; Atsutake Okamoto

    2008-01-01

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

  15. IgG4-related prostatitis progressed from localized IgG4-related lymphadenopathy

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

    2015-01-01

    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

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  17. Pathologies Associated with Serum IgG4 Elevation

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    Mikael Ebbo

    2012-01-01

    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.

  18. Topiramate-induced maculopathy in IgG4-related disease

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    DaCosta J

    2016-06-01

    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

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

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

    2015-01-01

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

  20. Serum IgG subclasses in autoimmune diseases.

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

    2015-01-01

    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.

  1. Cholangiocarcinoma with respect to IgG4 Reaction

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    Kenichi Harada

    2014-01-01

    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.

  2. Heat sensitivity of porcine IgG.

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

    1975-09-01

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

  3. IgG Subclass Staining in Routine Renal Biopsy Material.

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

    2016-05-01

    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.

  4. IgG4-Related Nasal Pseudotumor

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    L. K. Døsen

    2015-01-01

    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.

  5. IgG4-Related Perineural Disease

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    Dai Inoue

    2012-01-01

    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.

  6. IgG4 Related Lung Disease

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    Mihir Patel

    2016-01-01

    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.

  7. Reverse Logistics

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    Kulikova, Olga

    2016-01-01

    This thesis was focused on the analysis of the concept of reverse logistics and actual reverse processes which are implemented in mining industry and finding solutions for the optimization of reverse logistics in this sphere. The objective of this paper was the assessment of the development of reverse logistics in mining industry on the example of potash production. The theoretical part was based on reverse logistics and mining waste related literature and provided foundations for further...

  8. IgG abnormality in narcolepsy and idiopathic hypersomnia.

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    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.

  9. IgG4-related Disease of the Genitourinary Tract

    Directory of Open Access Journals (Sweden)

    Mukul K. Divatia

    2014-02-01

    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

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

    Directory of Open Access Journals (Sweden)

    Lucía Santamaría Ortiz

    1995-04-01

    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

  11. IgG4-related pleuritis with chylothorax.

    Science.gov (United States)

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

    2014-01-01

    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.

  12. 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.

  13. Phase transitions in human IgG solutions.

    Science.gov (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

    2013-09-28

    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

  14. Development of an IgG4-RD Responder Index

    Directory of Open Access Journals (Sweden)

    Mollie N. Carruthers

    2012-01-01

    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.

  15. Analysis of IgG kinetic stability by differential scanning calorimetry, probe fluorescence and light scattering.

    Science.gov (United States)

    Nemergut, Michal; Žoldák, Gabriel; Schaefer, Jonas V; Kast, Florian; Miškovský, Pavol; Plückthun, Andreas; Sedlák, Erik

    2017-08-19

    Monoclonal antibodies of the immunoglobulin G (IgG) type have become mainstream therapeutics for the treatment of many life-threatening diseases. For their successful application in the clinic and a favorable cost-benefit ratio, the design and formulation of these therapeutic molecules must guarantee long-term stability for an extended period of time. Accelerated stability studies, e.g., by employing thermal denaturation, have the great potential for enabling high-throughput screening campaigns to find optimal molecular variants and formulations in a short time. Surprisingly, no validated quantitative analysis of these accelerated studies has been performed yet, which clearly limits their application for predicting IgG stability. Therefore, we have established a quantitative approach for the assessment of the kinetic stability over a broad range of temperatures. To this end, differential scanning calorimetry (DSC) experiments were performed with a model IgG, testing chaotropic formulations and an extended temperature range, and they were subsequently analyzed by our recently developed three-step sequential model of IgG denaturation, consisting of one reversible and two irreversible steps. A critical comparison of the predictions from this model with data obtained by an orthogonal fluorescence probe method, based on 8-anilinonaphthalene-1-sulfonate binding to partially unfolded states, resulted in very good agreement. In summary, our study highlights the validity of this easy-to-perform analysis for reliably assessing the kinetic stability of IgGs, which can support accelerated formulation development of monoclonal antibodies by ranking different formulations as well as by improving colloidal stability models. © 2017 The Protein Society.

  16. Fractionation of rat IgG subclasses and screening for IgG Fc-binding to bacteria.

    Science.gov (United States)

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

    1982-01-01

    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.

  17. Epitope-Specific Suppression of IgG Responses by Passively Administered Specific IgG: Evidence of Epitope Masking

    Science.gov (United States)

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

    2017-01-01

    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.

  18. IgG subclasses in human chronic schistosomiasis: over-production of schistosome-specific and non-specific IgG4.

    Science.gov (United States)

    Boctor, F N; Peter, J B

    1990-12-01

    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.

  19. Macrophage triggering by aggregated immunoglobulins. II. Comparison of IgE and IgG aggregates or immune complexes.

    Science.gov (United States)

    Pestel, J; Dessaint, J P; Joseph, M; Bazin, H; Capron, A

    1984-01-01

    Macrophages incubated with complexed or aggregated IgE released beta-glucuronidase (beta-G) within 30 min. In contrast in the presence of aggregated or complexed IgG, macrophages liberated equivalent amount of beta-G only after 6 h incubation. In addition the rapid macrophage stimulation induced by aggregated IgE was also followed by a faster 3H-glucosamine incorporation when compared to the delayed activation caused by aggregated IgG. However, macrophages stimulated either by IgG or by IgE oligomers produced the same percentage of plasminogen activator at 24 h. In contrast, while the interaction between macrophages and aggregated IgE was only followed by a peak of cyclic GMP and a beta-G release during the first 30 min of incubation, the interaction between macrophages and IgG oligomers was accompanied by a simultaneous increase of cyclic GMP and AMP nucleotides and by an absence of beta-G exocytosis. Moreover, the beta-G release induced by aggregated IgE was increased when macrophages were preincubated with aggregated IgG. This additive effect was not observed in the reverse situation. Finally macrophages activated by IgG oligomers were demonstrated to exert a cytotoxic effect on tumour cells and to kill schistosomula in the presence of a low level of complement. Taken together these results underline the peculiar ability of aggregated or complexed IgE to trigger rapidly the macrophage activation compared to aggregated IgG and can explain the important role of complexed IgE in some macrophage dependent cytotoxicity mechanisms (i.e. in parasitic diseases). PMID:6088135

  20. IgG4 Inflammatory Pseudotumor of the Kidney

    Directory of Open Access Journals (Sweden)

    Ahmed N. Alkhasawneh

    2012-01-01

    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.

  1. Reverse logistics

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); S.D.P. Flapper; R. Dekker (Rommert)

    2002-01-01

    textabstractThis paper gives an overview of scientific literature that describes and discusses cases of reverse logistics activities in practice. Over sixty case studies are considered. Based on these studies we are able to indicate critical factors for the practice of reverse logistics. In addi

  2. IgG4-related disease and the kidney.

    Science.gov (United States)

    Cortazar, Frank B; Stone, John H

    2015-10-01

    IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition that involves almost every organ system. In this Review, we summarize current knowledge of IgG4-RD and its most frequent manifestations in the kidney—IgG4-related tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy (MGN). Diagnosis of IgG4-RD relies on histopathology: the typical features are a dense lymphoplasmacytic infiltrate and storiform fibrosis. A high percentage of plasma cells observed within lesions stain positively for IgG4. IgG4-related TIN bears the hallmark pathological findings of IgG4-RD; distinctive radiographic characteristics are also frequently observed with use of contrast-enhanced CT. MGN secondary to IgG4-RD seems to be distinct from idiopathic MGN. Humoral and cell-mediated immunity seem to have roles in the pathophysiology of IgG4-RD, but the details of these roles remain unclear. The IgG4 molecule itself is unlikely to be the primary driver of inflammation; rather, it probably downregulates the immune response. Fibrosis might be caused by activation of innate immune cells by polarized CD4(+) T cells. Glucocorticoids are the standard initial treatment for IgG4-RD, but their long-term adverse effects and the high frequency of relapse and renal damage associated with use of this treatment has prompted a search for more effective options. B-cell depletion and the targeting of plasmablasts are both promising approaches.

  3. High-dose intravenous IgG treatment and renal function.

    Science.gov (United States)

    Schifferli, J; Leski, M; Favre, H; Imbach, P; Nydegger, U; Davies, K

    1991-02-23

    In an open trial of high dose intravenous IgG (IVIG) treatment in nephrotic patients with glomerulonephritis, the first six patients so far studied showed a transient rise in plasma creatinine. This increase was not associated with any symptoms and the urinary deposit remained unchanged. Two other patients with pre-existing renal impairment but without nephrotic syndrome had a transient and reversible rise in plasma creatinine immediately after IVIG. These observations suggest that high-dose IVIG infusion can produce short-lived disturbances in renal function in patients with kidney diseases.

  4. IgG glycosylation changes and MBL2 polymorphisms

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  5. IgG4-Related Disease: A Multispecialty Condition

    Directory of Open Access Journals (Sweden)

    Iuri Usêda Santana

    2014-01-01

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

  6. Clinical study on IgG4-related autoimmune pancreatitis

    Institute of Scientific and Technical Information of China (English)

    吴庆军

    2013-01-01

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

  7. Heterogeneity of IgG glycosylation in adult periodontal disease.

    Science.gov (United States)

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

    2005-10-01

    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.

  8. IgG4-Related Disease Presenting as Isolated Scleritis

    Science.gov (United States)

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

    2017-01-01

    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

  9. IgG4-Seronegative Autoimmune Pancreatitis and Sclerosing Cholangitis

    Directory of Open Access Journals (Sweden)

    Allon Kahn

    2015-01-01

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

  10. TREATMENT OF IgG4-RELATED DISEASE

    Directory of Open Access Journals (Sweden)

    E. V. Sokol

    2016-01-01

    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.

  11. IgG4-Related Disease Presenting as Isolated Scleritis

    Directory of Open Access Journals (Sweden)

    Eran Berkowitz

    2017-01-01

    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.

  12. Fluorescent IgG fusion proteins made in E. coli.

    Science.gov (United States)

    Luria, Yael; Raichlin, Dina; Benhar, Itai

    2012-01-01

    Antibodies are among the most powerful tools in biological and biomedical research and are presently the fastest growing category of new bio-pharmaceutics. The most common format of antibody applied for therapeutic, diagnostic and analytical purposes is the IgG format. For medical applications, recombinant IgGs are made in cultured mammalian cells in a process that is too expensive to be considered for producing antibodies for diagnostic and analytical purposes. Therefore, for such purposes, mouse monoclonal antibodies or polyclonal sera from immunized animals are used. While looking for an easier and more rapid way to prepare full-length IgGs for therapeutic purposes, we recently developed and reported an expression and purification protocol for full-length IgGs, and IgG-based fusion proteins in E. coli, called "Inclonals." By applying the Inclonals technology, we could generate full-length IgGs that are genetically fused to toxins. The aim of the study described herein was to evaluate the possibility of applying the "Inclonals" technology for preparing IgG-fluorophore fusion proteins. We found that IgG fused to the green fluorescent proteins enhanced GFP (EGFP) while maintaining functionality in binding, lost most of its fluorescence during the refolding process. In contrast, we found that green fluorescent Superfolder GFP (SFGFP)-fused IgG and red fluorescent mCherry-fused IgG were functional in antigen binding and maintained fluorescence intensity. In addition, we found that we can link several SFGFPs in tandem to each IgG, with fluorescence intensity increasing accordingly. Fluorescent IgGs made in E. coli may become attractive alternatives to monoclonal or polyclonal fluorescent antibodies derived from animals.

  13. 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;

    2004-01-01

    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...

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

    Science.gov (United States)

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

    2015-01-01

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

  15. Bioavailability of IgG Administered by the Subcutaneous Route

    OpenAIRE

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

    2013-01-01

    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...

  16. In vitro functional characterization of feline IgGs.

    Science.gov (United States)

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

    2014-04-15

    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.

  17. Reversible Computing

    Science.gov (United States)

    1980-02-01

    will have been introduced. 9. Reversible celular autemata We shall assume the reader to have some familiarity with the concept of cel- lular...10003 Mr. Kin B. Thcmpson 1 copy Technical Director Information Systems Divisia.i Naval Research Laboratory (OP-91T) Technical Information Division

  18. IgG4-RELATED DISEASE. CLINICAL NOTES

    Directory of Open Access Journals (Sweden)

    Vladimir Ivanovich Vasilyev

    2013-01-01

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Localized IgG4-related Cholecystitis Mimicking Gallbladder Cancer.

    Science.gov (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

    2015-01-01

    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. 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

    2012-01-01

    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.

  2. Aggregated IgG inhibits the differentiation of human fibrocytes.

    Science.gov (United States)

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

    2006-06-01

    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.

  3. IgG4-Related Disease in a Urachal Tumor

    Directory of Open Access Journals (Sweden)

    Travis W. Dum

    2014-01-01

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

  4. IgG2 Fc structure and the dynamic features of the IgG CH2-CH3 interface.

    Science.gov (United States)

    Teplyakov, Alexey; Zhao, Yonghong; Malia, Thomas J; Obmolova, Galina; Gilliland, Gary L

    2013-11-01

    The analyses of two human IgG2 Fc structures, determined in different crystal forms, and the comparison with IgG1 Fc structures reveals molecular features that are involved in accommodating and stabilizing structural conformations. In the IgG2 Fc structures relative positions of the CH2 domains with respect to the CH3 domains vary significantly from those observed for IgG1 Fc structures in similar unit cells. The analysis reveals that the movement of the CH2 domain in all of the Fc structures results from a pivoting around a highly conserved ball-and-socket-like joint in which the CH2 L251 side chain (the ball) interacts with a pocket (the socket) formed by CH3 M428, H429, E430, and H435. Despite the change in positioning of the CH2 and CH3 domains, conserved hydrogen bonds and electrostatic interactions are retained, stabilizing the Fc domain interface. In the high resolution IgG2 and IgG1 Fc structures the position and number of water molecules, and water networks bridging the two domains differ significantly because of the difference in positions of CH2 relative to CH3. At the domain interface, only CH2 T339 in IgG2 differs from alanine found in IgG1 and IgG4. This residue's side chain influences the water structure at the interface by interacting either directly or through a bridging water molecule with D376 in the CH3 BC loop. Thus, the analyses of the IgG2 Fc structures and their comparisons with IgG1 Fc structures reveals similar, but distinctly different dynamic CH2-CH3 interfaces that can accommodate a wide range of CH2-CH3 conformations, that in conjunction with the amino acid residues in the hinge region, may influence FcγR effector function profiles. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Value of serum IgG4 in the diagnosis of IgG4-related disease and in differentiation from rheumatic diseases and other diseases.

    Science.gov (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

    2012-06-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Vasantha Nagendran

    2015-01-01

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

  7. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... in different ways. The presence and absence of diverse materials, both natural and political, is what distinguishes them from each other. Arguments are presented for a more symmetric relation between the scientific statistical text and the reader. I will argue that a more symmetric relation can be achieved...

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

    Directory of Open Access Journals (Sweden)

    Mitsuhiro Kawano

    2012-01-01

    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.

  9. Acute Painful Ptosis Secondary to IgG4 Dacryoadenitis

    Directory of Open Access Journals (Sweden)

    Rumana Hussain

    2016-02-01

    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.

  10. IgG2 immunodeficiency: association to pediatric patients with bacterial meningoencephalitis

    Directory of Open Access Journals (Sweden)

    ESCOBAR-PÉREZ XIOMARA

    2000-01-01

    Full Text Available An IgG subclass deficiency is often associated with bacterial infections. We studied four pediatric patients suffering from meningoencephalitis, two of them due to Streptococcus pneumoniae and two due to Haemophilus influenzae type b. Simultaneous diagnostic serum and cerebrospinal fluid samples were taken during income. The four subclasses of IgG and albumin were quantified in both biologic fluids by radial immunodiffusion. Very low levels of seric IgG2 with non detectable cerebrospinal fluid IgG2 were found in the patients. No intrathecal IgG subclass synthesis was found in two patients. One patient with S. pneumoniae had IgG3 intrathecal synthesis. Intrathecal IgG1, IgG3 and IgG4 synthesis was found in one patient suffering from H. influenzae according with reibergrams. Substitutive therapy with intravenous gammaglobulin was given to the patients as part of the treatment.

  11. 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

    2012-12-01

    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.

  12. A small subgroup of Hashimoto's thyroiditis is associated with IgG4-related disease.

    Science.gov (United States)

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

    2016-03-01

    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 Hashimoto's 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.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    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 (Ig)G1, 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...

  14. 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).

    Science.gov (United States)

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

    2016-10-20

    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.

  15. 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.

    Science.gov (United States)

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

    2010-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Jay H. Ryu

    2012-01-01

    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.

  17. IgG4-related epididymo-orchitis associated with bladder cancer: possible involvement of BAFF/BAFF-R interaction in IgG4-related urogenital disease.

    Science.gov (United States)

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

    2014-01-01

    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.

  18. 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

    1996-01-01

    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

  19. 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

    2014-01-01

    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

  20. [Raise awareness of IgG4 relative ocular disease].

    Science.gov (United States)

    Wei, Shihui; Li, Hongyang

    2015-12-01

    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.

  1. 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

  2. Aggregated IgG inhibits the differentiation of human fibrocytes

    OpenAIRE

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

    2006-01-01

    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...

  3. IgG subclass deficiencies in children: Facts and fiction.

    Science.gov (United States)

    Wahn, Volker; von Bernuth, Horst

    2017-09-01

    The chance to analyse the four IgG subclasses arose with the publication of Terry and Fahey(1) . Since then, a lot of new information on the role of subclasses and their deficiency states in humans has been obtained. This review tries to analyse critically our current knowledge of subclass deficiencies in children. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  4. Serological IgG avidity test for ocular toxoplasmosis

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    Suresh S

    2012-01-01

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

  5. 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

    1982-01-01

    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.

  6. 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.

    1982-01-01

    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.

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

    Science.gov (United States)

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

    2008-12-01

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

  8. IgG and IgG subclass specific antibody responses to diphtheria and tetanus toxoids in newborns and infants given DTP immunization.

    Science.gov (United States)

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

    1986-08-01

    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.

  9. Cross Reactivity between Dromedary Whey Proteins and IgG Anti Bovine α-Lactalbumin and Anti Bovine β-Lactoglobulin

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    N. Youcef

    2009-01-01

    Full Text Available Problem statement: Our aim was to enhance the data on antigenic properties of dromedary whey proteins. Approach: The identification of the whey proteins was carried by SDS-page and Reversed phase high performance liquid chromatography (RP-HPLC. The cross-reactivity of dromedary whey proteins with IgG anti bovine β-lactoglobulin and anti bovine α-lactalbumin, obtained by immunisation of Balb/c mice, was carried out by ELISA. Results: The SDS-page showed the presence of band corresponding to α-lactalbumin and albumin serum; this was confirmed by the chromatogram obtained by RP-HPLC, where we detected a pick corresponding to α-lactalbumin. There was a cross reaction of dromedary whey proteins with IgG anti bovin α-~­lactalbumin but it was very weak with IgG anti boin β-lactoglobulin. Conclusion: We detected a cross reactivity between dromedary whey proteins and IgG anti bovin α-lactalbumin.

  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

    2016-01-01

    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. Testing for IgG class antibodies in celiac disease patients with selective IgA deficiency. A comparison of the diagnostic accuracy of 9 IgG anti-tissue transglutaminase, 1 IgG anti-gliadin and 1 IgG anti-deaminated gliadin peptide antibody assays.

    Science.gov (United States)

    Villalta, Danilo; Alessio, Maria Grazia; Tampoia, Marilina; Tonutti, Elio; Brusca, Ignazio; Bagnasco, Marcello; Pesce, Giampaola; Stella, Sergio; Bizzaro, Nicola

    2007-07-01

    To evaluate the diagnostic characteristics of commercially available IgG anti-tTG assays in selective IgA deficiency (SIgAD), we tested different IgG anti-tTG methods and compared the results with those obtained from two other tests: one for IgG anti-gliadin (AGA) and one for IgG to deaminated gliadin peptides (DGP). 20 CD patients with SIgAD and 113 controls (9 patients with SIgAD without CD; 54 patients with chronic liver disease; 50 healthy subjects) were tested with 9 IgG anti-tTG assays (2 of which are enriched with gliadin peptides), one IgG AGA assay and one IgG anti-DGP assay. Using optimal cutoffs as determined by ROC curves, the sensitivity of IgG anti-tTG methods ranged from 75% (1 kit) to 95% (7 kits) and the specificity from 94% (1 kit) to 100% (5 kits). Sensitivity and specificity were 40% and 87% for IgG AGA, and 80% and 98% for IgG anti-DGP, respectively. All IgG anti-tTG methods evaluated are reliable serologic assays for the diagnosis of CD in patients with SIgAD and perform better than the gliadin-based assays used in this study. The tests containing both tTG and gliadinic peptides are burdened by a lower specificity than the anti-tTG assays.

  12. The Utility of Serum IgG4 Concentrations as a Biomarker

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    Shigeyuki Kawa

    2012-01-01

    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.

  13. Overlapping Morphologic and Immunohistochemical Features of Hashimoto Thyroiditis and IgG4-Related Thyroid Disease.

    Science.gov (United States)

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

    2015-05-01

    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.

  14. Biophysical and Functional Characterization of Rhesus Macaque IgG Subclasses

    Science.gov (United States)

    Boesch, Austin W.; Osei-Owusu, Nana Yaw; Crowley, Andrew R.; Chu, Thach H.; Chan, Ying N.; Weiner, Joshua A.; Bharadwaj, Pranay; Hards, Rufus; Adamo, Mark E.; Gerber, Scott A.; Cocklin, Sarah L.; Schmitz, Joern E.; Miles, Adam R.; Eckman, Joshua W.; Belli, Aaron J.; Reimann, Keith A.; Ackerman, Margaret E.

    2016-01-01

    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 immunoglobulin G (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 Fc gamma receptors (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. PMID:28018355

  15. Biophysical and Functional Characterization of Rhesus Macaque IgG Subclasses

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    Austin W. Boesch

    2016-12-01

    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.

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

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    K.C. Almeida

    2006-11-01

    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.

  17. IgG1 and IgG4 are the predominant subclasses among auto-antibodies against two citrullinated antigens in RA.

    Science.gov (United States)

    Engelmann, R; Brandt, J; Eggert, M; Karberg, K; Krause, A; Neeck, G; Mueller-Hilke, B

    2008-10-01

    Antibody subclasses reflect specific immunological processes and may be indicative of the underlying pathological pattern in an autoimmune disease like RA. We therefore quantified anti-cyclic citrullinated peptides (CCP) and anti- citrullinated vimentin (MCV) IgG subclass titres in RA patients and compared them with the respective titres of antibodies directed against the varicella zoster virus (VZV) and to total serum titres. Sera of 77 patients fulfilling the ACR criteria for RA were collected. An IgG subclass-specific ELISA system was then established and combined with commercially available MCV, CCP and VZV pre-coated microtitre plates. Even though IgG1 is the predominant subclass among antibodies against CCP and MCV in RA patients, IgG4 is second with respect to titres and frequencies. This increase in IgG4 among RA-specific antibodies is independent of disease duration and does not reflect a general skewing of the immune response in these patients as overall serum titres and antibodies directed against VZV show a normal distribution of IgG1, IgG2, IgG3 and IgG4. Elevated IgG4 titres are specific for auto-antibodies against citrullinated antigens in RA and are indicative of a Th2-biased environment during the generation of auto-reactive plasma cells. We discuss here an indirect role for IgG4 auto-antibodies in hindering the elimination of auto-reactive B and plasma cells and thus driving the autoimmune process.

