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Sample records for igg subclass autoantibodies

  1. IgG4 autoantibodies are inhibitory in the autoimmune disease bullous pemphigoid.

    Science.gov (United States)

    Zuo, Yagang; Evangelista, Flor; Culton, Donna; Guilabert, Antonio; Lin, Lin; Li, Ning; Diaz, Luis; Liu, Zhi

    2016-09-01

    The IgG4 subclass of antibodies exhibits unique characteristics that suggest it may function in an immunoregulatory capacity. The inhibitory function of IgG4 has been well documented in allergic disease by the demonstration of IgG4 blocking antibodies, but similar functions have not been explored in autoimmune disease. Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease characterized by autoantibodies directed against BP180 and an inflammatory infiltrate including eosinophils and neutrophils. Animal models have revealed that the NC16A region within BP180 harbors the critical epitopes necessary for autoantibody mediated disease induction. BP180 NC16A-specific IgG belong to the IgG1, IgG3, and IgG4 subclasses. The purpose of this study was to determine effector functions of different IgG subclasses of NC16A-specific autoantibodies in BP. We find that IgG4 anti-NC16A autoantibodies inhibit the binding of IgG1 and IgG3 autoantibodies to the NC16A region. Moreover, IgG4 anti-NC16A blocks IgG1 and IgG3 induced complement fixation, neutrophil infiltration, and blister formation clinically and histologically in a dose-dependent manner following passive transfer to humanized BP180-NC16A mice. These findings highlight the inhibitory role of IgG4 in autoimmune disease and have important implications for the treatment of BP as well as other antibody mediated inflammatory and autoimmune diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. A three-layer immunoradiometric assay for determination of IgG subclass antibodies in Human Sera (''IgG subclass RAST'')

    International Nuclear Information System (INIS)

    Djurup, R.; Soendergaard, I.; Weeke, B.; University of Copenhagen, Denmark); Magnusson, C.G.M.

    1984-01-01

    We report the development of a three-layer immunoradiometric assay (TIRA) for measurement of IgG antibodies of all four subclasses in human sera. The first layer consists of diluted human serum, the second layer is monoclonal mouse antibodies to human IgG subclasses, and the third layer is 125 I-labelled rabbit anti-mouse IgG. Monoclonal anti-IgGI, anti-IgG3 and anti-IgG4 reacted only with their complementary IgG subclass, whereas the anti-IgG2 showed slight cross-reactivity to immunoglobins of other subclasses and classes and to light chain proteins. The observed cross-reactivity was found to be without importance, when the TIRA was applied to measurement of IgG subclass antibodies. Equipotency was established by use of appropriate dilutions of the monoclonal antibodies, and the assay was calibrated by use of human reference serum. The TIRA therefore permits reliable inter-individual and intra-individual comparisons of the IgG antibody response in all four subclasses. Non-specific binding obtained with pooled normal human serum was below 0.33%. Inter-assay coefficient of variation was between 18 and 27%. The TIRA was applied to measurement of IgG subclass antibodies to timothy grass pollen in sera from grass pollen allergies undergoing immunotherapy. (author)

  3. Perfil de isotipos de imunoglobulinas e subclasses de IgG na leishmaniose tegumentar americana Immunoglobulin isotype and IgG subclass profiles in american tegumentary leishmaniasis

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    Maria Aparecida de Souza

    2005-04-01

    Full Text Available O presente trabalho avaliou o perfil de anticorpos em amostras de soro de 37 pacientes com diagnóstico clínico confirmado ou compatível com leishmaniose tegumentar americana atendidos no Hospital de Clínicas da Universidade Federal de Uberlândia, MG. Os perfis das classes de imunoglobulinas e subclasses de IgG foram analisados pelo teste ELISA indireto, utilizando-se antígeno solúvel de Leishmania (Leishmania amazonensis. A avidez dos anticorpos foi determinada pelo tratamento com uréia a 6 M, após incubação dos soros com o antígeno. Observou-se que 97%, 94,6%, 57,5 e 21,5% das amostras testadas apresentaram anticorpos anti-Leishmania das classes IgE, IgG, IgA e IgM, respectivamente e, os perfis das subclasses de IgG demonstraram, IgG1>IgG3>IgG2>IgG4. Os anticorpos IgE anti-Leishmania de alta avidez corresponderam a 44,4%. Por outro lado, IgG e IgA anti-Leishmania foram em sua maioria (62,8 e 47,8%, respectivamente, de média avidez. A variação do perfil de isotipos, bem como a avidez das imunoglobulinas refletiu a complexidade da resposta imune humoral contra a leishmaniose tegumentar americana.The present work investigated the serum antibody profiles in 37 patients with American tegumentary leishmaniasis, who were attended at Hospital de Clinicas - Universidade Federal de Uberlandia, MG, Brazil. The immunoglobulin class and IgG subclass profiles were analyzed by indirect ELISA using Leishmania (Leishmania amazonensis soluble antigen. The antibody avidity was determined by 6 M urea treatment after incubation with immunoenzymatic conjugate. It was observed that 97% of the serum samples presented anti-Leishmania antibodies for IgE class, 94.6% IgG, 57.5% IgA and 21.5% IgM class. For IgG subclasses the profiles were in the following order of frequency: IgG1>IgG3>IgG2>IgG4. High avidity of anti-Leishmania IgE antibodies was found in 44.4% of the samples. On the other hand, moderate avidity of specific IgG and IgA was observed in 62

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

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    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.

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

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    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.

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

    DEFF Research Database (Denmark)

    Tian, Xinsheng; Vestergaard, Bente; Thorolfsson, Matthias

    2015-01-01

    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 designe...... 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....

  7. IgG subclasses in previously healthy adult patients with acute ...

    African Journals Online (AJOL)

    t Ccmparing mean values of 19G1, 19G2, JgG3 and IgG4 between the critically ill and. rlOfl-sevet1! groups of patiems. Combined cases. Pooling of data on all cases allowed comparison of the various parameters indicating severity of pneumonia and the. IgG subclass levels between survivors and non-survivors. The results ...

  8. IgG subclass reactivity to Trypanosoma cruzi in chronic chagasic patients.

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    Hernández-Becerril, N; Nava, A; Reyes, P A; Monteón, V M

    2001-01-01

    The anti-Trypanosoma cruzi antibodies isotype profile in Chagas' disease has been studied in relation to different clinical manifestations. A high titer of IgG anti-T. cruzi antibodies is found in patients with cardiac involvement, while a high titer of IgA anti-T. cruzi antibodies is associated with digestive forms. The aim of this work was to analyze the IgG subclass reactivity of anti-T. cruzi antibodies in patients with chronic Chagasic cardiomyopathy. Twelve consecutive chagasic patients were analyzed for IgG subclass reactivity to a T. cruzi antigenic extract. They had a complete clinical evaluation, peripheral EKG, echocardiography, left ventriculogram, and coronariography. All patients came from rural areas of Mexico and had lived in endemic zones for over seven years. They presented left ventricular endsystolic dimension above 42 mm in 58% (7/12) and ejection fraction below 50% in 58% (7/12). We found that IgG1 and IgG2 anti-T. cruzi antibodies showed higher titer than IgG3 antibodies, with consistently low titer of IgG4 antibodies. Expression of the four IgG subclasses of anti-T. cruzi antibodies suggest a mixed Th1/Th2-like immune response under a probably continuous chronic antigenic stimulation. On the other hand, high levels of IgG2 anti-T. cruzi antibodies showed a tendency to be associated with severe cardiomegaly. Our results suggest that a mixed Th1/Th2-like immune response may take place in chronic chagasic patients under a chronic antigenic stimulation.

  9. Abnormal serum IgG subclass pattern in children with Down's syndrome.

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    Annerén, G; Magnusson, C G; Lilja, G; Nordvall, S L

    1992-05-01

    Susceptibility to infections is a well known feature of Down's syndrome. The possible relation between this predisposition and the serum concentrations of the IgG subclasses was studied in 38 children with Down's syndrome aged 1-12 years. An age matched group of 50 healthy children served as controls. The serum concentrations of IgG1 and IgG3 were significantly raised among children with Down's syndrome in all three age groups studied (that is 1-2.5, 4-8, and 9-12 years). The serum concentrations of IgG2 were normal in the first two groups but significantly reduced in the third age group. In contrast, the concentrations of IgG4 among children with Down's syndrome were significantly reduced in all three age groups. Moreover, among the children with Down's syndrome aged 4-12 years 68% (15/22) had IgG4 concentrations below 2 SDs of the geometrical mean of the controls. The results may partially explain the proneness of children with Down's syndrome to infections with encapsulated bacteria. Although the underlying cause of these abnormalities is unknown, IgG subclass determination seems relevant in the clinical evaluation of children with Down's syndrome.

  10. IgG4 subclass antibodies impair antitumor immunity in melanoma

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    Karagiannis, Panagiotis; Gilbert, Amy E.; Josephs, Debra H.; Ali, Niwa; Dodev, Tihomir; Saul, Louise; Correa, Isabel; Roberts, Luke; Beddowes, Emma; Koers, Alexander; Hobbs, Carl; Ferreira, Silvia; Geh, Jenny L.C.; Healy, Ciaran; Harries, Mark; Acland, Katharine M.; Blower, Philip J.; Mitchell, Tracey; Fear, David J.; Spicer, James F.; Lacy, Katie E.; Nestle, Frank O.; Karagiannis, Sophia N.

    2013-01-01

    Host-induced antibodies and their contributions to cancer inflammation are largely unexplored. IgG4 subclass antibodies are present in IL-10–driven Th2 immune responses in some inflammatory conditions. Since Th2-biased inflammation is a hallmark of tumor microenvironments, we investigated the presence and functional implications of IgG4 in malignant melanoma. Consistent with Th2 inflammation, CD22+ B cells and IgG4+-infiltrating cells accumulated in tumors, and IL-10, IL-4, and tumor-reactive IgG4 were expressed in situ. When compared with B cells from patient lymph nodes and blood, tumor-associated B cells were polarized to produce IgG4. Secreted B cells increased VEGF and IgG4, and tumor cells enhanced IL-10 secretion in cocultures. Unlike IgG1, an engineered tumor antigen-specific IgG4 was ineffective in triggering effector cell–mediated tumor killing in vitro. Antigen-specific and nonspecific IgG4 inhibited IgG1-mediated tumoricidal functions. IgG4 blockade was mediated through reduction of FcγRI activation. Additionally, IgG4 significantly impaired the potency of tumoricidal IgG1 in a human melanoma xenograft mouse model. Furthermore, serum IgG4 was inversely correlated with patient survival. These findings suggest that IgG4 promoted by tumor-induced Th2-biased inflammation may restrict effector cell functions against tumors, providing a previously unexplored aspect of tumor-induced immune escape and a basis for biomarker development and patient-specific therapeutic approaches. PMID:23454746

  11. IgG and IgG subclasses antibody responses to rK39 in Leishmania donovani infections

    International Nuclear Information System (INIS)

    Daifalla, N.S.; El Hassan, A.M.

    1998-01-01

    Leishmania donovani infection cause a wide spectrum of human diseases ranging from self-healing subclinical infections to severe visceral leishmaniasis, post kal-azar dermal leishmaiasis, and mucosal leishmaiasis. The infection associated with high levels of anti-leishmania antibodies which offer a potential parameter for the serological diagnosis of L. donovani infection replacing the invasive parasitological methods. rK39, a cloned antigen of L. chagasis was reported to have high levels of anti-leishmania antibodies in Sudanese and American visceral leishmaniasis patients. In an assessment of rK39-ELISA in detecting L. donovani infection we found that the antigen detected visceral leishmaniasis, post kala-azar dermal leishmaniasis, and mucosal leismaniasis with the sensitives of 96.6%, 95.91% and 90.91% respectively. The test has the specificity of 96.7%. Further investigation of 25 visceral leishmaniasis patients showed elevated anti-rK39 antibody responses of IgG subclasses with IgG1 and IgG3 significantly higher than IgG4. igG3 showed the highest sensitivity (84.00%) whereas IgG1 showed the highest sensitivity (100%). The dynamics of the serological reactivity to rK39 in l.donovani infections will be discussed in relation to exposure, infection, cure and relapse.(Author)

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

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

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    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.

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

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    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

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

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    Xinsheng Tian

    2015-01-01

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

  16. [EFFICACY OF IVIG TREATMENT IN BRONCHIECTASIS ASSOCIATED WITH IGG SUBCLASS DEFICIENCY].

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    Shostak, Yael; Kramer, Mordechai R

    2017-11-01

    Bronchiectasis is characterized by an abnormal dilatation of the bronchi leading to a chronic inflammatory process, airway blockage and impaired clearance of secretions. The damage to the airways is usually progressive and is the result of several pathogenic processes. In the past, healing of infections (especially pulmonary tuberculosis) was the main cause of airway dilatation and progression of chronic inflammation. Today, congenital illnesses, anatomical defects and immune deficiency play an important role in the pathogenesis of bronchiectasis formation. The immunoglobulin repertoire is vital for effective host protection against a wide variety of pathogens. Primary antibody deficiency diseases are defects of the humoral arm of the immune system and involve an absence/reduced levels of one or more immunoglobulin classes/subclasses or defects of specific antibody formation. Immunoglobulin G (IGG) subclass deficiency can occur in a healthy person and could be without clinical significance. However, in recent years there is emerging evidence that in patients with recurrent infections, early diagnosis of antibody deficiency affects the prognosis and prevention of ongoing lung damage. The use of IVIG has contributed significantly to the survival rate in primary antibody deficiencies. There is limited literature on the treatment of IVIG for patients with IGG subclass deficiency. However, all studies presented so far demonstrated that immunoglobulin therapy reduced the rate of bacterial infections, days of antibiotic usage, hospital admissions and significantly increased patients' quality of life. Therefore, in the appropriate clinical setting, ie: a patient with bronchiectasis and recurrent infections, it is justified to test whether there are humoral immune defects such as IGG subclass deficiency. In a patient with proven deficiency, we should recommend to start IVIG treatment until clinical benefit is achieved.

  17. Cutting Edge: The murine high-affinity IgG receptor FcγRIV is sufficient for autoantibody-induced arthritis.

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    Mancardi, David A; Jönsson, Friederike; Iannascoli, Bruno; Khun, Huot; Van Rooijen, Nico; Huerre, Michel; Daëron, Marc; Bruhns, Pierre

    2011-02-15

    K/BxN serum-induced passive arthritis was reported to depend on the activation of mast cells, triggered by the activating IgG receptor FcγRIIIA, when engaged by IgG1 autoantibodies present in K/BxN serum. This view is challenged by the fact that FcγRIIIA-deficient mice still develop K/BxN arthritis and because FcγRIIIA is the only activating IgG receptor expressed by mast cells. We investigated the contribution of IgG receptors, IgG subclasses, and cells in K/BxN arthritis. We found that the activating IgG2 receptor FcγRIV, expressed only by monocytes/macrophages and neutrophils, was sufficient to induce disease. K/BxN arthritis occurred not only in mast cell-deficient W(sh) mice, but also in mice whose mast cells express no activating IgG receptors. We propose that at least two autoantibody isotypes, IgG1 and IgG2, and two activating IgG receptors, FcγRIIIA and FcγRIV, contribute to K/BxN arthritis, which requires at least two cell types other than mast cells, monocytes/macrophages, and neutrophils.

  18. Absolute Quantitation of Glycoforms of Two Human IgG Subclasses Using Synthetic Fc Peptides and Glycopeptides

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    Roy, Rini; Ang, Evelyn; Komatsu, Emy; Domalaon, Ronald; Bosseboeuf, Adrien; Harb, Jean; Hermouet, Sylvie; Krokhin, Oleg; Schweizer, Frank; Perreault, Hélène

    2018-05-01

    Immunoglobulins, such as immunoglobulin G (IgG), are of prime importance in the immune system. Polyclonal human IgG comprises four subclasses, of which IgG1 and IgG2 are the most abundant in healthy individuals. In an effort to develop an absolute MALDI-ToF-MS quantitative method for these subclasses and their Fc N-glycoforms, (glyco)peptides were synthesized using a solid-phase approach and used as internal standards. Tryptic digest glycopeptides from monoclonal IgG1 and IgG2 samples were first quantified using EEQYN(GlcNAc)STYR and EEQFN(GlcNAc)STFR standards, respectively. For IgG1, a similar glycopeptide where tyrosine (Y) was isotopically labelled was used to quantify monoclonal IgG1 that had been treated with the enzyme Endo-F2, i.e., yielding tryptic glycopeptide EEQYN(GlcNAc)STYR. The next step was to quantify single subclasses within polyclonal human IgG samples. Although ion abundances in the MALDI spectra often showed higher signals for IgG2 than IgG1, depending on the spotting solvent used, determination of amounts using the newly developed quantitative method allowed to obtain accurate concentrations where IgG1 species were predominant. It was observed that simultaneous analysis of IgG1 and IgG2 yielded non-quantitative results and that more success was obtained when subclasses were quantified one by one. More experiments served to assess the respective extraction and ionization efficiencies of EEQYNSTYR/EEQFNSTFR and EEQYN(GlcNAc)STYR/EEQFN(GlcNAc)STFR mixtures under different solvent and concentration conditions.

  19. IgG4 autoantibodies against muscle-specific kinase undergo Fab-arm exchange in myasthenia gravis patients.

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    Koneczny, Inga; Stevens, Jo A A; De Rosa, Anna; Huda, Saif; Huijbers, Maartje G; Saxena, Abhishek; Maestri, Michelangelo; Lazaridis, Konstantinos; Zisimopoulou, Paraskevi; Tzartos, Socrates; Verschuuren, Jan; van der Maarel, Silvère M; van Damme, Philip; De Baets, Marc H; Molenaar, Peter C; Vincent, Angela; Ricciardi, Roberta; Martinez-Martinez, Pilar; Losen, Mario

    2017-02-01

    Autoimmunity mediated by IgG4 subclass autoantibodies is an expanding field of research. Due to their structural characteristics a key feature of IgG4 antibodies is the ability to exchange Fab-arms with other, unrelated, IgG4 molecules, making the IgG4 molecule potentially monovalent for the specific antigen. However, whether those disease-associated antigen-specific IgG4 are mono- or divalent for their antigens is unknown. Myasthenia gravis (MG) with antibodies to muscle specific kinase (MuSK-MG) is a well-recognized disease in which the predominant pathogenic IgG4 antibody binds to extracellular epitopes on MuSK at the neuromuscular junction; this inhibits a pathway that clusters the acetylcholine (neurotransmitter) receptors and leads to failure of neuromuscular transmission. In vitro Fab-arm exchange-inducing conditions were applied to MuSK antibodies in sera, purified IgG4 and IgG1-3 sub-fractions. Solid-phase cross-linking assays were established to determine the extent of pre-existing and inducible Fab-arm exchange. Functional effects of the resulting populations of IgG4 antibodies were determined by measuring inhibition of agrin-induced AChR clustering in C2C12 cells. To confirm the results, κ/κ, λ/λ and hybrid κ/λ IgG4s were isolated and tested for MuSK antibodies. At least fifty percent of patients had IgG4, but not IgG1-3, MuSK antibodies that could undergo Fab-arm exchange in vitro under reducing conditions. Also MuSK antibodies were found in vivo that were divalent (monospecific for MuSK). Fab-arm exchange with normal human IgG4 did not prevent the inhibitory effect of serum derived MuSK antibodies on AChR clustering in C2C12 mouse myotubes. The results suggest that a considerable proportion of MuSK IgG4 could already be Fab-arm exchanged in vivo. This was confirmed by isolating endogenous IgG4 MuSK antibodies containing both κ and λ light chains, i.e. hybrid IgG4 molecules. These new findings demonstrate that Fab-arm exchanged antibodies

  20. Early diagnosis of congenital toxoplasmosis in newborn infants using IgG subclasses against two Toxoplasma gondii recombinant proteins

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    Carlos Henryque de Souza e Silva

    2012-05-01

    Full Text Available The aim of this work was to evaluate the utility of ELISA-based testing of total IgG (IgGt antibodies and its subclasses (IgG1, IgG2, IgG3 and IgG4 against soluble (STAg and recombinant (rSAG1 and rMIC3 antigens of Toxoplasma gondii for diagnosing congenital toxoplasmosis. Sera from 217 newborns initially testing positive for specific IgM in filter paper dried blood spots were tested for specific IgM and IgG by ELFA-VIDAS®. Congenital toxoplasmosis was confirmed in 175 and ruled out in 42 infants. The validity of the ELISA tests was determined using the persistence of IgG antibodies (ELFA-VIDAS® kit at the end of 12 months, which is considered the reference test for the diagnosis of congenital toxoplasmosis. The frequency of positivity with IgGt against STAg, rSAG1 and rMIC3 was found in 97.2%, 96.3% and 80.2%, respectively, of the newborns with confirmed congenital toxoplasmosis. IgG1 reacted with all three antigens, while IgG3 and IgG4 reacted preferentially with rMIC3. Higher mean values of reactivity (sample optical density/cut-off were found for all subclasses when using rMIC3. All of the antigens showed high sensitivity and low specificity in detecting anti-T. gondii IgGt and IgG1 and low sensitivity and high specificity in detecting IgG3 and IgG4. In conclusion, the combined detection of IgG antibody subclasses against recombinant toxoplasmic antigens may be useful for the early diagnosis of congenital toxoplasmosis.

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

    DEFF Research Database (Denmark)

    Gaini, Shahin

    2015-01-01

    A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode...... revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis...... and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine....

  2. Neisseria meningitidis Group A IgG1 and IgG2 Subclass Immune Response in African Children Aged 12–23 Months Following Meningococcal Vaccination

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    Holme, Daniel; Findlow, Helen; Sow, Samba O.; Idoko, Olubukola T.; Preziosi, Marie-Pierre; Carlone, George; Plikaytis, Brian D.; Borrow, Ray

    2015-01-01

    Background. A group A meningococcal conjugate vaccine, PsA-TT, was licensed in 2010 and was previously studied in a phase 2 clinical trial to evaluate its safety and immunogenicity in African children 12–23 months of age. Methods. Subjects received either PsA-TT; meningococcal group A, C, W, Y polysaccharide vaccine (PsACWY); or Haemophilus influenzae type b conjugate vaccine (Hib-TT). Forty weeks following primary vaccination, the 3 groups were further randomized to receive either PsA-TT, one-fifth dose of PsACWY, or Hib-TT. Group A–specific immunoglobulin G (IgG) subclass response was characterized using an enzyme-linked immunosorbent assay. Results. The predominant IgG subclass response, regardless of vaccine, was IgG1. One month following primary vaccination, the geometric mean concentrations (GMCs) of IgG1 and IgG2 in the PsA-TT group were 21.73 µg/mL and 6.27 µg/mL, whereas in the PsACWY group the mean GMCs were 2.01 µg/mL and 0.97 µg/mL, respectively (P Group A–specific IgG1 and IgG2 GMCs remained greater in the PsA-TT group than in the PsACWY group 40 weeks following primary vaccination (P vaccines. Conclusions. Vaccination of African children aged 12–24 months with either PsA-TT or PsACWY elicited a predominantly IgG1 response. The IgG1:IgG2 mean ratio decreased following successive vaccination with PsACWY, indicating a shift toward IgG2, suggestive of the T-cell–independent immune response commonly associated with polysaccharide antigens. Clinical Trials Registration. SRCTN78147026. PMID:26553689

  3. Correlation of Fc(gamma)RIIa (CD32) Polymorphism and IgG Antibody Subclasses in Hemolytic Disease of Newborn.

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    Wu, QiangJu; Zhang, Yan; Liu, MengLi; Wang, Bo; Liu, Sheng; He, Chen

    2009-01-01

    ABO-HDN is a common disease of newborn in China and currently there is no satisfactory method to predict it in the antepartum period. It has been reported that Fc(gamma)RIIa (CD32) genotype is associated with both infectious diseases induced by bacteria and parasitemia. There is a relationship between IgG subclass and RH-HDN. To study the pathogenesis of ABO-HDN and to find reliable method to diagnose ABO-HDN, we investigated the polymorphism of Fc(gamma)RIIa (CD32) and distribution of IgG subclass in infants with ABO-HDN and their mothers by polymerase chain reaction or ELISA assay. We observed that the frequency of HH131 genotype is lower in infants with ABO-HDN than in controls (p < 0.01), while the frequency of HR131 genotype is higher in ABO-HDN infants than that in controls (p < 0.01). The genotype HR131 and concentrations of IgG1 and IgG3 are significantly correlated with ABO-HDN. Our results demonstrated, for the first time, that there is a correlation between ABO-HDN and CD32, and different IgG subclass distribution. Our study may contribute to the development of an early diagnostic method for HDN. Copyright 2009 S. Karger AG, Basel.

  4. 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

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Shahin Gaini

    2015-01-01

    Full Text Available A 51-year-old Caucasian woman with Listeria monocytogenes meningitis was treated and discharged after an uncomplicated course. Her medical history included immunosuppressive treatment with prednisolone and azathioprine for autoimmune hepatitis. A diagnostic work-up after the meningitis episode revealed that she had low levels of the IgG4 subclass. To our knowledge, this is the first case report describing a possible association between autoimmune hepatitis and the occurrence of Listeria monocytogenes meningitis, describing a possible association between Listeria monocytogenes meningitis and deficiency of the IgG4 subclass and finally describing a possible association between Listeria monocytogenes meningitis and immunosuppressive therapy with prednisolone and azathioprine.

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

    DEFF Research Database (Denmark)

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

    1992-01-01

    A monoclonal antibody was produced against the recombinant human alpha subunit of CK-2. The antibody was of the IgG1 subclass and it was isolated from serum-free cell culture media and purified by affinity chromatography on Protein G Sepharose. The antibody can be used to detect specifically the CK......-2 alpha subunit in immunoblots from tissue extracts. An ELISA detection test was also established which also allows the identification of the CK-2 alpha subunit....

  8. 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.

  9. Dynamics of Inter-heavy Chain Interactions in Human Immunoglobulin G (IgG) Subclasses Studied by Kinetic Fab Arm Exchange

    NARCIS (Netherlands)

    Rispens, Theo; Davies, Anna M.; Ooijevaar-de Heer, Pleuni; Absalah, Samira; Bende, Onno; Sutton, Brian J.; Vidarsson, Gestur; Aalberse, Rob C.

    2014-01-01

    Background: Fab arm exchange requires weak interactions between CH3 domains, such as in human IgG4. Results: CH3-CH3 interactions differ >1,000,000-fold between human subclasses and allotypes due to variations Lys/Asn-392, Val/Met-397, and Lys/Arg-409. Conclusion: For IgG2 and IgG3, but not IgG1,

  10. Pattern of pre-existing IgG subclass responses to a panel of asexual stage malaria antigens reported during the lengthy dry season in Daraweesh, Sudan

    DEFF Research Database (Denmark)

    Nasr, A; Iriemenam, N C; Troye-Blomberg, M

    2011-01-01

    The anti-malarial IgG immune response during the lengthy and dry season in areas of low malaria transmission as in Eastern Sudan is largely unknown. In this study, ELISA was used for the measurement of pre-existing total IgG and IgG subclasses to a panel of malaria antigens, MSP2-3D7, MSP2-FC27, ...

  11. Human IgG subclass antibodies to the 19 kilodalton carboxy ...

    African Journals Online (AJOL)

    IgG2 or IgG4 antibodies were virtually nonexistent. The cross-reactivity between the 4 sequence variants (E-KNG, E-TSR, Q-KNG and. Q-TSR) of MSP119 was confirmed; however, a minority of sera preferentially recognised the KNG but not the TSR variants. All 33 P. falciparum isolates from different parts ofm Uganda

  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. Autoantibodies Specifically Against β1 Adrenergic Receptors and Adverse Clinical Outcome in Patients With Chronic Systolic Heart Failure in the β-Blocker Era: The Importance of Immunoglobulin G3 Subclass.

    Science.gov (United States)

    Nagatomo, Yuji; Li, Daniel; Kirsop, Jennifer; Borowski, Alan; Thakur, Akanksha; Tang, W H Wilson

    2016-06-01

    To elucidate the prevalence and role of β1 adrenergic receptor autoantibodies (β1AR-AAb) belonging to the immunoglobulin (Ig)G3 subclass in patients with heart failure (HF) treated with β-adrenergic blockers. Several cardiac AAbs have been reported to be present in sera from patients with dilated cardiomyopathy and other etiologies. Among AAbs, those recognizing β1AR-AAbs show agonist-like effects, have detrimental effects on cardiomyocytes, and may induce persistent myocardial damage. We quantify total IgG and IgG3 subclass β1AR-AAb in subjects with chronic stable HF with long-term follow-up. In our study cohort of 121 subjects, non-IgG3-β1AR-AAb and IgG3-β1AR-AAb were found to be positive in 20 (17%) and 26 patients (21%), respectively. The positive rate of IgG3-β1AR-AAb was significantly higher for those with nonischemic compared with ischemic HF etiology (27% vs 8%, P = .01), but the positive rate for non-IgG3-β1AR-AAb was similar between the 2 groups (18% vs 16%, respectively, P = NS). There were no significant differences in clinical and echocardiographic measures among total β1AR-AAb negative, non-IgG3-β1AR-AAb positive, and IgG3-β1AR-AAb positive groups at baseline. During 2.2 ± 1.2 years of follow-up, we observed similar rates of the composite endpoint of all-cause mortality, cardiac transplantation, or hospitalization resulting from HF between total IgG-β1AR-AAb negative and positive patients. However, the composite endpoint events were significantly more common in the patients without than in those with IgG3-β1AR-AAb (P = .048, log-rank test). Presence of IgG3-β1AR-AAb, not total IgG, was associated with paradoxically more favorable outcomes in our cohort of patients with chronic systolic HF largely treated by β-blockers. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. [Serum immunoglobulin IgG subclass distribution of antibody responses to pertussis toxin and filamentous hemagglutinin of Bordetella pertussis in patients with whooping cough].

    Science.gov (United States)

    Rastawicki, Waldemar; Smietańska, Karolina; Rokosz-Chudziak, Natalia; Jagielski, Marek

    2013-01-01

    The present study was aimed at determining the IgG subclass distribution against pertussis toxin (PT) and filamentous hemagglutinin (FHA) of Bordetella pertussis in patients with whooping cough. The total number of 222 serum samples obtained from patients suspected in clinical investigation for pertussis were tested separately by in-house ELISA for the presence of IgG antibodies to pertussis toxin and filamentous hemagglutinin. The percentage distribution of specific anti-PT and anti-FHA IgG subclass response was calculated only on the basis of group of sera confirmed in the present study as positive for total IgG antibodies (183 sera to PT antigen and 129 to FHA antigen). Paired serum specimens were obtained from 36 patients. Based on the results of determining the level of antibodies in the sera of 40 blood donors, the cut-off limit of serum antibodies for each subclass was set at arithmetic mean plus two standard deviations. Antibodies of IgG1 to pertussis toxin and filamentous hemagglutinin were diagnosed in 151 (82.5%) and 99 (76.7%), IgG2 in 72 (39.0%) and 50 (38.8%), IgG3 in 17 (9.3%) and 43 (33.3%), IgG4 in 55 (30.1%) and 53 (41.1%) serum samples, respectively. There were no significant differences in percentage of sera with IgG1, IgG2 and IgG3 in relation to age of the patients. However, the frequency of occurrence of IgG4 antibodies was highest in the group of the youngest children to the age of 6 years old (61.8% for PT and 68.0% for FHA), and decrease with age, reaching the minimum in the group of patients above 40 years old (13.2% and 4.2% for PT and FHA, respectively). We also found significantly higher frequency of IgG4 to PT and FHA antigens in men than in women. Statistically significant, essential changes in the pattern of IgG subclass during the course of infection were not found. In conclusion, this study showed that all four subclasses of IgG antibodies to pertussis toxin and filamentous hemagglutinin are produced during whooping cough.

  15. Combined roles of human IgG subclass, alternative complement pathway activation, and epitope density in the bactericidal activity of antibodies to meningococcal factor h binding protein.

    Science.gov (United States)

    Giuntini, Serena; Reason, Donald C; Granoff, Dan M

    2012-01-01

    Meningococcal vaccines containing factor H binding protein (fHbp) are in clinical development. fHbp binds human fH, which enables the meningococcus to resist complement-mediated bacteriolysis. Previously, we found that chimeric human IgG1 mouse anti-fHbp monoclonal antibodies (MAbs) had human complement-mediated bactericidal activity only if the MAb inhibited fH binding. Since IgG subclasses differ in their ability to activate complement, we investigated the role of human IgG subclasses on antibody functional activity. We constructed chimeric MAbs in which three different murine fHbp-specific binding domains were each paired with human IgG1, IgG2, or IgG3. Against a wild-type group B isolate, all three IgG3 MAbs, irrespective of their ability to inhibit fH binding, had bactericidal activity that was >5-fold higher than the respective IgG1 MAbs, while the IgG2 MAbs had the least activity. Against a mutant with increased fHbp expression, the anti-fHbp MAbs elicited greater C4b deposition (classical pathway) and greater bactericidal activity than against the wild-type strain, and the IgG1 MAbs had similar or greater activity than the respective IgG3 MAbs. The bactericidal activity against both wild-type and mutant strains also was dependent, in part, on activation of the alternative complement pathway. Thus, at lower epitope density in the wild-type strain, the IgG3 anti-fHbp MAbs had the greatest bactericidal activity. At a higher epitope density in the mutant, the IgG1 MAbs had similar or greater bactericidal activity than the IgG3 MAbs, and the activity was less dependent on the inhibition of fH binding than at a lower epitope density.

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

    Science.gov (United States)

    Kakalacheva, Kristina; Regenass, Stephan; Wiesmayr, Silke; Azzi, Tarik; Berger, Christoph; Dale, Russell C; Brilot, Fabienne; Münz, Christian; Rostasy, Kevin; Nadal, David; Lünemann, Jan D

    2016-02-12

    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.

  17. Sudan ebolavirus long recovered survivors produce GP-specific Abs that are of the IgG1 subclass and preferentially bind FcγRI.