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

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    Teresa Carbone

    2015-01-01

    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.

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Science.gov (United States)

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

    2016-02-01

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

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

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    Okazaki,Morihiro

    1991-08-01

    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.

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

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    Kazuichi Okazaki

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  4. Managing Reverse Logistics or Reversing Logistics Management?

    OpenAIRE

    Brito, Marisa

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse logistics. The thesis brings insights on reverse logistics decision-making and it lays down theoretical principles for reverse logistics as a research field.In particular it puts together a framework ...

  5. 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.

    1977-07-01

    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.

  6. IgG Conformer's Binding to Amyloidogenic Aggregates.

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    Monichan Phay

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

  7. IgG Conformer's Binding to Amyloidogenic Aggregates

    Science.gov (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

    2015-01-01

    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

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

    OpenAIRE

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

    2015-01-01

    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 ...

  9. IgG4-related disease-experience of 100 consecutive cases from a specialist centre.

    Science.gov (United States)

    Bateman, Adrian C; Culver, Emma L

    2017-04-01

    To describe the features of 100 consecutive cases referred to a single UK institution in which a diagnosis of IgG4-related disease (IgG4-RD) was under consideration. The histological features were reviewed by a single histopathologist, and cases were categorized according to the 2012 Boston criteria: Category 1-histologically highly suggestive of IgG4-RD; Category 2-probable histopathological features of IgG4-RD; and Category 3-insufficient histopathological evidence of IgG4-RD. A 'global assessment' was performed with the available clinical information: Assessment group 1-'definite/very likely IgG4-RD'; Assessment group 2-'possible IgG4-RD'; Assessment group 3-'not IgG4-RD'; and Assessment group 4-insufficient information. The mean IgG4+ plasma cell count and IgG4+/IgG+ ratio were highest in Category 1 [134/high-power field (HPF); 57%] and Assessment group 1 (113/HPF; 52%), and lowest in Category 3 (11/HPF; 18%) and Assessment group 3 (43/HPF; 31%) (Category comparison of IgG4+ count and ratio, both P < 0.001; Assessment group comparison of IgG4+ count, P < 0.0002; and Assessment group comparison of ratio, P = 0.04). A non-IgG4-RD diagnosis was rare in Category 1 (7%) but common in Category 2 (60%) and Category 3 (47%). Stromal reactions to neoplasia and chronic oral ulceration were simulants of IgG4-RD. The Boston criteria are linked to the likelihood of IgG4-RD. Other conditions may show some histological features of IgG4-RD. The likelihood of IgG4-RD is much greater when the histological features reach the threshold for Category 1 than when they reach the thresholds for Categories 2 and 3. Despite the utility of the Boston criteria, this study highlights the crucial importance of careful clinicopathological correlation when a diagnosis of IgG4-RD is under consideration. © 2016 John Wiley & Sons Ltd.

  10. IgG4-related mastitis, a rare disease, can radiologically and histologically mimic malignancy.

    Science.gov (United States)

    Yamada, Rin; Horiguchi, Shin-ichiro; Yamashita, Toshinari; Kamisawa, Terumi

    2016-03-23

    IgG4-related disease (IgG4-RD) is characterised by high serum concentrations of IgG4, dense lymphoplasmacytic infiltrates, storiform fibrosis and increased IgG4-positive plasma cells in tissues. This systemic disease occurs in various organs metachronously, but IgG4-related mastitis appears extremely rare. We report a case of IgG4-related mastitis, radiologically considered to represent breast cancer mainly composed of intraductal component and requiring histological differentiation from mucosa-associated lymphoid tissue (MALT) lymphoma. The breast mass disappeared with steroid therapy. When patients have a breast mass, regardless of the presence or absence of IgG4-RD, IgG4-related mastitis should be considered in addition to breast cancer. If histological findings show dense lymphoplasmacytic infiltrates, IgG4-related mastitis should be suspected in addition to malignant lymphoma, and lack of monoclonality should be confirmed. To avoid unnecessary surgery or chemotherapy, knowledge and accurate diagnosis of the entity of IgG4-related mastitis is necessary. 2016 BMJ Publishing Group Ltd.

  11. Pancreatic cancer with a high serum IgG4 concentration

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Susana Corujeira

    2015-01-01

    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.

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

    Science.gov (United States)

    Tao, Xiaofeng; Liu, Chang; Song, Bo

    2015-11-01

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

  14. What are the characteristics of asthma patients with elevated serum IgG4 levels?

    Science.gov (United States)

    Flament, T; Marchand-Adam, S; Gatault, P; Dupin, C; Diot, P; Guilleminault, L

    2016-03-01

    IgG4 has recently been a subject of great interest in human pathology. No data are available about the characteristics of asthma patients with elevated IgG4 levels. An observational study was conducted from January 2006 to March 2015 in a difficult-to-treat population of asthma patients. Twenty-six difficult-to-treat asthma patients with elevated serum IgG4 levels (IgG4/IgG ratio up to 10%) were compared with a control population of 98 difficult-to-treat asthma patients with normal serum IgG4. Blood eosinophilia, total IgE and FeNO were compared between groups to better characterize asthma patients with elevated serum IgG4 levels. Median IgG4 concentrations were 1.72 g/l [1.19-2.36] and 0.22 g/l [0.10-0.49] in the elevated IgG4 group and normal Ig4 group, respectively. Median blood eosinophilia was more than three times higher in patients with elevated serum IgG4 levels than in controls (0.75 10(9)/L [IQR 0.54-1.78] vs 0.22 10(9)/L [IQR 0.09-0.54] respectively, p ppb vs 35 [IQR 23-51] ppb, p < 0.001). Allergic broncho-pulmonary aspergillosis (ABPA) and eosinophilic granulomatosis with polyangiitis (EGPA) were observed in the asthma patients with elevated serum IgG4. Ten patients had unexplained increased blood eosinophilia. Asthma patients with elevated IgG4 levels have significantly higher blood eosinophilia, total IgE and FeNO. ABPA and EGPA are observed in patients with elevated serum IgG4. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. 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.

  16. Managing Reverse Logistics or Reversing Logistics Management?

    NARCIS (Netherlands)

    M.P. de Brito (Marisa)

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse

  17. Managing Reverse Logistics or Reversing Logistics Management?

    NARCIS (Netherlands)

    M.P. de Brito (Marisa)

    2004-01-01

    textabstractIn the past, supply chains were busy fine-tuning the logistics from raw material to the end customer. Today an increasing flow of products is going back in the chain. Thus, companies have to manage reverse logistics as well.This thesis contributes to a better understanding of reverse log

  18. Characterization of cysteine related variants in an IgG2 antibody by LC-MS with an automated data analysis approach.

    Science.gov (United States)

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

    2015-08-01

    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.

  19. Reversible Thermoset Adhesives

    Science.gov (United States)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  20. Elevated serum IgG4 levels in two cases of paragonimiasis

    Science.gov (United States)

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

    2015-01-01

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

  1. A case of IgG4-related lymphadenopathy, pericarditis, coronary artery periarteritis and luminal stenosis.

    Science.gov (United States)

    Hourai, Ryoto; Miyamura, Masatoshi; Tasaki, Ryunosuke; Iwata, Akiko; Takeda, Yoshihiro; Morita, Hideaki; Hanaoka, Nobuharu; Tanigawa, Jun; Shibata, Kensaku; Takeshita, Atsushi; Kawano, Mitsuhiro; Sato, Yasuharu; Hirose, Yoshinobu; Ishizaka, Nobukazu

    2016-10-01

    Immunoglobulin G4 (IgG4)-related disease is an emerging new clinicopathological disorder that is characterized by elevation of serum IgG4 levels and histological findings of IgG4-positive plasmacytic infiltration. IgG4-related disease may appear synchronously or metachronously in a wide variety of organs. The current patient was found to have pericardial effusion and retroperitoneal fibrosis. He was subsequently diagnosed with coronary artery stenosis. (18)F-FDG positron emission tomography showed enhanced FDG uptake in lymph nodes as well as pericardial and peri-aortic tissue. Histopathology of the mediastinal lymph node showed the infiltration of numerous IgG4-positive cells, leading to the diagnosis of IgG4-related lymphadenopathy with pericardial and periarterial involvement.

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

    Directory of Open Access Journals (Sweden)

    Hiroshi Kobayashi

    2016-09-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2016-07-01

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

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

    Directory of Open Access Journals (Sweden)

    Seokhwi Kim

    2016-07-01

    Full Text Available 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.

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

    Science.gov (United States)

    Osaka, I; Matsui, Y; Terada, F

    2014-10-01

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

    Science.gov (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

    2015-01-01

    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

  8. Fibrosing variant of Hashimoto thyroiditis is an IgG4 related disease.

    Science.gov (United States)

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

    2012-08-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Lucas eRamirez

    2014-10-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Simona Buelli

    2015-05-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Xiaolong Liu

    2015-03-01

    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.

  12. Hinge-Region O-Glycosylation of Human Immunoglobulin G3 (IgG3)*

    Science.gov (United States)

    Plomp, Rosina; Dekkers, Gillian; Rombouts, Yoann; Visser, Remco; Koeleman, Carolien A.M.; Kammeijer, Guinevere S.M.; Jansen, Bas C.; Rispens, Theo; Hensbergen, Paul J.; Vidarsson, Gestur; Wuhrer, Manfred

    2015-01-01

    Immunoglobulin G (IgG) is one of the most abundant proteins present in human serum and a fundamental component of the immune system. IgG3 represents ∼8% of the total amount of IgG in human serum and stands out from the other IgG subclasses because of its elongated hinge region and enhanced effector functions. This study reports partial O-glycosylation of the IgG3 hinge region, observed with nanoLC-ESI-IT-MS(/MS) analysis after proteolytic digestion. The repeat regions within the IgG3 hinge were found to be in part O-glycosylated at the threonine in the triple repeat motif. Non-, mono- and disialylated core 1-type O-glycans were detected in various IgG3 samples, both poly- and monoclonal. NanoLC-ESI-IT-MS/MS with electron transfer dissociation fragmentation and CE-MS/MS with CID fragmentation were used to determine the site of IgG3 O-glycosylation. The O-glycosylation site was further confirmed by the recombinant production of mutant IgG3 in which potential O-glycosylation sites had been knocked out. For IgG3 samples from six donors we found similar O-glycan structures and site occupancies, whereas for the same samples the conserved N-glycosylation of the Fc CH2 domain showed considerable interindividual variation. The occupancy of each of the three O-glycosylation sites was found to be ∼10% in six serum-derived IgG3 samples and ∼13% in two monoclonal IgG3 allotypes. PMID:25759508

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

  14. Reverse logistics - a framework

    OpenAIRE

    Brito, Marisa; Dekker, Rommert

    2002-01-01

    textabstractIn this paper we define and compare Reverse Logistics definitions. We start by giving an understanding framework of Reverse Logistics: the why-what-how. By this means, we put in context the driving forces for Reverse Logistics, a typology of return reasons, a classification of products, processes and actors. In addition we provide a decision framework for Reverse Logistics and we present it according to long, medium and short term decisions, i.e. strategic-tactic-operational decis...

  15. Reverse cholesterol transport revisited

    Institute of Scientific and Technical Information of China (English)

    Astrid; E; van; der; Velde

    2010-01-01

    Reverse cholesterol transport was originally described as the high-density lipoprotein-mediated cholesterol flux from the periphery via the hepatobiliary tract to the intestinal lumen, leading to fecal excretion. Since the introduction of reverse cholesterol transport in the 1970s, this pathway has been intensively investigated. In this topic highlight, the classical reverse cholesterol transport concepts are discussed and the subject reverse cholesterol transport is revisited.

  16. 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

    1988-01-01

    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.

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

    Science.gov (United States)

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

    2011-02-01

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

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

    OpenAIRE

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

    2014-01-01

    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...

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

    Directory of Open Access Journals (Sweden)

    Kazushige Uchida

    2012-01-01

    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.

  20. A case of progressively transformed germinal center-type IgG4-related lymphadenopathy.

    Science.gov (United States)

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

    2015-08-01

    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.

  1. Reverse logistics - a framework

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); R. Dekker (Rommert)

    2002-01-01

    textabstractIn this paper we define and compare Reverse Logistics definitions. We start by giving an understanding framework of Reverse Logistics: the why-what-how. By this means, we put in context the driving forces for Reverse Logistics, a typology of return reasons, a classification of product

  2. Immunogenetics of IgG4-Related AIP.

    Science.gov (United States)

    Ota, Masao; Umemura, Takeji; Kawa, Shigeyuki

    2017-01-01

    Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis characterized by high serum IgG4 concentration and a variety of complicating extra-pancreatic lesions. AIP has the features of a complex disease that is caused by multifactorial genes. However, the genetic factors underlying AIP have not been elucidated conclusively. Association studies by the candidate-gene approach and genome-wide association studies (GWAS) have revealed several susceptibility genes for AIP, including HLA DRB1*04:05-DQB1*04:01, FCRL3, CTLA4, and KCNA3, albeit in small-scale analyses. Thus, GWAS of large sample sizes and multinational collaborative meta-analyses are needed to identify the precise genetic variants that are associated with AIP onset. Systems genetics approaches that integrate DNA sequencing, expression quantitative trait locus (eQTL) mapping, proteomics, and metabolomics will also be useful in clarifying the pathogenesis of AIP.

  3. [IgM, IgG and IgG subclass antibodies to herpes simplex virus in persons of different ages].

    Science.gov (United States)

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

    2000-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Serrano F.J

    2001-06-01

    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.

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

    Science.gov (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

    2014-11-01

    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.

  6. Effect of Type 2 Diabetes Mellitus and Diabetic Nephropathy on IgG Pharmacokinetics and Subcutaneous Bioavailability in the Rat.

    Science.gov (United States)

    Chadha, Gurkishan S; Morris, Marilyn E

    2015-07-01

    The objective of this research was to assess the effects of type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) on the pharmacokinetics of human IgG (hIgG), an antibody isotype, in Zucker diabetic fatty (ZDF) rats. Furthermore, the specific role of T2DM in the altered disposition of hIgG was evaluated by treating diabetic rats with pioglitazone, while the role of chronic kidney disease (CKD) was assessed using 5/6 nephrectomized Sprague Dawley rats. ZDF male (lean non-diabetic control and obese diabetic) and pioglitazone-treated ZDF rats were studied at ages 12-13 weeks (only DM was present), and at ages 29-30 weeks (progression to DN). All animals were dosed with 1 mg/kg of hIgG intravenously (IV) or subcutaneously (SC). ZDF rats had significantly higher blood glucose concentrations and urinary albumin excretion compared to control rats. Significant increases in total clearance (2.5-fold) and renal clearance (100-fold) of hIgG were observed; however the major increase in total clearance was due to increased non-renal clearance. Greater changes in urinary albumin excretion and total and renal clearances of IgG (3.5-fold and 300-fold, respectively) were observed with progression to DN. SC bioavailability of hIgG in all animal groups was similar (>84%). With pioglitazone-treatment, diabetic animals remained euglycemic and treatment was able to reverse the clearance changes, although incompletely. In the CKD group, no difference in hIgG clearance was observed when compared with controls. In conclusion, the increased clearance of hIgG in ZDF diabetic animals, reversal by pioglitazone treatment and lack of effect of CKD, demonstrate the influence of T2DM on hIgG pharmacokinetics.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    Aims: To investigate whether an immunoglobulin (Ig)G avidity ELISA can be used to differentiate between acute and persistent infection with Salmonella (S.) Dublin in cattle. To determine whether the IgG isotype, IgG(1) and IgG(2) responses in acute and persistent infections differ. Methods...... 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...

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tobias Peikert

    2012-01-01

    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.

  10. IgG subclass response to HIV in relation to antibody-dependent cellular cytotoxicity at different clinical stages.

    Science.gov (United States)

    Ljunggren, K; Broliden, P A; Morfeldt-Månson, L; Jondal, M; Wahren, B

    1988-01-01

    The anti-HIV IgG subclass response was analysed in sera from different clinical stages and related to virus specific antibody-dependent cellular cytotoxicity (ADCC). IgG1 was found to be the dominant subclass, present in all sera and with similar mean titres at different stages. The number of anti-HIV IgG3 positive sera, measured on whole viral lysate antigen plates, decreased during disease progression from 38% in symptom-free to 7% in AIDS patients. IgG2 and IgG4 subclasses were less prevalent although a slight increase of IgG4 frequency was found in AIDS patients. High IgG1 titres correlated with a positive ADCC reaction but there was no correlation between anti-HIV IgG1 and ADCC titres. Some sera which contained HIV IgG1 as the only subclass were able to mediate an ADCC reaction. In addition, when anti-HIV IgG3 was isolated, by protein A chromatography, no ADCC killing was induced by these antibodies. It is concluded that IgG1 is the major ADCC-active IgG subclass in HIV infected individuals. The lack of correlation between IgG1 and ADCC titres may be explained by a relatively small fraction of IgG1 antibodies mediating ADCC. PMID:3208446

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

    Directory of Open Access Journals (Sweden)

    Daniela Kao

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    María T. Bourlon

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Angel Guevara E.

    1995-08-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    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...

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

    NARCIS (Netherlands)

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

    2016-01-01

    Immunoglobulin G (IgG) Fc N-glycosylation affects antibody-mediated effector functions and varies with inflammation rooted in both communicable and non-communicable diseases. Worldwide, communicable and non-communicable diseases tend to segregate geographically. Therefore, we studied whether IgG Fc

  16. Prevalence of atopy, eosinophilia, and IgE elevation in IgG4-related disease.

    Science.gov (United States)

    Della Torre, Emanuel; Mattoo, Hamid; Mahajan, Vinay S; Carruthers, Mollie; Pillai, Shiv; Stone, John H

    2014-02-01

    IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that can affect virtually every organ system. T-helper type 2 responses have been presumed to be pathogenic in this disease, and a high proportion of patients with IgG4-RD are reported to have longstanding allergies, peripheral blood eosinophilia, and serum IgE elevation. It has therefore been proposed that allergic mechanisms drive IgG4-RD. However, no epidemiological assessment of atopy, peripheral blood eosinophilia, and serum IgE concentrations has ever been undertaken in patients with IgG4-RD. In this study, we evaluated these parameters in a large cohort of patients with IgG4-RD in whom a wide range of organs were affected by disease. Our results demonstrate that the majority of patients with IgG4-RD are nonatopic. Nevertheless, a subset of nonatopic subjects exhibit peripheral blood eosinophilia and elevated IgE, suggesting that processes inherent to IgG4-RD itself rather than atopy per se contribute to the eosinophilia and IgE elevation observed in the absence of atopy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. 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: gidi@migal.org.il [Laboratory of Immunology, MIGAL, P.O. Box 831, Kiryat Shmona 11016 (Israel); Department of Biotechnology, Tel-Hai Academic College, Upper Galilee 12210 (Israel)

    2009-08-21

    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.

  18. ROLE OF ENVIRONMENTAL ANTIGEN IN THE DEVELOPMENT OF IGG(+) CELLS IN THE BURSA OF FABRICIUS

    NARCIS (Netherlands)

    EKINO, S; RIWAR, B; KROESE, FGM; SCHWANDER, EH; NIEUWENHUIS, P

    1995-01-01

    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

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

    Science.gov (United States)

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

    2015-11-01

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

  20. IgG4-related inflammatory pseudotumor of the renal pelvis involving renal parenchyma, mimicking malignancy.

    Science.gov (United States)

    Park, Ho Gyun; Kim, Kyoung Min

    2016-01-22

    IgG4-related disease is a recently recognized systemic disease characterized by storiform fibrosis with infiltration of IgG4-positive plasma cells. In rare incidences, IgG4-related renal disease can present as a solitary mass lesion at renal pelvis and can pose a diagnostic challenge since these lesions mimic malignancy. Herein, we present a rare case of IgG4-related disease presenting as inflammatory pseudotumor lesion, involving the renal pelvis and also neighboring renal parenchyma. A 75-year-old man with no history of IgG4-related disease underwent computed tomography (CT) scan for evaluation of prostatic cancer. The CT scan incidentally revealed a mass lesion located at the right renal pelvis. Radiologic findings were highly suggestive of malignancy. Therefore, the patient underwent right nephroureterectomy. Microscopically, the mass lesion showed storiform fibrosis with diffuse and intense inflammatory cell infiltration. Infiltrating cells were mainly histiocytes and plasma cells. Tubulointerstitium adjacent to the lesion also showed fibrosis with abundant plasmacytic infiltration. Immunohistochemical staining revealed the presence of IgG4-positive plasma cells in both the mass lesion and tubulointerstitium (mean of 94/HPF per field). Considering these findings, we diagnosed the mass lesion as IgG4-related inflammatory pseudotumor of the renal pelvis. In patients with renal pelvic masses, IgG4-related inflammatory pesudotumor should be considered in the differential diagnosis to avoid unnecessary surgical intervention.

  1. Bovine IgG subclasses and fertility of Echinococcus granulosus hydatid cysts.

    Science.gov (United States)

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

    2014-09-15

    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.

  2. Intrathecal IgG Synthesis: A Resistant and Valuable Target for Future Multiple Sclerosis Treatments

    Directory of Open Access Journals (Sweden)

    Mickael Bonnan

    2015-01-01

    Full Text Available Intrathecal IgG synthesis is a key biological feature of multiple sclerosis (MS. When acquired early, it persists over time. A growing body of evidence suggests that intrathecal Ig-secreting cells may be pathogenic either by a direct action of toxic IgG or by locally secreting bystander toxic products. Intrathecal IgG synthesis depends on the presence of CNS lymphoid organs, which are strongly linked at anatomical level to cortical subpial lesions and at clinical level to the impairment slope in progressive MS. As a consequence, targeting CNS lymphoid lesions could be a valuable new target in MS, especially during the progressive phase. As intrathecal IgGs are end-products of these lymphoid lesions, intrathecal IgG synthesis may be considered as a specific marker of the persistence of these inflammatory lesions. Here we review the effect upon intrathecal IgG synthesis of all drugs ever used in MS. Except for steroids, all these therapeutic strategies, including rituximab, failed to decrease intrathecal IgG synthesis, with the exception of a questionable incomplete action of natalizumab. Thus, IgG synthesis is a robust marker of persistent intrathecal inflammation and its complete normalization should be one of the goals in future therapeutic strategies.

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

    Science.gov (United States)

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

    2015-12-01

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

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

    CERN Document Server

    de Thier, P

    2016-01-01

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

  5. [IgG4-related disease is a rare differential diagnosis of malignant and autoimmune diseases].

    Science.gov (United States)

    Storgaard, Anders; Detlefsen, Sönke

    2015-04-06

    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.