    Science.gov (United States)

    Radinsky, Olga; Edri, Avishay; Brusilovsky, Michael; Fedida-Metula, Shlomit; Sobarzo, Ariel; Gershoni-Yahalom, Orly; Lutwama, Julius; Dye, John; Lobel, Leslie; Porgador, Angel

    2017-07-20

    Ebolavirus is a highly lethal pathogen, causing a severe hemorrhagic disease with a high fatality rate. To better understand immune correlates of protection by virus specific IgG, we investigated the evolution of the Fcγ receptors (FcγRs)-activating capabilities of antiviral IgG in serum samples of long recovered survivors. To this end, longitudinal serum samples from survivors of Sudan ebolavirus (SUDV) infection, studied over years, were examined for the presence of Ebola-GP specific IgG subclasses, and for their binding to FcγRs. We developed a cell-based reporter system to quantitate pathogen-specific antibody binding to FcγRIIIA, FcγRIIA, FcγRIIB and FcγRI. With this system, we demonstrate that anti-GP-specific stimulation of the FcγRI reporter by survivors' sera was substantially high one year after acute infection, with a slight reduction in activity over a decade post infection. We further demonstrate that GP-specific IgG1 is by far the seroprevalent subclass that retained and even enhanced its presence in the sera, over ten years post infection; the prevalence of other GP-specific IgG subclasses was considerably reduced over time. In accordance, GP-specific FcγRI reporter response and GP-specific total IgG1 subclass correlated in the studied group of Ebola survivors. These observations are important for further informing Ebola vaccine and therapeutic development.

  18. Induction of a Th-1-biased IgG subclass response against equine herpesvirus type 1 in horses previously infected with type 4 virus.

    Science.gov (United States)

    Bannai, Hiroshi; Tsujimura, Koji; Kondo, Takashi; Nemoto, Manabu; Yamanaka, Takashi; Sugiura, Takeo; Maeda, Ken; Matsumura, Tomio

    2011-04-01

    An immunoglobulin G (IgG) subclass response against equine herpesvirus type 1 (EHV-1) infection was investigated in horses that were naïve to EHV-1/4 and those that had previously been exposed to EHV-4. The IgG subclass response was determined by an ELISA using EHV-1-specific recombinant gG protein as an antigen. In most horses naïve to EHV-1/4, IgGa, IgGb, and IgG(T) were induced after experimental infection with EHV-1. In contrast, a subclass response dominated by IgGa and IgGb, with no apparent increase in IgG(T), was observed after EHV-1 infection in horses previously infected with EHV-4. Horses naturally infected with EHV-1 in the field showed similar responses. These results indicated that pre-infection with EHV-4 induced a Th-1-biased IgG subclass response against subsequent EHV-1 infection.

  19. Prevalence of IgG Autoantibodies against GD3 Ganglioside in Acute Zika Virus Infection

    Science.gov (United States)

    Nico, Dirlei; Conde, Luciana; Rivera-Correa, Juan L.; Vasconcelos-dos-Santos, Andréia; Mesentier-Louro, Louise; Freire-de-Lima, Leonardo; Arruda, Mônica Barcellos; Freire-de-Lima, Celio Geraldo; Ferreira, Orlando da Costa; Lopes Moreira, Maria Elisabeth; Zin, Andrea Araújo; Vasconcelos, Zilton Farias Meira; Otero, Rosalia Mendez; Palatnik-de-Sousa, Clarisa Beatriz; Tanuri, Amilcar; Todeschini, Adriane Regina; Savino, Wilson; Rodriguez, Ana; Morrot, Alexandre

    2018-01-01

    Zika virus (ZIKV) disease has become a global health emergency with devastating effects on public health. Recent evidences implicate the virus as an emergent neuropathological agent promoting serious pathologies of the human nervous system, that include destructive and malformation consequences such as development of ocular and fetal brain lesions, microcephaly in neonates, and Guillain–Barré syndrome (GBS) in adults. These neurological disorders of both central and peripheral nervous systems are thought to be associated to the neurotropic properties of the virus that has ability to infect neural stem cells as well as peripheral neurons, a hallmark of its pathogenicity. The presence of autoantibodies against gangliosides plays a pivotal role in the etiogenesis of GBS and a variety of neurological disorders. Gangliosides are a class of galactose-containing cerebrosides mainly expressed in nervous system tissues playing a critical role in the physiology of neural cells and neurogenesis. Herein, our findings indicate that patients at acute phase of ZIKV infection without any neurological signs show increased levels of IgG autoantibody against GD3 gangliosides, a class of glycolipid found to be highly expressed in neural stem cell acting in the maintenance of their self-renewal cellular capacity. It is possible that a pathological threshold of these antibodies is only acquired in secondary or subsequent infections. In the light of these evidences, we propose that the target of GD3 by autoimmune responses may possibly has an effect in the neuropathy and neurogenesis disorder seen during ZIKV infection. PMID:29594116

  20. Correlation between the Amount of Anti-D Antibodies and IgG Subclasses with Severity of Haemolytic Disease of Foetus and Newborn

    Directory of Open Access Journals (Sweden)

    Emilija Velkova

    2015-05-01

    CONCLUSIONS: The titers of the pregnant women serum those are lower than 32 and those higher than 1000 can well predict HDFN. The titers of anti-D antibodies between 64 and 512 have no exact predictive value. IgG1 and IgG3 subclasses of anti-D have no predictive value by themselves, and cannot foresee the outcome of HDFN. The research study results suggest that IgG1 and IgG3 should be included in a multi – parameter protocol for evaluation of the HDFN intensity. They can give a real assessment of the expected HDFN intensity in combination with the titer hight and the significance of the antibodies.

  1. Natural IgG autoantibodies are abundant and ubiquitous in human sera, and their number is influenced by age, gender, and disease.

    Directory of Open Access Journals (Sweden)

    Eric P Nagele

    Full Text Available The presence of self-reactive IgG autoantibodies in human sera is largely thought to represent a breakdown in central tolerance and is typically regarded as a harbinger of autoimmune pathology. In the present study, immune-response profiling of human serum from 166 individuals via human protein microarrays demonstrates that IgG autoantibodies are abundant in all human serum, usually numbering in the thousands. These IgG autoantibodies bind to human antigens from organs and tissues all over the body and their serum diversity is strongly influenced by age, gender, and the presence of specific diseases. We also found that serum IgG autoantibody profiles are unique to an individual and remarkably stable over time. Similar profiles exist in rat and swine, suggesting conservation of this immunological feature among mammals. The number, diversity, and apparent evolutionary conservation of autoantibody profiles suggest that IgG autoantibodies have some important, as yet unrecognized, physiological function. We propose that IgG autoantibodies have evolved as an adaptive mechanism for debris-clearance, a function consistent with their apparent utility as diagnostic indicators of disease as already established for Alzheimer's and Parkinson's diseases.

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

    Directory of Open Access Journals (Sweden)

    Lisandra Akemi Suzuki

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

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

    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. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Complete elimination of cardiodepressant IgG3 autoantibodies by immunoadsorption in patients with severe heart failure

    International Nuclear Information System (INIS)

    Baba, Akiyasu; Akaishi, Makoto; Shimada, Megumi; Wakabayashi, Yasuhisa; Takahashi, Michiko; Monkawa, Toshiaki; Nagatomo, Yuji; Yoshikawa, Tsutomu

    2010-01-01

    Cardiodepressant IgG3 autoantibodies (CD-Abs) can be targeted by apheresis. Using blinded measurements of CD-Abs before and after immunoadsorption (IA), the cardiac function of patients who did or did not achieve complete CD-Abs elimination was compared. Autoantibodies were completely removed from 18 patients with heart failure (New York Heart Association class 3 or 4, left ventricular ejection fraction (LVEF) <30%) using a selective IgG3 adsorption column. All patients had anti-β1-adrenergic and/or M2-muscarinic autoantibodies before IA, and all LVEF were measured on radionuclide ventriculography. CD-Abs were measured before and after IA, and patient status was blinded until all measurements were collected. Treatment was defined as complete when CD-Abs status changed from positive to negative after IA. Other instances were defined as incomplete. Six-min walk test results and brain natriuretic peptide levels improved significantly after IA (P<0.01). The increase in LVEF 3 months after IA was significantly greater after complete treatment in comparison to the incomplete treatment group (19±8-29±9% vs 18±9-17±8%, P<0.01). Cardiac insufficiency events were also more frequent in the incomplete treatment group. Complete elimination of CD-Abs with apheresis may be related to improved cardiac function in the treatment of heart failure. (author)

  5. Correlation between the Amount of Anti-D Antibodies and IgG Subclasses with Severity of Haemolytic Disease of Foetus and Newborn.

    Science.gov (United States)

    Velkova, Emilija

    2015-06-15

    The aim of this study was to investigate the influence of subclasses to IgG anti-D on the intensity of hemolytic disease of fetus and newborn (HDFN) at 45 fetuses/newborns with symptoms of mild and severe HDFN in Republic of Macedonia. In retrospective and prospective studies, in a period of 10 years, from 2004 to 2014, there have been immunohemathology tests performed on 22 009 samples on serums of pregnant women. At 37.78% of the total number of tested patients, IgG1 and IgG3 was the reason for severe HDFN. At 17.77% of the total number of tested patients, which had only IgG1detected, was the reason for serious intensity of HDFN. The correlation of the titer to anti-D antibodies in the mother's serum and the intensity of HDFN were researched in 48 newborns. The titers between 1:8 and 1:32 resulted in 3 cases of HDFN with symptoms of severe disease and in 4 cases there were no signs of HDFN. At 12 women that had a titre between 1:32 and 1:512, five of the newborns developed severe HDFN, and seven had symptoms of mild and weak intensity form. In 3 cases the titer was higher than 512, and out of them one newborn had weak symptoms of HDFN, one developed severe HDFN and one ended with foetal death. Only in one case the titer reached a value higher than 1000, and it ended with a fetal death. The titers of the pregnant women serum those are lower than 32 and those higher than 1000 can well predict HDFN. The titers of anti-D antibodies between 64 and 512 have no exact predictive value. IgG1 and IgG3 subclasses of anti-D have no predictive value by themselves, and cannot foresee the outcome of HDFN. The research study results suggest that IgG1 and IgG3 should be included in a multi - parameter protocol for evaluation of the HDFN intensity. They can give a real assessment of the expected HDFN intensity in combination with the titer hight and the significance of the antibodies.

  6. 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

    IgE were detected using 125I-labelled rBet v 1.2801, a recombinant variant of the major allergen of Betula verrucosa pollen. Results show that IgG4-depletion resulted in equivalent reductions in binding and blocking activities. In contrast, a significant but less than two-fold higher relative...... for the clinical efficacy of SIT. In this study, fractionated serum samples from 14 SIT-treated birch pollen allergic individuals enabled determination of the inhibitory capacity of IgG4 alone versus non-IgG4 IgG. Allergen-binding activities of IgG and the IgG-mediated inhibition of allergen binding to autologous...

  7. Viscosity of high concentration protein formulations of monoclonal antibodies of the IgG1 and IgG4 subclass - Prediction of viscosity through protein-protein interaction measurements

    DEFF Research Database (Denmark)

    Neergaard, Martin S; Kalonia, Devendra S; Parshad, Henrik

    2013-01-01

    The purpose of this work was to explore the relation between protein-protein interactions (PPIs) and solution viscosity at high protein concentration using three monoclonal antibodies (mAbs), two of the IgG4 subclass and one of the IgG1 subclass. A range of methods was used to quantify the PPI...... low or high protein concentration determined using DLS. The PPI measurements were correlated with solution viscosity (measured by DLS using polystyrene nanospheres and ultrasonic shear rheology) as a function of pH (4-9) and ionic strength (10, 50 and 150mM). Our measurements showed that the highest...... solution viscosity was observed under conditions with the most negative kD, the highest apparent radius and the lowest net charge. An increase in ionic strength resulted in a change in the nature of the PPI at low pH from repulsive to attractive. In the neutral to alkaline pH region the mAbs behaved...

  8. Enhanced insight into the autoimmune component of glaucoma: IgG autoantibody accumulation and pro-inflammatory conditions in human glaucomatous retina.

    Science.gov (United States)

    Gramlich, Oliver W; Beck, Sabine; von Thun Und Hohenstein-Blaul, Nadine; Boehm, Nils; Ziegler, Anika; Vetter, Jan M; Pfeiffer, Norbert; Grus, Franz H

    2013-01-01

    There is accumulating evidence that autoimmune components, such as autoantibodies and autoantibody depositions, play a role in the pathogenesis of neurodegenerative diseases like Alzheimeŕs disease or Multiple Sclerosis. Due to alterations of autoantibody patterns in sera and aqueous humor, an autoimmune component is also assumed in the pathogenesis of glaucoma, a common reason for irreversible blindness worldwide. So far there has been no convincing evidence that autoantibodies are accumulated in the retina of glaucoma patients and that the local immune homeostasis might be affected. Six human glaucomatous donor eyes and nine samples from donors with no recorded ocular disease were included. Antibody microarrays were used to examine the patterns of pro-inflammatory proteins and complement proteins. Analysis of TNF-α and interleukin levels revealed a slight up-regulation exclusively in the glaucomatous group, while complement protein levels were not altered. IgG autoantibody accumulations and/or cellular components were determined by immunohistology (n = 4 per group). A significantly reduced number of retinal ganglion cells was found in the glaucomatous group (healthy: 104±7 nuclei/mm, glaucoma: 67±9 nuclei/mm; p = 0.0007). Cell loss was accompanied by strong retinal IgG autoantibody accumulations, which were at least twice as high as in healthy subjects (healthy: 5.0±0.5 IgG deposits/100 cells, glaucoma: 9.4±1.9 IgG deposits/100 cells; p = 0.004). CD27(+) cells and CD27(+)/IgG(+) plasma cells were observed in all glaucomatous subjects, but not in controls. This work provides serious evidence for the occurrence of IgG antibody deposition and plasma cells in human glaucomatous retina. Moreover, the results suggest that these IgG deposits occurred in a pro-inflammatory environment which seems to be maintained locally by immune-competent cells like microglia. Thereby, glaucoma features an immunological involvement comparable to other

  9. Enhanced insight into the autoimmune component of glaucoma: IgG autoantibody accumulation and pro-inflammatory conditions in human glaucomatous retina.

    Directory of Open Access Journals (Sweden)

    Oliver W Gramlich

    Full Text Available BACKGROUND: There is accumulating evidence that autoimmune components, such as autoantibodies and autoantibody depositions, play a role in the pathogenesis of neurodegenerative diseases like Alzheimeŕs disease or Multiple Sclerosis. Due to alterations of autoantibody patterns in sera and aqueous humor, an autoimmune component is also assumed in the pathogenesis of glaucoma, a common reason for irreversible blindness worldwide. So far there has been no convincing evidence that autoantibodies are accumulated in the retina of glaucoma patients and that the local immune homeostasis might be affected. METHODS AND RESULTS: Six human glaucomatous donor eyes and nine samples from donors with no recorded ocular disease were included. Antibody microarrays were used to examine the patterns of pro-inflammatory proteins and complement proteins. Analysis of TNF-α and interleukin levels revealed a slight up-regulation exclusively in the glaucomatous group, while complement protein levels were not altered. IgG autoantibody accumulations and/or cellular components were determined by immunohistology (n = 4 per group. A significantly reduced number of retinal ganglion cells was found in the glaucomatous group (healthy: 104±7 nuclei/mm, glaucoma: 67±9 nuclei/mm; p = 0.0007. Cell loss was accompanied by strong retinal IgG autoantibody accumulations, which were at least twice as high as in healthy subjects (healthy: 5.0±0.5 IgG deposits/100 cells, glaucoma: 9.4±1.9 IgG deposits/100 cells; p = 0.004. CD27(+ cells and CD27(+/IgG(+ plasma cells were observed in all glaucomatous subjects, but not in controls. CONCLUSION: This work provides serious evidence for the occurrence of IgG antibody deposition and plasma cells in human glaucomatous retina. Moreover, the results suggest that these IgG deposits occurred in a pro-inflammatory environment which seems to be maintained locally by immune-competent cells like microglia. Thereby, glaucoma features an

  10. IgA, IgE e subclasses de IgG anti-Candida albicans no soro e lavado vaginal de pacientes com candidíase vulvovaginal IgA, IgE and IgG subclasses to Candida albicans in serum and vaginal fluid from patients with vulvovaginal candidiasis

    Directory of Open Access Journals (Sweden)

    Ricardo José Victal de Carvalho

    2003-01-01

    Full Text Available OBJETIVO: Determinar níveis de anticorpos IgA, IgE, IgG e subclasses (IgG1, IgG4 específicos a C. albicans no soro e lavado vaginal de mulheres com ou sem candidíase vulvovaginal para avaliar o papel destes anticorpos na imunopatogênese desta doença. MÉTODOS: Foram selecionadas 30 mulheres com sintomas clínicos de candidíase vulvovaginal (15 com cultura de secreção vaginal positiva para C. albicans, 11 com cultura negativa e quatro com cultura positiva para Candida não-albicans e 12 mulheres controles assintomáticas (nove com cultura negativa. Amostras de soro e lavado vaginal foram obtidas para a detecção de anticorpos anti-C. albicans por ELISA. RESULTADOS: Pacientes sintomáticas com cultura positiva apresentaram níveis de IgA específicas significativamente maiores no lavado vaginal e menores no soro do que aquelas com cultura negativa. Níveis séricos de IgE específica foram extremamente baixos em relação ao lavado vaginal. Altos níveis de IgG total específica foram encontrados no soro e lavado vaginal em ambos os grupos, independente da presença do fungo. Níveis de IgG1 e IgG4 específicas foram significativamente maiores somente no lavado vaginal de mulheres sintomáticas e cultura positiva, com relação IgG1/IgG4 ligeiramente maior, indicando que a resposta de anticorpos IgG1 possa estar predominantemente envolvida na resolução da infecção fúngica. CONCLUSÕES: Nossos resultados indicam resposta acentuada de IgA, IgG1 e IgG4 anti-C. albicans no lavado vaginal de mulheres sintomáticas com cultura positiva, sugerindo importante papel destes anticorpos na resposta imune local estimulada pela presença do fungo.PURPOSE: To determine the levels of IgA, IgE, IgG and subclasses (IgG1, IgG4 antibodies specific to C. albicans in serum and vaginal washes from women with or without vulvovaginal candidiasis in order to evaluate the role of these antibodies in the immunopathogenesis of the disease. METHODS: Thirty women

  11. Characterization of autoantibodies in autoimmune hemolytic anemia following treatment with interferon alfa

    International Nuclear Information System (INIS)

    Bencomo Hernandez, Antonio; Gutierrez Diaz, Adys; Avila Cabrera, Onel; Rodriguez, Luis Ramon

    2012-01-01

    We studied 13 patients with chronic myeloid leukemia and autoimmune hemolytic anemia induced by interferon alfa. They underwent tests for immune protein detection and characterization of IgG subclasses in RBCs by direct antiglobulin test (PAD) and the microplate technique. Also they were applied ELISA test for quantifying immunoglobulins in the red blood cells. It was detected the presence of IgG and C3 in 53.84 % of cases, IgG alone in 23.07 % and in 15.38 % were identified IgG and IgA autoantibodies. In 11 patients the presence of IgG1 was showed and also in one case the subclass IgG3 autoantibodies was identified. The ELISA detected antibodies at concentrations of 183 IgG molecules per erythrocyte in a patient with negative PAD. In high-grade hemolysis patients, it was found a concentration of autoantibodies between 1 500 and 3 180 molecules of IgG per erythrocyte, while in low-grade hemolysis patients it behaved between 183 and 1 000 molecules. There was a negative correlation between Hb and plasma haptoglobin values with the number of IgG molecules per erythrocyte and a positive correlation between the latter with the reticulocyte count

  12. Marginal versus joint Box-Cox transformation with applications to percentile curve construction for IgG subclasses and blood pressures.

    Science.gov (United States)

    He, Xuming; Ng, K W; Shi, Jian

    2003-02-15

    When age-specific percentile curves are constructed for several correlated variables, the marginal method of handling one variable at a time has typically been used. We address the question, frequently asked by practitioners, of whether we can achieve efficiency gains by joint estimation. We focus on a simple but common method of Box-Cox transformation and assess the statistical impact of a joint transformation to multivariate normality on the percentile curve estimation for correlated variables. We find that there is little gain from the joint transformation for estimating percentiles around the median but a noticeable reduction in variances is possible for estimating extreme percentiles that are usually of main interest in medical and biological applications. Our study is motivated by problems in constructing percentile charts for IgG subclasses of children and for blood pressures in adult populations, both of which are discussed in the paper as examples, and yet our general findings are applicable to a wide range of other problems. Copyright 2003 John Wiley & Sons, Ltd.

  13. Functional immunomics: microarray analysis of IgG autoantibody repertoires predicts the future response of mice to induced diabetes.

    Science.gov (United States)

    Quintana, Francisco J; Hagedorn, Peter H; Elizur, Gad; Merbl, Yifat; Domany, Eytan; Cohen, Irun R

    2004-10-05

    One's present repertoire of antibodies encodes the history of one's past immunological experience. Can the present autoantibody repertoire be consulted to predict resistance or susceptibility to the future development of an autoimmune disease? Here, we developed an antigen microarray chip and used bioinformatic analysis to study a model of type 1 diabetes developing in nonobese diabetic male mice in which the disease was accelerated and synchronized by exposing the mice to cyclophosphamide at 4 weeks of age. We obtained sera from 19 individual mice, treated the mice to induce cyclophosphamide-accelerated diabetes (CAD), and found, as expected, that 9 mice became severely diabetic, whereas 10 mice permanently resisted diabetes. We again obtained serum from each mouse after CAD induction. We then analyzed, by using rank-order and superparamagnetic clustering, the patterns of antibodies in individual mice to 266 different antigens spotted on the chip. A selected panel of 27 different antigens (10% of the array) revealed a pattern of IgG antibody reactivity in the pre-CAD sera that discriminated between the mice resistant or susceptible to CAD with 100% sensitivity and 82% specificity (P = 0.017). Surprisingly, the set of IgG antibodies that was informative before CAD induction did not separate the resistant and susceptible groups after the onset of CAD; new antigens became critical for post-CAD repertoire discrimination. Thus, at least for a model disease, present antibody repertoires can predict future disease, predictive and diagnostic repertoires can differ, and decisive information about immune system behavior can be mined by bioinformatic technology. Repertoires matter.

  14. Evaluation of cysticercus-specific IgG (total and subclasses and IgE antibody responses in cerebrospinal fluid samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies Avaliação das respostas de anticorpos anti-cisticercos IgG (total e subclasses e IgE em amostras de líquido cefalorraquidiano de pacientes com neurocisticercose apresentando produção intratecal de anticorpos específicos IgG

    Directory of Open Access Journals (Sweden)

    Lisandra Akemi Suzuki

    2013-01-01

    Full Text Available In the present study, an enzyme-linked immunosorbent assay (ELISA standardized with vesicular fluid of Taenia solium cysticerci was used to screen for IgG (total and subclasses and IgE antibodies in cerebrospinal fluid (CSF samples from patients with neurocysticercosis showing intrathecal production of specific IgG antibodies and patients with other neurological disorders. The following results were obtained: IgG-ELISA: 100% sensitivity (median of the ELISA absorbances (MEA=1.17 and 100% specificity; IgG1-ELISA: 72.7% sensitivity (MEA=0.49 and 100% specificity; IgG2-ELISA: 81.8% sensitivity (MEA=0.46 and 100% specificity; IgG3-ELISA: 63.6% sensitivity (MEA=0.12 and 100% specificity; IgG4-ELISA: 90.9% sensitivity (MEA=0.85 and 100% specificity; IgE-ELISA 93.8% sensitivity (MEA=0.60 and 100% specificity. There were no significant differences between the sensitivities and specificities in the detection of IgG-ELISA and IgE-ELISA, although in CSF samples from patients with neurocysticercosis the MEA of the IgG-ELISA was significantly higher than that of the IgE-ELISA. The sensitivity and MEA values of the IgG4-ELISA were higher than the corresponding values for the other IgG subclasses. Future studies should address the contribution of IgG4 and IgE antibodies to the physiopathology of neurocysticercosis.No presente estudo, uma reação imunoenzimática (ELISA padronizada com o fluido vesicular de cisticercos de Taenia solium foi utilizada para avaliar as respostas de anticorpos anti-cisticercos IgG (total e subclasses e IgE em amostras de líquido cefalorraquidiano (LCR de pacientes com neurocisticercose apresentando produção intratecal de anticorpos específicos IgG e pacientes com outras desordens neurológicas. Os seguintes resultados foram obtidos: ELISA-IgG: 100% de sensibilidade (mediana das absorbâncias das reações ELISA (MAE=1,17 e especificidade 100%; ELISA-IgG1: sensibilidade 72,7% (MAE=0,49 e especificidade 100%; ELISA-IgG2

  15. HLA-A and -B alleles and haplotypes in 240 index patients with common variable immunodeficiency and selective IgG subclass deficiency in central Alabama

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    Barton James C

    2003-06-01

    Full Text Available Abstract Background We wanted to quantify HLA-A and -B phenotype and haplotype frequencies in Alabama index patients with common variable immunodeficiency (CVID and selective IgG subclass deficiency (IgGSD, and in control subjects. Methods Phenotypes were detected using DNA-based typing (index cases and microlymphocytotoxicity typing (controls. Results A and B phenotypes were determined in 240 index cases (114 CVID, 126 IgGSD and 1,321 controls and haplotypes in 195 index cases and 751 controls. Phenotyping revealed that the "uncorrected" frequencies of A*24, B*14, B*15, B*35, B*40, B*49, and B*50 were significantly greater in index cases, and frequencies of B*35, B*58, B*62 were significantly lower in index cases. After Bonferroni corrections, the frequencies of phenotypes A*24, B*14, and B*40 were significantly greater in index cases, and the frequency of B*62 was significantly lower in index cases. The most common haplotypes in index cases were A*02-B*44 (frequency 0.1385, A*01-B*08 (frequency 0.1308, and A*03-B*07 (frequency 0.1000, and the frequency of each was significantly greater in index cases than in control subjects ("uncorrected" values of p p p = 0.0166. Most phenotype and haplotype frequencies in CVID and IgGSD were similar. 26.7% of index patients were HLA-haploidentical with one or more other index patients. We diagnosed CVID or IgGSD in first-degree or other relatives of 26 of 195 index patients for whom HLA-A and -B haplotypes had been ascertained; A*01-B*08, A*02-B*44, and A*29-B*44 were most frequently associated with CVID or IgGSD in these families. We conservatively estimated the combined population frequency of CVID and IgGSD to be 0.0092 in adults, based on the occurrence of CVID and IgGSD in spouses of the index cases. Conclusions CVID and IgGSD in adults are significantly associated with several HLA haplotypes, many of which are also common in the Alabama Caucasian population. Immunoglobulin phenotype variability

  16. Effect of IgG subclasses on in vivo bioavailability and metabolic fate of immune-complexed insulin in Lewis rats

    International Nuclear Information System (INIS)

    Arquilla, E.R.; Stenger, D.; McDougall, B.; Ulich, T.R.

    1987-01-01

    The bioavailability, distribution, and metabolic fate of 125 I-labeled insulin complexed to antibodies in guinea pig antiserum, purified guinea pig IgG1, IgG2, a mixture of IgG1 and IgG2, and homologous Lou/m rat antiserum were studied in inbred Lewis rats. 125 I-insulin complexed to purified guinea pig IgG2 antibodies was rapidly cleared from the blood and sequestered in increasing amounts with time in the liver. Large amounts of the 125 I-insulin complexed to guinea pig IgG1 antibodies remained in the blood for at least 30 min. The bioavailability of 125 I-insulin bound to IgG1 and IgG2 antibodies was inhibited for at least 30 min because significantly less was available for rapid binding to insulin receptors on hepatocytes and renal tubular cells and its subsequent rapid degradation. The bioavailability of 125 I-insulin was further decreased when bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies compared with the 125 I-insulin complexed to either purified IgG1 or IgG2 antibodies alone. The 125 I-insulin bound to antibodies in native guinea pig antiserum or a mixture of IgG1 and IgG2 antibodies was distributed in vivo in a manner reflecting the relative concentrations of the IgG1 and IgG2 antibodies present. The bioavailability, distribution, and metabolic fate of 125 I-insulin in immune complexes prepared with homologous Lou/m rat insulin antiserum was qualitatively similar to that observed with immune complexes prepared with guinea pig insulin antiserum. It appears that the Lewis rat can be used as an in vivo model to study the bioavailability,distribution,and metabolic fate of insulin bound to xenogenic or homologous insulin antibodies

  17. Isotypes and antigenic profiles of pemphigus foliaceus and pemphigus vulgaris autoantibodies.

    Science.gov (United States)

    Hacker, Mary K; Janson, Marleen; Fairley, Janet A; Lin, Mong-Shang

    2002-10-01

    In this study we systematically characterized isotype profiles and antigenic and tissue specificity of antidesmoglein autoantibodies from patients with pemphigus foliaceus (PF) and pemphigus vulgaris (PV) using enzyme-linked immunoabsorbent assays (ELISA), indirect immunofluorescence (IIF) staining, and immunoblotting (IB). In PF, we found that IgG1 antidesmoglein-1 (Dsg1) reacts with a linear epitope(s) on the ectodomain of Dsg1, while its IgG4 counterpart recognizes a conformational epitope(s). These two subclasses of anti-Dsg1 are both capable of recognizing tissues from monkey esophagus and adult human skin, but IgG1 is not able to react with mouse skin, which may explain why this isotype of anti-Dsg1 failed to induce PF-like lesions in the passive transfer animal model. In mucosal PV patients, we found that both IgG1 and IgG4 only recognized monkey esophagus tissue by IIF, except in one patient, indicating that these antibodies react with a unique conformational epitope(s) that is present in mucosal but not skin tissue. In generalized PV, IgG1 anti-Dsg3 autoantibodies appeared to recognize a linear epitope(s) on the Dsg3 ectodomain. In contrast, IgG4 anti-Dsg3 antibodies recognized both linear and conformational epitopes on the Dsg3 molecule. Interestingly, the IgG1 anti-Dsg3 antibodies failed to react with human and mouse skin tissues, suggesting that this subclass of autoantibodies may not play an essential role in the development of PV suprabasilar lesions. In summary, we conclude that this study further elucidates the pathological mechanisms of PF and PV autoantibodies by revealing their distinct isotype and antigenic profiles. This information may help us to better understand the autoimmune mechanisms underlying the development of pemphigus.

  18. Total lymphoid irradiation reduces IgG autoantibody production and enhances specific antibody responses in NZB/NZW F1 mice

    Energy Technology Data Exchange (ETDEWEB)

    Farinas, M.C.; Strober, S.

    1989-07-01

    Thymus-independent primary antibody responses were studied in young and old (9 months) untreated and TLI-treated NZB/NZW and BALB/c mice. Untreated old NZB/NZW mice had a low primary response to Brucella abortus (BA) as compared to that of young NZB/NZW and BALB/c mice. However, TLI treatment resulted in a 130-fold increase in the IgG anti-BA primary antibody response at day 21 postimmunization, achieving similar levels to those of young NZB/NZW or nonautoimmune BALB/c mice. Anti-TNP responses to trinitrophenylated BA or Ficoll were masked by high background levels of anti-TNP antibodies. Despite the increase in the anti-BA response, spontaneous immunoglobulin secretion and autoantibody levels were markedly decreased after TLI in old NZB/NZW mice.

  19. Total lymphoid irradiation reduces IgG autoantibody production and enhances specific antibody responses in NZB/NZW F1 mice

    International Nuclear Information System (INIS)

    Farinas, M.C.; Strober, S.

    1989-01-01

    Thymus-independent primary antibody responses were studied in young and old (9 months) untreated and TLI-treated NZB/NZW and BALB/c mice. Untreated old NZB/NZW mice had a low primary response to Brucella abortus (BA) as compared to that of young NZB/NZW and BALB/c mice. However, TLI treatment resulted in a 130-fold increase in the IgG anti-BA primary antibody response at day 21 postimmunization, achieving similar levels to those of young NZB/NZW or nonautoimmune BALB/c mice. Anti-TNP responses to trinitrophenylated BA or Ficoll were masked by high background levels of anti-TNP antibodies. Despite the increase in the anti-BA response, spontaneous immunoglobulin secretion and autoantibody levels were markedly decreased after TLI in old NZB/NZW mice

  20. 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.

  1. CERTIFICATION REPORT The certification of the mass concentration of immunoglobulin G proteinase 3 anti-neutrophil cytoplasmic autoantibodies (IgG PR3 ANCA) in human serum: ERM® - DA483/IFCC

    OpenAIRE

    MONOGIOUDI EVANTHIA; HUTU DANA PETRONELA; CHAROUD-GOT JEAN; SHELDON JOANNA; SCHIMMEL HEINZ; TRAPMANN STEFANIE; MERONI PIERLUIGI; EMONS HENDRIK; ZEGERS INGRID

    2017-01-01

    This report describes the production and certification of ERM-DA483/IFCC, a serum protein reference material intended for the standardisation of measurements of immunoglobulin G proteinase 3 anti-neutrophil cytoplasmic autoantibodies (IgG PR3 ANCA). The material was produced according to ISO Guide 34:2009 [ ] and is certified in accordance with ISO Guide 35:2006. The raw material used to prepare ERM-DA483/IFCC was a plasmapheresis material containing a high concentration of IgG PR3 ANCA. A...

  2. 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

    BACKGROUND: Antibodies against chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) are markers of the development of resistance of P aeruginosa to beta-lactam antibiotics in patients with cystic fibrosis and chronic lung infection. The role of these antibodies in patients with chronic...... of the chronic infection the a beta ab titres were higher in patients with good lung function than in those with poor lung function. CONCLUSIONS: The association of a weak IgG3 and a strong IgG4 a beta ab response suggests that the contribution of a beta ab antibodies to lung diseases mediated by immune...... complexes might be less important than other antipseudomonal antibodies. A beneficial neutralising effect of the a beta ab antibodies on the antibiotic destroying enzymes may be an additional factor....

  3. Prospective estimation of IgG, IgG subclass and IgE antibodies to dietary proteins in infants with cow milk allergy. Levels of antibodies to whole milk protein, BLG and ovalbumin in relation to repeated milk challenge and clinical course of cow milk allergy

    DEFF Research Database (Denmark)

    Høst, A; Husby, S; Gjesing, B

    1992-01-01

    Prospectively, serum levels of IgE, specific IgE antibodies (AB) to whole cow milk protein (CMP), bovine se-albumin, bovine immunoglobulin, bovine lactoferrin, bovine lactalbumin and beta-lactoglobulin (BLG), IgG and IgG subclass antibodies to ovalbumin (OA) and BLG, and IgG4 RAST to CMP (bovine...... whey) were measured in 39 infants with cow milk protein allergy (CMPA) at birth (cord blood), at time of diagnosis and before and after milk challenge at the age of 12 months. Immunological measurements were also undertaken in 33 control infants without CMPA at birth, at 6 months and at 18 months...... of the type of CMPA (IgE-mediated (CMA) or non-IgE-mediated (CMI)), and irrespective of whether remission had occurred. In cord blood 25/33 (76%) of the infants with CMPA had specific IgE-AB to one or more of the bovine milk proteins indicating a prenatal intrauterine sensitization to cow milk protein. At 6...

  4. First report of real-time monitoring of coagulation function potential and IgG subtype of anti-FVIII autoantibodies in a child with acquired hemophilia A associated with streptococcal infection and amoxicillin.

    Science.gov (United States)

    Takeyama, Masahiro; Nogami, Keiji; Kajimoto, Takahiro; Ogiwara, Kenichi; Matsumoto, Tomoko; Shima, Midori

    2018-01-01

    We describe an 8-year-old boy with acquired hemophilia A (AHA) associated with streptococcal infection and amoxicillin. Laboratory data revealed low factor VIII activity (FVIII:C, 1.5 IU/dl), and FVIII inhibitor (15.9 BU/ml). Comprehensive coagulation function assays, including rotation thromboelastometry (ROTEM ® ), revealed a markedly prolonged clotting time. Thrombin and plasmin generation (TG/PG) appeared to be moderately impaired. The inhibitor epitope of his anti-FVIII autoantibody recognized light and heavy chains. He was treated with Novoseven ® and prednisolone, resulting in rapid improvement. ROTEM showed the return of coagulation time to normal level on day 20, and TG gradually improved. PG was moderately reduced in the clinical early phase, but improved at day 20. The patient's IgG subtype was IgG 4 at onset. IgG 1 was transiently positive on day 20, but negative on day 46. FVIII inhibitor gradually decreased and was completely absent after day 46, along with the elevated FVIII:C. IgG4 was again elevated on day 83, followed by a rapid decrease, indicative of the presence of non-neutralizing antibody, which remains currently undetected. We for the first time report changes in comprehensive coagulation function and IgG subtype of anti-FVIII antibody in a rare pediatric case of AHA.

  5. Autoantibodies in chronic pancreatitis

    DEFF Research Database (Denmark)

    Rumessen, J J; Marner, B; Pedersen, N T

    1985-01-01

    In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane, and reti......In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane......, and reticulin, and the IgG- and IgA-type pancreas-specific antibodies against islet cells, acinus cells, and ductal cells (DA) were estimated blindly. In 23 of the patients chronic pancreatitis was verified, whereas chronic pancreatitis was rejected in 37 patients (control group). IgG and IgA were found...... in significantly higher concentrations in the patients with chronic pancreatitis than in the control group but within the normal range. ANA and DA occurred very frequently in both groups but with no statistical difference. Other autoantibodies only occurred sporadically. The findings of this study do not support...

  6. Immunoglobulin subclass in experimental murine Toxocara cati infection

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    Kusnoto

    2017-11-01

    Full Text Available Aim: The aim of this study was to detect specific immunoglobulin (Ig that could be used to determine monoclonal antibody in conjugate-making an effort for the indirect enzyme-linked immunosorbent assay (ELISA diagnostic kit of toxocariasis in human. Materials and Methods: The study was conducted to assess the Ig profile, based on ELISA-isotyping, in mice infected with second stage larvae eggs of Toxocara cati. The optical density values of anti-T. cati mice serum IgG subclasses were analyzed by applying ANOVA factorial. Results: The specific IgG subclass in mice infected with T. cati mice was found to be IgG2β. Conclusion: Subclass of IgG, especially IgG2β, can provide leads about the use of the monoclonal antibody in conjugate making an effort for the indirect ELISA diagnostic kit.

  7. IgG4 antibodies in Egyptian patients with schistosomiasis

    NARCIS (Netherlands)

    Iskander, R.; Das, P. K.; Aalberse, R. C.

    1981-01-01

    Serum immunoglobulins were determined in 40 Egyptian patients with schistosomiasis. In addition to the well-established elevation in total IgE, a striking imbalance in the IgG subclass levels was found: IgG3 and IgG4 levels were markedly elevated, whereas IgG2 levels were normal. The IgG4 level did

  8. Immunochemical characteristics of IgG4 antibodies

    NARCIS (Netherlands)

    van der Zee, J. S.; Aalberse, R. C.

    1988-01-01

    Although a small part of the IgG4 subclass probably can bind to basophils (and mast cells), IgG4 antibodies usually do not behave as anaphylactic antibodies. Therefore, detection of IgG4 antibodies in serum is not a suitable in vitro assay for IgG-S-TS activity. Furthermore, differences between IgG4

  9. Distinct patterns of blood-stage parasite antigens detected by plasma IgG subclasses from individuals with different level of exposure to Plasmodium falciparum infections

    DEFF Research Database (Denmark)

    Olesen, Cathrine Holm; Brahimi, Karima; Vandahl, Brian

    2010-01-01

    ABSTRACT: BACKGROUND: In endemic regions naturally acquired immunity against Plasmodium falciparum develops as a function of age and exposure to parasite infections and is known to be mediated by IgG. The targets of protective antibodies remain to be fully defined. Several immunoepidemiological s...

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

    Directory of Open Access Journals (Sweden)

    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

  11. The Essence of Subclassing

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann; Møller-Pedersen, Birger

    The essence of subclassing is the ability to represent classification hierarchies reflecting domain concepts. With the right class mechanism there is no need for a separate type/subtype mechanism, and general classes may have behavior specifications so that subclassing also implies code reuse....... Sometimes the application is so well defined (known) that developers may readily start out with classes that represent domain concepts. Singular objects have been around for some time, so a new kind of language with equal support for both objects and classes would simply ask for tool support for objects...

  12. Structural characterization of the Man5 glycoform of human IgG3 Fc

    Energy Technology Data Exchange (ETDEWEB)

    Shah, Ishan S.; Lovell, Scott; Mehzabeen, Nurjahan; Battaile, Kevin P.; Tolbert, Thomas J. (Kansas); (HWMRI)

    2017-12-01

    Immunoglobulin G (IgG) consists of four subclasses in humans: IgG1, IgG2, IgG3 and IgG4, which are highly conserved but have unique differences that result in subclass-specific effector functions. Though IgG1 is the most extensively studied IgG subclass, study of other subclasses is important to understand overall immune function and for development of new therapeutics. When compared to IgG1, IgG3 exhibits a similar binding profile to Fcγ receptors and stronger activation of complement. All IgG subclasses are glycosylated at N297, which is required for Fcγ receptor and C1q complement binding as well as maintaining optimal Fc conformation. We have determined the crystal structure of homogenously glycosylated human IgG3 Fc with a GlcNAc2Man5 (Man5) high mannose glycoform at 1.8 Å resolution and compared its structural features with published structures from the other IgG subclasses. Although the overall structure of IgG3 Fc is similar to that of other subclasses, some structural perturbations based on sequence differences were revealed. For instance, the presence of R435 in IgG3 (and H435 in the other IgG subclasses) has been implicated to result in IgG3-specific properties related to binding to protein A, protein G and the neonatal Fc receptor (FcRn). The IgG3 Fc structure helps to explain some of these differences. Additionally, protein-glycan contacts observed in the crystal structure appear to correlate with IgG3 affinity for Fcγ receptors as shown by binding studies with IgG3 Fc glycoforms. Finally, this IgG3 Fc structure provides a template for further studies aimed at engineering the Fc for specific gain of function.

  13. A microfluorometric assay for immunoglobulin class and subclass levels in murine serum

    NARCIS (Netherlands)

    Haaijman, J.J.; Brinkhof, J.

    1977-01-01

    The IgG fractions of rabbit antisera specific for the Fc part of mouse IgA, IgM, and the four subclasses of IgG (1, 2a, 2b, and 3) were coupled covalently to Sepharose beads by the cyanogen bromide method. The beads were then incubated with different dilutions of mouse serum. The mouse

  14. Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with tumour necrosis factor blocking agents in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Bos, W. H.; Bartelds, G. M.; Vis, M.; van der Horst, A. R.; Wolbink, G. J.; van de Stadt, R. J.; van Schaardenburg, D.; Dijkmans, B. A. C.; Lems, W. F.; Nurmohamed, M. T.; Aarden, L.; Hamann, D.

    2009-01-01

    To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody (ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated fibrinogen (ACF) and IgG1 :

  15. The Role of Pathogenic Autoantibodies in Autoimmunity

    Directory of Open Access Journals (Sweden)

    Merrill J. Rowley

    2015-11-01

    Full Text Available The serological presence of autoantibodies is diagnostic of autoimmunity, and these autoantibodies may be present for many years before the presentation of autoimmune disease (AID. Although a pathogenic role has been demonstrated for various autoantibodies reactive with cell surface and extracellular autoantigens, studies using monoclonal antibodies (mAb show not all antibodies in the polyclonal response are pathogenic. Differences depend on Fab-mediated diversity in epitope specificity, Fc-mediated effects based on immunoglobulin (Ig class and subclass, activation of complement, and the milieu in which the reaction occurs. These autoantibodies often occur in organ-specific AID and this review illustrates their pathogenic and highly specific effects. The role of autoantibodies associated with intracellular antigens is less clear. In vitro they may inhibit or adversely affect well-defined intracellular biochemical pathways, yet, in vivo they are separated from their autoantigens by multiple cellular barriers. Recent evidence that Ig can traverse cell membranes, interact with intracellular proteins, and induce apoptosis has provided new evidence for a pathogenic role for such autoantibodies. An understanding of how autoantibodies behave in the polyclonal response and their role in pathogenesis of AID may help identify populations of culprit B-cells and selection of treatments that suppress or eliminate them.

  16. Indices of anti-dengue immunoglobulin G subclasses in adult Mexican patients with febrile and hemorrhagic dengue in the acute phase.

    Science.gov (United States)

    Posadas-Mondragón, Araceli; Aguilar-Faisal, José Leopoldo; Chávez-Negrete, Adolfo; Guillén-Salomón, Edith; Alcántara-Farfán, Verónica; Luna-Rojas, Lucero; Ávila-Trejo, Amanda Marineth; Del Carmen Pacheco-Yépez, Judith

    2017-10-01

    Heterologous secondary infections are at increased risk of developing dengue hemorrhagic fever (DHF) because of antibody-dependent enhancement (ADE). IgG subclasses can fix and activate complement and bind to Fcɣ receptors. These factors may also play an important role in the development of ADE and thus in the pathogenesis of DHF. The aim of this study was to analyze the indices of anti-dengue IgG subclasses in adult patients with febrile and hemorrhagic dengue in the acute phase. In 2013, 129 patients with dengue fever (DF) and 57 with DHF in Veracruz, Mexico were recruited for this study and anti-dengue IgM and IgG determined by capture ELISA. Anti-dengue IgG subclasses were detected by indirect ELISA. Anti-dengue IgG2 and IgG3 subclasses were detected in patients with dengue. IgG1 increased significantly in the sera of patients with both primary and secondary infections and DHF, but was higher in patients with secondary infections. The IgG4 subclass index was significantly higher in the sera of patients with DHF than in that of those with DF, who were in the early and late acute phase of both primary and secondary infection. In conclusion, indices of subclasses IgG1 and IgG4 were higher in patients with DHF. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  17. Increased immune complexes of hypocretin autoantibodies in narcolepsy.

    Science.gov (United States)

    Deloumeau, Aude; Bayard, Sophie; Coquerel, Quentin; Déchelotte, Pierre; Bole-Feysot, Christine; Carlander, Bertrand; Cochen De Cock, Valérie; Fetissov, Sergueï O; Dauvilliers, Yves

    2010-10-13

    Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune complexes. Serum levels of free and dissociated (total) autoantibodies reacting with hypocretin-1 peptide were measured by enzyme-linked immunosorbent assay and analyzed with regard to clinical parameters in 82 subjects with narcolepsy-cataplexy, narcolepsy without cataplexy or idiopathic hypersomnia and were compared to 25 healthy controls. Serum levels of total but not free IgG autoantibodies against hypocretin-1 were increased in narcolepsy-cataplexy. Increased levels of complexed IgG autoantibodies against hypocretin-1 were found in all patients groups with a further increase in narcolepsy-cataplexy. Levels of total IgM hypocretin-1 autoantibodies were also elevated in all groups of patients. Increased levels of anti-idiotypic IgM autoantibodies reacting with hypocretin-1 IgG autoantibodies affinity purified from sera of subjects with narcolepsy-cataplexy were found in all three groups of patients. Disease duration correlated negatively with serum levels of hypocretin-1 IgG and IgM autoantibodies and with anti-idiotypic IgM autoantibodies. Central hypersomnias and particularly narcolepsy-cataplexy are characterized by higher serum levels of autoantibodies directed against hypocretin-1 which are present as immune complexes most likely with anti-idiotypic autoantibodies suggesting their relevance to the mechanism of sleep-wake cycle regulation.

  18. Increased immune complexes of hypocretin autoantibodies in narcolepsy.

    Directory of Open Access Journals (Sweden)

    Aude Deloumeau

    Full Text Available BACKGROUND: Hypocretin peptides participate in the regulation of sleep-wake cycle while deficiency in hypocretin signaling and loss of hypocretin neurons are causative for narcolepsy-cataplexy. However, the mechanism responsible for alteration of the hypocretin system in narcolepsy-cataplexy and its relevance to other central hypersomnias remain unknown. Here we studied whether central hypersomnias can be associated with autoantibodies reacting with hypocretin-1 peptide present as immune complexes. METHODOLOGY: Serum levels of free and dissociated (total autoantibodies reacting with hypocretin-1 peptide were measured by enzyme-linked immunosorbent assay and analyzed with regard to clinical parameters in 82 subjects with narcolepsy-cataplexy, narcolepsy without cataplexy or idiopathic hypersomnia and were compared to 25 healthy controls. PRINCIPAL FINDINGS: Serum levels of total but not free IgG autoantibodies against hypocretin-1 were increased in narcolepsy-cataplexy. Increased levels of complexed IgG autoantibodies against hypocretin-1 were found in all patients groups with a further increase in narcolepsy-cataplexy. Levels of total IgM hypocretin-1 autoantibodies were also elevated in all groups of patients. Increased levels of anti-idiotypic IgM autoantibodies reacting with hypocretin-1 IgG autoantibodies affinity purified from sera of subjects with narcolepsy-cataplexy were found in all three groups of patients. Disease duration correlated negatively with serum levels of hypocretin-1 IgG and IgM autoantibodies and with anti-idiotypic IgM autoantibodies. CONCLUSION: Central hypersomnias and particularly narcolepsy-cataplexy are characterized by higher serum levels of autoantibodies directed against hypocretin-1 which are present as immune complexes most likely with anti-idiotypic autoantibodies suggesting their relevance to the mechanism of sleep-wake cycle regulation.

  19. IgG4 Cholangiopathy

    Directory of Open Access Journals (Sweden)

    Yoh Zen

    2012-01-01

    Full Text Available IgG4 cholangiopathy can involve any level of the biliary tree which exhibits sclerosing cholangitis or pseudotumorous hilar lesions. Most cases are associated with autoimmune pancreatitis, an important diagnostic clue. Without autoimmune pancreatitis, however, the diagnosis of IgG4-cholangiopathy is challenging. Indeed such cases have been treated surgically. IgG4-cholangiopathy should be diagnosed based on serological examinations including serum IgG4 concentrations, radiological features, and histological evidence of IgG4+ plasma cell infiltration. Steroid therapy is very effective even at disease relapse. A Th2-dominant immune response or the activation of regulatory T cells seems to be involved in the underlying immune reaction. It is still unknown why IgG4 levels are specifically elevated in patients with this disease. IgG4 might be secondarily overexpressed by Th2 or regulatory cytokines given the lack of evidence that IgG4 is an autoantibody.

  20. Heritability of antibody isotype and subclass responses to Plasmodium falciparum antigens.

    Directory of Open Access Journals (Sweden)

    Nancy O Duah

    2009-10-01

    Full Text Available It is important to understand the extent to which genetic factors regulate acquired immunity to common infections. A classical twin study design is useful to estimate the heritable component of variation in measurable immune parameters.This study assessed the relative heritability of different plasma antibody isotypes and subclasses (IgG1, IgG2, IgG3, IgG4, IgM, IgA and IgE naturally acquired to P. falciparum blood stage antigens AMA1, MSP1-19, MSP2 (two allelic types and MSP3 (two allelic types. Separate analyses were performed on plasma from 213 pairs of Gambian adult twins, 199 child twin pairs sampled in a dry season when there was little malaria transmission, and another set of 107 child twin pairs sampled at the end of the annual wet season when malaria was common. There were significantly positive heritability (h(2 estimates for 48% (20/42 of the specific antibody assays (for the seven isotypes and subclasses to the six antigens tested among the adults, 48% (20/42 among the children in the dry season and 31% (13/42 among the children in the wet season. In children, there were significant heritability estimates for IgG4 reactivity against each of the antigens, and this subclass had higher heritability than the other subclasses and isotypes. In adults, 75% (15/20 of the significantly heritable antigen-specific isotype responses were attributable to non-HLA class II genetic variation, whereas none showed a significant HLA contribution.Genome-wide approaches are now warranted to map the major genetic determinants of variable antibody isotype and subclass responses to malaria, alongside evaluation of their impact on infection and disease. Although plasma levels of IgG4 to malaria antigens are generally low, the exceptionally high heritability of levels of this subclass in children deserves particular investigation.

  1. Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with tumour necrosis factor blocking agents in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Bos, W.H.; Bartelds, G.M.; Vis, M.; van der Horst, A.R.; Wolbink, G.J.; van de Stadt, R.J.; van Schaardenburg, D.; Dijkmans, B.A.C.; Lems, W.F.; Nurmohamed, M.T.; Aarden, L.; Hamann, D.

    2009-01-01

    Objective: To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody ( ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis ( RA). Methods: IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated

  2. Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with tumour necrosis factor blocking agents in patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Bos, W.H.; Bartelds, G.M.; Vis, M.; Horst, A.; Wolbink, G.; van de Stadt, R.J.; van Schaardenburg, D.; Dijkmans, B.A.C.; Lems, W.F.; Nurmohamed, M.T.; Aarden, L.; Hamann, D.

    2009-01-01

    Objective: To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody (ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). Methods: IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated

  3. Different Somatic Hypermutation Levels among Antibody Subclasses Disclosed by a New Next-Generation Sequencing-Based Antibody Repertoire Analysis

    Directory of Open Access Journals (Sweden)

    Kazutaka Kitaura

    2017-05-01

    Full Text Available A diverse antibody repertoire is primarily generated by the rearrangement of V, D, and J genes and subsequent somatic hypermutation (SHM. Class-switch recombination (CSR produces various isotypes and subclasses with different functional properties. Although antibody isotypes and subclasses are considered to be produced by both direct and sequential CSR, it is still not fully understood how SHMs accumulate during the process in which antibody subclasses are generated. Here, we developed a new next-generation sequencing (NGS-based antibody repertoire analysis capable of identifying all antibody isotype and subclass genes and used it to examine the peripheral blood mononuclear cells of 12 healthy individuals. Using a total of 5,480,040 sequences, we compared percentage frequency of variable (V, junctional (J sequence, and a combination of V and J, diversity, length, and amino acid compositions of CDR3, SHM, and shared clones in the IgM, IgD, IgG3, IgG1, IgG2, IgG4, IgA1, IgE, and IgA2 genes. The usage and diversity were similar among the immunoglobulin (Ig subclasses. Clonally related sequences sharing identical V, D, J, and CDR3 amino acid sequences were frequently found within multiple Ig subclasses, especially between IgG1 and IgG2 or IgA1 and IgA2. SHM occurred most frequently in IgG4, while IgG3 genes were the least mutated among all IgG subclasses. The shared clones had almost the same SHM levels among Ig subclasses, while subclass-specific clones had different levels of SHM dependent on the genomic location. Given the sequential CSR, these results suggest that CSR occurs sequentially over multiple subclasses in the order corresponding to the genomic location of IGHCs, but CSR is likely to occur more quickly than SHMs accumulate within Ig genes under physiological conditions. NGS-based antibody repertoire analysis should provide critical information on how various antibodies are generated in the immune system.

  4. Molecular cloning and differential IgG responses to a histidine-rich ...

    African Journals Online (AJOL)

    C1 immunoglobulin G (IgG) subclass levels were assessed by ELISA in 15 pairs and 18 pairs of selected and cross-matched infected and putatively immune subjects from Cameroon and Ecuador, respectively. IgG3 and IgG4 levels were shown to be significantly higher in putatively immune (immune protected) subjects.

  5. Pass-by-Subclass Parameters

    DEFF Research Database (Denmark)

    Madsen, Anders Bach; Ernst, Erik

    2010-01-01

    where computations involving types are used. Such subclasses are not optimized for being beautiful expositions of application domain concepts, they are much more like function applications or method calls: They occur inline in "client code", they may bind relatively complex expressions, and they rely...

  6. Serum IgG2 and tissue IgG2 plasma cell elevation in orbital IgG4-related disease (IgG4-RD): Potential use in IgG4-RD assessment.

    Science.gov (United States)

    Chan, Anita S Y; Mudhar, Hardeep; Shen, Sunny Yu; Lang, Stephanie S; Fernando, Malee; Hilmy, Maryam Hazly; Guppy, Naomi Jayne; Rennie, Ian; Dunkley, Lisa; Al Jajeh, Issam

    2017-11-01

    To determine the role of serum and tissue IgG2 in orbital biopsies with the histological features of IgG4-related disease (IgG4-RD) in comparison with non-IgG4-related orbital inflammatory disorders (OID), including autoimmune disorders. This is an international (Sheffield, UK, and Singapore) collaborative, retrospective case review of 69 patients (38 from Singapore National Eye Centre and 31 from Royal Hallamshire Hospital, Sheffield) with orbital inflammatory biopsies between 2002 and 2016. Clinical information and histology were reviewed and cases were classified into three groups: Group 1: IgG4-RD orbital inflammation (n=43); Group 2: idiopathic OID (n=12) and Group 3: autoimmune OID (n=14). Serum IgG1, IgG2, IgG3 and IgG4 levels were collated where available and immunohistochemistry (IHC) for tissue IgG2 plasma cells was performed. Dual IHC showed IgG2 plasma cells as a distinct population from IgG4 plasma cells. Significant (twofold) serum IgG2 elevation was noted among IgG4-RD (group 1), idiopathic (group 2) and autoimmune OID (group 3). Similarly, significant elevation of tissue IgG2 plasma cells was also seen among IgG4-RD (group 1), idiopathic and autoimmune OID (groups 2 and 3). Significant elevations of serum IgG2 and tissue IgG2 plasma cells are present in orbital IgG4-RD in comparison with non-IgG4 orbital inflammation (idiopathic and autoimmune OID), suggesting that IgG2 may play a role in IgG4-RD. A serum IgG2 cut-off >5.3 g/L was found to be 80% sensitive and 91.7% specific for orbital IgG4-RD, with an accuracy of 0.90. Tissue IgG2 and IgG4 subclass reporting may provide additional insight regarding the 'IgG4-RD' pathogenesis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. The determination of thyroid hormone autoantibodies and its clinical significance

    International Nuclear Information System (INIS)

    Zhu Li; Zhao Zhiying; Wang Zhenghua Lian Xiaolan; Guo Zhisheng; Bai Yao; Su Wei

    2003-01-01

    To study the reasons of falsely high concentrations of serum thyroid hormone and the way of determination of thyroid hormone autoantibodies, the experiments of thyroid hormone autoantibodies binding reaction, dilution testing, calibration curves and their check analysis were performed. Results showed that the combination of the autoantibodies with 125 I-T 3 or 125 I-T 4 was specific, the binding rates were 58.77% and 49.05% respectively and 7-12 times higher than control groups. The radioactive peaks of the autoantibodies and rabbit anti-T 3 or T 4 antibody appeared on the same position in radio electrophoretogram analysis and these antibodies were considered as IgG. The important reasons of falsely high concentrations of serum thyroid hormone are the presence of anti-thyroid hormone antibodies. Determination of thyroid hormone autoantibodies significantly benefits diagnosis and treatment of thyroid disease

  8. Transfer of IgG in the female genital tract by MHC class I-related neonatal Fc receptor (FcRn) confers protective immunity to vaginal infection

    Science.gov (United States)

    IgG is a major immunoglobulin subclass in mucosal secretions of human female genital tract, where it predominates over the IgA isotype. Despite the abundance of IgG, surprisingly little is known about whether and how IgG enters the lumen of the genital tract and the exact role of local IgG may play ...

  9. Characterization and potential clinical applications of autoantibodies against cytokines

    DEFF Research Database (Denmark)

    de Lemos Rieper, Carina; Galle, Pia; Hansen, Morten Bagge

    2009-01-01

    Autoantibodies recognizing cytokines arise in certain patients during the course of therapy with recombinant cytokines, although they may arise spontaneously as well. They are typically high avidity and in vitro neutralizing IgG antibodies present in picomolar to nanomolar concentrations. Methodo......Autoantibodies recognizing cytokines arise in certain patients during the course of therapy with recombinant cytokines, although they may arise spontaneously as well. They are typically high avidity and in vitro neutralizing IgG antibodies present in picomolar to nanomolar concentrations...

  10. Human IgG4: a structural perspective.

    Science.gov (United States)

    Davies, Anna M; Sutton, Brian J

    2015-11-01

    IgG4, the least represented human IgG subclass in serum, is an intriguing antibody with unique biological properties, such as the ability to undergo Fab-arm exchange and limit immune complex formation. The lack of effector functions, such as antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, is desirable for therapeutic purposes. IgG4 plays a protective role in allergy by acting as a blocking antibody, and inhibiting mast cell degranulation, but a deleterious role in malignant melanoma, by impeding IgG1-mediated anti-tumor immunity. These findings highlight the importance of understanding the interaction between IgG4 and Fcγ receptors. Despite a wealth of structural information for the IgG1 subclass, including complexes with Fcγ receptors, and structures for intact antibodies, high-resolution crystal structures were not reported for IgG4-Fc until recently. Here, we highlight some of the biological properties of human IgG4, and review the recent crystal structures of IgG4-Fc. We discuss the unexpected conformations adopted by functionally important Cγ2 domain loops, and speculate about potential implications for the interaction between IgG4 and FcγRs. © 2015 The Authors. Immunological Reviews Published by John Wiley & Sons Ltd.

  11. Concurrent IgG4-related tubulointerstitial nephritis and IgG4 myeloperoxidase-anti-neutrophil cytoplasmic antibody positive crescentic glomerulonephritis: A case report.

    Science.gov (United States)

    Su, Tao; Yang, Li; Cui, Zhao; Wang, Su-Xia; Zhao, Ming-Hui

    2017-05-01

    IgG4-related disease (IgG4-RD) is a newly recognized systemic disease. The typical pathological finding in the kidney is abundant IgG4-positive plasma cell infiltration with characteristic storiform fibrosis in the interstitium. Antibodies of the IgG4 subclass have been linked to certain autoimmune diseases including antiproteinase 3 (PR3) anti-neutrophil cytoplasmic antibody (ANCA) of the IgG4 subclass. Here, we report a rare case of kidney injury with concurrent typical IgG4-related tubulointerstitial nephritis and IgG4 subclass of myeloperoxidase (MPO) ANCA-positive necrotizing crescentic glomerulonephritis. A 42-year-old Chinese man presented with repeated epigastric pain, sausage-shaped pancreas observed morphologically in computed tomography, effectiveness of prednisone therapy and was diagnosed with autoimmune pancreatitis. He subsequently developed acute kidney injury. The patient had an elevated serum IgG4, eosinophilia, and positive MPO-ANCA of IgG4-dominant subclass. Renal biopsy revealed necrotizing crescentic nephritis and typical IgG4-related tubulointerstitial nephritis. The patient was treated with a combination of corticosteroids and cyclophosphamide, and a course of rituximab was later added to deplete peripheral B cells. The patient responded well and his renal function improved. This is the first case report of an IgG4-RD with concurrent IgG4-related tubulointerstitial nephritis and IgG4 MPO-ANCA-associated necrotizing crescentic glomerulonephritis. It raises the difficulty in differentiation diagnosis of the two separate diseases that is worthy of further study.

  12. Family analysis of immunoglobulin classes and subclasses in children with autistic disorder.

    Science.gov (United States)

    Spiroski, Mirko; Trajkovski, Vladimir; Trajkov, Dejan; Petlichkovski, Aleksandar; Efinska-Mladenovska, Olivija; Hristomanova, Slavica; Djulejic, Eli; Paneva, Meri; Bozhikov, Jadranka

    2009-11-01

    Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG) and subclasses (IgG1, IgG2, IgG3, and IgG4) were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001), female autistic from the mothers (p = 0,008), as well as healthy sisters from the fathers (p = 0,011). Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister) independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations.

  13. Family Analysis of Immunoglobulin Classes and Subclasses in Children with Autistic Disorder

    Directory of Open Access Journals (Sweden)

    Mirko Spiroski

    2009-11-01

    Full Text Available Autistic disorder is a severe neurodevelopment disorder characterized by a triad of impairments in reciprocal social interaction, verbal and nonverbal communication, and a pattern of repetitive stereotyped activities, behaviours and interests. There are strong lines of evidence to suggest that the immune system plays an important role in the pathogenesis of autistic disorder. The aim of this study was to analyze quantitative plasma concentration of immunoglobulin classes, and subclasses in autistic patients and their families. The investigation was performed retrospectively in 50 persons with autistic disorder in the Republic of Macedonia. Infantile autistic disorder was diagnosed by DSM-IV and ICD-10 criteria. Plasma immunoglobulin classes (IgM, IgA, and IgG and subclasses (IgG1, IgG2, IgG3, and IgG4 were determined using Nephelometer Analyzer BN-100. Multiple comparisons for the IgA variable have shown statistically significant differences between three pairs: male autistic from the fathers (p = 0,001, female autistic from the mothers (p = 0,008, as well as healthy sisters from the fathers (p = 0,011. Statistically significant differences found between three groups regarding autistic disorder (person with autistic disorder, father/mother of a person with autistic disorder, and brother/sister independent of sex belongs to IgA, IgG2, and IgG3 variables. Multiple comparisons for the IgA variable have shown statistically significant differences between children with autistic disorder from the fathers and mothers (p < 0,001, and healthy brothers and sisters from the fathers and mothers (p < 0,001. Comparison between healthy children and children with autistic disorder from the same family should be tested for immunoglobulin classes and subclasses in order to avoid differences between generations.

  14. [Autoantibodies as biomarkers].

    Science.gov (United States)

    Tron, François

    2014-01-01

    Activation and differentiation of autoreactive B-lymphocytes lead to the production of autoantibodies, which are thus the direct consequence of the autoimmune process. They often constitute biomarkers of autoimmune diseases and are measured by tests displaying various diagnosis sensitivity and specificity. Autoantibody titers can be correlated to the disease activity and certain autoantibody populations associated with particular clinical manifestations or tissue lesions. The demonstration that autoantibodies appear years before the onset of autoimmune diseases indicates that their presence in healthy individuals may be a predictive marker of the occurrence of disease. Certain autoantibodies could also be predictive markers of a therapeutic response to biologics and of the occurrence of side effects as well. Thus, autoantibodies are useful tools in the diagnosis and the management of patients with organ specific or non-organ specific autoimmune diseases at different steps of the autoimmune process. Copyright © 2013. Published by Elsevier Masson SAS.

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

    Directory of Open Access Journals (Sweden)

    Lucía Santamaría Ortiz

    1995-04-01

    G deficiency was found in four steroid. dependent patients. Serum levels of IgG subclasses 1 to 4 were measured by means of a sandwich-like ELISA with specific monoclonal antibodies. One or more subclass deficiencies were present In 55.6% of the patients. Significant differences were not found between the following groups: steroid and nonsteroid dependent patients; allergic or intrinsic, asthma; and individuals with or without history of infection. IgG 1 deficiency was the most commonly found: It was present in 46.7% of the patients, either as an isolated disorder or combined with alteration of other subclasses. Deficiency of other subclasses was present in the following proportions: 31.1% for IgG2; 24.4% for IgG3 and 17.8 for IgG4. The high incidence of subclass deficiency may be due to steroid action or to primary Immune defects leading to disorders of IgG synthesis. Such situation might be responsible for the aggressive behavior of the disease.

  16. Immunospecific red cell binding of iodine 125-labeled immunoglobulin G erythrocyte autoantibodies

    International Nuclear Information System (INIS)

    Masouredis, S.P.; Branks, M.J.; Garratty, G.; Victoria, E.J.

    1987-01-01

    The primary interaction of autoantibodies with red cells has been studied by using labeled autoantibodies. Immunoglobulin G red cell autoantibodies obtained from IgG antiglobulin-positive normal blood donors were labeled with radioactive iodine and compared with alloanti-D with respect to their properties and binding behavior. Iodine 125 -labeled IgG autoantibody migrated as a single homogeneous peak with the same relative mobility as human IgG on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoelectric focusing pattern of labeled autoantibodies varied from donor to donor but was similar to that of alloanti-D, consisting of multiple IgG populations with isoelectric points in the neutral to alkaline range. 125 I-autoantibody bound to all human red cells of common Rh phenotypes. Evidence for immunospecific antibody binding of the labeled autoantibody was based on variation in equilibrium binding to nonhuman and human red cells of common and rare phenotypes, enhanced binding after red cell protease modification, antiglobulin reactivity of cell-bound IgG comparable to that of cell-bound anti-D, and saturation binding in autoantibody excess. Scatchard analysis of two 125 I-autoantibody preparations yielded site numbers of 41,500 and 53,300 with equilibrium constants of 3.7 and 2.1 X 10(8) L X mol-1. Dog, rabbit, rhesus monkey, and baboon red cells were antigen(s) negative by quantitative adsorption studies adsorbing less than 3% of the labeled autoantibody. Reduced ability of rare human D--red blood cells to adsorb the autoantibody and identification of donor autoantibodies that bind to Rh null red blood cells indicated that eluates contained multiple antibody populations of complex specificities in contrast to anti-D, which consists of a monospecific antibody population. Another difference is that less than 70% of the autoantibody IgG was adsorbed by maximum binding red blood cells as compared with greater than 85% for alloanti-D

  17. Potential of Murine IgG1 and Human IgG4 to Inhibit the Classical Complement and Fcγ Receptor Activation Pathways

    Directory of Open Access Journals (Sweden)

    Gina-Maria Lilienthal

    2018-05-01

    Full Text Available IgG antibodies (Abs mediate their effector functions through the interaction with Fcγ receptors (FcγRs and the complement factors. The main IgG-mediated complement activation pathway is induced through the binding of complement C1q to IgG Abs. This interaction is dependent on antigen-dependent hexamer formation of human IgG1 and IgG3 to increase the affinity for the six-headed C1q molecule. By contrast, human IgG4 fails to bind to C1q. Instead, it has been suggested that human IgG4 can block IgG1 and IgG3 hexamerization required for their binding to C1q and activating the complement. Here, we show that murine IgG1, which functionally resembles human IgG4 by not interacting with C1q, inhibits the binding of IgG2a, IgG2b, and IgG3 to C1q in vitro, and suppresses IgG2a-mediated complement activation in a hemolytic assay in an antigen-dependent and IgG subclass-specific manner. From this perspective, we discuss the potential of murine IgG1 and human IgG4 to block the complement activation as well as suppressive effects of sialylated IgG subclass Abs on FcγR-mediated immune cell activation. Accumulating evidence suggests that both mechanisms seem to be responsible for preventing uncontrolled IgG (autoAb-induced inflammation in mice and humans. Distinct IgG subclass distributions and functionally opposite IgG Fc glycosylation patterns might explain different outcomes of IgG-mediated immune responses and provide new therapeutic options through the induction, enrichment, or application of antigen-specific sialylated human IgG4 to prevent complement and FcγR activation as well.