  6. Attachment of IgG to dermal extracellular matrix in patients with fibromyalgia.

    Science.gov (United States)

    Eneström, S; Bengtson, A; Lindström, F; Johan, K

    1990-01-01

    Deposits of IgG localized to collagen bundles/extracellular matrix components occurred in skin biopsies from patients with primary fibromyalgia (PF). None of these patients demonstrated a positive lupus band test. Control skin biopsies from healthy controls were negative but showed intense reactivity for IgG after collagenase treatment. PF-skin attached both homologous and heterologous serum IgG in indirect immunofluorescence, which may point to a qualitative alteration of dermal matrix components in PF. Skin from patients with systemic lupus erythematosus and rheumatoid arthritis showed a lower dermal fluorescence intensity than in PF patients. The cause of the presence of IgG in dermal tissue from PF patients is unclear. It may be caused by a non-specific attachment of IgG to the extracellular matrix related, for example, to tissue hypoxia and/or increased capillary leakage due to an increased number of mast cells in the PF-skin.

  7. Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange.

    Science.gov (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

    2007-09-14

    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.

  8. 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

    2003-01-01

    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

  9. First case of IgG4-related sclerosing cholangitis associated with autoimmune hemolytic anemia.

    Science.gov (United States)

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

    2014-07-14

    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.

  10. Reversible cortical blindness: posterior reversible encephalopathy syndrome.

    Science.gov (United States)

    Bandyopadhyay, Sabyasachi; Mondal, Kanchan Kumar; Das, Somnath; Gupta, Anindya; Biswas, Jaya; Bhattacharyya, Subir Kumar; Biswas, Gautam

    2010-11-01

    Cortical blindness is defined as visual failure with preserved pupillary reflexes in structurally intact eyes due to bilateral lesions affecting occipital cortex. Bilateral oedema and infarction of the posterior and middle cerebral arterial territory, trauma, glioma and meningioma of the occipital cortex are the main causes of cortical blindness. Posterior reversible encephalopathy syndrome (PRES) refers to the reversible subtype of cortical blindness and is usually associated with hypertension, diabetes, immunosuppression, puerperium with or without eclampsia. Here, 3 cases of PRES with complete or partial visual recovery following treatment in 6-month follow-up are reported.

  11. Introduction to reversible computing

    CERN Document Server

    Perumalla, Kalyan S

    2013-01-01

    Few books comprehensively cover the software and programming aspects of reversible computing. Filling this gap, Introduction to Reversible Computing offers an expanded view of the field that includes the traditional energy-motivated hardware viewpoint as well as the emerging application-motivated software approach. Collecting scattered knowledge into one coherent account, the book provides a compendium of both classical and recently developed results on reversible computing. It explores up-and-coming theories, techniques, and tools for the application of rever

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

    Directory of Open Access Journals (Sweden)

    D. Eric Ewing, MD

    2016-06-01

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

  13. IgG4-related Hashimoto's thyroiditis--a new variant of a well known disease.

    Science.gov (United States)

    Luiz, Henrique Vara; Gonçalves, Diogo; Silva, Tiago Nunes da; Nascimento, Isabel; Ribeiro, Ana; Mafra, Manuela; Manita, Isabel; Portugal, Jorge

    2014-11-01

    Hashimoto's thyroiditis (HT) has been characterized for many years as a well-defined clinicopathologic entity, but is now considered a heterogeneous disease. IgG4-related HT is a new subtype characterized by thyroid inflammation rich in IgG4-positive plasma cells and marked fibrosis. It may be part of the systemic IgG4-related disease. We report a case of a 56-year-old Portuguese man who presented with a one-month history of progressive neck swelling and dysphagia. Laboratory testing revealed increased inflammatory parameters, subclinical hypothyroidism and very high levels of thyroid autoantibodies. Cervical ultrasound (US) demonstrated an enlarged and heterogeneous thyroid gland and two hypoechoic nodules. US-guided fine needle aspiration cytology was consistent with lymphocytic thyroiditis. The patient was submitted to total thyroidectomy and microscopic examination identified typical findings of HT, marked fibrosis limited within the thyroid capsule and lymphoplasmacytic infiltration, with >50 IgG4-positive plasma cells per high-power field and an IgG4/IgG ratio of >40%. After surgery, serum IgG4 concentration was high-normal. Symptoms relief and reduction in laboratory inflammatory parameters were noticed. Thyroid function is controlled with levothyroxine. To our knowledge we report the first case of IgG4-related HT in a non-Asian patient. We also perform a review of the literature regarding IgG4-related disease and IgG4-related HT. Our case highlights this new variant of the well known HT, and helps physicians in recognizing its main clinical features, allowing for proper diagnosis and treatment.

  14. Reversible Logic Circuit Synthesis

    CERN Document Server

    Shende, V V; Markov, I L; Prasad, A K; Hayes, John P.; Markov, Igor L.; Prasad, Aditya K.; Shende, Vivek V.

    2002-01-01

    Reversible, or information-lossless, circuits have applications in digital signal processing, communication, computer graphics and cryptography. They are also a fundamental requirement for quantum computation. We investigate the synthesis of reversible circuits that employ a minimum number of gates and contain no redundant input-output line-pairs (temporary storage channels). We propose new constructions for reversible circuits composed of NOT, Controlled-NOT, and TOFFOLI gates (the CNT gate library) based on permutation theory. A new algorithm is given to synthesize optimal reversible circuits using an arbitrary gate library. We also describe much faster heuristic algorithms. We also pursue applications of the proposed techniques to the synthesis of quantum circuits.

  15. Reverse Core Engine with Thrust Reverser

    Science.gov (United States)

    Suciu, Gabriel L. (Inventor); Chandler, Jesse M. (Inventor)

    2017-01-01

    An engine system has a gas generator, a bi-fi wall surrounding at least a portion of the gas generator, a casing surrounding a fan, and the casing having first and second thrust reverser doors which in a deployed position abut each other and the bi-fi wall.

  16. Generation of Recombinant Monoclonal Antibodies from Immunised Mice and Rabbits via Flow Cytometry and Sorting of Antigen-Specific IgG+ Memory B Cells.

    Directory of Open Access Journals (Sweden)

    Dale O Starkie

    Full Text Available Single B cell screening strategies, which avoid both hybridoma fusion and combinatorial display, have emerged as important technologies for efficiently sampling the natural antibody repertoire of immunized animals and humans. Having access to a range of methods to interrogate different B cell subsets provides an attractive option to ensure large and diverse panels of high quality antibody are produced. The generation of multiple antibodies and having the ability to find rare B cell clones producing IgG with unique and desirable characteristics facilitates the identification of fit-for-purpose molecules that can be developed into therapeutic agents or research reagents. Here, we describe a multi-parameter flow cytometry single-cell sorting technique for the generation of antigen-specific recombinant monoclonal antibodies from single IgG+ memory B cells. Both mouse splenocytes and rabbit PBMC from immunised animals were used as a source of B cells. Reagents staining both B cells and other unwanted cell types enabled efficient identification of class-switched IgG+ memory B cells. Concurrent staining with antigen labelled separately with two spectrally-distinct fluorophores enabled antigen-specific B cells to be identified, i.e. those which bind to both antigen conjugates (double-positive. These cells were then typically sorted at one cell per well using FACS directly into a 96-well plate containing reverse transcriptase reaction mix. Following production of cDNA, PCR was performed to amplify cognate heavy and light chain variable region genes and generate transcriptionally-active PCR (TAP fragments. These linear expression cassettes were then used directly in a mammalian cell transfection to generate recombinant antibody for further testing. We were able to successfully generate antigen-specific recombinant antibodies from both the rabbit and mouse IgG+ memory B cell subset within one week. This included the generation of an anti-TNFR2 blocking

  17. An Extended Minimal Physiologically Based Pharmacokinetic Model: Evaluation of Type II Diabetes Mellitus and Diabetic Nephropathy on Human IgG Pharmacokinetics in Rats.

    Science.gov (United States)

    Chadha, Gurkishan S; Morris, Marilyn E

    2015-11-01

    Although many studies have evaluated the effects of type 2 diabetes mellitus (T2DM) on the pharmacokinetics (PK) of low molecular weight molecules, there is limited information regarding effects on monoclonal antibodies. Our previous studies have reported significant increases in total (2-4 fold) and renal (100-300 fold) clearance of human IgG, an antibody isotype, in Zucker diabetic fatty (ZDF) rats. Pioglitazone treatment incompletely reversed the disease-related PK changes. The objective of this study was to construct a mechanistic model for simultaneous fitting plasma and urine data, to yield physiologically relevant PK parameters. We propose an extended minimal physiologically based PK (mPBPK) model specifically for IgG by classifying organs as either leaky or tight vascular tissues, and adding a kidney compartment. The model incorporates convection as the primary mechanism of IgG movement from plasma into tissues, interstitial fluid (ISF) in extravascular distribution space, and glomerular filtration rate (GFR), sieving coefficient and fraction reabsorbed in the kidney. The model captured the plasma and urine PK profiles well, and simulated concentrations in ISF. The model estimated a 2-4 fold increase in nonrenal clearance from plasma and 30-120 fold increase in renal clearance with T2DM, consistent with the experimental findings, and these differences in renal clearance were related to changes in GFR, sieving coefficient, and proximal tubular reabsorption. In conclusion, the mPBPK model offers a more relevant approach for analyzing plasma and urine IgG concentration-time data than conventional models and provides insight regarding alterations in distributional and elimination parameters occurring with T2DM.

  18. Circulating IgG autoantibodies to IgE in atopic syndromes.

    Science.gov (United States)

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

    1986-04-01

    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)

  19. Toxoplasma-SPECIFIC IgG SUBCLASS ANTIBODY RESPONSE IN CEREBROSPINAL FLUID SAMPLES FROM PATIENTS WITH CEREBRAL TOXOPLASMOSIS

    Directory of Open Access Journals (Sweden)

    Fernanda S. NASCIMENTO

    2015-10-01

    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.

  20. Toxoplasma-SPECIFIC IgG SUBCLASS ANTIBODY RESPONSE IN CEREBROSPINAL FLUID SAMPLES FROM PATIENTS WITH CEREBRAL TOXOPLASMOSIS.

    Science.gov (United States)

    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

    2015-01-01

    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.

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

    DEFF Research Database (Denmark)

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

    1996-01-01

    lung infection with P aeruginosa was further investigated by correlating the a beta ab IgG subclasses with pulmonary function in patients with cystic fibrosis. METHODS: Immunoglobulin G (IgG) and IgG subclass a beta ab were investigated by western blotting and quantified by laser scanning densitometry...

  2. Quantum reverse hypercontractivity

    Energy Technology Data Exchange (ETDEWEB)

    Cubitt, Toby [Department of Computer Science, University College London, London, United Kingdom and Centre for Quantum Information and Foundations, DAMTP, University of Cambridge, Cambridge (United Kingdom); Kastoryano, Michael [NBIA, Niels Bohr Institute, University of Copenhagen, 2100 Copenhagen (Denmark); Montanaro, Ashley [School of Mathematics, University of Bristol, Bristol (United Kingdom); Temme, Kristan [Institute for Quantum Information and Matter, California Institute of Technology, Pasadena, California 91125 (United States)

    2015-10-15

    We develop reverse versions of hypercontractive inequalities for quantum channels. By generalizing classical techniques, we prove a reverse hypercontractive inequality for tensor products of qubit depolarizing channels. We apply this to obtain a rapid mixing result for depolarizing noise applied to large subspaces and to prove bounds on a quantum generalization of non-interactive correlation distillation.

  3. Clocked Thrust Reversers

    Science.gov (United States)

    Suciu, Gabriel L. (Inventor); Chandler, Jesse M. (Inventor)

    2017-01-01

    An aircraft includes a fuselage including a propulsion system supported within an aft portion. A thrust reverser is mounted proximate to the propulsion system for directing thrust in a direction to slow the aircraft. The thrust reverser directs thrust at an angle relative to a vertical plane to reduce interference on control surfaces and reduce generation of underbody lift.

  4. Atrioventricular Pacemaker Lead Reversal

    Directory of Open Access Journals (Sweden)

    Mehmet K Aktas, MD

    2007-01-01

    Full Text Available During cardiac surgery temporary epicardial atrial and ventricular leads are placed in case cardiac pacing is required postoperatively. We present the first reported series of patients with reversal of atrioventricular electrodes in the temporary pacemaker without any consequent deleterious hemodynamic effect. We review the electrocardiographic findings and discuss the findings that lead to the discovery of atrioventricular lead reversal.

  5. Reversible cerebral vasoconstriction syndrome

    Directory of Open Access Journals (Sweden)

    Saini Monica

    2009-01-01

    Full Text Available Reversible cerebral vasoconstriction syndromes (RCVS are a group of disorders that have in common an acute presentation with headache, reversible vasoconstriction of cerebral arteries, with or without neurological signs and symptoms. In contrast to primary central nervous system vasculitis, they have a relatively benign course. We describe here a patient who was diagnosed with RCVS.

  6. IgM, IgA, IgG1 and IgG2 specific responses in blood and gut secretion of calves fed soyabean products.

    Science.gov (United States)

    Dréau, D; Lallès, J P; Salmon, H; Toullec, R

    1995-07-01

    Calves fed soya proteins may develop severe gastrointestinal disorders. Whether these are predominantly associated with particular Ig subclasses and (or) dietary proteins remains unclear. Therefore, antibody responses to soyabean protein were analysed by dot- and blot-immunobinding in plasma and intestinal mucous secretions. One-month-old calves were fed for 2.5 months liquid diets based on skim milk powder (SMP) or a mixture (2:3, protein basis) of whey and soyabean products including a low antigenic hydrolysed soya protein isolate (HSPI) and a highly antigenic heated soya flour (HSF). Specific antibodies (Abs) of the main isotypes (IgM, IgA, IgG1, IgG2) were characterised by immunostaining of samples which had been previously incubated with nitrocellulose sheets coated with SMP, HSPI or HSF extracts. Plasma collected before feeding experimental diets showed very little specific Abs. By contrast, 2.5 months later, a three-fold increase (P IgA titres against HSF antigens was observed in calves fed HSF compared with those fed the control or HSPI diet. IgG1 immunoblotting revealed many protein bands from soya in the molecular range of 22-32 and 38-42 kDa. Immunorecognition of specific proteins from SMP and HSPI remained low and similar among animal groups. Specific IgM, IgA and IgG1 titres against HSF, and to a lesser extent HSPI, were significantly higher (P IgA and IgG1. By contrast, only weak bands were found for IgM and IgG2 in all groups of calves. Thus, calves fed antigenic HSF do present specific Abs including IgG1 and IgA isotypes, both systemically and locally. Therefore, IgG1 and (or) IgA rather than IgM and IgG2 Abs may be preferred for assessing the immunogenicity of soyabean products in calves. Interestingly, soyabean immunogenicity was drastically reduced by adequate proteolysis.

  7. Towards Reversible Sessions

    Directory of Open Access Journals (Sweden)

    Francesco Tiezzi

    2014-06-01

    Full Text Available In this work, we incorporate reversibility into structured communication-based programming, to allow parties of a session to automatically undo, in a rollback fashion, the effect of previously executed interactions. This permits taking different computation paths along the same session, as well as reverting the whole session and starting a new one. Our aim is to define a theoretical basis for examining the interplay in concurrent systems between reversible computation and session-based interaction. We thus enrich a session-based variant of pi-calculus with memory devices, dedicated to keep track of the computation history of sessions in order to reverse it. We discuss our initial investigation concerning the definition of a session type discipline for the proposed reversible calculus, and its practical advantages for static verification of safe composition in communication-centric distributed software performing reversible computations.

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

    Science.gov (United States)

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

    2012-01-14

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

  9. Enhanced FCGR2A and FCGR3A signaling by HIV viremic controller IgG

    Science.gov (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.

    2017-01-01

    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.

  10. A new atomic absorption spectral assay for the determination of trace IgG using immunonanogold.

    Science.gov (United States)

    Tang, Yafang; Jiang, Caina; Liang, Aihui; Li, Jishun; Jiang, Zhiliang

    2011-05-01

    Nanogold in size of 10 nm was used to label goat anti-human IgG (GIgG) to obtain an immunonanogold probe (AuGIgG) for IgG. In pH 6.8 phosphate buffer solution and in the presence of immunoprecipitator polyethylene glycol 6000 (PEG 6000), IgG reacted with the probe (AuGIgG) to form AuGIgG-IgG-PEG immunocomplex. After the centrifugation to remove the immunocomplex, AuGIgG in the supernatant can be measured by atomic absorption spectrophotometry at gold absorption line 242.8 nm. The results showed that the absorption value decreased as the concentration of IgG increased, and the decreased absorption value was linear to IgG concentration in the range 0.025-0.375 μg/mL, with a detection limit of 0.008 μg/mL. On this base, a new nanogold-labeled atomic absorption spectral assay for IgG was established. The assay was applied to determine IgG in human serum sample with satisfactory results.

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  13. Clinicopathological features of Riedel's thyroiditis associated with IgG4-related disease in Japan.

    Science.gov (United States)

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

    2015-01-01

    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.

  14. Myocarditis in different experimental models infected by Trypanosoma cruzi is correlated with the production of IgG1 isotype.

    Science.gov (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

    2017-03-01

    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.

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

    Science.gov (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

    2016-01-01

    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

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

    Science.gov (United States)

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

    2012-01-01

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

  17. Distinct histopathological features of Hashimoto's thyroiditis with respect to IgG4-related disease.

    Science.gov (United States)

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

    2012-08-01

    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

  18. Development time of IgG antibodies to West Nile virus.

    Science.gov (United States)

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

    2011-09-01

    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.

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

    OpenAIRE

    2015-01-01

    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...

  20. A circulating complex between ASAT and IgG in serum in an apparently healthy woman.

    Science.gov (United States)

    Fex, G; Berntorp, K

    1987-04-15

    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.

  1. IgG4-Related Hypophysitis: Case Report and Literature Review.

    Science.gov (United States)

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

    2016-12-01

    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.

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

    DEFF Research Database (Denmark)

    Tian, Xinsheng; Vestergaard, Bente; Thorolfsson, Matthias

    2015-01-01

    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......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...

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

    Science.gov (United States)

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

    2016-05-01

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

  4. 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.

    Science.gov (United States)

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

    2001-02-01

    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.

  5. An algebra of reversible computation

    OpenAIRE

    2016-01-01

    We design an axiomatization for reversible computation called reversible ACP (RACP). It has four extendible modules, basic reversible processes algebra (BRPA), algebra of reversible communicating processes (ARCP), recursion and abstraction. Just like process algebra ACP in classical computing, RACP can be treated as an axiomatization foundation for reversible computation.

  6. An Algebra of Reversible Computation

    OpenAIRE

    Yong WANG

    2014-01-01

    We design an axiomatization for reversible computation called reversible ACP (RACP). It has four extendible modules, basic reversible processes algebra (BRPA), algebra of reversible communicating processes (ARCP), recursion and abstraction. Just like process algebra ACP in classical computing, RACP can be treated as an axiomatization foundation for reversible computation.

  7. An algebra of reversible computation.

    Science.gov (United States)

    Wang, Yong

    2016-01-01

    We design an axiomatization for reversible computation called reversible ACP (RACP). It has four extendible modules: basic reversible processes algebra, algebra of reversible communicating processes, recursion and abstraction. Just like process algebra ACP in classical computing, RACP can be treated as an axiomatization foundation for reversible computation.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-07-01

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

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

    DEFF Research Database (Denmark)

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

    (anti-CD59a). A total of five mice received AQP4-IgG + C + anti-CD59a, four mice received normal-IgG + C + anti-CD59a, four mice received AQP4-IgG+ C and one normal-IgG + C. Mice were killed four days later. The optic nerves were isolated and fixed in paraformaldehyde. Paraffin embedded optic nerves...... was coincident with deposition of complement. Histopathological lesions were markedly enhanced with extensive/long-segment astrocytopathy of optic nerve and optic chiasm involvement in AQP4- IgG+ C + anti-CD59a treated mice. Such pathology was not seen in mice receiving normal human IgG, C and anti-CD59a...

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

    Science.gov (United States)

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

    2009-02-12

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

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

    Directory of Open Access Journals (Sweden)

    S. Monti

    2014-11-01

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

  12. IgG4-related cholecystitis presenting as biliary malignancy: report of three cases.

    Science.gov (United States)

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

    2014-09-01

    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.

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

    Science.gov (United States)

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

    2016-02-15

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

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

    Science.gov (United States)

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

    2015-12-01

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

  15. (IgG) Density and Apgar Score in Normal Term Pregnancy

    African Journals Online (AJOL)

    AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING AJOL ... Ex-vivo, term placenta of forty euthyroid mothers, the maternal serum, and cord blood ... Keywords: APGAR score, IgG density, Term placenta, Cord blood ...

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

    Institute of Scientific and Technical Information of China (English)

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

    2000-01-01

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

  17. Reversible Data Hiding Techniques

    Directory of Open Access Journals (Sweden)

    Dhananjay Yadav

    2012-03-01

    Full Text Available Reversible data hiding is a technique that is used to hide data inside an image. The data is hidden in such a way that the exact or original data is not visible. The hidden data can be retrieved as and when required. There are several methods that are used in reversible data hiding techniques like Watermarking, Lossless embedding and encryption. In this paper we present a review of reversible watermarking techniques and show different methods that are used to get reversible data hiding technique with higher embedding capacity and invisible objects. Watermark need not be hidden. Watermarking can be applied to 1. Images, 2. Text, 3. Audio/video, 4. Software.

  18. Reversible flowchart languages and the structured reversible program theorem

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2008-01-01

    Many irreversible computation models have reversible counterparts, but these are poorly understood at present. We introduce reversible flowcharts with an assertion operator and show that any reversible flowchart can be simulated by a structured reversible flowchart using only three control flow o...... justification for low-level machine code for reversible microprocessors as well as high-level block-structured reversible languages. We give examples for both such languages and illustrate them with a lossless encoder for permutations given by Dijkstra....

  19. IgG1 variations in the colostrum of Holstein dairy cows.

    Science.gov (United States)

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

    2016-02-01

    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

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

    Directory of Open Access Journals (Sweden)

    Sebastian P Fuchs

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

  1. Adaptive Pairing Reversible Watermarking.

    Science.gov (United States)

    Dragoi, Ioan-Catalin; Coltuc, Dinu

    2016-05-01

    This letter revisits the pairwise reversible watermarking scheme of Ou et al., 2013. An adaptive pixel pairing that considers only pixels with similar prediction errors is introduced. This adaptive approach provides an increased number of pixel pairs where both pixels are embedded and decreases the number of shifted pixels. The adaptive pairwise reversible watermarking outperforms the state-of-the-art low embedding bit-rate schemes proposed so far.

  2. IgG4-related disease and other causes of inflammatory meningeal disease.

    Science.gov (United States)

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

    2014-09-01

    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.

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

    DEFF Research Database (Denmark)

    Detlefsen, Sönke

    2013-01-01

    diseases on their own, others have been included under the umbrella of "multifocal fibrosclerosis". Biopsies or resection specimens from affected organs in IgG4-RD reveal several common microscopic features irrespective of the site of the lesion. Cellular and storiform fibrosis, lymphoplasmacytic...... on the microscopic features, diagnosis and differential diagnosis of the different organ manifestations of IgG4-RD, and the current concepts of its pathogenesis will also be addressed....