  18. Immunoglobulin G1 Allotype Influences Antibody Subclass Distribution in Response to HIV gp140 Vaccination

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    Sven Kratochvil

    2017-12-01

    Full Text Available Antibody subclasses exhibit extensive polymorphisms (allotypes that could potentially impact the quality of HIV-vaccine induced B cell responses. Allotypes of immunoglobulin (Ig G1, the most abundant serum antibody, have been shown to display altered functional properties in regard to serum half-life, Fc-receptor binding and FcRn-mediated mucosal transcytosis. To investigate the potential link between allotypic IgG1-variants and vaccine-generated humoral responses in a cohort of 14 HIV vaccine recipients, we developed a novel protocol for rapid IgG1-allotyping. We combined PCR and ELISA assays in a dual approach to determine the IgG1 allotype identity (G1m3 and/or G1m1 of trial participants, using human plasma and RNA isolated from PBMC. The IgG1-allotype distribution of our participants mirrored previously reported results for caucasoid populations. We observed elevated levels of HIV gp140-specific IgG1 and decreased IgG2 levels associated with the G1m1-allele, in contrast to G1m3 carriers. These data suggest that vaccinees homozygous for G1m1 are predisposed to develop elevated Ag-specific IgG1:IgG2 ratios compared to G1m3-carriers. This elevated IgG1:IgG2 ratio was further associated with higher FcγR-dimer engagement, a surrogate for potential antibody-dependent cellular cytotoxicity (ADCC and antibody-dependent cellular phagocytosis (ADCP function. Although preliminary, these results suggest that IgG1 allotype may have a significant impact on IgG subclass distribution in response to vaccination and associated Fc-mediated effector functions. These results have important implications for ongoing HIV vaccine efficacy studies predicated on engagement of FcγR-mediated cellular functions including ADCC and ADCP, and warrant further investigation. Our novel allotyping protocol provides new tools to determine the potential impact of IgG1 allotypes on vaccine efficacy.

  19. Autoantibodies in Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Carolin Hoffmann

    2016-04-01

    Full Text Available Little is known about the etiology of neuropsychiatric disorders. The identification of autoantibodies targeting the N-methyl-d-aspartate receptor (NMDA-R, which causes neurological and psychiatric symptoms, has reinvigorated the hypothesis that other patient subgroups may also suffer from an underlying autoimmune condition. In recent years, a wide range of neuropsychiatric diseases and autoantibodies targeting ion-channels or neuronal receptors including NMDA-R, voltage gated potassium channel complex (VGKC complex, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R, γ-aminobutyric acid receptor (GABA-R and dopamine receptor (DR were studied and conflicting reports have been published regarding the seroprevalence of these autoantibodies. A clear causative role of autoantibodies on psychiatric symptoms has as yet only been shown for the NMDA-R. Several other autoantibodies have been related to the presence of certain symptoms and antibody effector mechanisms have been proposed. However, extensive clinical studies with large multicenter efforts to standardize diagnostic procedures for autoimmune etiology and animal studies are needed to confirm the pathogenicity of these autoantibodies. In this review, we discuss the current knowledge of neuronal autoantibodies in the major neuropsychiatric disorders: psychotic, major depression, autism spectrum, obsessive-compulsive and attention-deficit/hyperactivity disorders.

  20. Autoantibodies in Autoimmune Hepatitis.

    Science.gov (United States)

    Muratori, Luigi; Deleonardi, Gaia; Lalanne, Claudine; Barbato, Erica; Tovoli, Alessandra; Libra, Alessia; Lenzi, Marco; Cassani, Fabio; Muratori, Paolo

    2015-01-01

    The detection of diagnostic autoantibodies such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (SMA), anti-liver/kidney microsomal type 1 (anti-LKM1), anti-liver cytosol type 1 (anti-LC1) and anti-soluble liver antigen (anti-SLA) is historically associated with the diagnosis of autoimmune hepatitis. When autoimmune hepatitis is suspected, the detection of one or any combination of diagnostic autoantibodies, by indirect immunofluorescence or immuno-enzymatic techniques with recombinant antigens, is a pivotal step to reach a diagnostic score of probable or definite autoimmune hepatitis. Diagnostic autoantibodies (ANA, SMA, anti-LKM1, anti-LC1, anti-SLA) are a cornerstone in the diagnosis of autoimmune hepatitis. Other ancillary autoantibodies, associated with peculiar clinical correlations, appear to be assay-dependent and institution-specific, and validation studies are needed. © 2015 S. Karger AG, Basel.

  1. Measurement of the IgG2 response to Pneumococcal capsular polysaccharides may identify an antibody deficiency in individuals referred for immunological investigation.

    Science.gov (United States)

    Parker, Antony; Irure Ventura, Juan; Sims, Dawn; Echeverría de Carlos, Ainara; Gómez de la Torre, Ricardo; Tricas Aizpún, Lourdes; Ocejo-Vinyals, J Gonzalo; López-Hoyos, Marcos; Wallis, Gregg; Harding, Stephen

    2017-01-01

    IgG2 is the most efficient subclass for providing protection against pneumococcal pathogens. We hypothesised that some individuals may be unable to mount an effective pneumococcal capsular polysaccharide (PCP) IgG2 response despite having a normal PCP IgG concentration (PCP IgG2 deficient). The median pre-vaccination PCP IgG2 concentration was significantly lower in individuals referred for immunological investigation compared to healthy controls (2.8 mg/L range, 95% CI 1.1-88 vs. 29.5mg/L, 95% CI 13.5-90, p = 0.0002). PCP IgG:IgG2 ratios were significantly higher for the referral population than for healthy controls suggesting the increased production of PCP specific subclasses other than IgG2. The percentage of individuals with PCP IgG2 deficiency was significantly higher in referral groups compared to controls (31% vs. 5%; p = 0.0009) and in an individual with PCP IgG2 deficiency, the balance of PCP specific IgG subclass antibodies post vaccination changed from IgG2>IgG1>IgG3>IgG4 to IgG1>IgG3>IgG2>IgG4. The median PCP IgG2 concentration in those with PCP IgG2 deficiency was significantly lower in the referral groups compared to controls (7.8 mg/L, 95% CI 1.1-12 vs. 12.7 mg/L, 95% CI 11.8-13.1; p = 0.006). The data suggests a defect in the production PCP IgG2 may be present in individuals with normal PCP IgG referred for immunological investigation.

  2. Differential patterns of human immunoglobulin G subclass responses to distinct regions of a single protein, the merozoite surface protein 1 of Plasmodium falciparum

    DEFF Research Database (Denmark)

    Cavanagh, D R; Dobaño, C; Elhassan, I M

    2001-01-01

    Comparisons of immunoglobulin G (IgG) subclass responses to the major polymorphic region and to a conserved region of MSP-1 in three cohorts of African villagers exposed to Plasmodium falciparum revealed that responses to Block 2 are predominantly IgG3 whereas antibodies to MSP-1(19) are mainly IgG......1. The striking dominance of IgG3 to Block 2 may explain the short duration of this response and also the requirement for continuous stimulation by malaria infection to maintain clinical immunity....

  3. 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.

  4. Novel enzyme immunoassay system for simultaneous detection of six subclasses of antiphospholipid antibodies for differential diagnosis of antiphospholipid syndrome.

    Science.gov (United States)

    Nojima, Junzo; Motoki, Yukari; Hara, Kazusa; Sakata, Toshiyuki; Ichihara, Kiyoshi

    2017-06-01

    : Antiphospholipid syndrome, which often complicates systemic lupus erythematosus (SLE), features high occurrence of arterial and/or venous thrombosis and recurrent fetal loss. However, which antibody subclass contributes to which clinical event remains uncertain. We newly developed an up-to-date enzyme immunoassay system using the AcuStar automated analyzer (Instrumentation Laboratory, Bedford, Massachusetts, USA) for parallel detection of six subclasses of antiphospholipid antibodies (aPLs): anticardiolipin antibodies (aCL) of IgG, IgM, and IgA and anti-β2-glycoprotein I antibodies (aβ2GPI) of IgG, IgM, and IgA. They were measured in 276 healthy volunteers and 138 patients with SLE: 45 with thromboembolic complications (29 arterial; 16 venous) and 93 without. Lupus anticoagulant activity in their plasma was measured according to the guidelines recommended by the Subcommittee on Lupus Anticoagulant/Phospholipid-Dependent Antibodies. aCL/β2GPI was measured with a standard ELISA kit commonly used in Japan. The positive results of IgG aCL, IgA aCL, and IgG aβ2GPI were closely associated with thromboembolic complications, whereas IgM aCL and IgM aβ2GPI were not. receiver operating characteristic analysis revealed that the accuracy of predicting thromboembolic complications based on the composite test results of the former three antibodies were obviously higher than by each alone. Regarding agreement with the test results of lupus anticoagulant activity, IgG aβ2GPI showed the closest match. Patients with SLE frequently possess various combinations of the six aPL subclasses, and this antibody spectrum is closely associated with thromboembolic events in these patients. This new automated enzyme immunoassay system allows simultaneous analysis of the profile of aPL subclasses for the differential diagnosis of antiphospholipid antibody syndrome in its early stage.

  5. Natural autoantibodies: from 'horror autotoxicus' to 'gnothi seauton'.

    Science.gov (United States)

    Avrameas, S

    1991-05-01

    The immune system of normal unimmunized animals is characterized by the presence of B cells synthesizing and secreting mainly polyreactive, but also monoreactive, IgM and IgG natural antibodies that can react with a variety of self constituents. These antibodies, like the autoantibodies appearing in several immunopathological states, use the same genetic elements as the antibodies directed against environmental antigens, and seem to be encoded by unmutated germ-line genes. Accumulating evidence indicates that these natural auto-antibodies exert various biological roles, both related and unrelated to the immune system. In this article, Stratis Avrameas proposes that natural auto-antibodies, by interacting with the large number of self constituents present in an organism, establish an extensive dynamic network that contributes to the general homeostasis of the organism.

  6. Autoantibodies associated with prenatal and childhood exposure to environmental chemicals in faroese children

    DEFF Research Database (Denmark)

    Osuna, Christa E; Grandjean, Philippe; Weihe, Pál

    2014-01-01

    to both neural (neurofilaments, cholineacetyltransferase, astrocyte glial fibrillary acidic protein, and myelin basic protein) and non-neural (actin, desmin, and keratin) antigens were measured and the associations of these autoantibody concentrations with chemical exposures were assessed using linear...... of autoantibodies. However, it is not known if autoantibodies similarly will be generated and detectable in humans following toxicant exposures. Therefore, we conducted a pilot study to investigate if autoantibodies specific for neural and non-neural antigens could be detected in children at age 7 years who have...... been exposed to environmental chemicals. Both prenatal and age-7 exposures to mercury, PCBs, and PFCs were measured in 38 children in the Faroe Islands who were exposed to widely different levels of these chemicals due to their seafood-based diet. Concentrations of IgM and IgG autoantibodies specific...

  7. 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.

  8. Quantitative analysis of rat Ig (sub)classes binding to cell surface antigens

    International Nuclear Information System (INIS)

    Nilsson, R.; Brodin, T.; Sjoegren, H.-O.

    1982-01-01

    An indirect 125 I-labeled protein A assay for detection of cell surface-bound rat immunoglobulins is presented. The assay is quantitative and rapid and detects as little as 1 ng of cell surface-bound Ig. It discriminates between antibodies belonging to different IgG subclasses, IgM and IgA. The authors describe the production and specificity control of the reagents used and show that the test can be used for quantitative analysis. A large number of sera from untreated rats are tested to evaluate the frequency of falsely positive responses and variation due to age, sex and strain of rat. With this test it is relatively easy to quantitate the binding of classes and subclasses of rat immunoglobulins in a small volume (6 μl) of untreated serum. (Auth.)

  9. Fc-Glycosylation in Human IgG1 and IgG3 Is Similar for Both Total and Anti-Red-Blood Cell Anti-K Antibodies

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    Myrthe E. Sonneveld

    2018-01-01

    Full Text Available After albumin, immunoglobulin G (IgG are the most abundant proteins in human serum, with IgG1 and IgG3 being the most abundant subclasses directed against protein antigens. The quality of the IgG-Fc-glycosylation has important functional consequences, which have been found to be skewed toward low fucosylation in some antigen-specific immune responses. This increases the affinity to IgG1-Fc-receptor (FcγRIIIa/b and thereby directly affects downstream effector functions and disease severity. To date, antigen-specific IgG-glycosylation have not been analyzed for IgG3. Here, we analyzed 30 pregnant women with anti-K alloantibodies from a prospective screening cohort and compared the type of Fc-tail glycosylation of total serum- and antigen-specific IgG1 and IgG3 using mass spectrometry. Total serum IgG1 and IgG3 Fc-glycoprofiles were highly similar. Fc glycosylation of antigen-specific IgG varied greatly between individuals, but correlated significantly with each other for IgG1 and IgG3, except for bisection. However, although the magnitude of changes in fucosylation and galactosylation were similar for both subclasses, this was not the case for sialylation levels, which were significantly higher for both total and anti-K IgG3. We found that the combination of relative IgG1 and IgG3 Fc-glycosylation levels did not improve the prediction of anti-K mediated disease over IgG1 alone. In conclusion, Fc-glycosylation profiles of serum- and antigen-specific IgG1 and IgG3 are highly similar.

  10. Effects of pregnancy and intensity of Plasmodium falciparum transmission on immunoglobulin G subclass responses to variant surface antigens

    DEFF Research Database (Denmark)

    Megnekou, Rosette; Staalsoe, Trine; Taylor, Diane W

    2005-01-01

    Placenta-sequestering Plasmodium falciparum involved in the pathogenesis of pregnancy-associated malaria (PAM) in otherwise clinically immune women expresses particular variant surface antigens (VSA(PAM)) on the surface of infected erythrocytes that differ from VSA found in parasitized nonpregnant...... individuals (non-PAM type VSA). We studied levels of immunoglobulin G (IgG) and IgG subclasses with specificity for VSA(PAM) and for non-PAM type VSA in pregnant and nonpregnant women from two sites with different endemicities in Cameroon. We found that VSA(PAM)-specific responses depended on the pregnancy......(PAM)-specific immunity to pregnancy-associated malaria....

  11. Two cases of erosive oral lichen planus with autoantibodies to desmoglein 3.

    Science.gov (United States)

    Muramatsu, Ken; Nishie, Wataru; Natsuga, Ken; Fujita, Yasuyuki; Iwata, Hiroaki; Yamada, Tamaki; Yamashita, Emi; Asaka, Takuya; Shimizu, Hiroshi

    2016-11-01

    Oral lichen planus (OLP) is a chronic inflammatory disorder of the oral mucosa of unknown etiology. Clinically, the erosive type of OLP (erosive OLP) can show features similar to those of pemphigus vulgaris (PV), an autoimmune blistering disorder in which desmoglein (Dsg)3 is targeted. In addition to clinical and histopathological findings, immunological studies, including direct immunofluorescence (IF), indirect IF and enzyme-linked immunosorbent assay (ELISA) that detect autoantibodies to Dsg3, are helpful in differentiating erosive OLP from PV. Here, we show two cases of erosive OLP with autoantibodies to Dsg3. Patient 1 was a 68-year-old woman with chronic erosions of the oral mucosa, in which elevated levels of immunoglobulin (Ig)G autoantibodies to Dsg1 and Dsg3 were detected by ELISA. Patient 2 was an 85-year-old woman with white striae with erosions on the lateral sides of the buccal mucosa with elevated levels of IgG autoantibodies to Dsg3 detected by ELISA. Histopathological findings from both cases showed lichenoid dermatitis, and both direct and indirect IF showed no tissue-bound IgG autoantibodies. From these findings, the diagnosis of erosive OLP was made. Immunological assays revealed both cases to have IgG-directing calcium-independent linear epitopes on Dsg3, which are suggestive of non-pathogenic autoantibodies. In addition, autoantibodies to Dsg3 in patient 2 reacted with a prosequence-possessing precursor form of Dsg3 but not with the mature form of the molecule. The present study suggests that erosive OLP may develop anti-Dsg3 autoantibodies, which should be carefully assessed. © 2016 Japanese Dermatological Association.

  12. Establishment of a serum IgG4 cut-off value for the differential diagnosis of IgG4-related disease in Chinese population.

    Science.gov (United States)

    Li, Ping; Chen, Hua; Deng, Chuiwen; Wu, Ziyan; Lin, Wei; Zeng, Xiaofeng; Zhang, Wen; Zhang, Fengchun; Li, Yongzhe

    2016-07-01

    This study was performed to better know diagnosis associated with serum IgG4 concentration, and to explore the possibility for development of a serum IgG4 for IgG4-related disease (IgG4-RD) in Chinese populations. We studied retrospectively 497 IgG4 serum subclass measurements from Peking Union Medical College Hospital during the four-year period, including 242 IgG4-RD, 130 other diseases and 125 healthy individuals. Serum IgG4 concentrations were significantly higher in IgG4-RD than in other pathologies (1662.9 ± 3760.9 mg/L, p IgG4 level between other pathologies group and healthy individuals (p = 0.075). Among the 242 IgG4-RD patients analyzed, serum IgG4 concentrations were normal in 46 patients (19.0%). We found 32 patients (24.6%) with elevated serum IgG4 levels among the 130 patients who suffered from other pathologies. There were seven (5.6%) with serum IgG4 over 1350 mg/L in healthy individuals. The ROC curve analysis revealed that the optimal sensitivity and specificity were 80.0% and 88.2%, respectively, at the concentration of 1575 mg/L for Chinese patients. Our study demonstrated that serum IgG4 elevation was not specific of IgG4-RD. Further studies are needed to define the sensibility and specificity of IgG4 values for the diagnosis of IgG4-RD.

  13. IgG4-related sclerosing cholangitis overlapping with autoimmune hepatitis: Report of a case.

    Science.gov (United States)

    Li, Hongyan; Sun, Li; Brigstock, David R; Qi, Lina; Gao, Runping

    2017-05-01

    IgG4-related sclerosing cholangitis (IgG4-SC) is the biliary manifestation of IgG4-related disease (IgG4-RD) but the presence of IgG4-SC in the porta hepatis is difficult to differentiate from hilar cholangiocarcinoma (HCCA). IgG4-related autoimmune hepatitis (IgG4-related AIH) is extremely rare and it is not fully clear whether IgG4-related AIH is a hepatic manifestation of IgG4-RD or a subtype of AIH. We present a rare case of a 52-year-old male who was admitted with obstructive jaundice and itchy skin. He primarily presented a severe bile duct stricture in the porta hepatis and an elevated serum level of carbohydrate antigen 19-9 (CA19-9) mimicking HCCA. The patient underwent a surgical resection of the left hepatic lobular and cholecyst as well as common bile duct with a right hepatico-jejunostomy. He was finally diagnosed as IgG4-SC accompanied with IgG4-related AIH by immunohistochemistry, but he lacked conventional autoantibodies. The patient responded well to steroid therapy and remains healthy with no signs of recurrence at six-month follow-up. This is the first case report that hepatic portal IgG4-SC overlapping with IgG4-related AIH without the presence of conventional autoantibodies. Additionally, we suggest that IgG4-RD should be always considered in case of a bile duct stricture in the porta hepatis to avoid unnecessary surgical operation. Copyright © 2017 Elsevier GmbH. All rights reserved.

  14. Autoantibodies to folate receptor alpha during early pregnancy and risk of oral clefts in Denmark

    DEFF Research Database (Denmark)

    Bille, Camilla; Pedersen, Dorthe Almind; Andersen, Anne-Marie Nybo

    2010-01-01

    The objective of this study was to determine whether IgG and IgM autoantibodies to folate receptor alpha (FRalpha) in pregnant women are associated with an increased risk of oral cleft-affected offspring. A case-control study nested in the prospective Danish National Birth Cohort (100,418 pregnan...

  15. β2-glycoprotein-1 autoantibodies from patients with antiphospholipid syndrome are sufficient to potentiate arterial thrombus formation in a mouse model

    Science.gov (United States)

    Arad, Ariela; Proulle, Valerie; Furie, Richard A.; Furie, Barbara C.

    2011-01-01

    Antiphospholipid syndrome is characterized by thrombosis, recurrent fetal loss, and the presence of the lupus anticoagulant, anticardiolipin antibodies, or anti–β2-glycoprotein-1 (anti–β2-GP1) antibodies. Although anti–β2-GP1 antibodies have been documented as a biomarker for diagnosis of antiphospholipid syndrome, their direct role in the pathogenesis of thrombosis is unknown. We have demonstrated using intravital microscopy that anti–β2-GP1 autoantibodies purified from the sera of patients with antiphospholipid syndrome complicated by thrombosis greatly amplify thrombus size after laser-induced vessel wall injury in live mice. Anti–β2-GP1 autoantibodies from 3 patients with antiphospholipid syndrome were affinity-purified using human β2-GP1 bound to agarose. The effects of purified anti–β2-GP1 IgG autoantibodies, of anti–β2-GP1–depleted IgG, and of IgG from normal human sera on thrombus formation were measured in mice after arterial injury in the cremaster muscle. Before injury, purified anti–β2-GP1 IgG autoantibodies, anti–β2-GP1 antibody–depleted IgG, or IgG from normal human sera were infused. Increasing amounts of purified anti–β2-GP1 autoantibodies increased thrombus size in a dose-dependent manner, whereas neither anti–β2-GP1 antibody-depleted IgG nor IgG from normal serum affected thrombus size. These results indicate that anti–β2-GP1 IgG autoantibodies in antiphospholipid syndrome patient sera are not only a marker of antiphospholipid syndrome but are directly involved in the pathogenesis of thrombosis. PMID:21245481

  16. Multiple nuclear dots and rim-like/membranous IgG isotypes in primary biliary cirrhosis.

    Science.gov (United States)

    Muratori, Paolo; Granito, Alessandro; Ferri, Silvia; Pappas, Georgios; Volta, Umberto; Menichella, Rita; Bianchi, Francesco B; Lenzi, Marco; Muratori, Luigi

    2009-03-01

    Anti nuclear (ANA) immunomorphological patterns such as multiple nuclear dots (MND) and rim-like/membranous (RL/M) are considered highly specific but little sensitive for primary biliary cirrhosis (PBC) diagnosis. To evaluate frequency and clinical significance of MND and RL/M in PBC patients when investigated at the level of immunoglobulin G isotypes. MND and RL/M pattern have been tested in 141 PBC sera and 230 pathological controls using HEp-2 cells as substrate and anti- total IgG and individual IgG subclasses (IgG1, IgG2, IgG3, IgG4) as specific antisera. One hundred and fourteen of 141 (80%) PBC patients had RL/M or MND pattern when IgG subclasses were used as revealing reagents (vs. 34% when anti total IgG were used, p < 0.0001). The prevalent isotype was IgG1 for RL/M, and IgG2 for MND pattern. None of controls was positive. No clinical differences in terms of severity and outcome of disease have been observed in PBC patients positive for MND and RL/M when investigated with IgG isotypes. The research for RL/M and MND pattern at level of IgG isotype determines a wide gain in terms of sensitivity without a loss of specificity. In Italian PBC patients MND and RL/M pattern did not seem to characterize any subgroup of patients with a poorer prognosis.

  17. Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.

    Science.gov (United States)

    Tay, Matthew Zirui; Liu, Pinghuang; Williams, LaTonya D; McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T; Dennison, S Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S Munir; Moody, M Anthony; Hope, Thomas J; Haynes, Barton F; Tomaras, Georgia D

    2016-08-01

    Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

  18. A new and rapid method for immunoglobulin class and subclass determination of mouse monoclonal antibodies using a solid-phase immunoradiometric assay

    International Nuclear Information System (INIS)

    Storch, M.-J.; Lohmann-Matthes, M.-L.

    1984-01-01

    A solid-phase immunoradiometric assay is described for the detection of mouse immunoglobulin classes and subclasses in unpurified and unconcentrated supernatants of hybridomas. IgG fractions from rabbit antisera specific for mouse immunoglobulin classes and subclasses are used for coating the wells of flexible microtiter plates. Monoclonal antibody present in hybridoma supernatants is bound only to wells that contain the appropriate anti-subclass antibody. The binding of hybridoma antibodies to corresponding IgG subclasses or IgM is then detected by a labeled rabbit anti-mouse antibody binding to all mouse immunoglobulins (heavy and light chains). Thus, only 1 labeled antibody is needed for all assays. The advantages of the method described are the following: results are obtained within a few hours and antibody containing hybridoma supernatants may be used without a concentration step since minute amounts of antibody are detected by the immunoradiometric assay. Cultures producing several subclasses may be early recognized as oligo/polyclonal. (Auth.)

  19. Contactin-1 and Neurofascin-155/-186 Are Not Targets of Auto-Antibodies in Multifocal Motor Neuropathy.

    Directory of Open Access Journals (Sweden)

    Kathrin Doppler

    Full Text Available Multifocal motor neuropathy is an immune mediated disease presenting with multifocal muscle weakness and conduction block. IgM auto-antibodies against the ganglioside GM1 are detectable in about 50% of the patients. Auto-antibodies against the paranodal proteins contactin-1 and neurofascin-155 and the nodal protein neurofascin-186 have been detected in subgroups of patients with chronic inflammatory demyelinating polyneuropathy. Recently, auto-antibodies against neurofascin-186 and gliomedin were described in more than 60% of patients with multifocal motor neuropathy. In the current study, we aimed to validate this finding, using a combination of different assays for auto-antibody detection. In addition we intended to detect further auto-antibodies against paranodal proteins, specifically contactin-1 and neurofascin-155 in multifocal motor neuropathy patients' sera. We analyzed sera of 33 patients with well-characterized multifocal motor neuropathy for IgM or IgG anti-contactin-1, anti-neurofascin-155 or -186 antibodies using enzyme-linked immunosorbent assay, binding assays with transfected human embryonic kidney 293 cells and murine teased fibers. We did not detect any IgM or IgG auto-antibodies against contactin-1, neurofascin-155 or -186 in any of our multifocal motor neuropathy patients. We conclude that auto-antibodies against contactin-1, neurofascin-155 and -186 do not play a relevant role in the pathogenesis in this cohort with multifocal motor neuropathy.

  20. Prevention of autoantibody-mediated Graves'-like hyperthyroidism in mice with IL-4, a Th2 cytokine.

    Science.gov (United States)

    Nagayama, Yuji; Mizuguchi, Hiroyuki; Hayakawa, Takao; Niwa, Masami; McLachlan, Sandra M; Rapoport, Basil

    2003-04-01

    Graves' hyperthyroidism has long been considered to be a Th2-type autoimmune disease because it is directly mediated by autoantibodies against the thyrotropin receptor (TSHR). However, several lines of evidence have recently challenged this concept. The present study evaluated the Th1/Th2 paradigm in Graves' disease using a recently established murine model involving injection of adenovirus expressing the TSHR (AdCMVTSHR). Coinjection with adenovirus expressing IL-4 (AdRGDCMVIL-4) decreased the ratio of Th1/Th2-type anti-TSHR Ab subclasses (IgG2a/IgG1) and suppressed the production of IFN-gamma by splenocytes in response to TSHR Ag. Importantly, immune deviation toward Th2 was accompanied by significant inhibition of thyroid-stimulating Ab production and reduction in hyperthyroidism. However, in a therapeutic setting, injection of AdRGDCMVIL-4 alone or in combination with AdCMVTSHR into hyperthyroid mice had no beneficial effect. In contrast, coinjection of adenoviruses expressing IL-12 and the TSHR promoted the differentiation of Th1-type anti-TSHR immune responses as demonstrated by augmented Ag-specific IFN-gamma secretion from splenocytes without changing disease incidence. Coinjection of adenoviral vectors expressing IL-4 or IL-12 had no effect on the titers of anti-TSHR Abs determined by ELISA or thyroid-stimulating hormone-binding inhibiting Ig assays, suggesting that Ab quality, not quantity, is responsible for disease induction. Our observations demonstrate the critical role of Th1 immune responses in a murine model of Graves' hyperthyroidism. These data may raise a cautionary note for therapeutic strategies aimed at reversing Th2-mediated autoimmune responses in Graves' disease in humans.

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

    Directory of Open Access Journals (Sweden)

    XIOMARA ESCOBAR-PÉREZ

    2000-03-01

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

  2. Targeting IgG in Arthritis: Disease Pathways and Therapeutic Avenues

    Directory of Open Access Journals (Sweden)

    Kutty Selva Nandakumar

    2018-02-01

    Full Text Available Rheumatoid arthritis (RA is a polygenic and multifactorial syndrome. Many complex immunological and genetic interactions are involved in the final outcome of the clinical disease. Autoantibodies (rheumatoid factors, anti-citrullinated peptide/protein antibodies are present in RA patients’ sera for a long time before the onset of clinical disease. Prior to arthritis onset, in the autoantibody response, epitope spreading, avidity maturation, and changes towards a pro-inflammatory Fc glycosylation phenotype occurs. Genetic association of epitope specific autoantibody responses and the induction of inflammation dependent and independent changes in the cartilage by pathogenic autoantibodies emphasize the crucial contribution of antibody-initiated inflammation in RA development. Targeting IgG by glyco-engineering, bacterial enzymes to specifically cleave IgG/alter N-linked Fc-glycans at Asn 297 or blocking the downstream effector pathways offers new avenues to develop novel therapeutics for arthritis treatment.

  3. Autoantibodies in breast cancer sera are not epiphenomena and may participate in carcinogenesis

    International Nuclear Information System (INIS)

    Fernández Madrid, Félix; Maroun, Marie-Claire; Olivero, Ofelia A; Long, Michael; Stark, Azadeh; Grossman, Lawrence I; Binder, Walter; Dong, Jingsheng; Burke, Matthew; Nathanson, S David; Zarbo, Richard; Chitale, Dhananjay; Zeballos-Chávez, Rocío; Peebles, Carol

    2015-01-01

    The objective of this work was to demonstrate that autoantibodies in breast cancer sera are not epiphenomena, and exhibit unique immunologic features resembling the rheumatic autoimmune diseases. We performed a comprehensive study of autoantibodies on a collection of sera from women with breast cancer or benign breast disease, undergoing annual screening mammography. All women in this study had suspicious mammography assessment and underwent a breast biopsy. We used indirect immunofluorescence, the crithidia assay for anti-dsDNA antibodies, and multiple ELISAs for extractable nuclear antigens. Autoantibodies were detected in virtually all patients with breast cancer, predominantly of the IgG1 and IgG3 isotypes. The profile detected in breast cancer sera showed distinctive features, such as antibodies targeting mitochondria, centrosomes, centromeres, nucleoli, cytoskeleton, and multiple nuclear dots. The majority of sera showing anti-mitochondrial antibodies did not react with the M2 component of pyruvate dehydrogenase, characteristic of primary biliary cirrhosis. Anti-centromere antibodies were mainly anti-CENP-B. ELISAs for extractable nuclear antigens and the assays for dsDNA were negative. The distinctive autoantibody profile detected in BC sera is the expression of tumor immunogenicity. Although some of these features resemble those in the rheumatic autoimmune diseases and primary biliary cirrhosis, the data suggest the involvement of an entirely different set of epithelial antigens in breast cancer. High titer autoantibodies targeting centrosomes, centromeres, and mitochondria were detected in a small group of healthy women with suspicious mammography assessment and no cancer by biopsy; this suggests that the process triggering autoantibody formation starts in the pre-malignant phase and that future studies using validated autoantibody panels may allow detection of breast cancer risk in asymptomatic women. Autoantibodies developing in breast cancer are not

  4. Autoantibodies in cryptogenic fibrosing alveolitis

    Directory of Open Access Journals (Sweden)

    du Bois Ron

    2001-02-01

    Full Text Available Abstract The pathogenesis of cryptogenic fibrosing alveolitis (CFA involves injury, an immune/inflammatory response and fibrosis. The cause of the injury is unknown, but the identification of serum autoantibodies makes an autoimmune aetiology attractive. The core study on which this commentary is based used novel cloning and serum screening technologies in order to identify new public and private autoantibodies in sera from 12 patients with CFA. Largely negative conclusions were drawn from that study. However, we suggest that the prevalence of autoantibodies may have been underestimated, that the study was timely and that this approach is worth pursuing further.

  5. Sensitivity of some Immunoglobulin G class and subclass antibodies ...

    African Journals Online (AJOL)

    Indirect sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure serum antibody responses in onchocerciasis patients. Apparently, IgG antibody class was more sensitive than IgG1, IgG3 and IgG4 responses to Onchocerca volvulus adult worms sodium duodecyl sulphate (SDS) extracted crude ...

  6. Coefficient Estimate Problem for a New Subclass of Biunivalent Functions

    OpenAIRE

    N. Magesh; T. Rosy; S. Varma

    2013-01-01

    We introduce a unified subclass of the function class Σ of biunivalent functions defined in the open unit disc. Furthermore, we find estimates on the coefficients |a2| and |a3| for functions in this subclass. In addition, many relevant connections with known or new results are pointed out.

  7. Insights from LGI1 and CASPR2 potassium channel complex autoantibody subtyping.

    Science.gov (United States)

    Klein, Christopher J; Lennon, Vanda A; Aston, Paula A; McKeon, Andrew; O'Toole, Orna; Quek, Amy; Pittock, Sean J

    2013-02-01

    To determine, in patients identified as seropositive for neuronal voltage-gated potassium channel (VGKC) complex autoantibodies, the spectrum of clinical presentations and frequency of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) as defined antigenic neuronal targets in the VGKC macromolecular complex. Retrospective cohort study. Clinical practice, Mayo Clinic Neuroimmunology Laboratory and Department of Neurology. A total of 54 853 patients were evaluated, of whom 1992 were found to be VGKC complex IgG positive. From June 1, 2008, to June 30, 2010, comprehensive service serologic evaluation performed on 54853 patients with unexplained neurologic symptoms identified 1992 patients (4%) who were positive for VGKC complex IgG (values ≥ 0.03 nmol/L). Among 316 seropositive patients evaluated clinically at our institution, 82 (26%) were seropositive for LGI1 IgG and/or CASPR2 IgG. Of these 82 patients, 27% had low (0.03-0.09 nmol/L), 51% had medium (0.10-0.99 nmol/L), and 22% had high (≥ 1.00 nmol/L) VGKC complex IgG values. Leucine-rich glioma-inactivated protein 1 IgG positivity was associated with higher VGKC complex IgG values (PVGKC complex IgG values and varying LGI1 IgG and CASPR2 IgG specificities. The frequent occurrence of LGI1 IgG and CASPR2 IgG in serum samples with low and medium VGKC complex IgG values supports the clinical significance of low values in clinical evaluation. Additional antigenic components of VGKC macromolecular complexes remain to be defined.

  8. [Hashimoto's encephalopathy and autoantibodies].

    Science.gov (United States)

    Yoneda, Makoto

    2013-04-01

    Encephalopathy occasionally occurs in association with thyroid disorders, but most of these are treatable. These encephalopathies include a neuropsychiatric disorder associated with hypothyroidism, called myxedema encephalopathy. Moreover, Hashimoto's encephalopathy (HE) has been recognized as a new clinical disease based on an autoimmune mechanism associated with Hashimoto's thyroiditis. Steroid treatment was successfully administered to these patients. Recently, we discovered that the serum autoantibodies against the NH2-terminal of α-enolase (NAE) are highly specific diagnostic biomarkers for HE. Further, we analyzed serum anti-NAE autoantibodies and the clinical features in many cases of HE from institutions throughout Japan and other countries. Approximately half of assessed HE patients carry anti-NAE antibodies. The age was widely distributed with 2 peaks (20-30 years and 50-70 years). Most HE patients were in euthyroid states, and all patients had anti-thyroid (TG) antibodies and anti-thyroid peroxidase (TPO) antibodies. Anti-TSH receptor (TSH-R) antibodies were observed in some cases. The common neuropsychiatry features are consciousness disturbance and psychosis, followed by cognitive dysfunction, involuntary movements, seizures, and ataxia. Abnormalities on electroencephalography (EEG) and decreased cerebral blood flow on brain SPECT were common findings, whereas abnormal findings on brain magnetic resonance imaging (MRI) were rare. HE patients have various clinical phenotypes such as the acute encephalopathy form, the chronic psychiatric form, and other particular clinical forms, including limbic encephalitis, progressive cerebellar ataxia, and Creutzfeldt-Jakob disease (CJD)-like form. The cerebellar ataxic form of HE clinically mimics spinocerebellar degeneration (SCD) and is characterized by the absence of nystagmus, absent or mild cerebellar atrophy, and lazy background activities on EEG. Taken together, these data suggest that the possibility of

  9. Pituitary autoantibodies in endocrine disorders

    OpenAIRE

    Bensing, Sophie

    2005-01-01

    Autoimmune endocrine disorders are characterised by the development of autoantibodies to specific autoantigens in the target organs. Lymphocytic hypophysitis (LyH) is a disease characterised by inflammation of the pituitary gland, often resulting in hypopituitarism. The aetiology of LyH is considered to be autoimmune. However, only a few pituitary autoantigens have so far been identified. Reliable autoantibody markers are requested in the diagnostic procedure of LyH to avoid...

  10. Differential expression of IgE and IgG4 specific antibody responses in asymptomatic and chronic human filariasis

    NARCIS (Netherlands)

    Kurniawan, A.; Yazdanbakhsh, M.; van Ree, R.; Aalberse, R.; Selkirk, M. E.; Partono, F.; Maizels, R. M.

    1993-01-01

    A population of 164 adult individuals resident in an area endemic for Brugia malayi lymphatic filariasis has been studied for humoral immune responses to filarial parasites. Antibody levels to Ag extracted from adult worms were determined for each of the IgG subclasses, for IgM and for IgE. The

  11. Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis.

    Science.gov (United States)

    Iwata, Naoko; Iwama, Shintaro; Sugimura, Yoshihisa; Yasuda, Yoshinori; Nakashima, Kohtaro; Takeuchi, Seiji; Hagiwara, Daisuke; Ito, Yoshihiro; Suga, Hidetaka; Goto, Motomitsu; Banno, Ryoichi; Caturegli, Patrizio; Koike, Teruhiko; Oshida, Yoshiharu; Arima, Hiroshi

    2017-06-01

    IgG4-related disease is a systemic inflammatory disease characterized by infiltration of IgG4-positive plasma cells into multiple organs, including the pituitary gland. Autoimmunity is thought to be involved in the pathogenesis of IgG4-related disease. The diagnosis of IgG4-related hypophysitis (IgG4-RH) is difficult because its clinical features, such as pituitary swelling and hypopituitarism, are similar to those of other pituitary diseases, including lymphocytic hypophysitis and sellar/suprasellar tumors. The presence and significance of anti-pituitary antibodies (APA) in IgG4-RH is unclear. In this case-control study, we used single indirect immunofluorescence on human pituitary substrates to assess the prevalence of serum APA in 17 patients with IgG4-RH, 8 control patients with other pituitary diseases (lymphocytic infundibulo-neurohypophysitis, 3; craniopharyngioma, 2; germinoma, 3), and 9 healthy subjects. We further analyzed the endocrine cells targeted by the antibodies using double indirect immunofluorescence. APA were found in 5 of 17 patients with IgG4-RH (29%), and in none of the pituitary controls or healthy subjects. The endocrine cells targeted by the antibodies in the 5 IgG4-RH cases were exclusively corticotrophs. Antibodies were of the IgG1 subclass, rather than IgG4, in all 5 cases, suggesting that IgG4 is not directly involved in the pathogenesis. Finally, antibodies recognized pro-opiomelanocortin in 2 of the cases. Our study suggests that autoimmunity is involved in the pathogenesis of IgG4-RH and that corticotrophs are the main antigenic target, highlighting a possible new diagnostic marker for this condition.

  12. Myositis specific autoantibodies: changing insights in pathophysiology and clinical associations.

    NARCIS (Netherlands)

    Hengstman, G.J.D.; Engelen, B.G.M. van; Venrooij, W.J.W. van

    2004-01-01

    PURPOSE OF REVIEW: Defined autoantibodies are found in about half of the patients with myositis. Traditionally, these autoantibodies have been divided into myositis specific autoantibodies (MSAs) and myositis associated autoantibodies. Several studies have shown that MSAs are associated with

  13. Generation of Antigen Microarrays to Screen for Autoantibodies in Heart Failure and Heart Transplantation.

    Directory of Open Access Journals (Sweden)

    Andrzej Chruscinski

    Full Text Available Autoantibodies directed against endogenous proteins including contractile proteins and endothelial antigens are frequently detected in patients with heart failure and after heart transplantation. There is evidence that these autoantibodies contribute to cardiac dysfunction and correlate with clinical outcomes. Currently, autoantibodies are detected in patient sera using individual ELISA assays (one for each antigen. Thus, screening for many individual autoantibodies is laborious and consumes a large amount of patient sample. To better capture the broad-scale antibody reactivities that occur in heart failure and post-transplant, we developed a custom antigen microarray technique that can simultaneously measure IgM and IgG reactivities against 64 unique antigens using just five microliters of patient serum. We first demonstrated that our antigen microarray technique displayed enhanced sensitivity to detect autoantibodies compared to the traditional ELISA method. We then piloted this technique using two sets of samples that were obtained at our institution. In the first retrospective study, we profiled pre-transplant sera from 24 heart failure patients who subsequently received heart transplants. We identified 8 antibody reactivities that were higher in patients who developed cellular rejection (2 or more episodes of grade 2R rejection in first year after transplant as defined by revised criteria from the International Society for Heart and Lung Transplantation compared with those who did have not have rejection episodes. In a second retrospective study with 31 patients, we identified 7 IgM reactivities that were higher in heart transplant recipients who developed antibody-mediated rejection (AMR compared with control recipients, and in time course studies, these reactivities appeared prior to overt graft dysfunction. In conclusion, we demonstrated that the autoantibody microarray technique outperforms traditional ELISAs as it uses less patient

  14. Autoantibody profiling in APS.

    Science.gov (United States)

    Roggenbuck, D; Somma, V; Schierack, P; Borghi, M O; Meroni, P L

    2014-10-01

    The international consensus for the classification of antiphospholipid syndrome (APS) requires clinical and laboratory criteria to be considered at an equal level for diagnosing APS. Thus, detection of antiphospholipid antibodies (aPL) being a hallmark of APS has been the object of intensive investigation over the past 40 years. However, appropriate detection of aPL still remains a laboratory challenge due to their heterogeneity comprising autoantibodies reactive to different phospholipid-binding plasma proteins, such as beta-2 glycoprotein I (β2GPI) and prothrombin. The relevance of aPL interacting with phospholipids other than cardiolipin (CL, diphosphatidylglycerol), such as phosphatidylserine (PS), remains elusive with regard to the diagnosis of APS. Recently, the concept of aPL profiling has been introduced to assess the risk of thrombotic complications in patients with APS. New assay techniques, apart from enzyme-linked immunosorbent assays (ELISAs) recommended by the international consensus for the classification of APS, have been proposed for multiplexing of aPL testing. Line immunoassays (LIAs) employing a novel hydrophobic solid phase for the simultaneous detection of different aPL seem to be an intriguing alternative. We evaluated a novel multiplex LIA employing a hydrophobic membrane coated with different phospholipid (PL)-binding proteins or PLs. The performance characteristics of this new multiplexing assay technique demonstrated its usefulness for aPL profiling. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  15. Prevalence of serum anti-neuronal autoantibodies in patients admitted to acute psychiatric care

    DEFF Research Database (Denmark)

    Schou, M; Sæther, S G; Borowski, K

    2016-01-01

    BACKGROUND: Autoimmune encephalitis associated with anti-neuronal antibodies may be challenging to distinguish from primary psychiatric disorders. The significance of anti-neuronal antibodies in psychiatric patients without clear evidence of autoimmune encephalitis is unknown. We investigated...... the serum prevalence of six anti-neuronal autoantibodies in a cohort of unselected patients admitted to acute psychiatric care. METHOD: Serum was drawn from 925 patients admitted to acute psychiatric in-patient care. Psychiatric diagnoses were set according to International Classification of Diseases (ICD......)-10 criteria. Antibody analysis was performed with an indirect immunofluorescence test for N-methyl d-aspartate receptor (NMDAR) antibodies and five other anti-neuronal autoantibodies of the immunoglobulin (Ig) classes IgA, IgG and IgM isotype. RESULTS: Anti-neuronal autoantibodies were found in 11...

  16. The Fab Conformations in the Solution Structure of Human Immunoglobulin G4 (IgG4) Restrict Access to Its Fc Region

    Science.gov (United States)

    Rayner, Lucy E.; Hui, Gar Kay; Gor, Jayesh; Heenan, Richard K.; Dalby, Paul A.; Perkins, Stephen J.

    2014-01-01

    Human IgG4 antibody shows therapeutically useful properties compared with the IgG1, IgG2, and IgG3 subclasses. Thus IgG4 does not activate complement and shows conformational variability. These properties are attributable to its hinge region, which is the shortest of the four IgG subclasses. Using high throughput scattering methods, we studied the solution structure of wild-type IgG4(Ser222) and a hinge mutant IgG4(Pro222) in different buffers and temperatures where the proline substitution suppresses the formation of half-antibody. Analytical ultracentrifugation showed that both IgG4 forms were principally monomeric with sedimentation coefficients s20,w0 of 6.6–6.8 S. A monomer-dimer equilibrium was observed in heavy water buffer at low temperature. Scattering showed that the x-ray radius of gyration Rg was unchanged with concentration in 50–250 mm NaCl buffers, whereas the neutron Rg values showed a concentration-dependent increase as the temperature decreased in heavy water buffers. The distance distribution curves (P(r)) revealed two peaks, M1 and M2, that shifted below 2 mg/ml to indicate concentration-dependent IgG4 structures in addition to IgG4 dimer formation at high concentration in heavy water. Constrained x-ray and neutron scattering modeling revealed asymmetric solution structures for IgG4(Ser222) with extended hinge structures. The IgG4(Pro222) structure was similar. Both IgG4 structures showed that their Fab regions were positioned close enough to the Fc region to restrict C1q binding. Our new molecular models for IgG4 explain its inability to activate complement and clarify aspects of its stability and function for therapeutic applications. PMID:24876381

  17. Mechanisms of Autoantibody-Induced Pathology

    Directory of Open Access Journals (Sweden)

    Ralf J. Ludwig

    2017-05-01

    Full Text Available Autoantibodies are frequently observed in healthy individuals. In a minority of these individuals, they lead to manifestation of autoimmune diseases, such as rheumatoid arthritis or Graves’ disease. Overall, more than 2.5% of the population is affected by autoantibody-driven autoimmune disease. Pathways leading to autoantibody-induced pathology greatly differ among different diseases, and autoantibodies directed against the same antigen, depending on the targeted epitope, can have diverse effects. To foster knowledge in autoantibody-induced pathology and to encourage development of urgently needed novel therapeutic strategies, we here categorized autoantibodies according to their effects. According to our algorithm, autoantibodies can be classified into the following categories: (1 mimic receptor stimulation, (2 blocking of neural transmission, (3 induction of altered signaling, triggering uncontrolled (4 microthrombosis, (5 cell lysis, (6 neutrophil activation, and (7 induction of inflammation. These mechanisms in relation to disease, as well as principles of autoantibody generation and detection, are reviewed herein.

  18. Increase in serum concentrations of IgG2 and IgG4 by selenium supplementation in children with Down's syndrome.

    Science.gov (United States)

    Annerén, G; Magnusson, C G; Nordvall, S L

    1990-01-01

    In a previous study on children with Down's syndrome a reduced rate of infections was reported by their parents after the children had received six months' treatment with selenium supplements. In the present study the concentrations of the four IgG subclasses were measured in 29 of these children in samples of serum obtained before and immediately after the period of supplementation and one year after it had finished. Selenium had a significant augmentative effect on the serum concentrations of IgG2 and IgG4, but not of IgG1 and IgG3. This effect was not related to age, as among children over the age of 6 years the serum concentrations of IgG2 and IgG4 had decreased significantly one year after the treatment had been stopped. This study suggests that selenium has an immunoregulatory effect, which might be of importance in both basic research and clinical practice. PMID:2148668

  19. Autoantibodies and human immunodeficiency viruses infection: a case-control study.

    Science.gov (United States)

    Chretien, P; Monier, J C; Oksman, F; San Marco, M; Escande, A; Goetz, J; Cohen, J; Baquey, A; Humbel, R L; Sibilia, J

    2003-01-01

    To determine the prevalence of organ-specific and non-specific autoantibodies in HIV-infected patients. A multicentric collaborative case-control study including 105 HIV patients and 100 sex- and age-matched HIV-negative healthy volunteers. Antinuclear, anti-ds DNA, anti-histone, anti-Sm, rheumatoid factor(IgM), anti-beta 2 glycoprotein 1, antineutrophil cytoplasmic, anti-LKM1, anti-LCA1, anti-gastric parietal cell, antiplatelet, anti-intermediate filament, anti-mitotic spindle apparatus, anti-Golgi, anti-ribosome and anti-thyroid autoantibodies were screened in six European laboratories. Only IgG and IgM anticardiolipin, IgG antiplatelet, anti-smooth muscle and anti-thyroglobulin antibodies were statistically more frequent in HIV patients. There was no correlation with the numbers of CD4+ cells except in the case of anti-smooth muscle antibodies. We were unable to find specific autoantibodies such as anti-ds DNA, anti-Sm, AMA, anti-LKM1, anti-LCA1 or anti-beta 2 GP1 antibodies in these patients. Our results indicate that the autoantibody profile of HIV infections is comparable to those of other chronic viral infections. HIV does not seem to be more autoimmunogenic than other viruses.

  20. Ganglioside-specific IgG and IgA recruit leukocyte effector functions in Guillain-Barre syndrome

    NARCIS (Netherlands)

    Sorge, N.M. van; Yuki, N.; Koga, M.; Susuki, K.; Jansen, M.D.; Kooten, C. van; Wokke, J.H.; Winkel, J.G.J. van de; Pol, W.L. van der; Berg, L.H. van den

    2007-01-01

    The capacity of ganglioside-specific autoantibodies to recruit leukocyte effector functions was studied. Serum samples from 87 patients with Guillain–Barré (GBS) or Miller Fisher syndrome (MFS), containing GM1-, GQ1b-, or GD1b-specific IgG or IgA, were tested for leukocyte activating capacity.

  1. [Autoantibody profile in myositis].

    Science.gov (United States)

    Allenbach, Y; Benveniste, O

    2014-07-01

    Patients suffering from muscular symptoms or with an increase of creatine kinase levels may present a myopathy. In such situations, clinicians have to confirm the existence of a myopathy and determine if it is an acquired or a genetic muscular disease. In the presence of an acquired myopathy after having ruled out an infectious, a toxic agent or an endocrine cause, physicians must identify which type of idiopathic myopathy the patient is presenting: either a myositis including polymyositis, dermatomyositis, and inclusion body myositis, or an immune-mediated necrotizing myopathy. Histopathology examination of a muscle biopsy is determinant but detection of autoantibody is now also crucial. The myositis-specific antibodies and myositis-associated antibodies lead to a serologic approach complementary to the histological classification, because strong associations of myositis-specific antibodies with clinical features and survival have been documented. The presence of anti-synthetase antibodies is associated with an original histopathologic pattern between polymyositis and dermatomyositis, and defines a syndrome where interstitial lung disease drives the prognosis. Anti-MDA-5 antibody are specifically associated with dermatomyositis, and define a skin-lung syndrome with a frequent severe disease course. Anti-TIF1-γ is also associated with dermatomyositis but its presence is frequently predictive of a cancer association whereas anti-MI2 is associated with the classical dermatomyositis. Two specific antibodies, anti-SRP and anti-HMGCR, are observed in patients with immune-mediated necrotizing myopathies and may be very useful to distinguish acquired myopathies from dystrophic muscular diseases in case of a slow onset and to allow the initiation of effective therapy. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  2. Thoracic Paravertebral Mass as an Infrequent Manifestation of IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Melissa Matzumura Kuan

    2017-01-01

    Full Text Available Case. A 50-year-old African American male presented with abdominal pain and significant weight loss. On physical examination, he had parotid and submandibular gland enlargement associated with right eye proptosis. Computed tomography showed a thoracic paravertebral soft tissue mass, enlarged lymph nodes, and ascending aortic aneurysm. Laboratory results were remarkable for elevated total IgG and IgG4 subclass. The submandibular gland pathology revealed chronic sclerosing sialadenitis, with a large subset of inflammatory cells positively staining for IgG4. The histology of the paravertebral mass demonstrated fibrosclerosis with increased lymphocytic infiltrate, associated with increased IgG4 plasma cells. He was diagnosed with immunoglobulin G4-related disease (IgG4-RD. Steroid therapy initially yielded improvement; however, after steroids were stopped, there was disease recurrence. Prednisone was restarted, and the plan was to start him on rituximab. Interestingly, the patient’s brother also had IgG4-RD. Conclusion. IgG4-RD can present as a paravertebral mass which is usually responsive to steroids; however, recurrent and resistant disease can be seen for which steroid-sparing agents such as rituximab should be considered. In addition, to the best of our knowledge, this is the first reported case of IgG4-RD in two family members presenting as a paravertebral mass, highlighting an exciting area for more research in the future.

  3. Hinge-deleted IgG4 blocker therapy for acetylcholine receptor myasthenia gravis in rhesus monkeys.

    Science.gov (United States)

    Losen, Mario; Labrijn, Aran F; van Kranen-Mastenbroek, Vivianne H; Janmaat, Maarten L; Haanstra, Krista G; Beurskens, Frank J; Vink, Tom; Jonker, Margreet; 't Hart, Bert A; Mané-Damas, Marina; Molenaar, Peter C; Martinez-Martinez, Pilar; van der Esch, Eline; Schuurman, Janine; de Baets, Marc H; Parren, Paul W H I

    2017-04-20

    Autoantibodies against ion channels are the cause of numerous neurologic autoimmune disorders. Frequently, such pathogenic autoantibodies have a restricted epitope-specificity. In such cases, competing antibody formats devoid of pathogenic effector functions (blocker antibodies) have the potential to treat disease by displacing autoantibodies from their target. Here, we have used a model of the neuromuscular autoimmune disease myasthenia gravis in rhesus monkeys (Macaca mulatta) to test the therapeutic potential of a new blocker antibody: MG was induced by passive transfer of pathogenic acetylcholine receptor-specific monoclonal antibody IgG1-637. The effect of the blocker antibody (IgG4Δhinge-637, the hinge-deleted IgG4 version of IgG1-637) was assessed using decrement measurements and single-fiber electromyography. Three daily doses of 1.7 mg/kg IgG1-637 (cumulative dose 5 mg/kg) induced impairment of neuromuscular transmission, as demonstrated by significantly increased jitter, synaptic transmission failures (blockings) and a decrease in the amplitude of the compound muscle action potentials during repeated stimulations (decrement), without showing overt symptoms of muscle weakness. Treatment with three daily doses of 10 mg/kg IgG4Δhinge-637 significantly reduced the IgG1-637-induced increase in jitter, blockings and decrement. Together, these results represent proof-of principle data for therapy of acetylcholine receptor-myasthenia gravis with a monovalent antibody format that blocks binding of pathogenic autoantibodies.

  4. Antibody classes & subclasses induced by mucosal immunization of mice with Streptococcus pyogenes M6 protein & oligodeoxynucleotides containing CpG motifs.

    Science.gov (United States)

    Teloni, R; von Hunolstein, C; Mariotti, S; Donati, S; Orefici, G; Nisini, R

    2004-05-01

    Type-specific antibodies against M protein are critical for human protection as they enhance phagocytosis and are protective. An ideal vaccine for the protection against Streptococcus pyogenes would warrant mucosal immunity, but mucosally administered M-protein has been shown to be poorly immunogenic in animals. We used a recombinant M type 6 protein to immunize mice in the presence of synthetic oligodeoxynucleotides containing CpG motifs (immunostimulatory sequences: ISS) or cholera toxin (CT) to explore its possible usage in a mucosal vaccine. Mice were immunized by intranasal (in) or intradermal (id) administration with four doses at weekly intervals of M6-protein (10 microg/mouse) with or without adjuvant (ISS, 10 microg/mouse or CT, 0,5 microg/mouse). M6 specific antibodies were measured by enzyme linked immunosorbent assay using class and subclass specific monoclonal antibodies. The use of ISS induced an impressive anti M-protein serum IgG response but when id administered was not detectable in the absence of adjuvant. When used in, M-protein in the presence of both ISS and CT induced anti M-protein IgA in the bronchoalveolar lavage, as well as specific IgG in the serum. IgG were able to react with serotype M6 strains of S. pyogenes. The level of antibodies obtained by immunizing mice in with M-protein and CT was higher in comparison to M-protein and ISS. The analysis of anti-M protein specific IgG subclasses showed high levels of IgG1, IgG2a and IgG2b, and low levels of IgG3 when ISS were used as adjuvant. Thus, in the presence of ISS, the ratio IgG2a/IgG1 and (IgG2a+IgG3)/IgG1 >1 indicated a type 1-like response obtained both in mucosally or systemically vaccinated mice. Our study offers a reproducible model of anti-M protein vaccination that could be applied to test new antigenic formulations to induce an anti-group A Streptococcus (GAS) vaccination suitable for protection against the different diseases caused by this bacterium.

  5. Detection of autoantibodies to cytokines

    DEFF Research Database (Denmark)

    Bendtzen, K; Hansen, M B; Ross, C

    2000-01-01

    Autoantibodies to various cytokines have been reported in normal individuals and in patients with various infectious and immunoinflammatory disorders, and similar antibodies (Ab) may be induced in patients receiving human recombinant cytokines. The clinical relevance of these Ab is often difficul...

  6. Plasma autoantibodies against heat shock protein 70, enolase 1 and ribonuclease/angiogenin inhibitor 1 as potential biomarkers for cholangiocarcinoma.

    Directory of Open Access Journals (Sweden)

    Rucksak Rucksaken

    Full Text Available The diagnosis of cholangiocarcinoma (CCA is often challenging, leading to poor prognosis. CCA arises via chronic inflammation which may be associated with autoantibodies production. This study aims to identify IgG antibodies directed at self-proteins and tumor-associated antigens. Proteins derived from immortalized cholangiocyte cell line (MMNK1 and CCA cell lines (M055, M214 and M139 were separated using 2-dimensional electrophoresis and incubated with pooled plasma of patients with CCA and non-neoplastic controls by immunoblotting. Twenty five immunoreactive spots against all cell lines-derived proteins were observed on stained gels and studied by LC-MS/MS. Among these, heat shock protein 70 (HSP70, enolase 1 (ENO1 and ribonuclease/angiogenin inhibitor 1 (RNH1 obtained the highest matching scores and were thus selected for further validation. Western blot revealed immunoreactivity against HSP70 and RNH1 in the majority of CCA cases and weakly in healthy individuals. Further, ELISA showed that plasma HSP70 autoantibody level in CCA was significantly capable to discriminate CCA from healthy individuals with an area under the receiver operating characteristic curve of 0.9158 (cut-off 0.2630, 93.55% sensitivity and 73.91% specificity. Plasma levels of IgG autoantibodies against HSP70 were correlated with progression from healthy individuals to cholangitis to CCA (r = 0.679, P<0.001. In addition, circulating ENO1 and RNH1 autoantibodies levels were also significantly higher in cholangitis and CCA compared to healthy controls (P<0.05. Moreover, the combinations of HSP70, ENO1 or RNH1 autoantibodies positivity rates improved specificity to over 78%. In conclusion, plasma IgG autoantibodies against HSP70, ENO1 and RNH1 may represent new diagnostic markers for CCA.

  7. A radiolabeled antiglobulin assay to identify human cervical mucus immunoglobulin (Ig) A and IgG antisperm antibodies

    International Nuclear Information System (INIS)

    Haas, G.G. Jr.; D'Cruz, O.J.

    1989-01-01

    Antisperm immunoglobulin (Ig) A and IgG antibodies in human cervical mucus (CM) were identified by a radiolabeled antiglobulin assay. Cervical mucus samples from fertile and infertile women were exposed to a 1:3,200 dilution of 2-mercaptoethanol (2-ME), and 5 micrograms of the solubilized CM protein were assayed for the presence of IgA and IgG antisperm and anti-Candida activity by the radiolabeled antiglobulin assay. Purified human secretory IgA and IgG exposed to 2-ME retained the molecular integrity and functional activity of the untreated antibody molecules. CM aliquots collected after high-performance liquid chromatography (HPLC) fractionation were assessed for antisperm antibody activity; antisperm antibody activity was retained in the appropriate IgA or IgG CM fractions. The incidence of CM antisperm antibodies was minimally affected when the radiolabeled antiglobulin assay was performed with a motile sperm population. Approximately 70% of the CM IgA antisperm antibodies were of the IgA1 subclass; CM IgG was primarily of the IgG4 subclass. When Candida antigen was substituted for sperm in the radiolabeled antiglobulin assay, the CM antisperm antibodies were found to be exclusively sperm-specific. These data indicate that the radiolabeled antiglobulin assay using 2-ME to extract CM antibodies is a specific method for the assay of antisperm antibodies in CM

  8. Extrapancreatic Autoantibody Profiles in Type I Diabetes

    Science.gov (United States)

    Burbelo, Peter D.; Lebovitz, Evan E.; Bren, Kathleen E.; Bayat, Ahmad; Paviol, Scott; Wenzlau, Janet M.; Barriga, Katherine J.; Rewers, Marian; Harlan, David M.; Iadarola, Michael J.

    2012-01-01

    Type I diabetes (T1D) is an autoimmune disease characterized by destruction of insulin-producing β-cells in the pancreas. Although several islet cell autoantigens are known, the breadth and spectrum of autoantibody targets has not been fully explored. Here the luciferase immunoprecipitation systems (LIPS) antibody profiling technology was used to study islet and other organ-specific autoantibody responses in parallel. Examination of an initial cohort of 93 controls and 50 T1D subjects revealed that 16% of the diabetic subjects showed anti-gastric ATPase autoantibodies which did not correlate with autoantibodies against GAD65, IA2, or IA2-β. A more detailed study of a second cohort with 18 potential autoantibody targets revealed marked heterogeneity in autoantibody responses against islet cell autoantigens including two polymorphic variants of ZnT8. A subset of T1D subjects exhibited autoantibodies against several organ-specific targets including gastric ATPase (11%), thyroid peroxidase (14%), and anti-IgA autoantibodies against tissue transglutaminase (12%). Although a few T1D subjects showed autoantibodies against a lung-associated protein KCNRG (6%) and S100-β (8%), no statistically significant autoantibodies were detected against several cytokines. Analysis of the overall autoantibody profiles using a heatmap revealed two major subgroups of approximately similar numbers, consisting of T1D subjects with and without organ-specific autoantibodies. Within the organ-specific subgroup, there was minimal overlap among anti-gastric ATPase, anti-thyroid peroxidase, and anti-transglutaminase seropositivity, and these autoantibodies did not correlate with islet cell autoantibodies. Examination of a third cohort, comprising prospectively collected longitudinal samples from high-risk individuals, revealed that anti-gastric ATPase autoantibodies were present in several individuals prior to detection of islet autoantibodies and before clinical onset of T1D. Taken together

  9. 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.

  10. Serum Autoantibody Measurement for the Detection of Hepatocellular Carcinoma

    Science.gov (United States)

    Middleton, Catrin H.; Irving, William; Robertson, John F. R.; Murray, Andrea; Parsy-Kowalska, Celine B.; Macdonald, Isabel K.; McElveen, Jane; Allen, Jared; Healey, Graham F.; Thomson, Brian J.; Ryder, Stephen J.; Holdenrieder, Stefan; Chapman, Caroline J.

    2014-01-01

    Background Individuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC) which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs) in the serum of patients with HCC. Methods Serum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA. Results Varying autoantibody specificities (97–100%) and sensitivities (0–10%) were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel. Conclusions This minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography) and to similar tests in other cancers (EarlyCDT-Lung). PMID:25093332

  11. Serum autoantibody measurement for the detection of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Catrin H Middleton

    Full Text Available BACKGROUND: Individuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs in the serum of patients with HCC. METHODS: Serum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA. RESULTS: Varying autoantibody specificities (97-100% and sensitivities (0-10% were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel. CONCLUSIONS: This minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography and to similar tests in other cancers (EarlyCDT-Lung.

  12. Evaluation of a radioreceptor assay for TSH receptor autoantibodies

    Energy Technology Data Exchange (ETDEWEB)

    Rootwelt, K.

    1988-02-01

    A commercial radioreceptor assay for TSH receptor autoantibodies (TRAb), based on solubilized porcine receptor and purified radio-iodinated bovine TSH, was tested in 264 subjects with a variety of thyroid disorders. The sensitivity of the assay for the detection of hyperthyroid Graves' disease was 91%. The assay specificity for Graves' disease was 95%. With the exception of one patient with Hashimoto's disease and one patient with de Quervain's subacute thyroiditis no subjects other than Graves' patients had detectable TRAb. Thus purely blocking TSII receptor autoantibodies were not detected with the assay. One female with thyroxine-treated idiopathic primary hypothyroidism who had given birth to two children with transiently elevated TSH, was found to have a circulating TSH-binding substance that resulted in an abnormally negative TRAb value, and highly discrepant results when TSH was measured with a double antibody TSH radioimmunoassay and an immunoradiometric assay. The TSH-binding substance was precipitated like a protein, but was not IgG. Similar findings have not previously been reported.

  13. A toolbox of anti–mouse and anti–rabbit IgG secondary nanobodies

    Science.gov (United States)

    2018-01-01

    Polyclonal anti–immunoglobulin G (anti-IgG) secondary antibodies are essential tools for many molecular biology techniques and diagnostic tests. Their animal-based production is, however, a major ethical problem. Here, we introduce a sustainable alternative, namely nanobodies against all mouse IgG subclasses and rabbit IgG. They can be produced at large scale in Escherichia coli and could thus make secondary antibody production in animals obsolete. Their recombinant nature allows fusion with affinity tags or reporter enzymes as well as efficient maleimide chemistry for fluorophore coupling. We demonstrate their superior performance in Western blotting, in both peroxidase- and fluorophore-linked form. Their site-specific labeling with multiple fluorophores creates bright imaging reagents for confocal and superresolution microscopy with much smaller label displacement than traditional secondary antibodies. They also enable simpler and faster immunostaining protocols, and allow multitarget localization with primary IgGs from the same species and of the same class. PMID:29263082

  14. Presence of specific IgG antibody to grain dust does not go with respiratory symptoms.

    Science.gov (United States)

    Park, H S; Suh, C H; Nahm, D H; Kim, H Y

    1999-02-01

    A high prevalence of work-related symptoms in relation to grain dust exposure has been reported in grain dust workers, but the role of the specific IgG antibody is unknown. To study the possible role of specific IgG (sIgG) and specific IgG4 (sIgG4) in the development of work-related symptoms, sIgG and sIgG4 subclass antibodies against grain dust antigens were determined by ELISA in sera from 43 workers and 27 non-exposed controls. They were compared with results of specific IgE antibodies, exposure intensity and the presence of respiratory symptoms. SIgG and sIgG4 antibodies were detectable in almost all sera of exposed workers, and the prevalence were significantly higher than those of controls (pgrain dust exposure and may unlikely play a role in the etiology of respiratory symptoms.