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

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

  6. Idiopathic granulomatous orchitis: morphology and evaluation of its relationship to IgG4 related disease.

    Science.gov (United States)

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

    2014-04-01

    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.

  7. Association between IgG4-related disease and progressively transformed germinal centers of lymph nodes.

    Science.gov (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

    2012-07-01

    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.

  8. [IgG4-related kidney disease: what the nephrologist needs to know].

    Science.gov (United States)

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

    2016-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Saeed Jamshidi Far

    2014-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-15

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

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

    Science.gov (United States)

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

    2015-12-16

    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. 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.

  13. Is MuSK myasthenia gravis linked to IgG4-related disease?

    Science.gov (United States)

    Raibagkar, Pooja; Ferry, Judith A; Stone, John H

    2017-04-15

    Immunoglobulin (Ig) G4-related disease (IgG4-RD) is an immune-mediated inflammatory condition that affects a wide variety of sites, including the nervous system, where it can involve the meninges or the pituitary gland, and cause perineural mass lesions. A large subset of acetylcholine receptor antibody (Ab)-negative myasthenia gravis (MG) patients has muscle-specific tyrosine kinase (MuSK) Abs, generally of the IgG4 subclass. There has not been any association found between IgG4-RD and MuSK MG yet. We report the first case of MuSK MG associated with lymphadenopathy with histopathology consistent with IgG4-RD. A 54-year-old woman with MuSK MG developed eight compression fractures related to steroid therapy. Eighteen months after initial presentation she was found to have retroperitoneal lymphadenopathy with biopsy findings consistent with IgG4-RD. She was started on rituximab with clinical improvement and ability to taper immunomodulatory agents for the first time. Our case raises number of questions regarding a potential link between MuSK MG and IgG4-RD which may shed further light on the pathophysiology and management of these diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Recent advances in the concept and diagnosis of autoimmune pancreatitis and IgG4-related disease.

    Science.gov (United States)

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

    2011-03-01

    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.

  15. Antineutrophil cytoplasmic antibody-associated vasculitides and IgG4-related disease: A new overlap syndrome.

    Science.gov (United States)

    Danlos, François-Xavier; Rossi, Giovanni Maria; Blockmans, Daniel; Emmi, Giacomo; Kronbichler, Andreas; Durupt, Stéphane; Maynard, Claire; Luca, Luminita; Garrouste, Cyril; Lioger, Bertrand; Mourot-Cottet, Rachel; Dhote, Robin; Arlet, Jean-Benoit; Hanslik, Thomas; Rouvier, Philippe; Ebbo, Mikael; Puéchal, Xavier; Nochy, Dominique; Carlotti, Agnès; Mouthon, Luc; Guillevin, Loïc; Vaglio, Augusto; Terrier, Benjamin

    2017-10-01

    Atypical manifestations have been described in patients with ANCA-associated vasculitides (AAV), such as pachymeningitis, orbital mass or chronic periaortitis. Because these manifestations have been associated to the spectrum of IgG4-related disease (IgG4-RD), we hypothesized that both diseases could overlap. We conducted a European retrospective multicenter observational study including patients fulfilling ACR and Chapel Hill criteria for AAV and IgG4-RD Comprehensive Diagnostic Criteria. Eighteen patients were included (median age 55.5years, 13 men). AAV and IgG4-RD were diagnosed concomitantly in 13/18 (72%) patients; AAV preceded IgG4-RD in 3/18 (17%) while IgG4-RD preceded AAV in 2/18 (11%). AAV diagnoses included granulomatosis with polyangiitis in 14 (78%), microscopic polyangiitis in 3 (17%), and eosinophilic granulomatosis with polyangiitis in one case. IgG4-RD diagnosis included definite IgG4-RD in 5 (28%) cases, probable IgG4-RD in 5 (28%) and possible IgG4-RD in 8 (44%). IgG4-RD manifestations were chronic periaortitis in 9/18 (50%) patients, orbital mass and tubulointerstitial nephritis in 4 (22%) cases, prevertebral fibrosis in 3 (17%), pachymeningitis and autoimmune pancreatitis in 2 (11%) cases. Patients required median number of 2 (range 0-4) lines of immunosuppressants in combination with glucocorticoids. During the follow-up (median 49,8months, range 17,25-108months), AAV manifestations relapsed in 10/18 (56%) cases and IgG4-RD lesions in 5/18 (28%). When used, mainly for relapses, rituximab showed response in all cases. AAV and IgG4-RD may overlap. Clinicians should consider that atypical manifestations during AAV could be related to IgG4-RD rather than to refractory granulomatous or vasculitic lesions. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. On thermodynamic and microscopic reversibility

    Energy Technology Data Exchange (ETDEWEB)

    Crooks, Gavin E.

    2011-07-12

    The word 'reversible' has two (apparently) distinct applications in statistical thermodynamics. A thermodynamically reversible process indicates an experimental protocol for which the entropy change is zero, whereas the principle of microscopic reversibility asserts that the probability of any trajectory of a system through phase space equals that of the time reversed trajectory. However, these two terms are actually synonymous: a thermodynamically reversible process is microscopically reversible, and vice versa.

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

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava

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

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

    Science.gov (United States)

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

    2016-10-01

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  20. 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

    2014-01-01

    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。

  1. PREDOMINANCE OF IGG1 AND IGG4 SUBCLASSES OF ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES (ANCA) IN PATIENTS WITH WEGENERS GRANULOMATOSIS AND CLINICALLY RELATED DISORDERS

    NARCIS (Netherlands)

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

    1991-01-01

    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

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

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    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

  3. Reversible Communicating Processes

    Directory of Open Access Journals (Sweden)

    Geoffrey Brown

    2016-02-01

    Full Text Available Reversible distributed programs have the ability to abort unproductive computation paths and backtrack, while unwinding communication that occurred in the aborted paths. While it is natural to assume that reversibility implies full state recovery (as with traditional roll-back recovery protocols, an interesting alternative is to separate backtracking from local state recovery. For example, such a model could be used to create complex transactions out of nested compensable transactions where a programmer-supplied compensation defines the work required to "unwind" a transaction. Reversible distributed computing has received considerable theoretical attention, but little reduction to practice; the few published implementations of languages supporting reversibility depend upon a high degree of central control. The objective of this paper is to demonstrate that a practical reversible distributed language can be efficiently implemented in a fully distributed manner. We discuss such a language, supporting CSP-style synchronous communication, embedded in Scala. While this language provided the motivation for the work described in this paper, our focus is upon the distributed implementation. In particular, we demonstrate that a "high-level" semantic model can be implemented using a simple point-to-point protocol.

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

    Directory of Open Access Journals (Sweden)

    Zhen-qi LI

    2014-10-01

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

  5. 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

    2008-01-01

    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...

  6. 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.

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

    Directory of Open Access Journals (Sweden)

    Lang D

    2016-02-01

    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

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

    Directory of Open Access Journals (Sweden)

    Massimo De Paschale

    2010-03-01

    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.

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

    Science.gov (United States)

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

    2006-05-01

    Functional assays are commonly used to measure the antibodies of ADAMTS13 found in patients of thrombotic thrombocytopenic purpura (TTP). In this study we used an enzyme-linked immunoassay to analyze the ADAMTS13-binding IgG levels in six groups of individuals: normal, random hospitalized patients, acute TTP, TTP after receiving plasma therapy, TTP in remission, and other types of thrombotic microangiopathy (TMA). The results showed that ADAMTS13-binding IgG levels were elevated in 100% of the acute TTP group, 75% of the TTP group after receiving plasma therapy, and 40% of the remission group. Overall, the ADAMTS13-binding IgG levels correlated with the inhibitory activity levels againstADAMTS13 (r = -0.69, P < 0.0001). The assay also detected elevated IgG binding levels in 5% - 15% of the normal, random, and other TMA control groups. Addition of purified ADAMTS13 protein to the plasma samples suppressed the IgG binding in each of the acute TTP patients, but in none of the non-TTP groups. Serial measurement in a patient that had two exacerbations of TTP within the first three weeks revealed that the ADAMTS13 activity levels remained <0.1 U/ml during this period, and the ADAMTS13-binding IgG remained elevated, suggesting that ADAMTS13 analysis may provide valuable insight to the disease status during the course of therapy. Analysis of ADAMTS13-binding IgG is helpful for the diagnosis and management of TTP.

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

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    S Kaur

    2012-01-01

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

  11. Overexpression of Serpinb1 in Chinese hamster ovary cells increases recombinant IgG productivity.

    Science.gov (United States)

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

    2015-01-10

    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.

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

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    Arezou Khosroshahi

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-06-01

    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.

  14. Radiation controlling reversible window

    Energy Technology Data Exchange (ETDEWEB)

    Gell, H.A. Jr.

    1980-01-01

    A coated glass glazing system is presented including a transparent glass substrate having one surface coated with a radiation absorptive film which is overcoated with a radiation reflective film by a technique which renders the radiation reflective film radiation absorptive at the surface contracting the radiating absorptive film. The coated glass system is used as glazing for storm windows which are adapted to be reversible so that the radiation reflective surface may be exposed to the outside of the dwelling during the warm seasons to prevent excessive solar radiation from entering a dwelling and reversed during cold seasons to absorb solar radiation and utilize it to aid in keeping the dwelling interior warm.

  15. Sequential Polarity-Reversing Circuit

    Science.gov (United States)

    Labaw, Clayton C.

    1994-01-01

    Proposed circuit reverses polarity of electric power supplied to bidirectional dc motor, reversible electro-mechanical actuator, or other device operating in direction depending on polarity. Circuit reverses polarity each time power turned on, without need for additional polarity-reversing or direction signals and circuitry to process them.

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

    Science.gov (United States)

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

    2014-12-01

    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

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

    Science.gov (United States)

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

    2016-01-01

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

  18. IgG anti-GalNAc-GD1a antibody inhibits the voltage-dependent calcium channel currents in PC12 pheochromocytoma cells.

    Science.gov (United States)

    Nakatani, Yoshihiko; Nagaoka, Takumi; Hotta, Sayako; Utsunomiya, Iku; Yoshino, Hiide; Miyatake, Tadashi; Hoshi, Keiko; Taguchi, Kyoji

    2007-03-01

    We investigated the effects of IgG anti-GalNAc-GD1a antibodies, produced by immunizing rabbits with GalNAc-GD1a, on the voltage-dependent calcium channel (VDCCs) currents in nerve growth factor (NGF)-differentiated PC12 pheochromocytoma cells. VDCCs currents in NGF-differentiated PC12 cells were recorded using the whole-cell patch-clamp technique. Immunized rabbit serum that had a high titer of anti-GalNAc-GD1a antibodies inhibited the VDCCs currents in the NGF-differentiated PC12 cells (36.0+/-9.6% reduction). The inhibitory effect of this serum was reversed to some degree within 3-4 min by washing with bath solution. Similarly, application of purified IgG from rabbit serum immunized with GalNAc-GD1a significantly inhibited the VDCCs currents in PC12 cells (30.6+/-2.5% reduction), and this inhibition was recovered by washing with bath solution. Furthermore, the inhibitory effect was also observed in the GalNAc-GD1a affinity column binding fraction (reduction of 31.1+/-9.85%), while the GalNAc-GD1a affinity column pass-through fraction attenuated the inhibitory effect on VDCCs currents. Normal rabbit serum and normal rabbit IgG did not affect the VDCCs currents in the PC12 cells. In an immunocytochemical study using fluorescence staining, the PC12 cells were stained using GalNAc-GD1a binding fraction. These results indicate that anti-GalNAc-GD1a antibodies inhibit the VDCCs currents in NGF-differentiated PC12 cells.

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

    OpenAIRE

    XIOMARA ESCOBAR-PÉREZ; Dorta-Contreras,Alberto J; MARIA TERESA INTERIÁN-MORALES; ELENA NORIS-GARCÍA; MARITZA FERRÁ-VALDÉS

    2000-01-01

    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...

  20. 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

    2012-01-01

    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.

  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

    2016-01-01

    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. Time reversal communication system

    Science.gov (United States)

    Candy, James V.; Meyer, Alan W.

    2008-12-02

    A system of transmitting a signal through a channel medium comprises digitizing the signal, time-reversing the digitized signal, and transmitting the signal through the channel medium. The channel medium may be air, earth, water, tissue, metal, and/or non-metal.

  3. Engineering Encounters: Reverse Engineering

    Science.gov (United States)

    McGowan, Veronica Cassone; Ventura, Marcia; Bell, Philip

    2017-01-01

    This column presents ideas and techniques to enhance your science teaching. This month's issue shares information on how students' everyday experiences can support science learning through engineering design. In this article, the authors outline a reverse-engineering model of instruction and describe one example of how it looked in our fifth-grade…

  4. Reverse Coherent Information

    Science.gov (United States)

    García-Patrón, Raúl; Pirandola, Stefano; Lloyd, Seth; Shapiro, Jeffrey H.

    2009-05-01

    In this Letter we define a family of entanglement distribution protocols assisted by feedback classical communication that gives an operational interpretation to reverse coherent information, i.e., the symmetric counterpart of the well-known coherent information. This leads to the definition of a new entanglement distribution capacity that exceeds the unassisted capacity for some interesting channels.

  5. Reversed extension flow

    DEFF Research Database (Denmark)

    Nielsen, Jens Kromann; Rasmussen, Henrik K.

    2008-01-01

    Afilament stretching rheometer (FSR) was used for measuring the start-up of uni-axial elongational flow followed by reversed bi-axial flow, both with a constant elongational rate. A narrow molecular mass distribution linear polystyrene with a molecular weight of 145 kg / mole wis subjected to the...

  6. REVERSE SUPPLY CHAIN

    Directory of Open Access Journals (Sweden)

    Tomasz DOMAGAŁA

    2013-10-01

    Full Text Available The paper focuses on the presentation of the reverse supply chain, of which the role in the modern business grows along with the increasing number of environmental regulations and possibilities of reducing an operating cost. The paper also describes main problems in developing the profitable chain and possibilities to take an action in order to overcome them.

  7. On reverse hypercontractivity

    CERN Document Server

    Mossel, Elchanan; Sen, Arnab

    2011-01-01

    We study the notion of reverse hypercontractivity. We show that reverse hypercontractive inequalities are implied by standard hypercontractive inequalities as well as by the modified log-Sobolev inequality. Our proof is based on a new comparison lemma for Dirichlet forms and an extension of the Strook-Varapolos inequality. A consequence of our analysis is that {\\em all} simple operators $L=Id-\\E$ as well as their tensors satisfy uniform reverse hypercontractive inequalities. That is, for all $qreverse hypercontractive inequalities established here imply new mixing and isoperimetric results for short random walks in product spaces, for certain card-shufflings, for Glauber dynamics in high-temperat...

  8. Reversing Discrimination: A Perspective

    Science.gov (United States)

    Pati, Gopal; Reilly, Charles W.

    1977-01-01

    Examines the debate over affirmative action and reverse discrimination, and discusses how and why the present dilemma has developed. Suggests that organizations can best address the problem through an honest, in-depth analysis of their organizational structure and management practices. (JG)

  9. Clinical evaluation of the Roche Elecsys CMV IgG Avidity assay.

    Science.gov (United States)

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

    2014-08-01

    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.

  10. Isolated Liver Hilar Infiltration by IgG4 Inflammation Mimicking Cholangiocarcinoma

    Science.gov (United States)

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

    2016-01-01

    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

  11. Defective anti-polysaccharide IgG vaccine responses in IgA deficient mice.

    Science.gov (United States)

    Furuya, Yoichi; Kirimanjeswara, Girish S; Roberts, Sean; Racine, Rachael; Wilson-Welder, Jennifer; Sanfilippo, Alan M; Salmon, Sharon L; Metzger, Dennis W

    2017-09-05

    We report that IgA(-/-) mice exhibit specific defects in IgG antibody responses to various polysaccharide vaccines (Francisella tularensis LPS and Pneumovax), but not protein vaccines such as Fluzone. This defect further included responses to polysaccharide-protein conjugate vaccines (Prevnar and Haemophilus influenzae type b-tetanus toxoid vaccine). In agreement with these findings, IgA(-/-) mice were protected from pathogen challenge with protein- but not polysaccharide-based vaccines. Interestingly, after immunization with live bacteria, IgA(+/+) and IgA(-/-) mice were both resistant to lethal challenge and their IgG anti-polysaccharide antibody responses were comparable. Immunization with live bacteria, but not purified polysaccharide, induced production of serum B cell-activating factor (BAFF), a cytokine important for IgG class switching; supplementing IgA(-/-) cell cultures with BAFF enhanced in vitro polyclonal IgG production. Taken together, these findings show that IgA deficiency impairs IgG class switching following vaccination with polysaccharide antigens and that live bacterial immunization can overcome this defect. Since IgA deficient patients also often show defects in antibody responses following immunization with polysaccharide vaccines, our findings could have relevance to the clinical management of this population. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Visciano Maria Luisa

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    April L. Barnado MD

    2013-09-01

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

  14. Isolated Liver Hilar Infiltration by IgG4 Inflammation Mimicking Cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Laurent Bochatay

    2016-10-01

    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.

  15. IgG4-related multiorgan disease: report of the first autopsy case

    Science.gov (United States)

    Ochoa, Minerva Lazos; Gabiño López, Belem; Cabello, Raúl Romero; Feregrino, Raúl Romero

    2013-01-01

    IgG4-related disease (IgG4RD) is a chronic recurring fibro-inflammatory pathology that is considered to be of autoimmune origin. Histopathology is considered to be the gold standard method for diagnosis. IgG4RD affects multiple organs. IgG4RD was first identified in the pancreas and was called autoimmune pancreatitis (AIP). During the following years, the disease spectrum was expanded and it was realised that the extrapancreatic lesions can precede, coexist or appear after the diagnosis of AIP. At present, several illnesses such as Mikulicz disease, Küttner tumour, multifocal fibrosclerosis, etc, are considered to be part of the IgG4RD spectrum. The symptoms of the disease tend to appear over months and years and diagnosis is achieved on average 13.5 months (4–60 months) after the onset. The purpose of this report was to provide information about a case that was sadly fatal but that permitted a complete histopathological study of the damaged tissues. PMID:23645656

  16. Proteolytic activity of IgGs from blood serum of wistar rats at experimental rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Yu. Ya. Kit

    2014-10-01

    Full Text Available The aim of this work was to study the proteolytic activity of IgGs purified from blood serum of Wistar rats at experimental rheumatoid arthritis (ERA induced by an injection of bovine collagen of type II. Twenty rats were immunized with a preparation of bovine collagen II (Sigma-Aldrich, USA in the presence of complete Freund’s adjuvant. ERA development was determined by inflammation in limbs of treated animals. IgG preparations were isolated from blood serum of immunized and non-immunized animals by precipitation of antibodies with 33% ammonium sulfate followed by chromatography on the Protein G-Sepharose column. Human histone H1, bovine collagen II, calf thymus histones, myelin basic protein (MBP, bovine serum albumin (BSA, and bovine casein were used as substrates of the proteolytic activity of IgGs. It was found that IgG preparations from blood serum of rats with ERA were capable of cleaving histone H1 and MBP, however, they were catalytically inactive towards collagen II, casein, BSA, and core histones. IgGs from blood serum of non-immunized rats were proteolytically inactive towards all used protein substrates. Thus, we demonstrated that immunization of rats with bovine collagen II induced IgG-antibodies possessing the proteolytic activity towards histone H1 and MBP. This activity might be associated with the development of inflammatory processes in the immunized rats.

  17. Rabbit IgG distribution in skin, spinal cord and DRG following systemic injection in rat.

    Science.gov (United States)

    Tonra, J R; Mendell, L M

    1997-12-01

    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.

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

    Science.gov (United States)

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

    1993-06-17

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

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

    Directory of Open Access Journals (Sweden)

    Berlin L. Londono-Renteria

    2016-09-01

    Full Text Available 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 regards 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.

  20. Malaria resistance genes are associated with the levels of IgG subclasses directed against Plasmodium falciparum blood-stage antigens in Burkina Faso

    Directory of Open Access Journals (Sweden)

    Afridi Sarwat

    2012-09-01

    Full Text Available Abstract Background HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms have been associated with malaria resistance in humans, whereas cytophilic immunoglobulin G (IgG antibodies are thought to play a critical role in immune protection against asexual blood stages of the parasite. Furthermore, HBB, IL4, TNF, and FCGR2A have been associated with both malaria resistance and IgG levels. This suggests that some malaria resistance genes influence the levels of IgG subclass antibodies. Methods In this study, the effect of HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms on the levels of IgG responses against Plasmodium falciparum blood-stage extract was investigated in 220 individuals living in Burkina Faso. The Pearson’s correlation coefficient among IgG subclasses was determined. A family-based approach was used to assess the association of polymorphisms with anti-P. falciparum IgG, IgG1, IgG2, IgG3 and IgG4 levels. Results After applying a multiple test correction, several polymorphisms were associated with IgG subclass or IgG levels. There was an association of i haemoglobin C with IgG levels; ii the FcγRIIa H/R131 with IgG2 and IgG3 levels; iii TNF-863 with IgG3 levels; iv TNF-857 with IgG levels; and, v TNF1304 with IgG3, IgG4, and IgG levels. Conclusion Taken together, the results support the hypothesis that some polymorphisms affect malaria resistance through their effect on the acquired immune response, and pave the way towards further comprehension of genetic control of an individual’s humoral response against malaria.

  1. Solely lung-involved IgG4-related disease : a case report and review of the literature.

    Science.gov (United States)

    Zhang, Xiao-Qin; Chen, Guo-Ping; Wu, Sheng-Chang; Yu, Sa; Wang, Hong; Chen, Xuan-Yi; Ren, Zhuo-Chao

    2016-12-23

    By analyzing the clinical data of 1 case of IgG4-related lung disease(IgG4-RLD) and the review of literature, the author investigated the clinical characteristics of IgG4-RLD. IgG4-RLD is a rare disease characterized by significant elevation of serum IgG4 and infiltration of a large number of IgG4+ plasma cells. The clinical manifestations of the disease were nonspecific, and the imaging features were mixed with several types. The disease can only be involved in the lung, but also multiple organ involvement. Solely lung-involved IgG4-RD is not only extremely rare but also easily misdiagnosed as tuberculosis, lung cancer, lymphoma and other common pulmonary diseases. Histopathological examination is the key to the diagnosis of the disease. Corticosteroids are the first choice of treatment, and the overall prognosis is good.

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

    Science.gov (United States)

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

    2009-06-01

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

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

    Science.gov (United States)

    2012-12-01

    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

  4. IgG4-related disease: a novel lymphoproliferative disorder discovered and established in Japan in the 21st century.

    Science.gov (United States)

    Masaki, Yasufumi; Kurose, Nozomu; Umehara, Hisanori

    2011-01-01

    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).

  5. Detection of IgG anti-A/B must be essential for safe transfusion support in patients undergoing ABO incompatible allogeneic HSCT.