  15. Coefficient inequality for certain subclass of analytic functions

    Directory of Open Access Journals (Sweden)

    D. Vamshee Krishna

    2013-03-01

    Full Text Available The objective of this paper is to an obtain an upper bound to the second Hankel determinant $|a_{2}a_{4}-a_{3}^{2}|$ for the function $f$, belonging to a certain subclass of analytic functions, using Toeplitz determinants.

  16. Some subclasses of multivalent functions involving a certain linear operator

    Science.gov (United States)

    Srivastava, H. M.; Patel, J.

    2005-10-01

    The authors investigate various inclusion and other properties of several subclasses of the class of normalized p-valent analytic functions in the open unit disk, which are defined here by means of a certain linear operator. Problems involving generalized neighborhoods of analytic functions in the class are investigated. Finally, some applications of fractional calculus operators are considered.

  17. Cluster analysis of autoantibodies in 852 patients with systemic lupus erythematosus from a single center.

    Science.gov (United States)

    Artim-Esen, Bahar; Çene, Erhan; Şahinkaya, Yasemin; Ertan, Semra; Pehlivan, Özlem; Kamali, Sevil; Gül, Ahmet; Öcal, Lale; Aral, Orhan; Inanç, Murat

    2014-07-01

    Associations between autoantibodies and clinical features have been described in systemic lupus erythematosus (SLE). Herein, we aimed to define autoantibody clusters and their clinical correlations in a large cohort of patients with SLE. We analyzed 852 patients with SLE who attended our clinic. Seven autoantibodies were selected for cluster analysis: anti-DNA, anti-Sm, anti-RNP, anticardiolipin (aCL) immunoglobulin (Ig)G or IgM, lupus anticoagulant (LAC), anti-Ro, and anti-La. Two-step clustering and Kaplan-Meier survival analyses were used. Five clusters were identified. A cluster consisted of patients with only anti-dsDNA antibodies, a cluster of anti-Sm and anti-RNP, a cluster of aCL IgG/M and LAC, and a cluster of anti-Ro and anti-La antibodies. Analysis revealed 1 more cluster that consisted of patients who did not belong to any of the clusters formed by antibodies chosen for cluster analysis. Sm/RNP cluster had significantly higher incidence of pulmonary hypertension and Raynaud phenomenon. DsDNA cluster had the highest incidence of renal involvement. In the aCL/LAC cluster, there were significantly more patients with neuropsychiatric involvement, antiphospholipid syndrome, autoimmune hemolytic anemia, and thrombocytopenia. According to the Systemic Lupus International Collaborating Clinics damage index, the highest frequency of damage was in the aCL/LAC cluster. Comparison of 10 and 20 years survival showed reduced survival in the aCL/LAC cluster. This study supports the existence of autoantibody clusters with distinct clinical features in SLE and shows that forming clinical subsets according to autoantibody clusters may be useful in predicting the outcome of the disease. Autoantibody clusters in SLE may exhibit differences according to the clinical setting or population.

  18. Cramp-fasciculation syndrome in patients with and without neural autoantibodies.

    Science.gov (United States)

    Liewluck, Teerin; Klein, Christopher J; Jones, Lyell K

    2014-03-01

    We investigated the clinical, electrophysiological and neural autoantibody characteristics in cramp-fasciculation syndrome (CFS) patients. We reviewed Mayo Clinic records from 2000 to 2011 to identify clinically defined CFS patients who underwent neural autoantibody testing. Stored sera of patients who tested positive for antibodies to voltage-gated potassium channel complex (VGKC complex) were analyzed further for leucine-rich glioma-inactivated 1 (LGI1) or contactin-associated protein-2 immunoglobulin G (CASPR2-IgG) antibodies. Thirty-seven patients were identified. Twelve were seropositive for neural autoantibodies. Clinical manifestations were similar in seropositive and seronegative patients, although central and autonomic neuronal hyperexcitability symptoms were more common in seropositive cases. No patients had a malignancy. Repetitive tibial nerve stimulation at 10 Hz revealed longer afterdischarges in seropositive patients. Two of 7 patients with VGKC-complex autoimmunity demonstrated LGI1 or CASPR2-IgG antibodies. Only 2 of 12 seropositive patients required immunotherapy. VGKC-complex autoimmunity occurs in a minority of CFS patients. Antibody positivity was associated with extramuscular manifestations, typically without malignancy. Target antigens within the VGKC complex remain unknown in most patients. Published 2013 by Wiley Periodicals, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.

  19. Determination of auto-antibodies to native and oxidized low-density lipoproteins (LDL) in serum of patients underwent coronariography in the Medical-Surgical Research Center (MSRC)

    International Nuclear Information System (INIS)

    Conde CerdeiraI, Hector; Soto Lopez, Yosdel; Aroche Aportela, Ronald

    2010-01-01

    Low-density lipoprotein (LDL) oxidation is an important event in atherosclerosis development. The relationship between oxidized LDL (oxLDL) autoantibodies and coronary artery disease (CAD) remains controversial. IgM and IgG autoantibodies to oxLDL were measured in twenty patients undergoing clinically indicated coronary angiography, and in ten young healthy volunteers from the Center of Molecular Immunology. The levels of IgM autoantibodies to oxLDL did not differ between no CAD patients and healthy subjects, but the levels of IgM autoantibodies to oxLDL of these two groups were higher compared with the one of CAD patient group. Our results, although preliminary, supports the hypothesis that this kind of Abs might be inversely associated with the presence of atherosclerosis

  20. An Autoimmune Myositis-Overlap Syndrome Associated With Autoantibodies to Nuclear Pore Complexes

    Science.gov (United States)

    Senécal, Jean-Luc; Isabelle, Catherine; Fritzler, Marvin J.; Targoff, Ira N.; Goldstein, Rose; Gagné, Michel; Raynauld, Jean-Pierre; Joyal, France; Troyanov, Yves; Dabauvalle, Marie-Christine

    2014-01-01

    Abstract Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immunomodulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr). By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n = 112), mixed connective tissue disease (n = 35), systemic lupus (n = 94), rheumatoid arthritis (n = 45), or other rheumatic diseases (n = 107), nor was it observed in 62 normal adults. Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic

  1. 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.

  2. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    Science.gov (United States)

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Myositis specific autoantibodies; specificity and clinical applications.

    NARCIS (Netherlands)

    Hengstman, G.J.D.

    2005-01-01

    The sera of about half of the patients with myositis contain autoantibodies that are specific for this group of diseases compared to other inflammatory connective tissue disorders. In a recent study we showed that these myositis specific autoantibodies (MSAs) are also specific for myositis as

  4. Autoantibodies and immunoglobulins among atomic-bomb survivors

    International Nuclear Information System (INIS)

    Fujiwara, Saeko; Carter, R.L.; Akiyama, Mitoshi

    1993-06-01

    The purpose of this study was to determine if exposure to atomic-bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody, and immunoglobulin levels (IgG, IgM, IgA, and IgE) were measured among 2061 Adult Health Study participants in Hiroshima and Nagasaki from December 1987 to November 1989. The prevalence and titers of rheumatoid factor increased in a statistically significant manner with increasing radiation dose. No radiation effect was found on the prevalence of antinuclear antibody, antithyroglobulin antibody, and anti-thyroid-microsomal antibody. A statistically significant relationship was also found between radiation exposure and the IgA level in females and the IgM levels in both sexes-both levels increased as radiation dose increased. However, the effects of radiation exposure were not large and accounted for less than 10% of the total variation in each measurement. Levels of IgG and IgE were not affected by radiation exposure. (author)

  5. Detection of autoantibodies to cytokines

    DEFF Research Database (Denmark)

    Bendtzen, K; Hansen, M B; Ross, C

    2000-01-01

    Autoantibodies to various cytokines have been reported in normal individuals and in patients with various infectious and immunoinflammatory disorders, and similar antibodies (Ab) may be induced in patients receiving human recombinant cytokines. The clinical relevance of these Ab is often difficult...... to evaluate. Not only are in vitro neutralizing cytokine Ab not necessarily neutralizing in vivo, but assays for binding and neutralizing Ab to cytokines are often difficult to interpret. For example, denaturation of immobilized cytokines in immunoblotting techniques and immunometric assays may leave Ab...

  6. IgG4-Related Sclerosing Disease, an Emerging Entity: A Review of a Multi-System Disease

    Science.gov (United States)

    Divatia, Mukul; Kim, Sun A

    2012-01-01

    Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies. PMID:22187229

  7. Evidence of IgY subclass diversification in snakes: evolutionary implications.

    Science.gov (United States)

    Wang, Tao; Sun, Yi; Shao, Wenwei; Cheng, Gang; Li, Lingxiao; Cao, Zubing; Yang, Zhi; Zou, Huiying; Zhang, Wei; Han, Binyue; Hu, Yang; Ren, Liming; Hu, Xiaoxiang; Guo, Ying; Fei, Jing; Hammarström, Lennart; Li, Ning; Zhao, Yaofeng

    2012-10-01

    Mammalian IgG and IgE are thought to have evolved from IgY of nonmammalian tetrapods; however, no diversification of IgY subclasses has been reported in reptiles or birds, which are phylogenetically close to mammals. To our knowledge, we report the first evidence of the presence of multiple IgY-encoding (υ) genes in snakes. Two υ genes were identified in the snake Elaphe taeniura, and three υ genes were identified in the Burmese python (Python molurus bivittatus). Although four of the υ genes displayed a conventional four-H chain C region exon structure, one of the υ genes in the Burmese python lacked the H chain C region 2 exon, thus exhibiting a structure similar to that of the mammalian γ genes. We developed mouse mAbs specific for the IgY1 and IgY2 of E. taeniura and showed that both were expressed in serum; each had two isoforms: one full-length and one truncated at the C terminus. The truncation was not caused by alternative splicing or transcriptional termination. We also identified the μ and δ genes, but no α gene, in both snakes. This study provides valuable clues for our understanding of Ig gene evolution in tetrapods.

  8. HLA class I antibodies trigger increased adherence of monocytes to endothelial cells by eliciting an increase in endothelial P-selectin and, depending on subclass, by engaging FcγRs.

    Science.gov (United States)

    Valenzuela, Nicole M; Mulder, Arend; Reed, Elaine F

    2013-06-15

    Ab-mediated rejection (AMR) of solid organ transplants is characterized by intragraft macrophages. It is incompletely understood how donor-specific Ab binding to graft endothelium promotes monocyte adhesion, and what, if any, contribution is made by the Fc region of the Ab. We investigated the mechanisms underlying monocyte recruitment by HLA class I (HLA I) Ab-activated endothelium. We used a panel of murine mAbs of different subclasses to crosslink HLA I on human aortic, venous, and microvascular endothelial cells and measured the binding of human monocytic cell lines and peripheral blood monocytes. Both anti-HLA I murine (m)IgG1 and mIgG2a induced endothelial P-selectin, which was required for monocyte adhesion to endothelium irrespective of subclass. mIgG2a but not mIgG1 could bind human FcγRs. Accordingly, HLA I mIgG2a but not mIgG1 treatment of endothelial cells significantly augmented recruitment, predominantly through FcγRI, and, to a lesser extent, FcγRIIa. Moreover, HLA I mIgG2a promoted firm adhesion of monocytes to ICAM-1 through Mac-1, which may explain the prominence of monocytes during AMR. We confirmed these observations using human HLA allele-specific mAbs and IgG purified from transplant patient sera. HLA I Abs universally elicit endothelial exocytosis leading to monocyte adherence, implying that P-selectin is a putative therapeutic target to prevent macrophage infiltration during AMR. Importantly, the subclass of donor-specific Ab may influence its pathogenesis. These results imply that human IgG1 and human IgG3 should have a greater capacity to trigger monocyte infiltration into the graft than IgG2 or IgG4 due to enhancement by FcγR interactions.

  9. HLA class I antibodies trigger increased adherence of monocytes to endothelial cells by eliciting an increase in endothelial P-selectin and, depending on subclass, by engaging FcγRs1

    Science.gov (United States)

    Valenzuela, Nicole M; Mulder, Arend; Reed, Elaine F

    2013-01-01

    Antibody-mediated rejection of solid organ transplants is characterized by intragraft macrophages. It is incompletely understood how donor specific antibody binding to graft endothelium promotes monocyte adhesion, and what, if any, contribution is made by the Fc region of the antibody. We investigated the mechanisms underlying monocyte recruitment by HLA class I antibody-activated endothelium. We used a panel of murine monoclonal antibodies of different subclasses to crosslink HLA I on human aortic, venous and microvascular endothelial cells, and measured the binding of human monocytic cell lines and peripheral blood monocytes. Both anti-HLA I murine IgG1 and mIgG2a induced endothelial P-selectin, which was required for monocyte adhesion to endothelium irrespective of subclass. Mouse IgG2a but not mIgG1 could bind human FcγRs. Accordingly, HLA I mIgG2a but not mIgG1 treatment of endothelial cells significantly augmented recruitment, predominantly through FcγRI, and, to a lesser extent, FcγRIIa. Moreover, HLA I mIgG2a promoted firm adhesion of monocytes to ICAM-1 through Mac-1, which may explain the prominence of monocytes during antibody mediated rejection. We confirmed these observations using human HLA allele specific monoclonal antibodies and IgG purified from transplant patient sera. HLA I antibodies universally elicit endothelial exocytosis leading to monocyte adherence, implying that P-selectin is a putative therapeutic target to prevent macrophage infiltration during antibody-mediated rejection. Importantly, the subclass of donor specific antibody may influence its pathogenesis. These results imply that hIgG1 and hIgG3 should have a greater capacity to trigger monocyte infiltration into the graft than IgG2 or IgG4 due to enhancement by FcγR interactions. PMID:23690477

  10. Autoantibodies

    Science.gov (United States)

    ... Antibodies Beta-2 Glycoprotein 1 Antibodies Antiphospholipid Antibodies (APA) Lupus anticoagulants (LA) Endocrine/metabolic system Diabetes-related ... Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO. What ...

  11. Histopathologie der IgG4-RD

    DEFF Research Database (Denmark)

    Detlefsen, S; Klöppel, G

    2016-01-01

    infiltrate, 2) storiform fibrosis and 3) obliterative phlebitis. The diagnosis is further supported by immunohistochemical demonstration of an increased infiltration of IgG4-positive plasma cells and an elevated IgG4/IgG ratio. The morphological criteria of IgG4-RD are in most cases detectable in biopsies...

  12. Pancreatic-specific autoantibodies to glycoprotein 2 mirror disease location and behaviour in younger patients with Crohn’s disease

    Directory of Open Access Journals (Sweden)

    Bogdanos Dimitrios P

    2012-08-01

    Full Text Available Abstract Background Glycoprotein 2 (GP2 was discovered as the major autoantigen of Crohn’s disease (CD-specific pancreatic autoantibodies (PAB. We investigated anti-GP2 IgA and IgG antibodies as novel serological parameters in CD and assessed their association with distinct disease phenotypes. Methods Anti-GP2 and anti-Saccharomyces cerevisiae (ASCA IgA and IgG were detected by ELISA employing recombinant human GP2 and phosphopeptidomannan, respectively and PAB by indirect immunofluorescence (IIF in 271 sera, 169 with CD and 102 with ulcerative colitis (UC. As healthy controls 160 adult blood donors and 65 children were included. Results Anti-GP2 IgG and/or IgA were more prevalent in CD (51/169, 30.2% than in UC (9/102, 8.9% patients and in controls (9/225, 4% (p  Conclusions Anti-GP2 IgG and IgA, constituting novel CD specific autoantibodies, appear to be associated with distinct disease phenotypes identifying patients at a younger age, with ileocolonic location, and stricturing behaviour with perianal disease.

  13. 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.

  14. Chagas' disease: IgG isotypes against cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive antigens of Trypanosoma cruzi in chronic Chagasic patients.

    Science.gov (United States)

    Verçosa, A F A; Lorena, V M B; Carvalho, C L; Melo, M F A D; Cavalcanti, M G A; Silva, E D; Ferreira, A G P; Pereira, V R A; Souza, W V; Gomes, Y M

    2007-01-01

    The wide range of clinical Chagas' disease manifestations, of which heart involvement is the most significant, because of its characteristics, frequency and consequences, and lack of treatment and cure, justify research in this area. Specific immunoglobulin G (IgG) antibody subclasses have been associated with human Chagas' disease. Thus, in this study, the profile of IgG subclasses against cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive T. cruzi-specific antigens was correlated with cardiac (CARD, n=33), cardiodigestive (CD, n=7), and indeterminate (IND, n=20) forms of Chagas' disease by indirect enzyme-linked immunosorbent assay (ELISA). IgG subclasses were detected in almost all Chagas patients studied. Nevertheless, only specific IgG2 isotype FRA was found with a significant statistical difference in CARD patients when compared to IND patients. This result suggests the potential use of this isotype for prognostic purposes, for monitoring the progression of chronic Chagas' disease, and for predicting the risk of CARD damage. This is important information, as it could help physicians to evaluate and manage the treatment of their patients. However, a follow-up study is necessary to confirm our result. (c) 2007 Wiley-Liss, Inc.

  15. IgG4-Related Tubulointerstitial Nephritis.

    Science.gov (United States)

    Zhang, Pingchuan; Cornell, Lynn D

    2017-03-01

    Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a fibroinflammatory disorder that can involve nearly any organ. The disorder has increasingly become known as a distinct clinical entity during the last decade. IgG4-related tubulointerstitial nephritis (IgG4-TIN) is the most common manifestation of IgG4-RD in the kidney. Many patients with IgG4-TIN are diagnosed after IgG4-RD has been recognized in other organ systems, but the kidney may also be the first or only site involved. The presenting clinical features of IgG4-TIN are most commonly kidney insufficiency, kidney mass lesion(s), or both. On biopsy, IgG4-TIN shows a dense lymphoplasmacytic infiltrate, increased IgG4+ plasma cells, storiform fibrosis, and often tubular basement membrane immune complex deposits. Elevation of serum IgG4 often accompanies IgG4-RD; however, it is not specific in reaching the diagnosis. Like IgG4-RD in other organs, IgG4-TIN characteristically responds promptly to steroids, although there is a high relapse rate on discontinuation of immunosuppression. The pathogenesis of IgG4-RD is not understood. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  16. Antineuronal Autoantibodies : Molecular Characterization and Clinical Implication

    NARCIS (Netherlands)

    Hameete, M.H.|info:eu-repo/dai/nl/371750539

    2017-01-01

    Neurological autoimmune disorders associated with antineuronal autoantibodies result from an immune reaction directed at neuronal self-antigens. When affecting the central nervous system these can be divided into two subgroups: ‘classical’ paraneoplastic neurological syndromes (PNS) and autoimmune

  17. Autoantibodies to Posttranslational Modifications in Rheumatoid Arthritis

    Science.gov (United States)

    Burska, Agata N.; Hunt, Laura; Strollo, Rocky; Ryan, Brent J.; Vital, Ed; Nissim, Ahuva; Winyard, Paul G.; Emery, Paul; Ponchel, Frederique

    2014-01-01

    Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases (AIDs). Rheumatoid factor (RF) is known since the late 1930s to be associated with rheumatoid arthritis (RA). The discovery of anticitrullinated protein antibodies in the last century has changed this and other posttranslational modifications (PTM) relevant to RA have since been described. Such PTM introduce neoepitopes in proteins that can generate novel autoantibody specificities. The recent recognition of these novel specificities in RA provides a unique opportunity to understand human B-cell development in vivo. In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation. With the advancement of research methodologies it should be expected that other autoantibodies against PTM proteins could be discovered in patients with autoimmune diseases. Many of such autoantibodies may provide significant biomarker potential. PMID:24782594

  18. Autoantibodies in systemic sclerosis: Unanswered questions

    Directory of Open Access Journals (Sweden)

    CRISTIANE eKAYSER

    2015-04-01

    Full Text Available Systemic sclerosis (SSc is an autoimmune disease characterized by vascular abnormalities, and cutaneous and visceral fibrosis. Serum autoantibodies directed to multiple intracellular antigens are present in more than 95% of patients and are considered a hallmark of SSc. They are helpful biomarkers for the early diagnosis of SSc and are associated with distinctive clinical manifestations. With the advent of more sensitive, multiplexed immunoassays, new and old questions about the relevance of autoantibodies in SSc are emerging. In this review we discuss the clinical relevance of autoantibodies in SSc emphasizing the more recently published data. Moreover, we will summarize recent advances regarding the stability of SSc autoantibodies over the course of disease, whether they are mutually exclusive and their potential roles in the disease pathogenesis.

  19. Neuromyelitis optica study model based on chronic infusion of autoantibodies in rat cerebrospinal fluid.

    Science.gov (United States)

    Marignier, R; Ruiz, A; Cavagna, S; Nicole, A; Watrin, C; Touret, M; Parrot, S; Malleret, G; Peyron, C; Benetollo, C; Auvergnon, N; Vukusic, S; Giraudon, P

    2016-05-18

    Devic's neuromyelitis optica (NMO) is an autoimmune astrocytopathy, associated with central nervous system inflammation, demyelination, and neuronal injury. Several studies confirmed that autoantibodies directed against aquaporin-4 (AQP4-IgG) are relevant in the pathogenesis of NMO, mainly through complement-dependent toxicity leading to astrocyte death. However, the effect of the autoantibody per se and the exact role of intrathecal AQP4-IgG are still controversial. To explore the intrinsic effect of intrathecal AQP4-IgG, independent from additional inflammatory effector mechanisms, and to evaluate its clinical impact, we developed a new animal model, based on a prolonged infusion of purified immunoglobulins from NMO patient (IgG(AQP4+), NMO-rat) and healthy individual as control (Control-rat) in the cerebrospinal fluid (CSF) of live rats. We showed that CSF infusion of purified immunoglobulins led to diffusion in the brain, spinal cord, and optic nerves, the targeted structures in NMO. This was associated with astrocyte alteration in NMO-rats characterized by loss of aquaporin-4 expression in the spinal cord and the optic nerves compared to the Control-rats (p = 0.001 and p = 0.02, respectively). In addition, glutamate uptake tested on vigil rats was dramatically reduced in NMO-rats (p = 0.001) suggesting that astrocytopathy occurred in response to AQP4-IgG diffusion. In parallel, myelin was altered, as shown by the decrease of myelin basic protein staining by up to 46 and 22 % in the gray and white matter of the NMO-rats spinal cord, respectively (p = 0.03). Loss of neurofilament positive axons in NMO-rats (p = 0.003) revealed alteration of axonal integrity. Then, we investigated the clinical consequences of such alterations on the motor behavior of the NMO-rats. In a rotarod test, NMO-rats performance was lower compared to the controls (p = 0.0182). AQP4 expression, and myelin and axonal integrity were preserved in AQP4-Ig

  20. Pathogenicity of IgG in patients with IgG4-related disease.

    Science.gov (United States)

    Shiokawa, Masahiro; Kodama, Yuzo; Kuriyama, Katsutoshi; Yoshimura, Kenichi; Tomono, Teruko; Morita, Toshihiro; Kakiuchi, Nobuyuki; Matsumori, Tomoaki; Mima, Atsushi; Nishikawa, Yoshihiro; Ueda, Tatsuki; Tsuda, Motoyuki; Yamauchi, Yuki; Minami, Ryuki; Sakuma, Yojiro; Ota, Yuji; Maruno, Takahisa; Kurita, Akira; Sawai, Yugo; Tsuji, Yoshihisa; Uza, Norimitsu; Matsumura, Kazuyoshi; Watanabe, Tomohiro; Notohara, Kenji; Tsuruyama, Tatsuaki; Seno, Hiroshi; Chiba, Tsutomu

    2016-08-01

    IgG4-related disease (IgG4-RD) is a systemic disease characterised by elevated serum IgG4 and IgG4-positive lymphoplasmacytic infiltration in the affected tissues. The pathogenic role of IgGs, including IgG4, in patients with IgG4-RD, however, is unknown. We examined the pathogenic activity of circulating IgGs in patients with IgG4-RD by injecting their IgGs into neonatal male Balb/c mice. Binding of patient IgGs to pancreatic tissue was also analysed in an ex vivo mouse organ culture model and in tissue samples from patients with autoimmune pancreatitis (AIP). Subcutaneous injection of patient IgG, but not control IgG, resulted in pancreatic and salivary gland injuries. Pancreatic injury was also induced by injecting patient IgG1 or IgG4, with more destructive changes induced by IgG1 than by IgG4. The potent pathogenic activity of patient IgG1 was significantly inhibited by simultaneous injection of patient IgG4. Binding of patient IgG, especially IgG1 and IgG4, to pancreatic tissue was confirmed in both the mouse model and AIP tissue samples. IgG1 and IgG4 from patients with IgG4-RD have pathogenic activities through binding affected tissues in neonatal mice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  1. Cognitive functions and autoantibodies in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Anna Bogaczewicz

    2016-06-01

    Full Text Available Introduction: Autoantibodies may occur in the course of various diseases. In the case of systemic lupus erythematosus the presence of specific autoantibodies is included in the classification criteria of the disease. The aim of the study was to investigate whether the presence of the serologic markers of systemic lupus erythematosus, i.e. anti-dsDNA, anti-Sm and anticardiolipin antibodies of the class IgM and IgG are linked with the results of neuropsychological tests evaluating selected cognitive functions in patients without overt neuropsychiatric lupus and without antiphospholipid syndrome. Material and methods: The study included 22 patients with systemic lupus erythematosus. For the assessment of anti-dsDNA, anti-Sm and anticardiolipin antibodies the immunoenzymatic method was used. For neuropsychological estimation of the selected cognitive functions the attention switching test and the choice reaction time were applied, in which the results are expressed as the average delay i.e. mean correct latency, using the computer-based Cambridge Neuropsychological Test Automated Battery (CANTAB. Results: The results of attention switching test in patients with anti-Sm antibodies were lower, but not significantly different from those obtained by the patients without such antibodies: 75.0 (73.12–88.12 vs. 92.5 (85–95. Choice reaction time was significantly longer in patients with anti-Sm antibodies in comparison to the patients without antiSm antibodies: 614.9 (520.6–740.8 vs. 476.7 (396.6–540 (p = 0.01. No significant difference was demonstrated in the results of attention switching test and choice reaction time with regard to the presence of anti-dsDNA antibodies. The results of attention switching test and choice reaction time were not different between the groups of patients with and without anticardiolipin antibodies in the IgM and IgG class. Conclusions: Anti-Sm antibodies seem to contribute to

  2. IgG autoantibodies against interleukin 1 alpha in sera of normal individuals

    DEFF Research Database (Denmark)

    Svenson, M; Poulsen, L K; Fomsgaard, A

    1989-01-01

    A pool of human sera from healthy blood donors was found to interfere competitively with the binding of 125I-labelled human recombinant interleukin 1 alpha (rIL-1 alpha) to the murine T-cell line EL4. The interference was reversible at the cellular level, and direct binding of the ligand to serum...

  3. Automated microfluidic assay system for autoantibodies found in autoimmune diseases using a photoimmobilized autoantigen microarray.

    Science.gov (United States)

    Matsudaira, Takahiro; Tsuzuki, Saki; Wada, Akira; Suwa, Akira; Kohsaka, Hitoshi; Tomida, Maiko; Ito, Yoshihiro

    2008-01-01

    Autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and autoimmune diabetes are characterized by the production of autoantibodies that serve as useful diagnostic markers, surrogate markers, and prognostic factors. We devised an in vitro system to detect these clinically pivotal autoantibodies using a photoimmobilized autoantigen microarray. Photoimmobilization was useful for preparing the autoantigen microarray, where autoantigens are covalently immobilized on a plate, because it does not require specific functional groups of the autoantigens and any organic material can be immobilized by a radical reaction induced by photoirradiation. Here, we prepared the microarray using a very convenient method. Aqueous solutions of each autoantigen were mixed with a polymer of poly(ethylene glycol) methacrylate and a photoreactive crosslinker, and the mixtures were microspotted on a plate and dried in air. Finally, the plate was irradiated with an ultraviolet lamp to obtain immobilization. In the assay, patient serum was added to the microarray plate. Antigen-specific IgG adsorbed on the microspotted autoantigen was detected by peroxidase-conjugated anti-IgG antibody. The chemical luminescence intensities of the substrate decomposed by the peroxidase were detected with a sensitive CCD camera. All autoantigens were immobilized stably by this method and used to screen antigen-specific IgG. In addition, the plate was covered with a polydimethylsiloxane sheet containing microchannels and automated measurement was carried out.

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

    International Nuclear Information System (INIS)

    Martins, Estefania M.N.; Andrade, Antero S.R.; Reis, Bernardo S.; Goes, Alfredo M.

    2007-01-01

    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)

  5. 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)

  6. Clinical significance of autoantibodies in autoimmune hepatitis.

    Science.gov (United States)

    Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego

    2013-10-01

    The accurate diagnosis and classification of autoimmune hepatitis (AIH) rely upon the detection of characteristic autoantibodies. Positivity for anti-nuclear (ANA) and/or anti-smooth muscle (SMA) autoantibodies defines AIH type 1 (AIH-1), whereas anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) define AIH type 2 (AIH-2). ANA and SMA, and less commonly anti-LKM1, have also been detected in de-novo autoimmune hepatitis developing after liver transplantation, a condition that may affect patients transplanted for non-autoimmune liver disease. The diagnostic autoantibodies associated with AIH-1 are also detected in the paediatric AIH/sclerosing cholangitis overlap syndrome, referred to as autoimmune sclerosing cholangitis (ASC). ASC, like adult primary sclerosing cholangitis, is often associated with atypical perinuclear anti-neutrophil cytoplasmic autoantibodies (p-ANCA), although p-ANCA are also detected in other autoimmune liver diseases. These associations highlight the necessity for simple and prompt diagnostic autoantibody testing, and the requirement for the accurate interpretation of the results of the tests in the clinical context. Fine-mapping of antigenic autoantibody targets has facilitated the development of rapid molecular assays that have the potential to revolutionise the field if properly standardised and when used in combination with classical immunofluorescence. Despite their diagnostic significance, the pathogenic role of the various autoantibodies and the mechanisms by which they can potentially inflict damage onto the liver cell remain a topic for further research. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Obesity-Associated Autoantibody Production Requires AIM to Retain the Immunoglobulin M Immune Complex on Follicular Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Satoko Arai

    2013-04-01

    Full Text Available Natural immunoglobulin M (IgM is reactive to autoantigens and is believed to be important for autoimmunity. Blood pentameric IgM loaded with antigens forms a large immune complex (IC that contains various elements, including apoptosis inhibitor of macrophage (AIM. Here we demonstrate that this IgM-AIM association contributes to autoantibody production under obese conditions. In mice fed a high-fat diet, natural IgM increased through B cell TLR4 stimulation. AIM associated with IgM and protected AIM from renal excretion, increasing blood AIM levels along with the obesity-induced IgM augmentation. Meanwhile, the AIM association inhibited IgM binding to the Fcα/μ receptor on splenic follicular dendritic cells, thereby protecting the IgM IC from Fcα/μ receptor-mediated internalization. This supported IgM-dependent autoantigen presentation to B cells, stimulating IgG autoantibody production. Accordingly, in obese AIM-deficient (AIM−/− mice, the increase of multiple IgG autoantibodies observed in obese wild-type mice was abrogated. Thus, the AIM-IgM association plays a critical role in the obesity-associated autoimmune process.

  8. Viral control in chronic HIV-1 subtype C infection is associated with enrichment of p24 IgG1 with Fc effector activity.

    Science.gov (United States)

    Chung, Amy; Makuba, Jenniffer M; Ndlovu, Bongiwe; Licht, Anna; Robinson, Hannah; Ramlakhan, Yathisha; Ghebremichael, Musie; Reddy, Tarylee; Goulder, Philip; Walker, Bruce; Ndung'u, Thumbi; Alter, Galit

    2018-04-03

    Postinfection HIV viral control and immune correlates analysis of the RV144 vaccine trial indicate a potentially critical role for Fc receptor-mediated antibody functions. However, the influence of functional antibodies in clade C infection is largely unknown. Plasma samples from 361 chronic subtype C-infected, antiretroviral therapy-naïve participants were tested for their HIV-specific isotype and subclass distributions, along with their Fc receptor-mediated functional potential. Total IgG, IgG subclasses and IgA binding to p24 clade B/C and gp120 consensus C proteins were assayed by multiplex. Antibody-dependent uptake of antigen-coated beads and Fc receptor-mediated natural killer cell degranulation were evaluated as surrogates for antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC), respectively. p24 IgG1 was the only subclass associated with viral control (P = 0.01), with higher p24-specific ADCP and ADCC responses detected in individuals with high p24 IgG1. Although p24 IgG1 levels were enriched in patients with elevated Gag-specific T-cell responses, these levels remained an independent predictor of low-viral loads (P = 0.04) and high CD4 counts (P = 0.004) after adjusting for Gag-specific T-cell responses and for protective HLA class I alleles. p24 IgG1 levels independently predict viral control in HIV-1 clade C infection. Whether these responses contribute to direct antiviral control via the recruited killing of infected cells via the innate immune system or simply mark a qualitatively superior immune response to HIV, is uncertain, but highlights the role of p24-specific antibodies in control of clade C HIV-1 infection.

  9. IgG4-related disease

    DEFF Research Database (Denmark)

    Detlefsen, Sönke; Klöppel, Günter

    2018-01-01

    disease (IgG4-RD). The histologic key findings are lymphoplasmacytic infiltration rich in IgG4-positive plasma cells combined with storiform fibrosis and obliterative phlebitis. Among the organs mainly affected by IgG4-RD are the pancreas and the extrahepatic bile ducts. The pancreatic and biliary...... alterations have been described under the terms autoimmune pancreatitis (AIP) and sclerosing cholangitis, respectively. These diseases are currently more precisely called IgG4-related pancreatitis (or type 1 AIP to distinguish it from type 2 AIP that is unrelated to IgG4-RD) and IgG4-related sclerosing...... cholangitis (IgG4-related SC). Clinically and grossly, both diseases commonly imitate pancreatic and biliary adenocarcinoma, tumors that are well known for their dismal prognosis. As IgG4-RD responds to steroid treatment, making a resection of a suspected tumor unnecessary, a biopsy is often required...

  10. Catalytic activity of autoantibodies toward myelin basic protein correlates with the scores on the multiple sclerosis expanded disability status scale.