    Science.gov (United States)

    Liu, Feng; Li, Guining; Mao, Xiaolu; Hu, Lihua

    2011-04-01

    Recipients of ABO incompatible allogeneic HSCT present with unusual ABO groups and crossmatch problems accompanied by change of the ABO group from that of the host to the donor. We report on a patient undergoing major ABO incompatible allogeneic HSCT (donor/recipient: A/O) whose blood group was wrongly established to have completely switched to blood group A when using a routine tube method and micro gel column blood grouping card on the 68th day post transplantation. The major crossmatch test with added antiglobulin and blood group A red cells was still positive. After further investigation, an explanation was found because we could not detect IgG anti-A in the serum. At the same time, anti-A coated the patient's RBCs and could be identified using a heat elution method although the DAT was negative. We also found an obvious mixed field with the LISS-IAT gel card. Hence, routine methods of ABO grouping are unfit for ABO incompatible allogeneic HSCT patients and a micro column neutral gel card is recommended for forward typing especially to detect mixed fields and a LISS-IAT gel card or IAT tube method for detecting IgG anti-A/B in reverse typing. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. Isolation and Purification of Bovine Colostrum sIgA and IgG

    Institute of Scientific and Technical Information of China (English)

    YAO Yonghao; GAO Xuejun; LIU Xiaofei

    2008-01-01

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

  7. Homogeneous Detection of Human IgG by Gold Nanoparticle Probes

    Institute of Scientific and Technical Information of China (English)

    CAO Qihua; YUAN Hong; CAI Ruxiu

    2009-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Dipankar Das

    2016-01-01

    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.

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  11. Global and Local Conformation of Human IgG Antibody Variants Rationalizes Loss of Thermodynamic Stability.

    Science.gov (United States)

    Edgeworth, Matthew J; Phillips, Jonathan J; Lowe, David C; Kippen, Alistair D; Higazi, Daniel R; Scrivens, James H

    2015-12-07

    Immunoglobulin G (IgG) monoclonal antibodies (mAbs) are a major class of medicines, with high specificity and affinity towards targets spanning many disease areas. The antibody Fc (fragment crystallizable) region is a vital component of existing antibody therapeutics, as well as many next generation biologic medicines. Thermodynamic stability is a critical property for the development of stable and effective therapeutic proteins. Herein, a combination of ion-mobility mass spectrometry (IM-MS) and hydrogen/deuterium exchange mass spectrometry (HDX-MS) approaches have been used to inform on the global and local conformation and dynamics of engineered IgG Fc variants with reduced thermodynamic stability. The changes in conformation and dynamics have been correlated with their thermodynamic stability to better understand the destabilising effect of functional IgG Fc mutations and to inform engineering of future therapeutic proteins.

  12. Proliferative glomerulonephritis with monoclonal IgG deposits in a patient with autoimmune hemolytic anemia.

    Science.gov (United States)

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

    2013-06-01

    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.

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

    Science.gov (United States)

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

    2015-06-01

    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.

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

    Science.gov (United States)

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

    2014-08-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

  16. Significance of specific IgG against sensitizing antigens in extrinsic allergic alveolitis: serological methods in EAA.

    Science.gov (United States)

    Sterclova, M; Vasakova, M; Metlicka, M

    2011-01-01

    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. Copyright © 2010. Published by Elsevier España.

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

    Directory of Open Access Journals (Sweden)

    M. Hermet

    2012-01-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Gengozian, N.; McLaughlin, C.L.

    1978-06-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Anna Popławska-Kita

    2015-01-01

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

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

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    Eman El Masry El Damarany

    2010-02-01

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

  2. Antigliadin Antibodies (AGA IgG Are Related to Neurochemistry in Schizophrenia

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    Laura M. Rowland

    2017-06-01

    Full Text Available Inflammation may play a role in schizophrenia; however, subgroups with immune regulation dysfunction may serve as distinct illness phenotypes with potential different treatment and prevention strategies. Emerging data show that about 30% of people with schizophrenia have elevated antigliadin antibodies of the IgG type, representing a possible subgroup of schizophrenia patients with immune involvement. Also, recent data have shown a high correlation of IgG-mediated antibodies between the periphery and cerebral spinal fluid in schizophrenia but not healthy controls, particularly AGA IgG suggesting that these antibodies may be crossing the blood–brain barrier with resulting neuroinflammation. Proton magnetic resonance spectroscopy (MRS is a non-invasive technique that allows the quantification of certain neurochemicals in vivo that may proxy inflammation in the brain such as myoinositol and choline-containing compounds (glycerophosphorylcholine and phosphorylcholine. The objective of this exploratory study was to examine the relationship between serum AGA IgG levels and MRS neurochemical levels. We hypothesized that higher AGA IgG levels would be associated with higher levels of myoinositol and choline-containing compounds (glycerophosphorylcholine plus phosphorylcholine; GPC + PC in the anterior cingulate cortex. Thirty-three participants with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder had blood drawn and underwent neuroimaging using MRS within 9 months. We found that 10/33 (30% had positive AGA IgG (≥20 U similar to previous findings. While there were no significant differences in myoinositol and GPC + PC levels between patients with and without AGA IgG positivity, there were significant relationships between both myoinositol (r = 0.475, p = 0.007 and GPC + PC (r = 0.36, p = 0.045 with AGA IgG levels. This study shows a possible connection of AGA IgG antibodies to putative brain

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Cinzia Rizzo

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

  5. Reversible quantum cellular automata

    CERN Document Server

    Schumacher, B

    2004-01-01

    We define quantum cellular automata as infinite quantum lattice systems with discrete time dynamics, such that the time step commutes with lattice translations and has strictly finite propagation speed. In contrast to earlier definitions this allows us to give an explicit characterization of all local rules generating such automata. The same local rules also generate the global time step for automata with periodic boundary conditions. Our main structure theorem asserts that any quantum cellular automaton is structurally reversible, i.e., that it can be obtained by applying two blockwise unitary operations in a generalized Margolus partitioning scheme. This implies that, in contrast to the classical case, the inverse of a nearest neighbor quantum cellular automaton is again a nearest neighbor automaton. We present several construction methods for quantum cellular automata, based on unitaries commuting with their translates, on the quantization of (arbitrary) reversible classical cellular automata, on quantum c...

  6. Partial Reversible Gates(PRG) for Reversible BCD Arithmetic

    CERN Document Server

    Thapliyal, Himanshu; Bajpai, Rajnish; Sharma, Kamal K

    2007-01-01

    IEEE 754r is the ongoing revision to the IEEE 754 floating point standard and a major enhancement to the standard is the addition of decimal format. Furthermore, in the recent years reversible logic has emerged as a promising computing paradigm having its applications in low power CMOS, quantum computing, nanotechnology, and optical computing. The major goal in reversible logic is to minimize the number of reversible gates and garbage outputs. Thus, this paper proposes the novel concept of partial reversible gates that will satisfy the reversibility criteria for specific cases in BCD arithmetic. The partial reversible gate is proposed to minimize the number of reversible gates and garbage outputs, while designing the reversible BCD arithmetic circuits.

  7. Reversible hysteresis loop tuning

    Science.gov (United States)

    Berger, A.; Binek, Ch.; Margulies, D. T.; Moser, A.; Fullerton, E. E.

    2006-02-01

    We utilize antiferromagnetically coupled bilayer structures to magnetically tune hysteresis loop properties. Key element of this approach is the non-overlapping switching field distribution of the two magnetic layers that make up the system: a hard magnetic CoPtCrB layer (HL) and a soft magnetic CoCr layer (SL). Both layers are coupled antiferromagnetically through an only 0.6-nm-thick Ru interlayer. The non-overlapping switching field distribution allows the measurement of magnetization reversal in the SL at low fields while keeping the magnetization state of the HL unperturbed. Applying an appropriate high field or high field sequence changes the magnetic state of the HL, which then influences the SL magnetization reversal due to the interlayer coupling. In this way, the position and shape of the SL hysteresis loop can be changed or tuned in a fully reversible and highly effective manner. Here, we study specifically how the SL hysteresis loop characteristics change as we move the HL through an entire high field hysteresis loop sequence.

  8. Reversible multi-head finite automata characterize reversible logarithmic space

    DEFF Research Database (Denmark)

    Axelsen, Holger Bock

    2012-01-01

    Deterministic and non-deterministic multi-head finite automata are known to characterize the deterministic and non- deterministic logarithmic space complexity classes, respectively. Recently, Morita introduced reversible multi-head finite automata (RMFAs), and posed the question of whether RMFAs...... characterize reversible logarithmic space as well. Here, we resolve the question affirmatively, by exhibiting a clean RMFA simulation of logarithmic space reversible Turing machines. Indirectly, this also proves that reversible and deterministic multi-head finite automata recognize the same languages....

  9. [Reverse Chaddock sign].

    Science.gov (United States)

    Tashiro, Kunio

    2011-08-01

    It is widely accepted that the Babinski reflex is the most well-known and important pathological reflex in clinical neurology. Among many other pathological reflexes that elicit an upgoing great toe, such as Chaddock, Oppenheim, Gordon, Schaefer, and Stransky, only the Chaddock reflex is said to be as sensitive as the Babinski reflex. The optimal receptive fields of the Babinski and Chaddock reflexes are the lateral plantar surface and the external inframalleolar area of the dorsum, respectively. It has been said that the Babinski reflex, obtained by stroking the sole, is by far the best and most reliable method of eliciting an upgoing great toe. However, the Chaddock reflex, the external malleolar sign, is also considered sensitive and reliable according to the literature and everyday neurological practice. The major problems in eliciting the Babinski reflex by stroking the lateral part of the sole are false positive or negative responses due to foot withdrawal, tonic foot response, or some equivocal movements. On the other hand, according to my clinical experience, the external inframalleolar area, which is the receptive field of the Chaddock reflex, is definitely suitable for eliciting the upgoing great toe. In fact, the newly proposed method to stimulate the dorsum of the foot from the medial to the lateral side, which I term the "reversed Chaddock method," is equally sensitive to demonstrate pyramidal tract involvement. With the "reversed Chaddock method", the receptive field of the Chaddock reflex may be postulated to be in the territory of the sural nerve, which could be supported by the better response obtained on stimulation of the postero-lateral calf than the anterior shin. With regard to the receptive fields of the Babinski and Chaddock reflexes, the first sacral dermatome (S1) is also considered a reflexogenous zone, but since the dermatome shows marked overlapping, the zones vary among individuals. As upgoing toe responses are consistently observed in

  10. A brief contextualization on IgG4 tubulointerstitial nephritis based on a case report in south Brazil.

    Science.gov (United States)

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

    2016-06-01

    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.

  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

    2015-01-01

    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. Age-dependent association between IgG2 and IgG3 subclasses to Pf332-C231 antigen and protection from malaria, and induction of protective antibodies by sub-patent malaria infections, in Daraweesh

    DEFF Research Database (Denmark)

    Giha, Hayder A; Nasr, Amre; Iriemenam, Nnaemeka C

    2010-01-01

    The certainty of the protective role of acquired immunity in malaria is the major drive for malaria vaccine development. In this study, we measured the levels of total IgG and IgG subclasses to four candidate malaria vaccine antigens; MSP2-3D7, MSP2-FC27, AMA-1 and Pf332-C231, in plasma obtained ...

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

    Directory of Open Access Journals (Sweden)

    R. Sharma

    2010-02-01

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

  14. 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.

  15. Three Cases of Bronchial Asthma Preceding IgG4-Related Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Satoru Ito

    2012-01-01

    Discussion: It is possible that atopy and increased Th2 cell activity are related to a higher coincidence of IgG4-related diseases such as type 1 autoimmune pancreatitis. Because the present cases are few in number, further studies are necessary.

  16. [Serum IgG antibodies to GD1a and GM1 gangliosides in elderly people].

    Science.gov (United States)

    Kolyovska, V

    2016-01-01

    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.

  17. Anti-Pseudomonas aeruginosa IgG antibodies and chronic airway infection in bronchiectasis.

    Science.gov (United States)

    Suarez-Cuartin, Guillermo; Smith, Alex; Abo-Leyah, Hani; Rodrigo-Troyano, Ana; Perea, Lidia; Vidal, Silvia; Plaza, Vicente; Fardon, Thomas C; Sibila, Oriol; Chalmers, James D

    2017-07-01

    Identification of chronic Pseudomonas aeruginosa (PA) infection is important in the management of bronchiectasis, but requires repeated sputum sampling. We hypothesized that serum anti-PA IgG antibodies could diagnose chronic PA infection at a single visit. Clinically stable bronchiectasis patients were studied prospectively. Chronic PA infection was defined as 2 or more positive sputum samples at least 3 months apart and/or failure to clear PA following eradication treatment. Baseline serum anti-PA IgG was determined by a validated ELISA kit. A total of 408 patients were included. Sixty of them (14.7%) had chronic PA infection and had higher anti-PA IgG levels (median 6.2 vs. 1.3 units, p < 0.001). Antibody levels showed direct significant correlations with exacerbation frequency, the bronchiectasis severity index and sputum inflammatory markers. Fifty-seven patients with chronic PA infection had a positive test, giving 95% sensitivity, 74.4% specificity and AUROC of 0.87. During follow-up, 38 patients had a new PA isolation. Eradication at 12 months was achieved in 89.5% of subjects with a negative antibody test and 15.8% of patients with a positive test. Anti-PA IgG test is highly accurate to detect chronic PA infection in bronchiectasis patients. In addition, it may be a marker of disease severity and treatment response. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. 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;

    1995-01-01

    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...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...

  20. Anti-amyloidogenic Activity of IgGs Contained in Normal Plasma

    Science.gov (United States)

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

    2010-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Heath A. Smith

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Xinsheng Tian

    2015-01-01

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

  3. Isolated IgG4-related cholecystitis mimicking gallbladder cancer: a case report.

    Science.gov (United States)

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

    2013-01-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2002-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Toshiyuki Oshitari

    2010-12-01

    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

  6. Increased RP105-Negative B Cells in IgG4-Related Disease.

    Science.gov (United States)

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

    2013-01-01

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

    Directory of Open Access Journals (Sweden)

    Erdal Özbek

    2016-03-01

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

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

    NARCIS (Netherlands)

    Jaarsma, AS; Muis, N; DeGraaf, SSN

    1996-01-01

    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. Functionalization of SU-8 Photoresist Surfaces with IgG Proteins

    DEFF Research Database (Denmark)

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

    2008-01-01

    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...

  10. IgG antibodies in patients with pemphigus vulgaris before and after diagnosing with immunofluorescence.

    Science.gov (United States)

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

    2013-06-15

    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.

  11. Reverse Engineering of RFID devices

    OpenAIRE

    Bokslag, Wouter

    2015-01-01

    This paper discusses the relevance and potential impact of both RFID and reverse engineering of RFID technology, followed by a discussion of common protocols and internals of RFID technology. The focus of the paper is on providing an overview of the different approaches to reverse engineering RFID technology and possible countermeasures that could limit the potential of such reverse engineering attempts.

  12. Inhibition of murine fibrocyte differentiation by cross-linked IgG is dependent on FcγRI.

    Science.gov (United States)

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

    2014-08-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Jesse W. Williams

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

  16. O Blood Group as a Risk Factor for Helicobacter Pylori IgG Seropositivity Among Pregnant Sudanese Women.

    Science.gov (United States)

    Gasim, Gasim I; Elmugabil, Abdelmageed; Hamdan, Hamdan Z; Rayis, Duria A; Adam, Ishag

    2017-06-07

    The objective was to investigate the prevalence and the association between blood groups and Helicobacter pylori IgG seropositivity among pregnant Sudanese women. A cross-sectional survey was carried-out at Saad Abul Ela Maternity Hospital, Khartoum, Sudan during the period of July 2014 through December 2015. Questionnaires covering socio-demographic and obstetrics information were administered. Specific H. pylori IgG antibody was analysed using ELISA. One hundred eighty six pregnant women were enrolled. The mean (SD) of the age, parity was 28.3 (2.6) years and 2.6 (3.5), respectively. Of the 186 women, 42 (22.6%), 24 (12.9%), 11(5.9%) and 109 (58.6%) had blood group A, B, AB and O, respectively. H. pylori IgG seropositivity rate was 132/186 (71.0%). There was no significant difference in age and parity between women with H. pylori IgG seropositive and seronegative. Compared with the women with H. pylori IgG seronegative, significantly higher numbers of women with H. pylori IgG seropositive had O blood group, [84/132(63.6) versus 25/54(46.3), Ppylori IgG seropositivity. The current study showed that women with blood group O were at higher risk for H. pylori IgG seropositivity.

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2009-03-01

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

  19. 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

  20. Reverse Engineering Malicious Applications

    Directory of Open Access Journals (Sweden)

    Ioan Cristian Iacob

    2015-06-01

    Full Text Available Detecting new and unknown malware is a major challenge in today’s software. Security profession. A lot of approaches for the detection of malware using data mining techniques have already been proposed. Majority of the works used static features of malware. However, static detection methods fall short of detecting present day complex malware. Although some researchers proposed dynamic detection methods, the methods did not use all the malware features. In this work, an approach for the detection of new and unknown malware was proposed and implemented. Each sample was reverse engineered for analyzing its effect on the operating environment and to extract the static and behavioral features. 

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

    Directory of Open Access Journals (Sweden)

    Berrin Uzun

    2014-09-01

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

  2. Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein

    Directory of Open Access Journals (Sweden)

    Kristina Kakalacheva

    2016-02-01

    Full Text Available A history of infectious mononucleosis (IM, symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects. We detected frequent immunoglobulin M (IgM reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77% but rarely in control subjects (2/23; 9%. IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS, were detectable in 7/35 (20% patients with IM but not in control subjects. Normalization of anti-vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%, even after normalization to increased total IgG levels. Vimentin-specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms. We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM.

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

    Directory of Open Access Journals (Sweden)

    M Pedram

    2007-08-01

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

  4. IgG, IgA, and lysozyme in Martina Franca donkey jennies and their foals.

    Science.gov (United States)

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

    2014-04-01

    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.

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

    Science.gov (United States)

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

    2013-11-19

    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. A total of 1387 serum samples collected between 2010 and 2012 from individuals with ages ranging from 1 month to 85 years were investigated. Antibody concentrations were measured with an enzyme-linked immunosorbent assay (Anti-Diphtheria Toxoid ELISA IgG, Euroimmun, Germany). The results showed that among 1387 individuals examined, 547 (39.4%) had anti-diphtheria toxoid IgG antibody levels below 0.1 IU/ml (36.9% ≤ 18 years and 40.5% >18 years old, respectively). The 212 (50.8%) children and 542 (55.9%) adults showed only basic protection (0.1-1.0 IU/ml) and need immediate booster. High levels of anti-diphtheria toxoid IgG antibodies (>1.0 IU/ml) were found more often in children and adolescent (12.2%) than in adults (3.6%) and this was statistically significant (P 60 years old. Characteristically, in individuals > 40 years old high levels of anti-diphtheria toxoid IgG antibodies (>1.0 IU/ml) were not seen. There were no statistically significant differences in results in relation to gender. The present study showed inadequate immunity levels to diphtheria amongst the Polish population, especially in adults > 40 years old and children ≤ 2 years old. To prevent reemergence of diphtheria an information campaign reminding people about recommendations concerning diphtheria booster vaccination in adults should be conducted. Moreover, the immunogenicity of the DTP vaccine used in Poland should be verified.

  6. Prevalence of rubella-specific IgG antibodies in unimmunized young female population

    Directory of Open Access Journals (Sweden)

    Jayakrishnan Thayyil

    2016-01-01

    Full Text Available Context: Rubella is a mild self-limiting disease all over the world; nevertheless, it is of significant public health importance due to its teratogenic effect of congenital rubella syndrome. Rubella vaccine is currently not included in the national immunization program in India. Rubella-specific IgG in the unvaccinated population is a marker of previous rubella infection. Rubella IgG estimation in children will provide data for initiation and necessary modification to the immunization strategy. Aims: In this background, this study was conducted with an aim to know the age-specific susceptibility of acquiring rubella infections and future risk of congenital rubella syndrome (CRS among girls. Settings and Design: This was a community-based, observational study. Participants and Methods: The study was conducted at a randomly selected rural area Mavoor Panchayath of Kozhikode District, Kerala, among adolescent girls. The estimation of rubella-specific IgG antibody was done by quantitative enzyme-linked immunosorbent assay method. IgG titer value of >15 IU was taken positive, 8-15 IU as equivocal, and <8 IU as negative. Statistical Analysis Used: Statistical analysis was performed using Statistical program for Social science version 16 for Windows. Chi-square test was applied to find out significant difference and Fisher′s exact test wherever applicable. Results: The data and blood sample collection was done from 250 girls. The mean IgG titer was 151.93 ± 128.78 IU, and as per the criteria, 68.3% were positive, 28.5% were negative, and 3.2% were equivocal. At this age, majority (68.3% of the girls get protection by natural infection without any vaccine. Some girls (32% may remain susceptible to infection during adulthood and pregnancy. Conclusions: Natural rubella infection was widely prevalent among child population and at this age. An immunization policy recommending rubella-containing vaccine is highly desirable to prevent rubella and CRS.

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

    Science.gov (United States)

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

    2015-05-01

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

  8. Reversibly Bistable Flexible Electronics

    KAUST Repository

    Alfaraj, Nasir

    2015-05-01

    Introducing the notion of transformational silicon electronics has paved the way for integrating various applications with silicon-based, modern, high-performance electronic circuits that are mechanically flexible and optically semitransparent. While maintaining large-scale production and prototyping rapidity, this flexible and translucent scheme demonstrates the potential to transform conventionally stiff electronic devices into thin and foldable ones without compromising long-term performance and reliability. In this work, we report on the fabrication and characterization of reversibly bistable flexible electronic switches that utilize flexible n-channel metal-oxide-semiconductor field-effect transistors. The transistors are fabricated initially on rigid (100) silicon substrates before they are peeled off. They can be used to control flexible batches of light-emitting diodes, demonstrating both the relative ease of scaling at minimum cost and maximum reliability and the feasibility of integration. The peeled-off silicon fabric is about 25 µm thick. The fabricated devices are transferred to a reversibly bistable flexible platform through which, for example, a flexible smartphone can be wrapped around a user’s wrist and can also be set back to its original mechanical position. Buckling and cyclic bending of such host platforms brings a completely new dimension to the development of flexible electronics, especially rollable displays.

  9. Concomitant occurrence of IgG4-related pleuritis and periaortitis: a case report with review of the literature.

    Science.gov (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

    2014-01-01

    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.

  10. High Expression of Galectin-3 in Patients with IgG4-Related Disease: A Proteomic Approach

    Directory of Open Access Journals (Sweden)

    Adeeb Salah

    2017-01-01

    Full Text Available Objectives. Immunoglobulin G4-related disease (IgG4-RD is a multiorgan condition manifesting itself in different forms. This study aimed to investigate protein expression profiles and to find the possible biomarker for IgG4-RD by liquid chromatography mass spectrometry (LC-MS using tissue sections in IgG4-RD patients. Methods. Protein expression profiles in five IgG4-related pancreatitis and three normal pancreatic samples were compared using LC-MS and were validated by quantitative real-time PCR (qRT-PCR, immunoblotting, and immunohistochemistry. ELISA was employed in the serum of 20 patients with systemic IgG4-RD before and during steroid treatment. Results. LC-MS indicated that the levels of 17 proteins were significantly higher and 12 others were significantly lower in IgG4-related pancreatitis patients compared to controls. Among these proteins, galectin-3 levels were 13-fold higher in IgG4-related pancreatitis (P<0.01. These results were confirmed by immunoblotting and qRT-PCR. The average number of galectin-3 + cells in various organs of IgG4-RD patients, including salivary glands, lungs, and lymph nodes, was higher than in controls. Galectin-3 was detectable in macrophages, dendritic cells, and stromal myofibroblast-like cells, but not in lymphocytes by immunofluorescence staining. Serum galectin-3 levels were higher in patients with IgG4-RD compared with healthy donors and remained high during steroid therapy. Conclusion. Galectin-3 was overexpressed in IgG4-RD and the levels were indirectly related to clinical activity.

  11. VapA-specific IgG and IgG subclasses responses after natural infection and experimental challenge of foals with Rhodococcus equi.

    Science.gov (United States)

    Sanz, M G; Villarino, N; Ferreira-Oliveira, A; Horohov, D W

    2015-03-15

    Rhodococcus equi is a common cause of pneumonia in young foals worldwide and has considerable economic effects on the global equine industry. Despite ongoing efforts, no vaccine is currently available to prevent rhodococaal pneumonia. This is due, in part, to an incomplete understanding of the protective immune response to this bacterium. While antibodies to VapA, a lipoprotein produced by virulent R. equi, are useful in differentiating antibody production in response to pathogenic versus non-pathogenic strains, the significance of the humoral response of foals to this lipoprotein remains poorly defined. The objectives of this study were to evaluate changes in VapA-specific IgG and IgG subclasses after exposure and infection of neonatal foals. Experimental foals included those challenged with R. equi at 1 (n=18), 2 (n=4) and 3 (n=6) weeks of age. Confirmed naturally infected (n=7) and not infected (n=3) foals were also included. All foals were bled 24h after birth and weekly thereafter for a period of 8 weeks. Antibody changes over time were evaluated. Following birth, VapA-specific IgGs significantly (p<0.05) decreased over time in all foals as a result of normal decay of passively transferred antibodies. Both VapA-specific IgGa and IgG(T) significantly increased (p<0.05) after experimental challenge, however, the rise in IgG(T) occurred earlier. Only a significant (p<0.05) increase in VapA-specific IgG(T) over time was seen after natural infection. Whether VapA-specific IgG(T) can be used to differentiate rhodococcal from other pneumonias requires further investigation under field conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    H Ghasemian safaei

    2005-01-01

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

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

    Science.gov (United States)

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

    2014-09-01

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

  14. Fundamentals of reversible flowchart languages

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2016-01-01

    . Although reversible flowcharts are superficially similar to classical flowcharts, there are crucial differences: atomic steps are limited to locally invertible operations, and join points require an explicit orthogonalizing conditional expression. Despite these constraints, we show that reversible......Abstract This paper presents the fundamentals of reversible flowcharts. They are intended to naturally represent the structure and control flow of reversible (imperative) programming languages in a simple computation model, in the same way classical flowcharts do for conventional languages......, structured reversible flowcharts are as expressive as unstructured ones, as shown by a reversible version of the classic Structured Program Theorem. We illustrate how reversible flowcharts can be concretized with two example programming languages, complete with syntax and semantics: a low-level unstructured...

  15. Reversible posterior leukoencephalopathy syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ja; Yu, Won Jong; Ahn, Kook Jin; Jung, So Lyung; Lee, Yeon Soo; Kim, Ji Chang; Kang, Si Won [The Catholic Univ. of Korea, Taejon (Korea, Republic of); Song, Chang Joon [Chungnam National Univ. School of Medicine, Cheonju (Korea, Republic of); Song, Soon-Young; Koo, Ja Hong [Kwandong Univ. College of Medicine, Myungji Hospital, Seoul (Korea, Republic of); Kim, Man Deuk [College of Medicine Pochon CHA Univ., Seoul (Korea, Republic of)

    2001-10-01

    To review reversible posterior leukoencephalopathy syndrome. We reviewed 22 patients (M:F=3:19; age, 17-46 years) with the characteristic clinical and imaging features of reversible posterior leukoencephalopathy syndrome. All underwent brain MRI, and in three cases both CT and MRI were performed. In one, MRA was obtained, and in eleven, follow-up MR images were obtained. We evaluated the causes of this syndrome, its clinical manifestations, and MR findings including the locations of lesions, the presence or absence of contrast enhancement, and the changes seen at follow-up MRI. Of the 22 patients, 13 had eclampsia (six during pregnancy and seven during puerperium). Four were receiving immunosuppressive therapy (three, cyclosporine ; one, FK 506). Four suffered renal failure and one had complicated migraine. The clinical manifestations included headache (n=12), visual disturbance (n=13), seizure (n=15), focal neurologic sign (n=3), and altered mental status (n=2). Fifteen patients had hypertension and the others normotension. MRI revealed that lesions were bilateral (n=20) or unilateral (n=2). In all patients the lesion was found in the cortical and subcortical areas of the parieto-occipital lobes ; other locations were the basal ganglia (n=9), posterior temporal lobe (n=8), frontal lobe (n=5), cerebellum (n=5), pons (n=2), and thalamus (n=1). All lesions were of high signal intensity on T2-weighted images, and of iso to low intensity on T1-weighted images. One was combined with acute hematoma in the left basal ganglia. In eight of 11 patients who underwent postcontrast T1-weighted MRI, there was no definite enhancement ; in one, enhancement was mild, and in tow, patchy. CT studies showed low attenuation, and MRA revealed mild vasospasm. The symptoms of all patients improved. Follow-up MRI in nine of 11 patients depicted complete resolution of the lesions ; in two, small infarctions remained but the extent of the lesions had decreased. Reversible posterior

  16. Mosquitocidal properties of IgG targeting the glutamate-gated chloride channel in three mosquito disease vectors (Diptera: Culicidae).

    Science.gov (United States)

    Meyers, Jacob I; Gray, Meg; Foy, Brian D

    2015-05-15

    The glutamate-gated chloride channel (GluCl) is a highly sensitive insecticide target of the avermectin class of insecticides. As an alternative to using chemical insecticides to kill mosquitoes, we tested the effects of purified immunoglobulin G (IgG) targeting the extracellular domain of GluCl from Anopheles gambiae (AgGluCl) on the survivorship of three key mosquito disease vectors: Anopheles gambiae s.s., Aedes aegypti and Culex tarsalis. When administered through a single blood meal, anti-AgGluCl IgG reduced the survivorship of A. gambiae in a dose-dependent manner (LC50: 2.82 mg ml(-1), range 2.68-2.96 mg ml(-1)) but not A. aegypti or C. tarsalis. We previously demonstrated that AgGluCl is only located in tissues of the head and thorax of A. gambiae. To verify that AgGluCl IgG is affecting target antigens found outside the midgut, we injected it directly into the hemocoel via intrathoracic injection. A single, physiologically relevant concentration of anti-AgGluCl IgG injected into the hemocoel equally reduced mosquito survivorship of all three species. To test whether anti-AgGluCl IgG was entering the hemocoel of each of these mosquitoes, we fed mosquitoes a blood meal containing anti-AgGluCl IgG and subsequently extracted their hemolymph. We only detected IgG in the hemolymph of A. gambiae, suggesting that resistance of A. aegypti and C. tarsalis to anti-AgGluCl IgG found in blood meals is due to deficient IgG translocation across the midgut. We predicted that anti-AgGluCl IgG's mode of action is by antagonizing GluCl activity. To test this hypothesis, we fed A. gambiae blood meals containing anti-AgGluCl IgG and the GluCl agonist ivermectin (IVM). Anti-AgGluCl IgG attenuated the mosquitocidal effects of IVM, suggesting that anti-AgGluCl IgG antagonizes IVM-induced activation of GluCl. Lastly, we stained adult, female A. aegypti and C. tarsalis for GluCl expression. Neuronal GluCl expression in these mosquitoes was similar to previously reported A

  17. Dissecting the relationships of IgG subclasses and complements in membranous lupus nephritis and idiopathic membranous nephropathy

    Science.gov (United States)

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

    2017-01-01

    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

  18. Study of IgG subclass profiles of anti-HBs in populations with different HBV infection status.

    Science.gov (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

    2006-01-01

    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.

  19. Reverse photoacoustic standoff spectroscopy

    Science.gov (United States)

    Van Neste, Charles W [Kingston, TN; Senesac, Lawrence R [Knoxville, TN; Thundat, Thomas G [Knoxville, TN

    2011-04-12

    A system and method are disclosed for generating a reversed photoacoustic spectrum at a greater distance. A source may emit a beam to a target and a detector measures signals generated as a result of the beam being emitted on the target. By emitting a chopped/pulsed light beam to the target, it may be possible to determine the target's optical absorbance by monitoring the intensity of light collected at the detector at different wavelengths. As the wavelength of light is changed, the target may absorb or reject each optical frequency. Rejection may increase the intensity at the sensing element and absorption may decrease the intensity. Accordingly, an identifying spectrum of the target may be made with the intensity variation of the detector as a function of illuminating wavelength.

  20. Is Computation Reversible?

    CERN Document Server

    Parker, M C; Parker, Michael C.; Walker, Stuart D.

    2004-01-01

    Recent investigations into the physical nature of information and fundamental limits to information transmission have revealed questions such as the possibility of superluminal data transfer or not; and whether reversible computation (information processing) is feasible. In some respects these uncertainties stem from the determination of whether information is inherent in points of non-analyticity (discontinuities) or smoother functions. The close relationship between information and entropy is also well known, e.g. Brillouin's concept of negentropy (negative entropy) as a measure for information. Since the leading edge of a step-discontinuity propagates in any dispersive medium at the speed of light in vacuum as a precursor to the main body of the dispersed pulse, we propose in this paper to treat information as being intrinsic to points of non-analyticity (discontinuities). This allows us to construct a theory addressing these dilemmas in a fashion consistent with causality, and the fundamental laws of ther...

  1. Reverse Osmosis Optimization

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-08-01

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.

  2. Reverse Osmosis Optimization

    Energy Technology Data Exchange (ETDEWEB)

    McMordie Stoughton, Kate; Duan, Xiaoli; Wendel, Emily M.

    2013-08-26

    This technology evaluation was prepared by Pacific Northwest National Laboratory on behalf of the U.S. Department of Energy’s Federal Energy Management Program (FEMP). ¬The technology evaluation assesses techniques for optimizing reverse osmosis (RO) systems to increase RO system performance and water efficiency. This evaluation provides a general description of RO systems, the influence of RO systems on water use, and key areas where RO systems can be optimized to reduce water and energy consumption. The evaluation is intended to help facility managers at Federal sites understand the basic concepts of the RO process and system optimization options, enabling them to make informed decisions during the system design process for either new projects or recommissioning of existing equipment. This evaluation is focused on commercial-sized RO systems generally treating more than 80 gallons per hour.¬

  3. Multiple stimulus reversible hydrogels

    Science.gov (United States)

    Gutowska, Anna; Krzyminski, Karol J.

    2003-12-09

    A polymeric solution capable of gelling upon exposure to a critical minimum value of a plurality of environmental stimuli is disclosed. The polymeric solution may be an aqueous solution utilized in vivo and capable of having the gelation reversed if at least one of the stimuli fall below, or outside the range of, the critical minimum value. The aqueous polymeric solution can be used either in industrial or pharmaceutical environments. In the medical environment, the aqueous polymeric solution is provided with either a chemical or radioisotopic therapeutic agent for delivery to a specific body part. The primary advantage of the process is that exposure to one environmental stimuli alone will not cause gelation, thereby enabling the therapeutic agent to be conducted through the body for relatively long distances without gelation occurring.

  4. 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.

    Science.gov (United States)

    Suzuki, Lisandra Akemi; Rossi, Cláudio Lúcio

    2013-02-01

    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.

  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

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    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.

  6. A Reversible Processor Architecture and its Reversible Logic Design

    DEFF Research Database (Denmark)

    Thomsen, Michael Kirkedal; Axelsen, Holger Bock; Glück, Robert

    2012-01-01

    We describe the design of a purely reversible computing architecture, Bob, and its instruction set, BobISA. The special features of the design include a simple, yet expressive, locally-invertible instruction set, and fully reversible control logic and address calculation. We have designed...... an architecture with an ISA that is expressive enough to serve as the target for a compiler from a high-level structured reversible programming language. All-in-all, this paper demonstrates that the design of a complete reversible computing architecture is possible and can serve as the core of a programmable...

  7. Immunization with heat-inactivated Staphylococcus aureus induced an antibody response mediated by IgG1 and IgG2 in patients with recurrent tonsillitis.

    Science.gov (United States)

    Garcia-Romo, Gina Stella; Gonzalez-Ibarra, Misael; Donis-Hernandez, Felipe Raul; Zendejas-Buitron, Victor Manuel; Pedroza-Gonzalez, Alexander

    2015-04-01

    Currently Staphylococcus aureus is the predominant pathogen isolated from the respiratory tract of patients with recurrent tonsillitis. Because of an increase in multi-drug resistant strains of S. aureus, there is a pressing need for effective treatments and preventive approaches to reduce the risk of invasive and life-threatening infections. A preventive vaccine against S. aureus would have a tremendous clinical impact. However, multiple clinical trials have failed to identify an agent that can induce protective responses. Most trials have been based on subunit vaccines using one or a few purified antigens, which may not be enough to confer protection. Here, the impact of a whole-cell vaccine comprised of heat-inactivated S. aureus was investigated in patients with RT. The vaccine was well tolerated and had no significant local or systemic reactions. Immunization with heat-inactivated S. aureus elicited a significant antibody response characterized by production of IgG1 and IgG2 antibodies and, to a lesser extent, of IgA antibodies. Notably, this response was associated with an important decrease in the incidence of tonsillitis and bacterial colonization of the oropharyngeal mucosa. Our results show that whole-cell inactivated S. aureus is safe and capable of evoking specific antibody responses in patients with recurrent tonsillitis. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

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

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    Sadeq Eivazi

    2015-03-01

    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.

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

    Science.gov (United States)

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

    2015-09-01

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

  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: kimjhrad@amc.seoul.kr; Byun, Jae Ho; Kim, Hyoung Jung; Lee, Seung Soo; Kim, So Yeon; Lee, Moon-Gyu

    2014-07-15

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

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    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.

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

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    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.

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

    Science.gov (United States)

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

    2016-05-01

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

  14. Deficient IgA and IgG2 anti-pneumococcal antibody levels and response to vaccination in otitis prone children

    NARCIS (Netherlands)

    Dhooge, IJ; van Kempen, MJP; Sanders, LAM; Rijkers, GT

    2002-01-01

    Objective: To evaluate the isotype and IgG subclass distribution of anti-pneumococcal antibodies and response to polysaccharide vaccination in otitis prone children. Methods: IgG1, IgG2 and IgA antibodies to pneumococcal serotypes 3, 4, 6B, 9V, 14, 19F and 23F were determined in otitis prone

  15. IgG platelet antibodies in EDTA-dependent pseudothrombocytopenia bind to platelet membrane glycoprotein IIb.

    Science.gov (United States)

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

    1998-08-01

    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. Decreased HHV-6 IgG in Alzheimer’s Disease

    Science.gov (United States)

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

    2017-01-01

    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

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

    Directory of Open Access Journals (Sweden)

    Sumii,Hiroshi

    1989-06-01

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

  18. [Posterior reversible encephalopathy syndrome].

    Science.gov (United States)

    Petrović, Branko; Kostić, Vladimir; Sternić, Nadezda; Kolar, Jovo; Tasić, Nebojsa

    2003-01-01

    Reversible Posterior Leukoencephalopathy Syndrome was introduced into clinical practice in 1996 in order to describe unique syndrome, clinically expressed during hypertensive and uremic encephalopathy, eclampsia and during immunosuppressive therapy [1]. First clinical investigations showed that leucoencephalopathy is major characteristic of the syndrome, but further investigations showed no significant destruction in white cerebral tissue [2, 3, 4]. In majority of cases changes are localise in posterior irrigation area of the brain and in the most severe cases anterior region is also involved. Taking into consideration all above mentioned facts, the suggested term was Posterior Reversible Encephalopathy Syndrome (PRES) for the syndrome clinically expressed by neurological manifestations derived from cortical and subcortical changes localised in posterior regions of cerebral hemispheres, cerebral trunk and cerebellum [5]. Patient, aged 53 years, was re-hospitalized in Cardiovascular Institute "Dediwe" two months after successful aorto-coronary bypass performed in June 2001 due to the chest bone infection. During the treatment of the infection (according to the antibiogram) in September 2001, patient in evening hours developed headache and blurred vision. The recorded blood pressure was 210/120 mmHg so antihypertensive treatment was applied (Nifedipin and Furosemid). After this therapy there was no improvement and intensive headache with fatigue and loss of vision developed. Neurological examination revealed cortical blindness and left hemiparesis. Manitol (20%, 60 ccm every 3 hours) and i.v. Nytroglicerin (high blood pressure). Brain CT revealed oedema of parieto-occipital regions of both hemispheres, more emphasized on the right. (Figure 1a, b, c). There was no sign of focal ischemia even in deeper sections (Figure 1d, e, f). Following three days enormous high blood pressure values were registered. On the fourth day the significant clinical improvement occurred

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

    Directory of Open Access Journals (Sweden)

    Vikas Jain

    2016-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Le-Feng Chen

    2014-01-01

    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.

  1. Evaluation of an on-farm method to assess colostrum IgG content in sows.

    Science.gov (United States)

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

    2016-04-01

    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.

  2. Immunogenicity of Isogenic IgG in Aggregates and Immune Complexes

    Science.gov (United States)

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

    2017-01-01

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    Gengozian, N.; McLaughlin, C.L.

    1980-06-01

    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.

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

    Science.gov (United States)

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

    2014-01-23

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

  5. Toxocara Canis IgG Seropositivity in Patients with Chronic Urticaria

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    Mehmet Burak-Selek

    2015-10-01

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

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

    OpenAIRE

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

    2013-01-01

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

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

    OpenAIRE

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

    2014-01-01

    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 ...

  8. Comparison of chemiluminescent immunoassay and ELISA for measles IgG and IgM.

    Science.gov (United States)

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

    2015-08-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1981-01-01

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

  10. Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG.

    Science.gov (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

    2003-07-01

    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.

  11. ROLE OF LECTIN-SUBSTRANCE RECOGNITION IN IMMUNOREGULATORY INTERACTION BETWEEN INTERLEUKIN-2 IGG

    Directory of Open Access Journals (Sweden)

    S. M. Sobolev

    2010-01-01

    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

  12. 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.

  13. 49 CFR 230.89 - Reverse gear.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Reverse gear. 230.89 Section 230.89 Transportation... Reversing Gear § 230.89 Reverse gear. (a) General provisions. Reverse gear, reverse levers, and quadrants... quadrant. Proper counterbalance shall be provided for the valve gear. (b) Air-operated power reverse...

  14. Aspiration Level and the Reversal of the Preference Reversal Phenomenon.

    Science.gov (United States)

    1986-09-01

    American Economic Review , 69, 623- 638...Grether, D. M., & Plott, C. R. (1982). Economic theory of choice and the preference reversal phenomenon: Reply. The American Economic Review , 72, 575. Har...34 - . • . ...... ., .. . -. -.,- ... , .. ... - ., . . . . .. . ... . . . . . . . *~~~7 T, W.. 1 d~ I t Y ~ VVW ~ Page 26 1 loomes, G., & Sugden, R. (1983). A rationale for preference reversal. The American Economic Review ,

  15. Positive IgG Western Blot for Borrelia burgdorferi in Colombia

    Directory of Open Access Journals (Sweden)

    Palacios Ricardo

    1999-01-01

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

  16. IgG glycan hydrolysis by EndoS inhibits experimental autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Benkhoucha Mahdia

    2012-09-01

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

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

    Science.gov (United States)

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

    2015-11-16

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

  18. Atractylodis macrocephalae Koidz. polysaccharides enhance both serum IgG response and gut mucosal immunity.

    Science.gov (United States)

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

    2013-01-02

    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.

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

    Science.gov (United States)

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

    2012-08-01

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

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

    Science.gov (United States)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

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

    LENUS (Irish Health Repository)

    Coss, K P

    2012-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Latha G

    2005-01-01

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

  4. Design of Reversible Sequential Circuit Using Reversible Logic Synthesis

    Directory of Open Access Journals (Sweden)

    Md. Belayet Ali

    2011-12-01

    Full Text Available Reversible logic is one of the most vital issue at present time and it has different areas for its application,those are low power CMOS, quantum computing, nanotechnology, cryptography, optical computing, DNA computing, digital signal processing (DSP, quantum dot cellular auto meta, communication, computer graphics. It is not possible to realize quantum computing without implementation of reversible logic. The main purposes of designing reversible logic are to decrease quantum cost, depth of the circuits and the number of garbage outputs. In this paper, we have proposed a new reversible gate. And we have designed RS flip flop and D flip flop by using our proposed gate and Peres gate. The proposed designs are better than the existing proposed ones in terms of number of reversible gates and garbage outputs. So, this realization is more efficient and less costly than other realizations.

  5. Design of Reversible Sequential Circuit Using Reversible Logic Synthesis

    Directory of Open Access Journals (Sweden)

    Md. Mosharof Hossin

    2012-01-01

    Full Text Available Reversible logic is one of the most vital issue at present time and it has different areas for its application, those are low power CMOS, quantum computing, nanotechnology, cryptography, optical computing, DNA computing, digital signal processing (DSP, quantum dot cellular automata, communication, computer graphics. It is not possible to realize quantum computing without implementation of reversible logic. The main purposes of designing reversible logic are to decrease quantum cost, depth of the circuits and the number of garbage outputs. In this paper, we have proposed a new reversible gate. And we have designedRS flip flop and D flip flop by using our proposed gate and Peres gate. The proposed designs are better than the existing proposed ones in terms of number of reversible gates and garbage outputs. So, this realization is more efficient and less costly than other realizations.

  6. Time Reversal Violation

    Energy Technology Data Exchange (ETDEWEB)

    Quinn, H; /SLAC

    2009-01-27

    This talk briefly reviews three types of time-asymmetry in physics, which I classify as universal, macroscopic and microscopic. Most of the talk is focused on the latter, namely the violation of T-reversal invariance in particle physics theories. In sum tests of microscopic T-invariance, or observations of its violation, are limited by the fact that, while we can measure many processes, only in very few cases can we construct a matched pair of process and inverse process and observe it with sufficient sensitivity to make a test. In both the cases discussed here we can achieve an observable T violation making use of flavor tagging, and in the second case also using the quantum properties of an antisymmetric coherent state of two B mesons to construct a CP-tag. Both these tagging properties depend only on very general properties of the flavor and/or CP quantum numbers and so provide model independent tests for T-invariance violations. The microscopic laws of physics are very close to T-symmetric. There are small effects that give CP- and T-violating processes in three-generation-probing weak decays. Where a T-violating observable can be constructed we see the relationships between T-violation and CP-violation expected in a CPT conserving theory. These microscopic effects are unrelated to the 'arrow of time' that is defined by increasing entropy, or in the time direction defined by the expansion of our Universe.