    Science.gov (United States)

    Ponomarenko, Natalia A; Durova, Oxana M; Vorobiev, Ivan I; Belogurov, Alexey A; Telegin, Georgy B; Suchkov, Sergey V; Misikov, Victor K; Morse, Herbert C; Gabibov, Alexander G

    2006-02-28

    Autoantibodies toward myelin basic protein (MBP) evidently emerge in sera and cerebrospinal fluid of the patients with multiple sclerosis (MS), as well as in a MS rodent model, i.e., experimental autoimmune encephalomyelitis (EAE). The studies of the last two decades have unveiled somewhat controversial data on the diagnostic applicability of anti-MBP autoantibodies as a disease' marker. Here, we present the results of new functional analysis of the anti-MBP autoantibodies isolated from MS (in patients) and EAE (in mice) sera, based on their proteolytic activity against the targeted autoantigen. The activity was shown to be the intrinsic property of the IgG molecule. No activity was found in the sera-derived antibody fraction of healthy donors and control mice. Sera of 24 patients with clinically proven MS at different stages of the disease, and 20 healthy controls were screened for the anti-MBP antibody-mediated proteolytic activity. The activity correlated with the scores on the MS expanded disability status scale (EDSS) (r(2)=0.85, P<0.001). Thus, the anti-MBP autoantibody-mediated proteolysis may be regarded as an additional marker of the disease progression.

  11. Antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    Purpose of reviews This review focuses on recent advance in the diagnosis pathogenesis and treatment of antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis. Recent findings Antineutrophil cytoplasmic autoantibodies are closely associated with Wegener's granulomatosis and

  12. 21 CFR 866.5870 - Thyroid autoantibody immunological test system.

    Science.gov (United States)

    2010-04-01

    ... the thyroid autoantibodies (antibodies produced against the body's own tissues). Measurement of thyroid autoantibodies may aid in the diagnosis of certain thyroid disorders, such as Hashimoto's disease (chronic lymphocytic thyroiditis), nontoxic goiter (enlargement of thyroid gland), Grave's disease...

  13. IgG4 breaking the rules

    NARCIS (Netherlands)

    Aalberse, Rob C.; Schuurman, Janine

    2002-01-01

    Immunoglobulin G4 (IgG4) antibodies have been known for some time to be functionally monovalent. Recently, the structural basis for this monovalency has been elucidated: the in vivo exchange of IgG half-molecules (one H-plus one L-chain) among IgG4. This process results in bispecific antibodies that

  14. Apical versus Basal Neurogenesis Directs Cortical Interneuron Subclass Fate

    Directory of Open Access Journals (Sweden)

    Timothy J. Petros

    2015-11-01

    Full Text Available Fate determination in the mammalian telencephalon, with its diversity of neuronal subtypes and relevance to neuropsychiatric disease, remains a critical area of study in neuroscience. Most studies investigating this topic focus on the diversity of neural progenitors within spatial and temporal domains along the lateral ventricles. Often overlooked is whether the location of neurogenesis within a fate-restricted domain is associated with, or instructive for, distinct neuronal fates. Here, we use in vivo fate mapping and the manipulation of neurogenic location to demonstrate that apical versus basal neurogenesis influences the fate determination of major subgroups of cortical interneurons derived from the subcortical telencephalon. Somatostatin-expressing interneurons arise mainly from apical divisions along the ventricular surface, whereas parvalbumin-expressing interneurons originate predominantly from basal divisions in the subventricular zone. As manipulations that shift neurogenic location alter interneuron subclass fate, these results add an additional dimension to the spatial-temporal determinants of neuronal fate determination.

  15. Using constellation pharmacology to define comprehensively a somatosensory neuronal subclass

    Science.gov (United States)

    Teichert, Russell W.; Memon, Tosifa; Aman, Joseph W.; Olivera, Baldomero M.

    2014-01-01

    Change is intrinsic to nervous systems; change is required for learning and conditioning and occurs with disease progression, normal development, and aging. To better understand mammalian nervous systems and effectively treat nervous-system disorders, it is essential to track changes in relevant individual neurons. A critical challenge is to identify and characterize the specific cell types involved and the molecular-level changes that occur in each. Using an experimental strategy called constellation pharmacology, we demonstrate that we can define a specific somatosensory neuronal subclass, cold thermosensors, across different species and track changes in these neurons as a function of development. Cold thermosensors are uniformly responsive to menthol and innocuous cool temperature (17 °C), indicating that they express TRPM8 channels. A subset of cold thermosensors expressed α7 nicotinic acetylcholine receptors (nAChRs) but not other nAChR subtypes. Differences in temperature threshold of cold thermosensors correlated with functional expression of voltage-gated K channels Kv1.1/1.2: Relatively higher expression of KV1.1/1.2 channels resulted in a higher threshold response to cold temperature. Other signaling components varied during development and between species. In cold thermosensors of neonatal mice and rats, ATP receptors were functionally expressed, but the expression disappeared with development. This developmental change occurred earlier in low-threshold than high-threshold cold thermosensors. Most rat cold thermosensors expressed TRPA1 channels, whereas mouse cold thermosensors did not. The broad implications of this study are that it is now feasible to track changes in receptor and ion-channel expression in individual neuronal subclasses as a function of development, learning, disease, or aging. PMID:24469798

  16. Absence of anti-hypocretin receptor 2 autoantibodies in post pandemrix narcolepsy cases.

    Directory of Open Access Journals (Sweden)

    Guo Luo

    Full Text Available A recent publication suggested molecular mimicry of a nucleoprotein (NP sequence from A/Puerto Rico/8/1934 (PR8 strain, the backbone used in the construction of the reassortant strain X-179A that was used in Pandemrix® vaccine, and reported on anti-hypocretin (HCRT receptor 2 (anti-HCRTR2 autoantibodies in narcolepsy, mostly in post Pandemrix® narcolepsy cases (17 of 20 sera. In this study, we re-examined this hypothesis through mass spectrometry (MS characterization of Pandemrix®, and two other pandemic H1N1 (pH1N1-2009 vaccines, Arepanrix® and Focetria®, and analyzed anti-HCRTR2 autoantibodies in narcolepsy patients and controls using three independent strategies.MS characterization of Pandemrix® (2 batches, Arepanrix® (4 batches and Focetria® (1 batch was conducted with mapping of NP 116I or 116M spectrogram. Two sets of narcolepsy cases and controls were used: 40 post Pandemrix® narcolepsy (PP-N cases and 18 age-matched post Pandemrix® controls (PP-C, and 48 recent (≤6 months early onset narcolepsy (EO-N cases and 70 age-matched other controls (O-C. Anti-HCRTR2 autoantibodies were detected using three strategies: (1 Human embryonic kidney (HEK 293T cells with transient expression of HCRTR2 were stained with human sera and then analyzed by flow cytometer; (2 In vitro translation of [35S]-radiolabelled HCRTR2 was incubated with human sera and immune complexes of autoantibody and [35S]-radiolabelled HCRTR2 were quantified using a radioligand-binding assay; (3 Optical density (OD at 450 nm (OD450 of human serum immunoglobulin G (IgG binding to HCRTR2 stably expressed in Chinese hamster ovary (CHO-K1 cell line was measured using an in-cell enzyme-linked immunosorbent assay (ELISA.NP 116M mutations were predominantly present in all batches of Pandemrix®, Arepanrix® and Focetria®. The wild-type NP109-123 (ILYDKEEIRRIWRQA, a mimic to HCRTR234-45 (YDDEEFLRYLWR, was not found to bind to DQ0602. Three or four subjects were found positive

  17. Rheumatic Disease Autoantibodies in Autoimmune Liver Diseases.

    Science.gov (United States)

    Utiyama, Shirley R R; Zenatti, Katiane B; Nóbrega, Heloisa A J; Soares, Juliana Z C; Skare, Thelma L; Matsubara, Caroline; Muzzilo, Dominique A; Nisihara, Renato M

    2016-08-01

    Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.

  18. Serum TRPM1 autoantibodies from melanoma associated retinopathy patients enter retinal on-bipolar cells and attenuate the electroretinogram in mice.

    Directory of Open Access Journals (Sweden)

    Wei-Hong Xiong

    Full Text Available Melanoma-associated retinopathy (MAR is a paraneoplastic syndrome associated with cutaneous malignant melanoma and the presence of autoantibodies that label neurons in the inner retina. The visual symptoms and electroretinogram (ERG phenotype characteristic of MAR resemble the congenital visual disease caused by mutations in TRPM1, a cation channel expressed by both melanocytes and retinal bipolar cells. Four serum samples from MAR patients were identified as TRPM1 immunoreactive by 1. Labeling of ON-bipolar cells in TRPM1+/+ but not TRPM1-/- mouse retina, 2. Labeling of TRPM1-transfected CHO cells; and 3. Attenuation of the ERG b-wave following intravitreal injection of TRPM1-positive MAR IgG into wild-type mouse eyes, and the appearance of the IgG in the retinal bipolar cells at the conclusion of the experiment. Furthermore, the epitope targeted by the MAR autoantibodies was localized within the amino-terminal cytoplasmic domain of TRPM1. Incubation of live retinal neurons with TRPM1-positive MAR serum resulted in the selective accumulation of IgG in ON-bipolar cells from TRPM1+/+ mice, but not TRPM1-/- mice, suggesting that the visual deficits in MAR are caused by the uptake of TRPM1 autoantibodies into ON-bipolar cells, where they bind to an intracellular epitope of the channel and reduce the ON-bipolar cell response to light.

  19. Certain Subclasses of Analytic and Bi-Univalent Functions Involving Double Zeta Functions

    OpenAIRE

    Siregar, Saibah; Raman, Sintuja

    2012-01-01

    In the present paper, we introduce two new subclasses of the functions class Σ of bi-univalent functions involving double zeta functions in the open unit disc U={z:zEC, |z|<1}. The estimates on the coefficients |a2| and |a3| for functions in these new subclasses of the function class Σ are obtained in our investigation.

  20. Recombinant IgG1 Fc hexamers block cytotoxicity and pathological changes in experimental in vitro and rat models of neuromyelitis optica.

    Science.gov (United States)

    Tradtrantip, Lukmanee; Felix, Christian M; Spirig, Rolf; Morelli, Adriana Baz; Verkman, A S

    2018-05-01

    Intravenous human immunoglobulin G (IVIG) may have therapeutic benefit in neuromyelitis optica spectrum disorders (herein called NMO), in part because of the anti-inflammatory properties of the IgG Fc region. Here, we evaluated recombinant Fc hexamers consisting of the IgM μ-tailpiece fused with the Fc region of human IgG1. In vitro, the Fc hexamers prevented cytotoxicity in aquaporin-4 (AQP4) expressing cells and in rat spinal cord slice cultures exposed to NMO anti-AQP4 autoantibody (AQP4-IgG) and complement, with >500-fold greater potency than IVIG or monomeric Fc fragments. Fc hexamers at low concentration also prevented antibody-dependent cellular cytotoxicity produced by AQP4-IgG and natural killer cells. Serum from rats administered a single intravenous dose of Fc hexamers at 50 mg/kg taken at 8 h did not produce complement-dependent cytotoxicity when added to AQP4-IgG-treated AQP4-expressing cell cultures. In an experimental rat model of NMO produced by intracerebral injection of AQP4-IgG, Fc hexamers at 50 mg/kg administered before and at 12 h after AQP4-IgG fully prevented astrocyte injury, complement activation, inflammation and demyelination. These results support the potential therapeutic utility of recombinant IgG1 Fc hexamers in AQP4-IgG seropositive NMO. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Sialylated Autoantigen-Reactive IgG Antibodies Attenuate Disease Development in Autoimmune Mouse Models of Lupus Nephritis and Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Yannic C. Bartsch

    2018-06-01

    Full Text Available Pro- and anti-inflammatory effector functions of IgG antibodies (Abs depend on their subclass and Fc glycosylation pattern. Accumulation of non-galactosylated (agalactosylated; G0 IgG Abs in the serum of rheumatoid arthritis and systemic lupus erythematosus (SLE patients reflects severity of the diseases. In contrast, sialylated IgG Abs are responsible for anti-inflammatory effects of the intravenous immunoglobulin (pooled human serum IgG from healthy donors, administered in high doses (2 g/kg to treat autoimmune patients. However, whether low amounts of sialylated autoantigen-reactive IgG Abs can also inhibit autoimmune diseases is hardly investigated. Here, we explore whether sialylated autoantigen-reactive IgG Abs can inhibit autoimmune pathology in different mouse models. We found that sialylated IgG auto-Abs fail to induce inflammation and lupus nephritis in a B cell receptor (BCR transgenic lupus model, but instead are associated with lower frequencies of pathogenic Th1, Th17 and B cell responses. In accordance, the transfer of small amounts of immune complexes containing sialylated IgG Abs was sufficient to attenuate the development of nephritis. We further showed that administration of sialylated collagen type II (Col II-specific IgG Abs attenuated the disease symptoms in a model of Col II-induced arthritis and reduced pathogenic Th17 cell and autoantigen-specific IgG Ab responses. We conclude that sialylated autoantigen-specific IgG Abs may represent a promising tool for treating pathogenic T and B cell immune responses in autoimmune diseases.

  2. Proteolysis breaks tolerance toward intact α345(IV) collagen, eliciting novel anti-GBM autoantibodies specific for α345NC1 hexamers

    Science.gov (United States)

    Olaru, Florina; Wang, Xu-Ping; Luo, Wentian; Ge, Linna; Miner, Jeffrey H; Kleinau, Sandra; Geiger, Xochiquetzal J.; Wasiluk, Andrew; Heidet, Laurence; Kitching, A. Richard; Borza, Dorin-Bogdan

    2012-01-01

    Goodpasture disease is an autoimmune kidney disease mediated by autoAbs against NC1 monomers of α3(IV) collagen that bind to the glomerular basement membrane (GBM), usually causing rapidly progressive glomerulonephritis. We identified a novel type of human IgG4-restricted anti-GBM autoAbs associated with mild non-progressive glomerulonephritis, which specifically targeted α345NC1 hexamers but not α3NC1 monomers. The mechanisms eliciting these anti-GBM autoAbs were investigated in mouse models recapitulating this phenotype. Wild type and FcγRIIB−/− mice immunized with autologous murine GBM NC1 hexamers produced mouse IgG1-restricted autoAbs specific for α345NC1 hexamers, which bound to the GBM in vivo but did not cause glomerulonephritis. In these mice, intact collagen IV from murine GBM was not immunogenic. However, in Col4a3−/− Alport mice, both intact collagen IV and NC1 hexamers from murine GBM elicited IgG antibodies specific for α3α4α5NC1 hexamers, which were not subclass restricted. As heterologous antigen in COL4A3-humanized mice, murine GBM NC1 hexamers elicited mouse IgG1, IgG2a and IgG2b autoAbs specific for α345NC1 hexamers and induced anti-GBM Ab glomerulonephritis. These findings indicate that tolerance toward autologous intact α3α4α5(IV) collagen is established in hosts expressing this antigen, even though autoreactive B cells specific for α345NC1 hexamers are not purged from their repertoire. Proteolysis selectively breaches this tolerance by generating autoimmunogenic α3α4α5NC1 hexamers. This provides a mechanism eliciting autoAbs specific for α345NC1 hexamers, which are restricted to non-inflammatory IgG subclasses and non-nephritogenic. In Alport syndrome, lack of tolerance toward α3α4α5(IV) collagen promotes production of alloantibodies to α345NC1 hexamers, including pro-inflammatory IgG subclasses which mediate post-transplant anti-GBM nephritis. PMID:23303673

  3. Autoantibodies in SLE: Specificities, Isotypes and Receptors

    Directory of Open Access Journals (Sweden)

    Barbara Dema

    2016-01-01

    Full Text Available Systemic Lupus Erythematosus (SLE is characterized by a wide spectrum of auto-antibodies which recognize several cellular components. The production of these self-reactive antibodies fluctuates during the course of the disease and the involvement of different antibody-secreting cell populations are considered highly relevant for the disease pathogenesis. These cells are developed and stimulated through different ways leading to the secretion of a variety of isotypes, affinities and idiotypes. Each of them has a particular mechanism of action binding to a specific antigen and recognized by distinct receptors. The effector responses triggered lead to a chronic tissue inflammation. DsDNA autoantibodies are the most studied as well as the first in being characterized for its pathogenic role in Lupus nephritis. However, others are of growing interest since they have been associated with other organ-specific damage, such as anti-NMDAR antibodies in neuropsychiatric clinical manifestations or anti-β2GP1 antibodies in vascular symptomatology. In this review, we describe the different auto-antibodies reported to be involved in SLE. How autoantibody isotypes and affinity-binding to their antigen might result in different pathogenic responses is also discussed.

  4. Origins of anti-DNA autoantibodies

    International Nuclear Information System (INIS)

    Schwartz, R.S.

    1985-01-01

    The direction of research in autoimmunity was strongly influenced by three notable discoveries made more than 25 year ago: anti-DNA anti-bodies in lupus serum, the immunofluorescent antinuclar antibody test and the NZB mouse. Now another turning point has been reached for three new reasons: the discovery of the hybridoma technic, advances in cellular immunology and the use of molecular biology to solve immunological problems. These developments have motivated fresh approaches to questions about the origins and pathogenic mechanisms of autoantibodies. Systemic lupus erythematosus (SLE) has a conspicuous position in the field of autoimmunity for several reasons. Its diverse manifestations have attracted a correspondingly diverse group of investigators whose interests range from molecular biology to therapeutic trials; superb models of the disease occur spontaneously in animals; and the extensive variety of autoantibodies in SLE provides an abundance of investigative reagents. An explanation of the origins of these autoantibodies is one of the major goals of research in the disease. The autoantibodies that bind to DNA are of central interest. They occur in almost all patients with active SLE, they often fluctuate with its clinical activity, and they participate in forming its lesions

  5. Autoantibodies and their antigens in autoimmune hepatitis.

    Science.gov (United States)

    Bogdanos, Dimitrios P; Mieli-Vergani, Giorgina; Vergani, Diego

    2009-08-01

    Autoantibody detection assists in the diagnosis and allows differentiation of autoimmune hepatitis (AIH) type 1 (AIH-1), characterized by antinuclear antibody (ANA) and/or smooth muscle antibody (SMA), and type 2 (AIH-2), distinguished by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) and/or antibodies to liver cytosol type 1 (anti-LC1). Detection of atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-soluble liver antigen (SLA) antibodies can act as an additional pointer toward the diagnosis of AIH, particularly in the absence of the conventional autoantibodies. Routine autoantibody testing by indirect immunofluorescence has been recently complemented by molecular assays based on purified or recombinant antigens. Although the AIH-1-specific ANA and SMA targets need better definition, those of anti-LKM1 and anti-LC1 in AIH-2 have been clearly identified; the fine specificity of antibody reactivity and its clinical relevance to disease pathogenesis are the focus of ongoing investigation. This article critically discusses the current knowledge of the diagnostic and clinical significance of AIH-related autoantibody reactivities, focusing on key issues that the physician needs to be aware of to be able to request the appropriate testing and to interpret correctly the laboratory results within the clinical context of the patient. Copyright Thieme Medical Publishers.

  6. GPCR-autoantibodies in chronic heart failure.

    Science.gov (United States)

    Boivin-Jahns, Valerie; Jahns, Roland

    2018-06-01

    Chronic heart failure (CHF) is a syndrome characterized by shortness of breath, fluid retention, and a progressive reduction in cardiac function. More than 60% of the cases are ischemic in origin (i.e., due to myo-cardial infarction) and about 30% are caused by non-ischemic myocardial damage (i.e., due to genetic or non-genetic causes like myocardial inflammation). Because of alterations in both cellular and humoral immunity patients with non-ischemic CHF often develop abnormal or misled immune responses, including cross-reacting antibodies and/or autoantibodies to various cardiac anti-gens. Non-ischemic myo-cardial damage was found to progress to CHF particularly, when associated (a) with the generation of autoantibodies directed against distinct myocyte membrane proteins critically involved in cardiac function - like G-protein coup-led membrane receptors (GPCRs), or (b) with virus persistence in the myocardium. This article will review current knowledge on the pathophysiological relevance of GPCR-autoreactivity in CHF by giving an overview on the so far available evidence from pre-clinical, clinical and epidemiological studies on the CHF-inducing potential of GPCR-autoantibodies and thereon based novel therapeutic approaches in GPCR autoantibody-associated CHF.

  7. Increased serum level of prolactin is related to autoantibody production in systemic lupus erythematosus.

    Science.gov (United States)

    Yang, J; Li, Q; Yang, X; Li, M

    2016-04-01

    Prolactin (PRL) is known to aid effector B cells and augment autoimmunity, but the role of PRL in systemic lupus erythematosus (SLE) is not fully elucidated. The aim of this study was to determine the correlation between the serum levels of PRL and autoantibody production in SLE. Blood levels of PRL, anti-double-stranded DNA (ds-DNA) antibody, immunoglobulin M (IgM) and immunoglobulin G (IgG) were determined in samples from 30 adult patients with SLE and 25 healthy controls. The relationships between the serum level of PRL and SLE disease activity, as well as the titres of the ds-DNA antibody, IgM and IgG were determined. The serum level of PRL was higher in the SLE patients than in the healthy controls. PRL concentration increased during SLE flares-ups and decreased following disease remission. There was a positive correlation between the PRL concentration and serum levels of IgM, IgG and ds-DNA antibody titre. These data suggest that the serum level of PRL was closely related to the antibody production and disease activity of SLE patients. PRL concentration was dramatically reduced upon the remission of disease activity, indicating that PRL levels might be a promising predictor of SLE disease severity. © The Author(s) 2015.

  8. Frequency and levels of autoantibodies in healthy adult Omanis

    International Nuclear Information System (INIS)

    Al-Jabri, Ali A.; A-Belushi Mohammad; Nanze, Herburt

    2003-01-01

    A previous pilot study showed high frequency of anti-smooth muscle autoantibody in Omani blood donors and pregnant women. We conducted this larger-scale study to investigate the frequency and significance of several autoantibodies in healthy individuals from different regions of Oman. Sera obtained from 1537 healthy Omanis (1153 males and 384 females ), ranging in age from 18 to 57 years, tested for the presence of ten different autoantibodies using indirect immunofluoresence, haemagglutination and latex agglutination techniques. Low levels of autoantibodies were detected in 33.5%, whereas a few individuals (1.8%) showed high autoantibody titres. Anti-smooth muscle autoantibodies (ASMA) were the most prevalent (11%). Anti-nuclear autoantibodies (ANA) were the second most prevalent (7.6%). Anti-thyroid microsomal autoantibodies (ATMA) and anti-thyroglobulin autoantibodies (ATA) were present in 6.5% and 4.4% of individuals,respectively. The other autoantibodies were detected much less frequently: anti-parietal cells autoandibodies (APCA) were found in 1.6%,anti-brush border antibodies (ABBA) in 1.3% anti-reticulin autoantibodies (ARA) in 1%, anti-mitochondrial antibodies in 0.8%, antiglomerular basement membrane antibodies (AGBMA) in 0.7% and rheumatoid factor(RF) in 0.4%.Low levels of autoantibodies were detected in 33.5%, whereas a few individuals (1.8%) showed high autoantibody titres. Anti-smooth muscle autoantibodies (ASMA) were the most prevalent (11%). Anti-nuclear autoantibodies (ANA) were the second most prevalent (7.6%). Anti-thyroid microsomal autoantibodies (ATMA) and anti-thyroglobulin autoantibodies (ATA) were present in 6.5% and 4.4% of individuals,respectively. The other autoantibodies were detected much less frequently: anti-parietal cells autoandibodies (APCA) were found in 1.6%,anti-brush border antibodies (ABBA) in 1.3% anti-reticulin autoantibodies (ARA) in 1%, anti-mitochondrial antibodies in 0.8%, antiglomerular basement membrane antibodies

  9. Autoantibody signatures as biomarkers to distinguish prostate cancer from benign prostatic hyperplasia in patients with increased serum prostate specific antigen.

    Science.gov (United States)

    O'Rourke, Dennis J; DiJohnson, Daniel A; Caiazzo, Robert J; Nelson, James C; Ure, David; O'Leary, Michael P; Richie, Jerome P; Liu, Brian C-S

    2012-03-22

    Serum prostate specific antigen (PSA) concentrations lack the specificity to differentiate prostate cancer from benign prostate hyperplasia (BPH), resulting in unnecessary biopsies. We identified 5 autoantibody signatures to specific cancer targets which might be able to differentiate prostate cancer from BPH in patients with increased serum PSA. To identify autoantibody signatures as biomarkers, a native antigen reverse capture microarray platform was used. Briefly, well-characterized monoclonal antibodies were arrayed onto nanoparticle slides to capture native antigens from prostate cancer cells. Prostate cancer patient serum samples (n=41) and BPH patient samples (collected starting at the time of initial diagnosis) with a mean follow-up of 6.56 y without the diagnosis of cancer (n=39) were obtained. One hundred micrograms of IgGs were purified and labeled with a Cy3 dye and incubated on the arrays. The arrays were scanned for fluorescence and the intensity was quantified. Receiver operating characteristic curves were produced and the area under the curve (AUC) was determined. Using our microarray platform, we identified autoantibody signatures capable of distinguishing between prostate cancer and BPH. The top 5 autoantibody signatures were TARDBP, TLN1, PARK7, LEDGF/PSIP1, and CALD1. Combining these signatures resulted in an AUC of 0.95 (sensitivity of 95% at 80% specificity) compared to AUC of 0.5 for serum concentration PSA (sensitivity of 12.2% at 80% specificity). Our preliminary results showed that we were able to identify specific autoantibody signatures that can differentiate prostate cancer from BPH, and may result in the reduction of unnecessary biopsies in patients with increased serum PSA. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Quantification of the IgG2/4 kappa Monoclonal Therapeutic Eculizumab from Serum Using Isotype Specific Affinity Purification and Microflow LC-ESI-Q-TOF Mass Spectrometry.

    Science.gov (United States)

    Ladwig, Paula M; Barnidge, David R; Willrich, Maria A V

    2017-05-01

    As therapeutic monoclonal antibodies (mAbs) become more humanized, traditional tryptic peptide approaches used to measure biologics in serum become more challenging since unique clonotypic peptides used for quantifying the mAb may also be found in the normal serum polyclonal background. An alternative approach is to monitor the unique molecular mass of the intact light chain portion of the mAbs using liquid chromatography-mass spectrometry (LC-MS). Distinguishing a therapeutic mAb from a patient's normal polyclonal immunoglobulin (Ig) repertoire is the primary limiting factor when determining the limit of quantitation (LOQ) in serum. The ability to selectively extract subclass specific Igs from serum reduces the polyclonal background in a sample. We present here the development of an LC-MS method to quantify eculizumab in serum. Eculizumab is a complement component 5 (C5) binding mAb that is fully humanized and contains portions of both IgG2 and IgG4 subclasses. Our group developed a method that uses Life Technologies CaptureSelect IgG4 (Hu) affinity matrix. We show here the ability to quantitate eculizumab with a LOQ of 5 mcg/mL by removing the higher abundance IgG1, IgG2, and IgG3 from the polyclonal background, making this approach a simple and efficient procedure. Graphical Abstract ᅟ.

  11. Associations between an IgG3 polymorphism in the binding domain for FcRn, transplacental transfer of malaria-specific IgG3, and protection against Plasmodium falciparum malaria during infancy: A birth cohort study in Benin.

    Directory of Open Access Journals (Sweden)

    Celia Dechavanne

    2017-10-01

    Full Text Available Transplacental transfer of maternal immunoglobulin G (IgG to the fetus helps to protect against malaria and other infections in infancy. Recent studies have emphasized the important role of malaria-specific IgG3 in malaria immunity, and its transfer may reduce the risk of malaria in infancy. Human IgGs are actively transferred across the placenta by binding the neonatal Fc receptor (FcRn expressed within the endosomes of the syncytiotrophoblastic membrane. Histidine at position 435 (H435 provides for optimal Fc-IgG binding. In contrast to other IgG subclasses, IgG3 is highly polymorphic and usually contains an arginine at position 435, which reduces its binding affinity to FcRn in vitro. The reduced binding to FcRn is associated with reduced transplacental transfer and reduced half-life of IgG3 in vivo. Some haplotypes of IgG3 have histidine at position 435. This study examines the hypotheses that the IgG3-H435 variant promotes increased transplacental transfer of malaria-specific antibodies and a prolonged IgG3 half-life in infants and that its presence correlates with protection against clinical malaria during infancy.In Benin, 497 mother-infant pairs were included in a longitudinal birth cohort. Both maternal and cord serum samples were assayed for levels of IgG1 and IgG3 specific for MSP119, MSP2 (both allelic families, 3D7 and FC27, MSP3, GLURP (both regions, R0 and R2, and AMA1 antigens of Plasmodium falciparum. Cord:maternal ratios were calculated. The maternal IgG3 gene was sequenced to identify the IgG3-H435 polymorphism. A multivariate logistic regression was used to examine the association between maternal IgG3-H435 polymorphism and transplacental transfer of IgG3, adjusting for hypergammaglobulinemia, maternal malaria, and infant malaria exposure. Twenty-four percent of Beninese women living in an area highly endemic for malaria had the IgG3-H435 allele (377 women homozygous for the IgG3-R435 allele, 117 women heterozygous for the IgG

  12. Acute effects of interleukin-6 infusion on apo-B-containing lipoprotein subclasses in humans

    DEFF Research Database (Denmark)

    Bagdade, John; Pedersen, Bente K; Schwenke, Dawn

    2011-01-01

    B:E) apoB-containing subclasses present in VLDL. Therefore, we have directly measured these subclasses following their isolation by sequential immunoprecipitation in seven healthy male subjects during a 3-h infusion with recombinant human (rh) IL-6. Though plasma TG and apoB-containing particle number were...... unchanged by IL-6, the distribution of TG-rich subclasses was significantly altered. Compared to baseline values, LpB:E + LpB:C:E increased significantly at 0.5 h (p infused controls at 0.5 and 1 h (p

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

    Science.gov (United States)

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

    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.

  14. Anti-glomerular basement membrane autoantibodies in the Brown Norway rat: detection by a solid-phase radioimmunoassay

    International Nuclear Information System (INIS)

    Bowman, C.; Peters, D.K.; Lockwood, C.M.

    1983-01-01

    A solid-phase radioimmunoassay (RIA) is described for the detection of IgG autoantibodies to glomerular basement membrane (GBM) induced in the Brown Norway rat by mercuric chloride. The assay involves the adsorption of a collagenase digest of GBM to plastic microtitre plates and detection of bound antibody with affinity purified radiolabelled rabbit anti-rat IgG. Comparison with existing immunofluorescence methods for detection of anti-GBM antibody showed that the solid-phase RIA is highly sensitive, allowing detection of antibody in solutions with as low as 0.5 ng protein/ml. The assay is suitable for detection of anti-GBM antibody both in serum and in eluates from nephritic kidneys. The assay proved to be specific in competitive studies of inhibition brought about by GBM, keyhole limpet antigen and ovalbumin. This solid-phase RIA is reproducible, robust and easy to perform. (Auth.)

  15. IgG4-related nephropathy.

    Science.gov (United States)

    Quattrocchio, Giacomo; Roccatello, Dario

    2016-08-01

    IgG4-related disease (IgG4-RD) is a recently recognized disorder, often with multiple organ involvement, characterized by dense tissue infiltration of IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis and frequently elevated serum IgG4 concentration. The kidney can be involved either directly or indirectly. The most frequent direct renal manifestations of IgG4-RD are IgG4-related tubulointerstitial nephritis (TIN) and membranous glomerulonephropathy. Retroperitoneal fibrosis (RPF) is another condition that is frequently IgG4-related and that can indirectly affect the kidney causing ureteral obstruction and hydronephrosis. Contrast-enhanced computerized tomography, magnetic resonance imaging and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography show different imaging findings and are useful tools for monitoring therapeutic response. Steroid treatment is the first line of therapy, but relapsing or refractory forms of the disease are frequently observed and require more aggressive therapeutic approaches. At our centre, we treated three cases of aggressive IgG4-related TIN and two cases of IgG4-related RPF with an intensified, immune suppressive protocol, obtaining good results without severe adverse effects.

  16. IgG4-Related Sclerosing Cholangitis.

    Science.gov (United States)

    Nakazawa, Takahiro; Shimizu, Shuya; Naitoh, Itaru

    2016-08-01

    More men than women develop immunoglobulin G4-related sclerosing cholangitis (IgG4-SC). Age at clinical onset is significantly older in patients with IgG4-SC. Patients with IgG4-SC appear similar to those with cholangiocarcinoma and primary sclerosing cholangitis (PSC). The association between IgG4-SC and autoimmune pancreatitis (AIP) is useful for the diagnosis of IgG4-SC. However, some IgG4-SC cases are isolated from AIP and are difficult to diagnose. The authors focus on three distinct features of IgG4-SC. First, diffuse inflammation induces a longer stenosis on cholangiography in contrast to the short stenosis of patients with PSC. Second, fibroinflammatory involvement is observed mainly in the stroma of the bile duct wall, whereas the bile duct epithelium is intact. Third, steroid therapy results in remarkable improvement. Although the prognosis of patients with IgG4-SC is good, some cases have developed portal hypertension and liver cirrhosis during their clinical course. Further study is needed to elucidate the long-term outcomes and mechanism of IgG4-SC. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Thyrotropin-Blocking Autoantibodies and Thyroid-Stimulating Autoantibodies: Potential Mechanisms Involved in the Pendulum Swinging from Hypothyroidism to Hyperthyroidism or Vice Versa

    Science.gov (United States)

    Rapoport, Basil

    2013-01-01

    Background Thyrotropin receptor (TSHR) antibodies that stimulate the thyroid (TSAb) cause Graves' hyperthyroidism and TSHR antibodies which block thyrotropin action (TBAb) are occasionally responsible for hypothyroidism. Unusual patients switch from TSAb to TBAb (or vice versa) with concomitant thyroid function changes. We have examined case reports to obtain insight into the basis for “switching.” Summary TBAb to TSAb switching occurs in patients treated with levothyroxine (LT4); the reverse switch (TBAb to TSAb) occurs after anti-thyroid drug therapy; TSAb/TBAb alterations may occur during pregnancy and are well recognized in transient neonatal thyroid dysfunction. Factors that may impact the shift include: (i) LT4 treatment, usually associated with decreased thyroid autoantibodies, in unusual patients induces or enhances thyroid autoantibody levels; (ii) antithyroid drug treatment decreases thyroid autoantibody levels; (iii) hyperthyroidism can polarize antigen-presenting cells, leading to impaired development of regulatory T cells, thereby compromising control of autoimmunity; (iv) immune-suppression/hemodilution reduces thyroid autoantibodies during pregnancy and rebounds postpartum; (v) maternally transferred IgG transiently impacts thyroid function in neonates until metabolized; (vi) a Graves' disease model involving immunizing TSHR-knockout mice with mouse TSHR-adenovirus and transfer of TSHR antibody-secreting splenocytes to athymic mice demonstrates the TSAb to TBAb shift, paralleling the outcome of maternally transferred “term limited” TSHR antibodies in neonates. Finally, perhaps most important, as illustrated by dilution analyses of patients' sera in vitro, TSHR antibody concentrations and affinities play a critical role in switching TSAb and TBAb functional activities in vivo. Conclusions Switching between TBAb and TSAb (or vice versa) occurs in unusual patients after LT4 therapy for hypothyroidism or anti-thyroid drug treatment for Graves

  18. 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.