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

    Science.gov (United States)

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

    1995-01-01

    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.

  8. Molecular characterization of human IgG monoclonal antibodies specific for the major birch pollen allergen Bet v 1. Anti-allergen IgG can enhance the anaphylactic reaction.

    Science.gov (United States)

    Denépoux, S; Eibensteiner, P B; Steinberger, P; Vrtala, S; Visco, V; Weyer, A; Kraft, D; Banchereau, J; Valenta, R; Lebecque, S

    2000-01-07

    We report the molecular characterization of five human monoclonal antibodies, BAB1-5 (BAB1: IgG(1); BAB4: IgG(2); BAB2, 3, 5: IgG(4)), with specificity for the major birch pollen allergen, Bet v 1. BAB1-5 were obtained after immunotherapy and contained a high degree of somatic mutations indicative of an antigen-driven affinity maturation process. While BAB1 inhibited the binding of patients IgE to Bet v 1, BAB2 increased IgE recognition of Bet v 1, and, even as Escherichia coli-expressed Fab, augmented Bet v 1-induced immediate type skin reactions. The demonstration that IgG antibodies can enhance allergen-induced allergic reactions is likely to explain the unpredictability of specific immunotherapy.

  9. Enzymatic reactions in reversed micelles

    NARCIS (Netherlands)

    Hilhorst, M.H.

    1984-01-01

    It has been recognised that enzymes in reversed micelles have potential for application in chemical synthesis. Before these expectations will be realised many problems must be overcome. This thesis deals with some of them.In Chapter 1 the present knowledge about reversed micelles and micellar enzymo

  10. Enzyme recovery using reversed micelles.

    NARCIS (Netherlands)

    Dekker, M.

    1990-01-01

    The objective of this study was to develop a liquid-liquid extraction process for the recovery of extracellular enzymes. The potentials of reaching this goal by using reversed micelles in an organic solvent have been investigated.Reversed micelles are aggregates of surfactant molecules containing an

  11. Low positive predictive value of anti-Brugia malayi IgG and IgG4 serology for the diagnosis of Wuchereria bancrofti.

    Science.gov (United States)

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

    1994-01-01

    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.

  12. Glycoprofiling effects of media additives on IgG produced by CHO cells in fed-batch bioreactors

    DEFF Research Database (Denmark)

    Kildegaard, Helene Faustrup; Fan, Yuzhou; Wagtberg Sen, Jette

    2016-01-01

    . In this study, the effect on IgG N-glycosylation from feeding CHO cells with eight glycosylation precursors during cultivation was investigated. The study was conducted in fed-batch mode in bioreactors with biological replicates to obtain highly controlled and comparable conditions. We assessed charge......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...

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

    Science.gov (United States)

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

    2014-02-01

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

  14. Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations

    National Research Council Canada - National Science Library

    Chavez, Brittany K; Agarabi, Cyrus D; Read, Erik K; Boyne II, Michael T; Khan, Mansoor A; Brorson, Kurt A

    2016-01-01

    .... Using a model murine IgG3 produced in a bioreactor system, multiple formulation compositions were systematically explored in a DoE design to optimize the stability of a challenging antibody formulation worst case...

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

    Directory of Open Access Journals (Sweden)

    Tsukuru Minamiki

    2014-09-01

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

  16. What do reversible programs compute?

    DEFF Research Database (Denmark)

    Axelsen, Holger Bock; Glück, Robert

    2011-01-01

    Reversible computing is the study of computation models that exhibit both forward and backward determinism. Understanding the fundamental properties of such models is not only relevant for reversible programming, but has also been found important in other fields, e.g., bidirectional model...... transformation, program transformations such as inversion, and general static prediction of program properties. Historically, work on reversible computing has focussed on reversible simulations of irreversible computations. Here, we take the viewpoint that the property of reversibility itself should...... are not strictly classically universal, but that they support another notion of universality; we call this RTM-universality. Thus, even though the RTMs are sub-universal in the classical sense, they are powerful enough as to include a self-interpreter. Lifting this to other computation models, we propose r...

  17. Optimization of reversible sequential circuits

    CERN Document Server

    Sayem, Abu Sadat Md

    2010-01-01

    In recent years reversible logic has been considered as an important issue for designing low power digital circuits. It has voluminous applications in the present rising nanotechnology such as DNA computing, Quantum Computing, low power VLSI and quantum dot automata. In this paper we have proposed optimized design of reversible sequential circuits in terms of number of gates, delay and hardware complexity. We have designed the latches with a new reversible gate and reduced the required number of gates, garbage outputs, and delay and hardware complexity. As the number of gates and garbage outputs increase the complexity of reversible circuits, this design will significantly enhance the performance. We have proposed reversible D-latch and JK latch which are better than the existing designs available in literature.

  18. Circulating human IgG reactive to apoptotic cells are masked by plasma proteins%血浆蛋白可屏蔽人类循环中IgG抗体对凋亡细胞的反应活性

    Institute of Scientific and Technical Information of China (English)

    荣春书; 连鑫; 王伟刚; 郑宗宇; 高宝山

    2016-01-01

    Objective To confirm the influence of plasma proteins on the reactivity of circulating IgG to apoptotic cells and to develop an optimal methodology for studying these antibodies.Methods IgG reactivity to apoptotic cells was assessed before and after purification.The following sources of IgG were used:(1)Plasma specimens from 10 kid-ney transplant recipients with AMR;(2)purified IgG from the same 10 AMR patients;(3)supernatant from IgG-pro-ducing immortalized B cell clones;(4)purified IgG from the same B cell clone supernatants.Results Results Plasma IgG reactivity to apoptotic cells was dramatically increased following purification.We observed that reactivity to apop-totic cells could only be detected after purification for some monoclonal IgG produced by B cell clones.Fetal calf serum (FCS)partially reversed the apoptotic-binding potential of purified IgG.Conclusion The reactivity of circulating IgG to apoptotic cells is modified in the presence of plasma proteins.These antibodies must first be purified to remove plasma proteins in order to accurately assess their reactivity.%目的:明确血浆蛋白影响循环中 IgG抗体对凋亡细胞的反应性,并探索检测此类抗体活性的最佳条件。方法分别检测纯化前及纯化后的 IgG抗体对凋亡细胞的反应性。检测所用样本来源于:(1)10例发生移植肾抗体介导排异反应(AMR)患者的血浆样本;(2)从以上10例患者血浆中纯化的IgG抗体;(3)分泌IgG抗体的永生化B淋巴细胞克隆培养上清液;(4)从同一永生化B淋巴细胞克隆培养上清液中纯化的 IgG抗体。结果当 IgG从血浆中纯化出来时,其对凋亡细胞的反应性显著增强。对于某些单克隆 B细胞分泌的 IgG抗体,只有将此抗体从细胞培养上清液中纯化,才能检测到其对凋亡细胞的反应性。而胎牛血清(FCS)可部分阻滞纯化 IgG抗体对凋亡细胞的反应性。结论当血

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

    Directory of Open Access Journals (Sweden)

    Karasuyama Hajime

    2011-04-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  1. Reversed polarity patches at the CMB and geomagnetic field reversal

    Institute of Scientific and Technical Information of China (English)

    XU; Wenyao(徐文耀); WEI; Zigang(魏自刚)

    2002-01-01

    The International Geomagnetic Reference Field models (IGRF) for 1900-2000 are used to calculate the geomagnetic field distribution in the Earth' interior from the ground surface to the core-mantle boundary (CMB) under the assumption of insulated mantle. Four reversed polarity patches, as one of the most important features of the CMB field, are revealed. Two patches with +Z polarity (downward) at the southern African and the southern American regions stand out against the background of -Z polarity (upward) in the southern hemisphere, and two patches of -Z polarity at the North Polar and the northern Pacific regions stand out against the +Z background in the northern hemisphere. During the 1900-2000 period the southern African (SAF) patch has quickly drifted westward at a speed of 0.2-0.3°/a; meanwhile its area has expanded 5 times, and the magnetic flux crossing the area has intensified 30 times. On the other hand, other three patches show little if any change during this 100-year period. Extending upward, each of the reversed polarity patches at the CMB forms a chimney-shaped "reversed polarity column" in the mantle with the bottom at the CMB. The height of the SAF column has grown rapidly from 200km in 1900 to 900km in 2000. If the column grows steadily at the same rate in the future, its top will reach to the ground surface in 600-700 years. And then a reversed polarity patch will be observed at the Earth's surface, which will be an indicator of the beginning of a magnetic field reversal. On the basis of this study, one can describe the process of a geomagnetic polarity reversal, the polarity reversal may be observed firstly in one or several local regions; then the areas of these regions expand, and at the same time, other new reversed polarity regions may appear. Thus several poles may exist during a polarity reversal.

  2. O blood group as a risk factor for Helicobacter pylori IgG seropositivity among pregnant Sudanese women

    Directory of Open Access Journals (Sweden)

    Gasim I. Gasim

    2017-06-01

    Full Text Available The objective was to investigate the prevalence and the association between blood groups and Helicobacter pylori IgG seropositivity among pregnant Sudanese women. A cross-sectional survey was carried- out at Saad Abul Ela Maternity Hospital, Khartoum, Sudan during the period of July 2014 through December 2015. Questionnaires covering socio-demographic and obstetrics information were administered. Specific H. pylori IgG antibody was analysed using ELISA. One hundred eighty six pregnant women were enrolled. The mean (SD of the age, parity was 28.3 (2.6 years and 2.6 (3.5, respectively. Of the 186 women, 42 (22.6%, 24 (12.9%, 11(5.9% and 109 (58.6% had blood group A, B, AB and O, respectively. H. pylori IgG seropositivity rate was 132/186 (71.0%. There was no significant difference in age and parity between women with H. pylori IgG seropositive and seronegative. Compared with the women with H. pylori IgG seronegative, significantly higher numbers of women with H. pylori IgG seropositive had O blood group, [84/132(63.6 versus 25/54(46.3, P<0.001]. In binary logistic regression, women with O blood group (OR= 2.084, 95% CI=1.060 -4.097, P=0.033 were at a higher H. pylori IgG seropositivity. The current study showed that women with blood group O were at higher risk for H. pylori IgG seropositivity.

  3. Computational design of a specific heavy chain/κ light chain interface for expressing fully IgG bispecific antibodies.

    Science.gov (United States)

    Froning, K J; Leaver-Fay, A; Wu, X; Phan, S; Gao, L; Huang, F; Pustilnik, A; Bacica, M; Houlihan, K; Chai, Q; Fitchett, J R; Hendle, J; Kuhlman, B; Demarest, S J

    2017-07-20

    The use of bispecific antibodies (BsAbs) to treat human diseases is on the rise. Increasingly complex and powerful therapeutic mechanisms made possible by BsAbs are spurring innovation of novel BsAb formats and methods for their production. The long-lived in vivo pharmacokinetics, optimal biophysical properties and potential effector functions of natural IgG monoclonal (and monospecific) antibodies has resulted in a push to generate fully IgG BsAb formats with the same quaternary structure as monoclonal IgGs. The production of fully IgG BsAbs is challenging because of the highly heterogeneous pairing of heavy chains (HCs) and light chains (LCs) when produced in mammalian cells with two IgG HCs and two LCs. A solution to the HC heterodimerization aspect of IgG BsAb production was first discovered two decades ago; however, addressing the LC mispairing issue has remained intractable until recently. Here, we use computational and rational engineering to develop novel designs to the HC/LC pairing issue, and particularly for κ LCs. Crystal structures of these designs highlight the interactions that provide HC/LC specificity. We produce and characterize multiple fully IgG BsAbs using these novel designs. We demonstrate the importance of specificity engineering in both the variable and constant domains to achieve robust HC/LC specificity within all the BsAbs. These solutions facilitate the production of fully IgG BsAbs for clinical use. © 2017 The Protein Society.

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

    OpenAIRE

    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

    2015-01-01

    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...

  5. 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.

  6. Detection of impaired IgG antibody formation facilitates the decision on early immunoglobulin replacement in hypogammaglobulinemic patients

    Directory of Open Access Journals (Sweden)

    Hermann Maximilian Wolf

    2015-02-01

    Full Text Available Hypogammaglobulinemia (serum IgG lower than 2SD below the age-matched mean and clinical symptoms such as increased susceptibility to infection, autoimmune manifestations, granulomatous disease, unexplained polyclonal lymphoproliferation are considered to be diagnostic hallmarks in patients with common variable immunodeficiency (CVID, the most frequent clinically severe primary immunodeficiency syndrome. In the present study we investigated patients with hypogammaglobulinemia and no clinical or immunological signs of defective cell-mediated immunity and differentiated two groups on the basis of their IgG antibody formation capacity against a variety of different antigens (bacterial toxins, polysaccharide antigens, viral antigens. Patients with hypogammaglobulinemia and intact antibody production (HIAP displayed no or only mild susceptibility to infections, while CVID patients showed marked susceptibility to bacterial infections that normalized following initiation of IVIG or SCIG replacement therapy. There was a substantial overlap in IgG serum levels between the asymptomatic HIAP group and the CVID patients examined before immunoglobulin treatment. HIAP patients showed normal levels of switched B memory cells (CD19+CD27+IgD-, while both decreased and normal levels of switched B memory cells could be found in CVID patients. IgG antibody response to a primary antigen, tick borne encephalitis virus (TBEV, was defective in CVID patients, thus confirming their substantial defect in IgG antibody production. Defective IgG antibody production against multiple antigens could also be demonstrated in an adult patient with recurrent infections but normal IgG levels. To facilitate early treatment before recurrent infections may lead to organ damage the antibody formation capacity should be examined in hypogammaglobulinemic patients and the decision to treat should be based on the finding of impaired IgG antibody production.

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

    Directory of Open Access Journals (Sweden)

    Novilia Sjafri Bachtiar

    2011-03-01

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

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

    Science.gov (United States)

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

    2016-08-03

    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.

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

    Science.gov (United States)

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

    2016-01-01

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

  10. Local synthesis of IgG antibodies to HIV within the female and male genital tracts during asymptomatic and pre-AIDS stages of HIV infection.

    Science.gov (United States)

    Bélec, L; Tévi-Bénissan, C; Lu, X S; Prazuck, T; Pillot, J

    1995-06-01

    Paired sera and cervicovaginal secretions or seminal fluids, obtained from HIV-1-infected, clinically asymptomatic women (n = 41) and men (n = 12), were investigated in order to test the hypothesis of a local synthesis of IgG to HIV in the female and male reproductive tracts. Anti-gp41 + p24 IgG was evaluated by an IgG immunocapture assay, and anti-gp160 IgG by an indirect ELISA. Estimation of anti-HIV IgG-specific activities was carried out after ponderal determination of total IgG and evaluation of anti-HIV IgG activity. IgG to gp41 + p24, as well as IgG to gp160, were specifically detected in all sera, cervicovaginal secretions, and seminal fluid samples from all tested HIV-1-infected subjects. The mean specific activities of IgG to gp41 + p24 in cervicovaginal secretions and in seminal fluids were about 33-fold (in women) and 16-fold (in men) that of the corresponding sera; similarly, the mean specific activities of IgG to gp160 in genital secretions were about 17-fold (in women) and 10-fold (in men) that of the corresponding sera. IgGs to HIV are constantly detected in genital secretions from HIV-1-infected subjects, and appear to be largely synthesized in situ within the genital tract of both genders.

  11. Optimized reversible BCD adder using new reversible logic gates

    CERN Document Server

    Bhagyalakshmi, H R

    2010-01-01

    Reversible logic has received great attention in the recent years due to their ability to reduce the power dissipation which is the main requirement in low power digital design. It has wide applications advanced computing, low power CMOS design, Optical information processing, DNA computing, bio information, quantum computation and nanotechnology. This paper presents an optimized reversible BCD adder using a new reversible gate. A comparative result is presented which shows that the proposed design is more optimized in terms of number of gates, number of garbage outputs and quantum cost than the existing designs.

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

    Science.gov (United States)

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

    2012-12-01

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

  13. Serum or breast milk immunoglobulins mask the self-reactivity of human natural IgG antibodies.

    Science.gov (United States)

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

    2014-04-01

    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.

  14. Nano-visualization of oriented-immobilized IgGs on immunosensors by high-speed atomic force microscopy

    Science.gov (United States)

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

    2012-11-01

    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.

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

    Science.gov (United States)

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

    2016-01-01

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

  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

    2012-01-01

    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.

    Science.gov (United States)

    Gerhardt, N I; Dungan, S R

    2002-04-05

    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. NOVEL REVERSIBLE VARIABLE PRECISION MULTIPLIER USING REVERSIBLE LOGIC GATES

    National Research Council Canada - National Science Library

    M. Saravanan; K. Suresh Manic

    2014-01-01

    .... In this study a reversible logic gate based design of variable precision multiplier is proposed which have the greater efficiency in power consumption and speed since the partial products received...

  19. Supercritical fluid reverse micelle separation

    Science.gov (United States)

    Fulton, John L.; Smith, Richard D.

    1993-01-01

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W.sub.o that determines the maximum size of the reverse micelles. The maximum ratio W.sub.o of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions.

  20. Supercritical fluid reverse micelle separation

    Science.gov (United States)

    Fulton, J.L.; Smith, R.D.

    1993-11-30

    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W[sub o] that determines the maximum size of the reverse micelles. The maximum ratio W[sub o] of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions. 27 figures.

  1. NOVEL REVERSIBLE VARIABLE PRECISION MULTIPLIER USING REVERSIBLE LOGIC GATES

    OpenAIRE

    M. Saravanan; K. Suresh Manic

    2014-01-01

    Multipliers play a vital role in digital systems especially in digital processors. There are many algorithms and designs were proposed in the earlier works, but still there is a need and a greater interest in designing a less complex, low power consuming, fastest multipliers. Reversible logic design became the promising technologies gaining greater interest due to less dissipation of heat and low power consumption. In this study a reversible logic gate based design of variable precision multi...

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

    Science.gov (United States)

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

    2014-12-01

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

  3. Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus.

    Science.gov (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

    2015-05-01

    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

  4. Galactosylation of IgG1 modulates FcγRIIB-mediated inhibition of murine autoimmune hemolytic anemia.

    Science.gov (United States)

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

    2013-12-01

    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.

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

    2015-08-07

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

  6. 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.

  7. Monoclonal IgG1κ anti-glomerular basement membrane disease: a case report.

    Science.gov (United States)

    Coley, Shana M; Shirazian, Shayan; Radhakrishnan, Jai; D'Agati, Vivette D

    2015-02-01

    We report a case of anti-glomerular basement membrane (anti-GBM) nephritis with indolent course, monoclonal IgG1κ (immunoglobulin G, subclass 1, κ light chain) linear staining of the GBM, and multifocal GBM breaks but without crescents or detectable serum anti-GBM antibody in a patient followed over 9 years. Atypically, anti-GBM nephritis follows an indolent course. A very small fraction of patients with anti-GBM nephritis lack detectable circulating anti-GBM antibodies, and rare reports of monoclonal anti-GBM nephritis exist. We report what is to our knowledge the first case manifesting all 3 of these rare variations. Our patient initially presented with asymptomatic decreased kidney function following an upper respiratory tract infection. He was found to have microhematuria and subnephrotic proteinuria with mild diffuse endocapillary proliferative and exudative glomerulonephritis with linear IgG1κ staining of the GBM. He was treated with an induction regimen of intravenous cyclophosphamide and corticosteroids followed by maintenance monotherapy with mycophenolic acid. Nine years later, repeat kidney biopsy for worsening kidney function after an upper respiratory tract infection showed persistent monoclonal staining of the GBM and acute glomerulonephritis with increased chronicity, including a single fibrocellular crescent. Despite extensive clinical investigations spanning nearly a decade, no circulating anti-GBM antibody or monoclonal protein has been detected. In this case report, we explore the unique features of this monoclonal IgG1κ-associated anti-GBM nephritis. Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  8. The changing faces of IgG4-related disease: Clinical manifestations and pathogenesis.

    Science.gov (United States)

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

    2015-10-01

    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.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    M.E. Camargo

    1989-08-01

    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.

  11. CD163 and IgG codefend against cytotoxic hemoglobin via autocrine and paracrine mechanisms.

    Science.gov (United States)

    Subramanian, Karthik; Du, Ruijuan; Tan, Nguan Soon; Ho, Bow; Ding, Jeak Ling

    2013-05-15

    Lysis of RBCs during numerous clinical settings such as severe hemolytic anemia, infection, tissue injury, or blood transfusion releases the endogenous damage-associated molecular pattern, hemoglobin (Hb), into the plasma. The redox-reactive Hb generates cytotoxic reactive oxygen species, disrupting the redox balance and impairing the immune-responsive blood cells. Therefore, it is crucial to understand how the immune system defends against the cytotoxic Hb. We identified a shortcut "capture and quench" mechanism of detoxification of Hb by the monocyte scavenger receptor CD163, independent of the well-known dominant antioxidant, haptoglobin. Our findings support a highly efficient two-pass mechanism of detoxification and clearance of Hb: 1) a direct suppression of Hb-pseudoperoxidase activity by CD163, involving an autocrine loop of CD163 shedding, sequestration of Hb, recycling, and homeostasis of CD163 in human monocytes and 2) paracrine transactivation of endothelial cells by the shedded soluble CD163 (sCD163), which further detoxifies and clears residual Hb. We showed that sCD163 and IgG interact with free Hb in the plasma and subsequently the sCD163-Hb-IgG complex is endocytosed into monocytes via FcγR. The endocytosed sCD163 is recycled to restore the homeostasis of CD163 on the monocyte membrane in an autocrine cycle, whereas the internalized Hb is catabolized. Using ex vivo coculture experiments, we demonstrated that the monocyte-derived sCD163 and IgG shuttle residual plasma Hb into the proximal endothelial cells. These findings suggest that CD163 and IgG collaborate to engage monocytes and endothelial cells in a two-pass detoxification mechanism to mount a systemic defense against Hb-induced oxidative stress.

  12. A Typology of Reverse Innovation

    DEFF Research Database (Denmark)

    von Zedtwitz, Max; Corsi, Simone; Søberg, Peder Veng

    2015-01-01

    taking place in an emerging country. This analytical framework allows recasting of current research at the intersection between innovation and international business. Of the 10 reverse innovation flows, six are new and have not been covered in the literature to date. The study addresses questions......Reverse innovation commonly refers to an innovation initially launched in a developing country and later introduced to an advanced country. Adopting a linear innovation model with the four sequential phases of concept ideation, product development, primary target market introduction, and subsequent......, the paper then introduces a typology of global innovation with 16 different types of innovation flows between advanced and emerging countries, 10 of which are reverse innovation flows. The latter are further differentiated into weak and strong reverse innovation, depending on the number of innovation phases...

  13. Designing the Reverse Supply Chain

    DEFF Research Database (Denmark)

    Gobbi, Chiara

    2011-01-01

    for the reverse supply chain. Design/methodology/approach – In order to identify the relevance of the Fisher model, the model needs to be recast in terms of PRV, which, in this context, is considered the independent variable in the reverse logistics arena. Products defined as innovative in Fisher's taxonomy...... is associated with first-class recovery options (reconditioning and remarketing). When the recovery option is recycling, time is not relevant, the primary objective is cost reduction (efficiency), the chain is centralized, and actors and phases of the reverse chain are determined by the specificity...... of the recycling process. When the recovery option is reconditioning, time is primarily relevant, tradeoffs between costs and time efficiency are necessary, the chain presents a centralized structure, and the presence of other types of actors and phases influences the structure of the reverse supply chain...

  14. Towards a reversible functional language

    DEFF Research Database (Denmark)

    Yokoyama, Tetsuo; Axelsen, Holger Bock; Glück, Robert

    2012-01-01

    first-match policy for case expressions, we can write overlapping patterns in case branches, as is customary in ordinary functional languages, and also in leaf expressions, unlike existing inverse interpreter methods, which enables concise programs. In patterns, the use of a duplication......We identify concepts of reversibility for a functional language by means of a set of semantic rules with specific properties. These properties include injectivity along with local backward determinism, an important operational property for an efficient reversible language. We define a concise...... reversible first-order functional language in which access to the backward semantics is provided to the programmer by inverse function calls. Reversibility guarantees that in this language a backward run (inverse interpretation) is as fast as the corresponding forward run itself. By adopting a symmetric...

  15. An Overview of Reverse Logistics

    Institute of Scientific and Technical Information of China (English)

    WANG Jia-xiang; HE Xin

    2005-01-01

    Until recently, investment in logistics has focused mainly on the flows from companies to markets. Growing concerns for the environment and conserving resources have created new logistical approaches to more effectively manage the distribution function, and make better use of the resources available to an organization. One such approach is reverse logistics, which uses various methods to give scope for a back-load of finished products, components, waste, reusable packing, etc. from consumer to manufacturer. Back-loads allow manufacturers to reduce costs by using the distribution vehicle's return journey to create income or added value. This basic concept is now being developed to create novel solutions to the problems of reducing pollution, costs and vehicle movements, whilst maintaining high customer service levels. In this paper, the idea of reverse logistics is presented; motivations for it are analyzed, several successful practices are demonstrated and some important truths regarding successful reverse logistics are identified, trend of reverse logistics is provided.

  16. CONCEPTUAL ISSUES REGARDING REVERSE LOGISTICS

    National Research Council Canada - National Science Library

    Ioana Olariu

    2014-01-01

    ... of reverse logistics in companies. Many firms attracted by the value available in the flow, have proactively participated in handling returned products at the end of their usefulness or from other parts of the product life cycle...

  17. IgG4-Related Tubulointerstitial Nephritis Pattern in 18F-FDG PET/CT.

    Science.gov (United States)

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

    2015-10-01

    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.

  18. Antigen recognition by IgG4 antibodies in human trichinellosis

    Directory of Open Access Journals (Sweden)

    Pinelli E.

    2001-06-01

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

  19. 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

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

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    Sriandayani

    2014-09-01

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

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

    Science.gov (United States)

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

    2006-01-01

    Multiple myeloma is a neoplasm of mature and immature plasma cells. A 50-year-old woman with lumbago, dysphagia, and left arm pain was presented. Upper endoscopical examination was performed. There was an exudate-covered ulcer in the distal esophagus, located at 30-32 cm from the incisors, covering the whole mucosa. Histopathological examination of the specimens obtained from the lesion showed the involvement of plasma cells consistent with multiple myeloma of IgG kappa subtype. Esophageal involvement of multiple myeloma should be kept in mind in patients presenting with dysphagia. PMID:16610044

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

  3. 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: asilva@usp.br

    2009-07-01

    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)

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

    Directory of Open Access Journals (Sweden)

    Sriandayani Sriandayani

    2014-10-01

    Full Text Available Background Typhoid fever is endemic to Indonesia, with an annual incidence of 13/10,000 people. Vaccination has been shown to be an effective method to prevent typhoid fever. Of several vaccine types, the polysaccharide Vi vaccine is the most commonly used typhoid vaccine in developing countries. Results of previous studies remain inconclusive on the necessity of revaccination every 3 years. Objective To compare the mean serum anrioody 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-secrional study at Tuminring District, 11anado 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 0.12; 950/£1 0.17 to 0.44; P0.0381. The proportion of children with protective antiNi antioody level was higher in the vaccinated group (23.7% than in the control group  (10.5%, howevet; 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 ooth groups. Also, the proportion of children with protective antibody levels is not significantly

  5. Laparoscopic reversal of Hartmann's procedure

    DEFF Research Database (Denmark)

    Svenningsen, Peter Olsen; Bulut, Orhan; Jess, Per

    2010-01-01

    A change in procedure from open to laparoscopic reversal of Hartmann's colostomy was implemented at our department between May 2005 and December 2008. The aim of the study was to investigate if this change was beneficial for the patients.......A change in procedure from open to laparoscopic reversal of Hartmann's colostomy was implemented at our department between May 2005 and December 2008. The aim of the study was to investigate if this change was beneficial for the patients....

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2007-10-01

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

  8. High Maternal HIV-1 Viral Load During Pregnancy Is Associated With Reduced Placental Transfer of Measles IgG Antibody

    Science.gov (United States)

    Farquhar, Carey; Nduati, Ruth; Haigwood, Nancy; Sutton, William; Mbori-Ngacha, Dorothy; Richardson, Barbra; John-Stewart, Grace

    2012-01-01

    Background Studies among HIV-1–infected women have demonstrated reduced placental transfer of IgG antibodies against measles and other pathogens. As a result, infants born to women with HIV-1 infection may not acquire adequate passive immunity in utero and this could contribute to high infant morbidity and mortality in this vulnerable population. Methods To determine factors associated with decreased placental transfer of measles IgG, 55 HIV-1–infected pregnant women who were enrolled in a Nairobi perinatal HIV-1 transmission study were followed. Maternal CD4 count, HIV-1 viral load, and HIV-1–specific gp41 antibody concentrations were measured antenatally and at delivery. Measles IgG concentrations were assayed in maternal blood and infant cord blood obtained during delivery to calculate placental antibody transfer. Results Among 40 women (73%) with positive measles titers, 30 (75%) were found to have abnormally low levels of maternofetal IgG transfer (<95%). High maternal HIV-1 viral load at 32 weeks’ gestation and at delivery was associated with reductions in placental transfer (P < 0.0001 and P = 0.0056, respectively) and infant measles IgG concentrations in cord blood (P < 0.0001 and P = 0.0073, respectively). High maternal HIV-1–specific gp41 antibody titer was also highly correlated with both decreased placental transfer (P = 0.0080) and decreased infant IgG (P < 0.0001). Conclusions This is the first study to evaluate the relationship between maternal HIV-1 viremia, maternal HIV-1 antibody concentrations, and passive immunity among HIV-1–exposed infants. These data support the hypothesis that high HIV-1 viral load during the last trimester may impair maternofetal transfer of IgG and increases risk of measles and other serious infections among HIV-1–exposed infants. PMID:16280707

  9. Aktivitas IgY dan IgG Antitetanus setelah Perlakuan pada Berbagai pH, Suhu dan Enzim Proteolitik

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    I Gusti Ayu Agung Suartini

    2007-12-01

    Full Text Available A study was carried out to find out an alternative method of producing antitetanus antibody (IgY in chicken and to evaluate its activity at different levels of pH, temperatures and proteolytic enzymes. Antitetanus IgY was produced by immunization of chickens with tetanus toxoid, three times weekly at gradual doses of 100, 200, and 300 Lf, respectively. Serum samples were collected 4 weeks following the last immunization. IgY was purified by ammonium sulfat precipitation and gel filtration chromatography (Sephadex G. 120.The purified IgY was then treated at different levels of temperatures and pH as well as proteolytic enzymes. Commercial antitetanus IgG was used as control. The activities of treated IgY and IgG were tested by enzyme linked immunosorbent assay (ELISA. IgY and IgG activities were significantly reduced at 80ºC and completely destroyed at 90ºC. Treatment with pepsin significantly reduced IgY and IgG whereas trypsin slightly reduced IgY activities and has no effect on IgG activities. IgY and IgG activities were reduced significantly at pH < 3 and and only sightly reduced at pH>10. It is evident that heating at >90oC, pH at <3 and treatment with pepsin significantly reduced IgY activities and it appears that IgG was more resistent to the efect of temperatures, pH and proteolytic enzymes

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

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    Christoph Fickentscher

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

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    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.

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

    Science.gov (United States)

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

    2013-09-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-09-15

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

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

    Science.gov (United States)

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

    2015-11-01

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

  16. Glycation of polyclonal IgGs: Effect of sugar excipients during stability studies.

    Science.gov (United States)

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

    2016-05-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Chun-Xia Yi

    2012-09-01

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

  18. Direct electrical control of IgG conformation and functional activity at surfaces

    Science.gov (United States)

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

    2016-11-01

    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.

  19. [Hashimoto's thyroiditis(chronic thyroiditis), IgG4-related thyroiditis].

    Science.gov (United States)

    Itoh, Mitsuyasu

    2012-11-01

    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.

  20. Detection of IgG against Toxocara in Sera of Employees of Meat Industry

    Science.gov (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

    2015-01-01

    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

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

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    V. G. Levchenko

    2010-01-01

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

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

    Science.gov (United States)

    Yan, Boxu; Boyd, Daniel; Kaschak, Timothy; Tsukuda, Joni; Shen, Amy; Lin, Yuwen; Chung, Shan; Gupta, Priyanka; Kamath, Amrita; Wong, Anne; Vernes, Jean-Michel; Meng, Gloria Y; Totpal, Klara; Schaefer, Gabriele; Jiang, Guoying; Nogal, Bartek; Emery, Craig; Vanderlaan, Martin; Carter, Paul; Harris, Reed; Amanullah, Ashraf

    2012-02-17

    Upper hinge is vulnerable to radical attacks that result in breakage of the heavy-light chain linkage and cleavage of the hinge of an IgG1. To further explore mechanisms responsible for the radical induced hinge degradation, nine mutants were designed to determine the roles that the upper hinge Asp and His play in the radical reactions. The observation that none of these substitutions could inhibit the breakage of the heavy-light chain linkage suggests that the breakage may result from electron transfer from Cys(231) directly to the heavy-light chain linkage upon radical attacks, and implies a pathway separate from His(229)-mediated hinge cleavage. On the other hand, the substitution of His(229) with Tyr showed promising advantages over the native antibody and other substitutions in improving the stability and function of the IgG1. This substitution inhibited the hinge cleavage by 98% and suggests that the redox active nature of Tyr did not enable it to replicate the ability of His to facilitate radical induced degradation. We propose that the lower redox potential of Tyr, a residue that may be the ultimate sink for oxidizing equivalents in proteins, is responsible for the inhibition. More importantly, the substitution increased the antibody's binding to FcγRIII receptors by 2-3-fold, and improved ADCC activity by 2-fold, while maintaining a similar pharmacokinetic profile with respect to the wild type. Implications of these observations for antibody engineering and development are discussed.

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

    Science.gov (United States)

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

    2014-04-01

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

  4. Renal cell carcinoma mimicking IgG4-related pseudotumor in autoimmune pancreatitis.

    Science.gov (United States)

    Khan, Muhammad Ali; Kamal, Sehrish; Ahmad, Usman; Chowdhury, Mohammed Andaleeb; Nawras, Ali

    2014-09-28

    Autoimmune pancreatitis is classified into two distinct clinical profiles. Type 1 autoimmune pancreatitis (AIP) is considered to be a manifestation of a novel clinicopathological entity called IgG4 related sclerosing disease, diagnosed using the Mayo Clinic HISORt criteria. Extra-pancreatic manifestations can include involvement of bile ducts, salivary gland, lung nodules, thyroiditis, tubulointerstitial nephritis, renal masses, and retroperitoneal fibrosis. Type 2 autoimmune pancreatitis on the other hand is confirmed by histologically seen duct centric pancreatitis without elevation of IgG4 or involvement of other organs. In type 1 autoimmune pancreatitis, extrapancreatic manifestations like bile duct strictures, tubulointerstitial nephritis, renal nodules, retroperitoneal fibrosis respond to steroid therapy. We present 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.

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

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    Neil M. Gude BSc, MSc, PhD

    2013-10-01

    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.

  6. Determination of Seroprevalence of Borrelia burgdorferi IgG in Adult Population Living in Trabzon.

    Science.gov (United States)

    Cora, Merve; Kaklıkkaya, Neşe; Topbaş, Murat; Çan, Gamze; Yavuzyılmaz, Asuman; Tosun, İlknur; Aydın, Faruk

    2017-01-01

    Lyme borreliosis is a tick-borne, multi-systemic infectious disease that is thought to be wide spread in Turkey even though studies on its seroprevalence are limited. To determine the seroprevalence of Lyme borreliosis in part of north-eastern Tur-key (in the city of Trabzon), and to identify possible relationships between seropositivity and various factors such as location, gender, age group, occupation, income, and educational level. Retrospective cross-sectional study. A total of 884 blood samples collected from provincial and district health centers serving a population of about 800,000 were included in this study. ELISA was used to determine the anti-Borrelia IgG antibody levels in the samples. Samples that yielded positive results by ELISA were further subjected to western blot (WB). IgG antibodies were found in 128 samples (14.5%). Statistical analysis revealed significant differences between age groups and educational levels in terms of the incidence of seropositivity, whereas location, gender, occupational group and income level had no effect (p<0.001, p<0.001, p=0.948, p=0.645, p=0.131, p=0.080 respectively). The risk of contracting Lyme borreliosis in Trabzon is high, and necessary measures need to be taken to avoid the spread of disease.

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

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    Muhammad Ali Khan

    2014-09-01

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

  8. Monoclonal gammopathy of undeterminated significance and endoneurial IgG deposition

    Science.gov (United States)

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

    2016-01-01

    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

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

    Science.gov (United States)

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

    2009-01-01

    We constructed the eukaryotic expression vector of human IL-35-IgG4 (Fc)-pOptiVEC-TOPO by gene recombination technique and expressed the fusion protein human IL-35-IgG4 (Fc) in CHO/DG44 cells. The two components of the newly discovered cytokine human IL-35, EBI3 and IL-12p35, were amplified by PCR from the cDNA library derived from the KG-I cells after LPS induction. The two PCR-amplified cDNA fragments of human IL-35 were linked by over-lapping PCR and then cloned into the IgG4 (Fc)-pOptiVEC-TOPO vector. The constructed plasmid with the recombinant cDNA IL-35-IgG4 (Fc) was verified by restriction enzyme digestion analysis, PCR and DNA sequencing. The verified plasmid with the recombinant cDNA was transfected into CHO/DG44 cells using Lipofectamine 2000. The success of the transfection was examined and confirmed by RT-PCR. After selection in alpha-MEM (-) medium, the IL-35-Ig G4 (Fc) positive CHO/DG44 clones were chosen and the media from these positive clones were collected to be used to purify the fusion protein. The positive CHO/DG44 clones were further cultured in increasing concentrations of MTX and the expression levels of the fusion protein IL-35-Ig G4 (Fc) were repetitively induced by MTX-induced gene amplification. The IL-35-IgG4 (Fc) fusion protein was purified from the media collected from the positive CHO/DG44 clones by protein G affinity chromatography and then identified by SDS-PAGE and Western blotting. The results showed that one protein band was found to match well with the predicted relative molecular mass of human IL-35-IgG4 (Fc) and this protein could specifically bind to anti-human IgG4 (Fc) monoclonal antibody. In conclusion, our study successfully established an IL-35-IgG4 (Fc) positive DG44 cell line which could stably express IL-35-IgG4 (Fc) fusion protein.

  10. Specific IgG and IgA of common foods in Chinese children with eczema: friend or foe.

    Science.gov (United States)

    Hon, Kam Lun E; Poon, Terence Chuen W; Pong, Nga Hin H; Wong, Yuen Hung K; Leung, Sophie S; Chow, Chung Mo; Leung, Ting Fan

    2014-12-01

    Specific immunoglobulins G and A (IgG and IgA) for common food items have been extensively measured as surrogate markers of food allergy, and dietary avoidance based on the test results advocated. We reviewed the prevalence of specific food IgG and IgA in children with eczema and evaluated outcome of dietary avoidance in these children. Specific immunoglobulins of 96 food items were measured for 30 consecutive atopic dermatitis (AD) patients and disease severity [SCORing atopic dermatitis (SCORAD) and Nottingham eczema severity score (NESS)], Children Dermatology Life Quality Index (CDLQI), skin hydration (SH), transepidermal water loss (TEWL), topical corticosteroid and oral antihistamine usage were evaluated. Twenty seven of these patients received dietary avoidance advice based on IgG and IgA data. General acceptability of treatment (GAT) was documented at the end of 3 months. There were generally no correlations among levels of IgG or IgA of the 96 food items and disease severity, quality of life, SH or TEWL. Two-third patients reported very good or good and one-third reported fair or poor GAT following dietary avoidance advice. There was no difference in any clinical parameters between the two groups following dietary avoidance. Patient with lower sunflower seed IgA (p = 0.043), casein IgG (p = 0.041), milk IgG (p = 0.037) or whey IgG (p = 0.014) had improved SCORAD and objective SCORAD following dietary advice. Children with AD are sensitized to many food allergens via IgG and IgA mechanisms. Levels of food IgG or IgA do not seem to correlate with any clinical parameters in AD. Subjectively, two third of patients accepted dietary manipulations as very good or good for their AD. Objectively, dietary avoidance had few clinical effects on the clinical parameters. Sensitization should not be generalized to mean allergy to common food.

  11. Analysis of Fcgrt gene polymorphism in indigenous Chinese sheep and its association with colostrum IgG concentration.

    Science.gov (United States)

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

    2015-03-30

    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.

  12. Investigation of Serum Oxidized Low-Density Lipoprotein IgG Levels in Patients with Angiographically Defined Coronary Artery Disease

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    Mohsen Moohebati

    2014-01-01

    Full Text Available It has been suggested that antioxidized low-density lipoprotein (anti-oxLDL antibodies play a role in the pathogenesis of atherosclerosis. The aim of this study was to measure serum ox-LDL IgG levels in 31 patients with angiographically defined coronary artery disease (CAD (≥50% stenosis in at least one major coronary artery; CAD+ group and compare these levels with those of 32 subjects with <50% coronary stenosis (CAD− group and 24 healthy age- and sex-matched controls using ELISA. We did not find any significant difference between CAD+, CAD−, and control groups in regard to oxLDL IgG levels (P=0.83. Serum oxLDL IgG levels did not differ between 1VD (one vessel disease, 2VD (2 vessels disease, and 3VD (3 vessels disease subgroups of CAD+ patients (P=0.20. Serum anti-oxLDL titers were only significantly correlated with LDL-C in the CAD+ group (P<0.05 and waist and hip circumference (P<0.05 and P<0.01, resp. in the CAD− group. In stepwise regression analysis, none of the conventional cardiovascular risk factors was associated with serum ox-LDL IgG levels. The present results suggest that serum levels of ox-LDL IgG are neither associated with the presence and severity of CAD nor with the conventional cardiovascular risk factors.

  13. [Clinical and pathological features in IgA nephropathy with IgG deposition in the glomerular mesangial area].

    Science.gov (United States)

    Xu, Xiao-Meng; Zhu, Shuang-Shuang; Wang, Xiao-Hong; Shao, Xiao-Fei; Li, Bin; Zhang, Ying; Liu, Qin; Li, Jia-Min; Wang, Hong-Lei; Li, Yong-Qiang; Zou, He-Qun

    2017-03-20

    To investigate the relationship between the clinical and pathological findings in IgA nephropathy with or without IgG deposition in the glomerular mesangial area. The data were collected from 122 patients with a diagnosis of IgA nephropathy by renal biopsy in the Third Affiliated Hospital of Southern Medical University between November, 2009 and February, 2016. All the samples were examined by light microscopy, immunofluorescence and electron microscopy. According to the results of immunofluorescence assay, the patients were divided into IgA group (n=63) and IgA-IgG group (n=59). The pathological classification of IgA nephropathy was analyzed according to Oxford classification and Lee's classification. The clinical and pathological findings were compared between the two groups. Compared with the patients with IgA nephropathy but without IgG deposition, patients with IgA nephropathy with IgG deposition had higher serum creatinine, higher 24-h urine protein, higher blood uric acid, higher triglyceride levels (PIgA nephropathy with IgG deposition in the glomerular mesangial have severer clinical symptoms and more serious pathological changes. Measures should be taken to control IgG deposition in patients with IgA nephropathy to delay the progress of the disease.

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

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    Francesco Rapisarda

    2015-01-01

    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.

  15. 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

    2016-01-01

    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。

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

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    Balder Lai

    2014-01-01

    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.

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

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Nanogold particles of 10 nm were used to label goat anti-human IgG (GIgG) to obtain nanogold-labeled GIgG (AuGIgG). In a citrate-HCl buffer solution of pH 2.27,AuGIgG showed a strong catalytic effect on the reaction between HAuCl4 and NH2OH to form big gold particles that exhibited a resonance scatter-ing (RS) peak at 796 nm. Under the chosen conditions,AuGIgG combined with IgG to form immuno-complex AuGIgG-IgG that can be removed by centrifuging at 16000 r/min. AuGIgG in the centrifuging solution also showed catalytic effect on the reaction. On those grounds,an immunonanogold catalytic RS assay for IgG was designed. With addition of IgG,the amount of AuGIgG in the centrifuging solution decreased; the RS intensity at 796 nm (I796 nm) decreased linearly. The decreased intensity ΔI796 nm was linear with respect to the IgG concentration in the range of 0.08-16.0 ng·mL-1 with a detection limit of 0.02 ng·mL-1. This assay was applied to analysis of IgG in sera with satisfactory sensitivity,selectivity and rapidity.

  18. Natural Mosquito-Pathogen Hybrid IgG4 Antibodies in Vector-Borne Diseases: A Hypothesis

    Science.gov (United States)

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

    2016-01-01

    Chronic exposure to antigens may favor the production of IgG4 antibodies over other antibody types. Recent studies have shown that up to a 30% of normal human IgG4 is bi-specific and is able to recognize two antigens of different nature. A requirement for this specificity is the presence of both eliciting antigens in the same time and at the same place where the immune response is induced. During transmission of most vector-borne diseases, the pathogen is delivered to the vertebrate host along with the arthropod saliva during blood feeding and previous studies have shown the existence of IgG4 antibodies against mosquito salivary allergens. However, there is very little ongoing research or information available regarding IgG4 bi-specificity with regard to infectious disease, particularly during immune responses to vector-borne diseases, such as malaria, filariasis, or dengue virus infection. Here, we provide background information and present our hypothesis that IgG4 may not only be a useful tool to measure exposure to infected mosquito bites, but that these bi-specific antibodies may also play an important role in modulation of the immune response against malaria and other vector-borne diseases in endemic settings. PMID:27746778

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

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    Fabiana Maria Ruiz Lopes-Mori

    2013-08-01

    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.

  20. Induction of IgG3 to LPS via Toll-like receptor 4 co-stimulation.

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    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