  19. Strategies for building reference standards for autoantibodies

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    Joanna eSheldon

    2015-04-01

    Full Text Available Producing robust, certified, traceable reference material for autoantibody testing is a vital element in maintaining the validity of results that are generated in the daily clinical laboratory routine. This is a huge challenge because of the high number of variables involved in the detection and measurement of the autoantibodies. The production of such materials is time consuming and needs rigorous attention to detail; this is best achieved by an overarching independent body who will oversee the process in a not for profit manner.Much effort has been made to build international standards for quantitative and qualitative assays based on monoclonal antibodies, obtained from affinity purification and plasmapheresis. The big challenge is to respect individual differences in immune response to the same antigen. A promising ongoing initiative is the construction of pools with monospecific samples from different individuals.

  20. Muscle autoantibodies in myasthenia gravis: beyond diagnosis?

    Science.gov (United States)

    Meriggioli, Matthew N; Sanders, Donald B

    2012-01-01

    Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. A number of molecules, including ion channels and other proteins at the neuromuscular junction, may be targeted by autoantibodies leading to abnormal neuromuscular transmission. In approximately 85% of patients, autoantibodies, directed against the postsynaptic nicotinic acetylcholine receptor can be detected in the serum and confirm the diagnosis, but in general, do not precisely predict the degree of weakness or response to therapy. Antibodies to the muscle-specific tyrosine kinase are detected in approximately 50% of generalized myasthenia gravis patients who are seronegative for anti-acetylcholine receptor antibodies, and levels of anti-muscle-specific tyrosine kinase antibodies do appear to correlate with disease severity and treatment response. Antibodies to other muscle antigens may be found in the subsets of myasthenia gravis patients, potentially providing clinically useful diagnostic information, but their utility as relevant biomarkers (measures of disease state or response to treatment) is currently unclear. PMID:22882218

  1. Determination of Autoantibody Isotypes Increases the Sensitivity of Serodiagnostics in Rheumatoid Arthritis

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    Daniela Sieghart

    2018-04-01

    Full Text Available Anti-citrullinated protein antibodies (ACPA and rheumatoid factor (RF are the most commonly used diagnostic markers of rheumatoid arthritis (RA. These antibodies are predominantly of the immunoglobulin (Ig M (RF or IgG (ACPA isotype. Other subtypes of both antibodies—particularly IgA isotypes and other autoantibodies—such as RA33 antibodies—have been repeatedly reported but their diagnostic value has still not been fully elucidated. Here, we investigated the prevalence of IgA, IgG, and IgM subtypes of RF, ACPA, and RA33 antibodies in patients with RA. To determine the diagnostic specificity and sensitivity sera from 290 RA patients (165 early and 125 established disease, 261 disease controls and 100 healthy subjects were tested for the presence of IgA, IgG, and IgM isotypes of RF, ACPA, and RA33 by EliA™ platform (Phadia AB, Uppsala, Sweden. The most specific antibodies were IgG-ACPA, IgA-ACPA, and IgG-RF showing specificities >98%, closely followed by IgG- and IgA-RA33 while IgM subtypes were somewhat less specific, ranging from 95.8% (RA33 to 90% (RF. On the other hand, IgM-RF was the most sensitive subtype (65% followed by IgG-ACPA (59.5% and IgA-RF (50.7%. Other subtypes were less sensitive ranging from 35 (IgA-ACPA to 6% (IgA-RA33. RA33 antibodies as well as IgA-RF and IgA-ACPA were found to increase the diagnostic sensitivity of serological testing since they were detected also in seronegative patients reducing their number from 109 to 85. Moreover, analyzing IgM-RF by EliA™ proved more sensitive than measuring RF by nephelometry and further reduced the number of seronegative patients to 76 individuals. Importantly, among antibody positive individuals, RA patients were found having significantly more antibodies (≥3 than disease controls which generally showed one or two antibody species. Thus, increasing the number of autoantibodies in serological routine testing provides valuable additional information allowing to better

  2. Anti-laminin-1 Autoantibodies, Pregnancy Loss and Endometriosis

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    Junko Inagaki

    2004-01-01

    Full Text Available Laminin-1 is a major component and multifunctional glycoprotein of basement membranes that consists of three different subunits, α1, β1 and γ1 chains. It is the earliest synthesized network-forming protein during embryogenesis and plays an important role in embryonic development, embryonic implantation and placentation. We have recently shown that IgG anti-laminin-1 antibodies were significantly associated with recurrent first-trimester miscarriages and with subsequent pregnancy outcome. Interestingly, these antibodies were also observed in patients with endometriosis-associated infertility but not in patients with other causes of infertility, including tubal factors, hormonal and uterine abnormalities. Laminin-α1, -β1 and -γ1 mRNAs have been detected in 90% of endometriotic lesions and all laminin-α1, -β1 and -γ1 chains were localized in the basement membranes of glandular epithelium in endometriotic peritoneal lesions. Western blot analysis showed that anti-laminin-1 antibodies from those patients reacted with all laminin-1's chains. ELISA also confirmed that one of the target epitopes for these antibodies was located in a particular region of the laminin-1 molecule, i.e. the carboxyl-terminal globular G domain of α1 chain. IgM monoclonal anti-laminin-1 autoantibody, that we recently established, also recognized the G domain. Anti-laminin-1 antibodies from mice immunized with –mouse— laminin-1, caused a higher fetal resorption rate with lower embryonic and placental weights. Thus, anti-laminin-1 antibodies may be important in development of autoimmune-mediated reproductive failures and the assessment of the antibodies may provide a novel non-invasive diagnosis of endometriosis.

  3. Biological variation of thyroid autoantibodies and thyroglobulin

    DEFF Research Database (Denmark)

    Jensen, Esther; Petersen, Per Hyltoft; Blaabjerg, Ole

    2007-01-01

    BACKGROUND: It has been shown that the level of serum thyroid antibodies affects serum thyrotropin (TSH) concentrations in men and women, and that these autoantibodies in combination with serum TSH are predictive of future thyroid disease. As the biological variation of these autoantibodies.......5-258 kIU/L), the CV biological was 11.3%, while the CV analytical was 10.6%. For TgAb (5.6 to 148 kIU/L) CV biological was 8.5% and CV analytical was 9.0%. The woman with TRAb had a CV biological of 4.8%, while the analytical variation in duplicates was 3.9% at a level of 2.8 IU/L. CONCLUSIONS......: It is possible to measure TPOAb and TgAb in all samples with the AutoDELFIA. There is no systematic variation in autoantibodies during the menstrual cycle. The biological coefficient of variation for TPOAb and TgAb was 11.3% and 8.5%, respectively...

  4. IgG4-gerelateerde ziekte

    NARCIS (Netherlands)

    Maillette de Buy Wenniger, Lucas J.; Doorenspleet, Marieke E.; Verheij, Joanne; de Vries, Niek; Beuers, Ulrich

    2013-01-01

    The diagnosis IgG4-related disease (IgG4-RD) is often difficult to make. The clinical spectrum is diverse, with a variety of organ systems that may be affected simultaneously or sequentially. Patients often present with symptoms that mimic a malignant disease, for example, symptoms compatible with a

  5. IgG4-related disease.

    Science.gov (United States)

    Bozzalla Cassione, Emanuele; Stone, John H

    2017-05-01

    Remarkable insights have been gleaned recently with regard to the pathophysiology of IgG4-related disease (IgG4-RD). These findings have direct implications for the development of targeted strategies for the treatment of this condition. Oligoclonal expansions of cells of both the B and T lymphocyte lineages are present in the blood of patients with IgG4-RD. Oligoclonal expansions of plasmablasts are a good biomarker for disease activity. An oligoclonally expanded population of CD4+ cytotoxic T lymphocytes is found not only in the peripheral blood but also at tissue sites of active disease. This cell elaborates cytokines that may drive the fibrosis characteristic of IgG4-RD. T follicular helper cells (Tfhc), particularly the Tfhc2 subset, appear to play a major role in driving the class switch to IgG4 that typifies this disease. The relationship between malignancy and IgG4-RD remains an area of interest. Advances in understanding the pathophysiology of IgG4-RD have proceeded swiftly, leading to the identification of a number of potential targeted treatment strategies. The completion of classification criteria for IgG4-RD, an effort supported jointly by the American College of Rheumatology and the European League Against Rheumatism, will further facilitate studies on this disease.

  6. An intersectional gene regulatory strategy defines subclass diversity of C. elegans motor neurons.

    Science.gov (United States)

    Kratsios, Paschalis; Kerk, Sze Yen; Catela, Catarina; Liang, Joseph; Vidal, Berta; Bayer, Emily A; Feng, Weidong; De La Cruz, Estanisla Daniel; Croci, Laura; Consalez, G Giacomo; Mizumoto, Kota; Hobert, Oliver

    2017-07-05

    A core principle of nervous system organization is the diversification of neuron classes into subclasses that share large sets of features but differ in select traits. We describe here a molecular mechanism necessary for motor neurons to acquire subclass-specific traits in the nematode Caenorhabditis elegans . Cholinergic motor neuron classes of the ventral nerve cord can be subdivided into subclasses along the anterior-posterior (A-P) axis based on synaptic connectivity patterns and molecular features. The conserved COE-type terminal selector UNC-3 not only controls the expression of traits shared by all members of a neuron class, but is also required for subclass-specific traits expressed along the A-P axis. UNC-3, which is not regionally restricted, requires region-specific cofactors in the form of Hox proteins to co-activate subclass-specific effector genes in post-mitotic motor neurons. This intersectional gene regulatory principle for neuronal subclass diversification may be conserved from nematodes to mice.

  7. Crossreactive autoantibodies directed against cutaneous and joint antigens are present in psoriatic arthritis.

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    Marzia Dolcino

    Full Text Available Psoriatic arthritis (PsA is a chronic inflammatory disease of unknown origin, characterized by erosions and new bone formation. Diagnosis of PsA is mainly clinical and there are no biomarkers available. Moreover in PsA autoantibodies have not been described so far. Indeed an autoimmune origin has been suggested but never proven. Aim of the study was to investigate the possible presence of autoantibodies typically associated with PsA.We used pooled IgG immunoglobulins derived from 30 patients with PsA to screen a random peptide library in order to identify disease relevant autoantigen peptides.Among the selected peptides, one was recognised by nearly all the patients' sera. The identified peptide (PsA peptide: TNRRGRGSPGAL shows sequence similarities with skin autoantigens, such as fibrillin 3, a constituent of actin microfibrils, desmocollin 3, a constituent of the desmosomes and keratin 78, a component of epithelial cytoskeleton. Interestingly the PsA peptide shares homology with the nebulin-related anchoring protein (N-RAP, a protein localized in the enthesis (point of insertion of a tendon or ligament to the bone, which represents the first affected site during early PsA. Antibodies affinity purified against the PsA peptide recognize fibrillin, desmocollin, keratin and N-RAP. Moreover antibodies directed against the PsA peptide are detectable in 85% of PsA patients. Such antibodies are not present in healthy donors and are present in 13/100 patients with seroposive rheumatoid arthritis (RA. In seronegative RA these antibodies are detectable only in 3/100 patients.Our results indicate that PsA is characterized by the presence of serum autoantibodies crossreacting with an epitope shared by skin and joint antigens.

  8. Bronchus-associated lymphoid tissue in pulmonary hypertension produces pathologic autoantibodies.

    Science.gov (United States)

    Colvin, Kelley L; Cripe, Patrick J; Ivy, D Dunbar; Stenmark, Kurt R; Yeager, Michael E

    2013-11-01

    Autoimmunity has long been associated with pulmonary hypertension. Bronchus-associated lymphoid tissue plays important roles in antigen sampling and self-tolerance during infection and inflammation. We reasoned that activated bronchus-associated lymphoid tissue would be evident in rats with pulmonary hypertension, and that loss of self-tolerance would result in production of pathologic autoantibodies that drive vascular remodeling. We used animal models, histology, and gene expression assays to evaluate the role of bronchus-associated lymphoid tissue in pulmonary hypertension. Bronchus-associated lymphoid tissue was more numerous, larger, and more active in pulmonary hypertension compared with control animals. We found dendritic cells in and around lymphoid tissue, which were composed of CD3(+) T cells over a core of CD45RA(+) B cells. Antirat IgG and plasma from rats with pulmonary hypertension decorated B cells in lymphoid tissue, resistance vessels, and adventitia of large vessels. Lymphoid tissue in diseased rats was vascularized by aquaporin-1(+) high endothelial venules and vascular cell adhesion molecule-positive vessels. Autoantibodies are produced in bronchus-associated lymphoid tissue and, when bound to pulmonary adventitial fibroblasts, change their phenotype to one that may promote inflammation. Passive transfer of autoantibodies into rats caused pulmonary vascular remodeling and pulmonary hypertension. Diminution of lymphoid tissue reversed pulmonary hypertension, whereas immunologic blockade of CCR7 worsened pulmonary hypertension and hastened its onset. Bronchus-associated lymphoid tissue expands in pulmonary hypertension and is autoimmunologically active. Loss of self-tolerance contributes to pulmonary vascular remodeling and pulmonary hypertension. Lymphoid tissue-directed therapies may be beneficial in treating pulmonary hypertension.

  9. Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies

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    Suk Chon

    2011-02-01

    Full Text Available BackgroundType B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans.MethodsTo evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patient's dialyzed serum before and after immunosuppressive therapy.ResultsIn the patient's pre-treatment serum IgG, the binding of 125I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%.ConclusionWe treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patient's insulin receptor antibodies by measuring the inhibition of insulin binding.

  10. Genotoxic effect and antigen binding characteristics of SLE auto-antibodies to peroxynitrite-modified human DNA.

    Science.gov (United States)

    Khan, Md Asad; Alam, Khursheed; Mehdi, Syed Hassan; Rizvi, M Moshahid A

    2017-12-01

    Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by auto-antibodies against native deoxyribonucleic acid after modification and is one of the reasons for the development of SLE. Here, we have evaluated the structural perturbations in human placental DNA by peroxynitrite using spectroscopy, thermal denaturation and high-performance liquid chromatography (HPLC). Peroxynitrite is a powerful potent bi-functional oxidative/nitrative agent that is produced both endogenously and exogenously. In experimental animals, the peroxynitrite-modified DNA was found to be highly immunogenic. The induced antibodies showed cross-reactions with different types of DNA and nitrogen bases that were modified with peroxynitrite by inhibition ELISA. The antibody activity was inhibited by approximately 89% with its immunogen as the inhibitor. The antigen-antibodies interaction between induced antibodies with peroxynitrite-modified DNA showed retarded mobility as compared to the native form. Furthermore, significantly increased binding was also observed in SLE autoantibodies with peroxynitrite-modified DNA than native form. Moreover, DNA isolated from lymphocyte of SLE patients revealed significant recognition of anti-peroxynitrite-modified DNA immunoglobulin G (IgG). Our data indicates that DNA modified with peroxynitrite presents unique antigenic determinants that may induce autoantibody response in SLE. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Use of total lymphoid irradiation (TLI) in studies of the T cell dependence of autoantibody production in rheumatoid arthritis

    International Nuclear Information System (INIS)

    Tanay, A.; Strober, S.; Logue, G.L.; Schiffman, G.

    1984-01-01

    The effect of total lymphoid irradiation (TLI) on T cell-dependent and -independent humoral immune responses was studied in patients with intractable rheumatoid arthritis (RA). The serum levels of several autoantibodies and of antibodies to diphtheria (DT) and tetanus (TT) toxoids and to pneumococcal polysaccharide (PPS; 12 antigenic types) were studied before and after TLI. In addition, the patients were given a booster injection of DT and TT and a single injection of pneumococcal vaccine after radiotherapy. Antibody levels to DT and TT decreased about twofold after TLI and did not rise significantly after a booster injection. However, there was no reduction in antibody levels to PPS after TLI, and a significant rise in titers was observed after a single vaccination. The serum levels of rheumatoid factor (RF), anti-nuclear antibody (ANA), and granulocyte associated IgG rose slightly after TLI. Thus, the autoantibodies and antibodies to polysaccharides appear to be relatively independent of helper T cell function, which is markedly reduced after TLI. On the other hand, antibodies to protein antigens such as DT and TT appear to be more closely dependent upon T helper function in man, as has been reported in rodents. The findings suggest that T cell-independent autoantibody responses alone do not maintain the joint disease activity in RA, because improvement in joint disease after TLI has been reported

  12. The Prevalence of Antithyroid Autoantibodies in Normal Korean Population*

    Science.gov (United States)

    Lee, Myung Shik; Lee, Dong Soo; Han, Jin Suk; Cho, Bo Youn; Koh, Chang Soon; Lee, Munho

    1986-01-01

    The prevalence of antithyroid autoantibodies and the relationship between the presence of autoantibodies and thyroid functions were studied in 848 apparently normal Korean adults with tanned red cell agglutination technique. Results are summarized as follows: 1) The prevalence of antimicrosimal antibody (MCHA) and antithyroglobulin antibody (TGHA) were 4.4% and 1.9% in 458 males, and 12.4% and 5.0% in 390 females, respectively. Both autoantibodies were more prevalent in female (pantithyroid autoantibody of high titer (⩾1:1002) was related to alteration of thyroid functions suggesting the existence of “subclinical autoimmune thyroiditis” state. PMID:15759373

  13. IgG4-related spinal pachymeningitis.

    Science.gov (United States)

    Lu, Zhang; Tongxi, Liu; Jie, Luo; Yujuan, Jiao; Wei, Jiang; Xia, Liu; Yumin, Zheng; Xin, Lu

    2016-06-01

    The aim of this study is to study the clinical, laboratory, imaging pathology, and prognosis features of IgG4-related spinal pachymeningitis. We worked with a 55-year-old man suffering from IgG4-related spinal pachymeningitis who had the most widespread lesion in his dura mater. We also review previous related studies and discuss the clinical characteristics of this rare disease. In total, eight IgG4-related spinal pachymeningitis patients have been reported in the literature since 2009. They were mostly male patients, 51.7 ± 11.9 years old on average. Cervical and thoracic vertebrae were the most common sites for lesions. The most prominent symptom was varying numbness and weakness of the limbs and/or body associated with spinal cord compression. There was one patient (1/5) with elevated serum IgG4 levels and three patients (3/3) with increased cerebrospinal fluid (CSF) IgG4 index. Positive histopathologic findings are the strongest basis for a diagnosis. All the patients with IgG4-related spinal pachymeningitis responded well to glucocorticoid therapy. IgG4-related spinal pachymeningitis is an orphan disease that mainly occurs in cervical and thoracic vertebrae. Older males are the most susceptible group. Serum IgG4 levels were consistently normal in these cases, so analysis of CSF for IgG4 production (IgG4 index) could become a useful tool. Pathological findings remain the gold standard for diagnosis. Most patients responded favorably to glucocorticoid treatment.

  14. High Prevalence of Neutrophil Cytoplasmic Autoantibodies in Infants with Food Protein-Induced Proctitis/Proctocolitis: Autoimmunity Involvement?

    Directory of Open Access Journals (Sweden)

    Alena Sekerkova

    2015-01-01

    Full Text Available Background. Food protein-induced proctitis/proctocolitis (FPIP is the most common noninfectious colitis in children in the first year of life. Along with the overall clinical symptoms, diarrhoea and rectal bleeding are the main manifestations of the disease. There is no routine noninvasive test that would be specific for this type of colitis. The aim of our study was to find a noninvasive laboratory test or tests that may be helpful in differential diagnosis of food protein-induced proctitis/proctocolitis. Methods. ANA, ANCA, ASCA, a-EMA, a-tTg, specific IgE, total IgE, IgG, IgA, IgM, and concentration of serum calprotectin were measured in a group of 25 patients with colitis and 18 children with other diagnoses. Results. Atypical-pANCA antibodies of IgG isotype were detected in the sera of 24 patients by the method of indirect immunofluorescence, and 5 patients showed also the positivity of IgA isotype. In control samples these autoantibodies were not detected. Other autoantibodies were not demonstrated in either patient or control group. Conclusions. Of the parameters tested in noninfectious colitis, atypical-pANCA on ethanol-fixed granulocytes appears to be a suitable serological marker of food protein-induced proctitis/proctocolitis and suggests a possible involvement of an autoimmune mechanisms in the pathogenesis of this disease.

  15. An autoimmune myositis-overlap syndrome associated with autoantibodies to nuclear pore complexes: description and long-term follow-up of the anti-Nup syndrome.

    Science.gov (United States)

    Senécal, Jean-Luc; Isabelle, Catherine; Fritzler, Marvin J; Targoff, Ira N; Goldstein, Rose; Gagné, Michel; Raynauld, Jean-Pierre; Joyal, France; Troyanov, Yves; Dabauvalle, Marie-Christine

    2014-11-01

    Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immunomodulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr).By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n = 112), mixed connective tissue disease (n = 35), systemic lupus (n = 94), rheumatoid arthritis (n = 45), or other rheumatic diseases (n = 107), nor was it observed in 62 normal adults.Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic link to

  16. Development of Type 1 Diabetes in Wild Bank Voles Associated With Islet Autoantibodies and the Novel Ljungan Virus

    DEFF Research Database (Denmark)

    Niklasson, Bo; Heller, Knud Erik; Schønecker, Bryan

    2003-01-01

    Clethrionomys Glareolus, Glutamic Acid Decarboxylase Autoantibodies, IA-2 Autoantibodies, Insulin Autoantibodies, Insulin-Dependent Diabetes Mellitus, Ljungan Virus, Parechovirus, Picorna Virus......Clethrionomys Glareolus, Glutamic Acid Decarboxylase Autoantibodies, IA-2 Autoantibodies, Insulin Autoantibodies, Insulin-Dependent Diabetes Mellitus, Ljungan Virus, Parechovirus, Picorna Virus...

  17. Human IgG4 binds to IgG4 and conformationally altered IgG1 via Fc-Fc interactions

    NARCIS (Netherlands)

    Rispens, Theo; Ooievaar-de Heer, Pleuni; Vermeulen, Ellen; Schuurman, Janine; van der Neut Kolfschoten, Marijn; Aalberse, Rob C.

    2009-01-01

    The Fc fragment of IgG4 can interact with the Fc fragment of another IgG molecule. This interaction is a confounding factor when measuring IgG4 rheumatoid factor levels. Recently, we demonstrated that half-molecules of IgG4 can exchange to form a bispecific Ab. We expected these two phenomena to be

  18. Elevation of serum IgG4 in Western patients with autoimmune sclerosing pancreatocholangitis: a word of caution.

    Science.gov (United States)

    Hochwald, Steven N; Hemming, Alan W; Draganov, Peter; Vogel, Stephen B; Dixon, Lisa R; Grobmyer, Stephen R

    2008-04-01

    Autoimmune pancreatocholangitis is characterized by sclerosing inflammation of the biliary tree or pancreatic duct and can mimic pancreaticobiliary malignancy. Serum immunoglobin (Ig) G4 values seem to be helpful in distinguishing autoimmune pancreatocholangitis from pancreatic malignancy in the Japanese population; however, its significance in the Western population has not been well studied. We report a retrospective analysis of 7 consecutive patients with autoimmune pancreatocholangitis and compare them to 23 patients with pancreatic malignancy. Clinical presentation, diagnostic tests, and preoperative IgG4 levels were reviewed in all patients. Presence of autoimmune pancreatocholangitis or pancreatic malignancy was determined by pathologic analysis in all patients and reviewed by a single pathologist. In all patients, autoimmune pancreatocholangitis manifested in a similar fashion to pancreatic malignancy. Median IgG4 levels were far lower in pancreatic cancer patients with localized, resectable disease (24 mg/dL), locally advanced disease (24 mg/dL), and metastatic disease (28 mg/dL) as compared with patients with autoimmune pancreatocholangitis (142 mg/dL, P 100 mg/dL. In contrast, all patients with autoimmune pancreatitis or cholangitis had levels >100 mg/dL. However, in five of these seven patients, IgG4 levels were below the upper limits of normal. Autoimmune pancreatocholangitis mimics pancreatobiliary malignancy. Serum IgG4 values seem to be helpful in distinguishing autoimmune pancreatocholangitis from malignancy in the Western population. However, absolute values seem to be lower in the United States compared with Japan. The upper limit of normal as reported in laboratories in the United States may not be useful in identifying abnormally high IgG4 values. A new upper limit of normal may need to be defined because IgG subclass determinations are being used more frequently in Western patients with biliary obstruction.

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

    Science.gov (United States)

    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.

  20. Ly108 expression distinguishes subsets of invariant NKT cells that help autoantibody production and secrete IL-21 from those that secrete IL-17 in lupus prone NZB/W mice.

    Science.gov (United States)

    Tang, Xiaobin; Zhang, Bo; Jarrell, Justin A; Price, Jordan V; Dai, Hongjie; Utz, Paul J; Strober, Samuel

    2014-05-01

    Lupus is a systemic autoimmune disease characterized by anti-nuclear antibodies in humans and genetically susceptible NZB/W mice that can cause immune complex glomerulonephritis. T cells contribute to lupus pathogenesis by secreting pro-inflammatory cytokines such as IL-17, and by interacting with B cells and secreting helper factors such as IL-21 that promote production of IgG autoantibodies. In the current study, we determined whether purified NKT cells or far more numerous conventional non-NKT cells in the spleen of NZB/W female mice secrete IL-17 and/or IL-21 after TCR activation in vitro, and provide help for spontaneous IgG autoantibody production by purified splenic CD19(+) B cells. Whereas invariant NKT cells secreted large amounts of IL-17 and IL-21, and helped B cells, non-NKT cells did not. The subset of IL-17 secreting NZB/W NKT cells expressed the Ly108(lo)CD4(-)NK1.1(-) phenotype, whereas the IL-21 secreting subset expressed the Ly108(hi)CD4(+)NK1.1(-) phenotype and helped B cells secrete a variety of IgG anti-nuclear antibodies. α-galactocylceramide enhanced the helper activity of NZB/W and B6.Sle1b NKT cells for IgG autoantibody secretion by syngeneic B cells. In conclusion, different subsets of iNKT cells from mice with genetic susceptibility to lupus can contribute to pathogenesis by secreting pro-inflammatory cytokines and helping autoantibody production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Anti-IL-1alpha autoantibodies in early rheumatoid arthritis

    DEFF Research Database (Denmark)

    Forslind, K; Svensson, Birte; Svenson, M

    2001-01-01

    To investigate the potential predictive value of autoantibodies against IL1-alpha (anti-IL-1alpha) in patients with early rheumatoid arthritis (RA).......To investigate the potential predictive value of autoantibodies against IL1-alpha (anti-IL-1alpha) in patients with early rheumatoid arthritis (RA)....

  2. Measurement of anti- acetylcholine receptor auto-antibodies in ...

    African Journals Online (AJOL)

    auto-antibodies in myasthenia gravis. K. J. Steenkamp, W. Duim, M. s. Myer,. S. C. K. Malfeld, R. Anderson. Two different acetylcholine receptor (AChR) preparations derived from ... the detection of AChR auto-antibodies in serum specimens from 20 ... 4°C. Thereafter, 1 ml of washing solution (phosphate- buffered saline ...

  3. Association between habitual dietary intake and lipoprotein subclass profile in healthy young adults.

    Science.gov (United States)

    Bogl, L H; Pietiläinen, K H; Rissanen, A; Kangas, A J; Soininen, P; Rose, R J; Ala-Korpela, M; Kaprio, J

    2013-11-01

    Nutritional epidemiology is increasingly shifting its focus from studying single nutrients to the exploration of the whole diet utilizing dietary pattern analysis. We analyzed associations between habitual diet (including macronutrients, dietary patterns, biomarker of fish intake) and lipoprotein particle subclass profile in young adults. Complete dietary data (food-frequency questionnaire) and lipoprotein subclass profile (via nuclear magnetic resonance spectroscopy) were available for 663 subjects from the population-based FinnTwin12 study (57% women, age: 21-25 y). The serum docosahexaenoic to total fatty acid ratio was used as a biomarker of habitual fish consumption. Factor analysis identified 5 dietary patterns: "Fruit and vegetables", "Meat", "Sweets and desserts", "Junk food" and "Fish". After adjustment for sex, age, body mass index, waist circumference, physical activity, smoking status and alcohol intake, the "Junk food" pattern was positively related to serum triglycerides (r = 0.12, P = 0.002), a shift in the subclass distribution of VLDL toward larger particles (r = 0.12 for VLDL size, P consumption is related to favorable subclass distributions of VLDL and HDL, while junk food intake is associated with unfavorable alterations in the distribution of all lipoprotein subclasses independent of adiposity and other lifestyle factors. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. 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.

  5. Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Rasmussen, N S; Nielsen, C T; Houen, G

    2016-01-01

    We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse...... and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients...... concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P...

  6. Development of an Aquaporin-4 Orthogonal Array of Particle-Based ELISA for Neuromyelitis Optica Autoantibodies Detection.

    Directory of Open Access Journals (Sweden)

    Francesco Pisani

    Full Text Available Serological markers of Nuromyelitis Optica (NMO, an autoimmune disorder of the central nervous system, are autoantibodies targeting the astrocytic water channel aquaporin-4 (AQP4. We have previously demonstrated that the main epitopes for these autoantibodies (AQP4-IgG are generated by the supramolecular arrangement of AQP4 tetramers into an Orthogonal Array of Particles (OAPs. Many tests have been developed to detect AQP4-IgG in patient sera but several procedural issues affect OAP assembly and consequently test sensitivity. To date, the protein based ELISA test shows the lowest sensitivity while representing a valid alternative to the more sensitive cell based assay (CBA, which, however, shows economic, technical and interpretation problems. Here we have developed a high perfomance ELISA in which native OAPs are used as the molecular target. To this aim a native size exclusion chromatography method has been developed to isolate integral, highly pure and AQP4-IgG-recognized OAPs from rat brain. These OAPs were immobilized and oriented on a plastic plate by a sandwich approach and 139 human sera were tested, including 67 sera from NMO patients. The OAP-ELISA showed a 99% specificity and a higher sensitivity (91% compared to the CBA test. A comparative analysis revealed an end-point titer three orders of magnitude higher than the commercial ELISA and six times higher than our in-house CBA test. We show that CNS-extracted OAPs are crucial elements in order to perform an efficient AQP4-IgG test and the OAP-ELISA developed represents a valid alternative to the CBA currently used.

  7. Antiapolipoprotein A-1 IgG chronotropic effects require nongenomic action of aldosterone on L-type calcium channels.

    Science.gov (United States)

    Rossier, Michel F; Pagano, Sabrina; Python, Magaly; Maturana, Andres D; James, Richard W; Mach, François; Roux-Lombard, Pascale; Vuilleumier, Nicolas

    2012-03-01

    Autoantibodies to apolipoprotein A-1 (antiapoA-1 IgG) have been shown to be associated with higher resting heart rate and morbidity in myocardial infarction patients and to behave as a chronotropic agent in the presence of aldosterone on isolated neonatal rat ventricular cardiomyocytes (NRVC). We aimed at identifying the pathways accounting for this aldosterone-dependent antiapoA-1 IgG-positive chronotropic effect on NRVC. The rate of regular spontaneous contractions was determined on NRVC in the presence of different steroid hormones and antagonists. AntiapoA-1 IgG chronotropic response was maximal within 20 min and observed only in aldosterone-pretreated cells but not in those exposed to other steroids. The positive antiapoA-1 IgG chronotropic effect was already significant after 5 min aldosterone preincubation, was dependent on 3-kinase and protein kinase A activities, was not inhibited by actinomycin D, and was fully abrogated by eplerenone (but not by spironolactone), demonstrating the dependence on a nongenomic action of aldosterone elicited through the mineralocorticoid receptor (MR). Under oxidative conditions (but not under normal redox state), corticosterone mimicked the permissive action of aldosterone on the antiapoA-1 IgG chronotropic response. Pharmacological and patch-clamp studies identified L-type calcium channels as crucial effectors of antiapoA-1 IgG chronotropic action, involving two converging pathways that increase the channel activity. The first one involves the rapid, nongenomic activation of the phosphatidylinositol 3-kinase enzyme by MR, and the second one requires a constitutive basal protein kinase A activity. In conclusion, our results indicate that, on NRVC, the aldosterone-dependent chronotropic effects of antiapoA-1 IgG involve the nongenomic activation of L-type calcium channels.

  8. Autoantibodies in dilated cardiomyopathy induce vascular endothelial growth factor expression in cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Saygili, Erol, E-mail: erol.saygili@med.uni-duesseldorf.de [Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf (Germany); Noor-Ebad, Fawad; Schröder, Jörg W.; Mischke, Karl [Department of Cardiology, University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen (Germany); Saygili, Esra [Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich-Heine-University, Moorenstrasse 5, D-40225 Düsseldorf (Germany); Rackauskas, Gediminas [Department of Cardiovascular Medicine, Vilnius University Hospital Santariskiu Klinikos, Vilnius University (Lithuania); Marx, Nikolaus [Department of Cardiology, University RWTH Aachen, Pauwelsstr. 30, D-52074 Aachen (Germany); Kelm, Malte; Rana, Obaida R. [Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Moorenstrasse 5, D-40225 Düsseldorf (Germany)

    2015-09-11

    Background: Autoantibodies have been identified as major predisposing factors for dilated cardiomyopathy (DCM). Patients with DCM show elevated serum levels of vascular endothelial growth factor (VEGF) whose source is unknown. Besides its well-investigated effects on angiogenesis, evidence is present that VEGF signaling is additionally involved in fibroblast proliferation and cardiomyocyte hypertrophy, hence in cardiac remodeling. Whether autoimmune effects in DCM impact cardiac VEGF signaling needs to be elucidated. Methods: Five DCM patients were treated by the immunoadsorption (IA) therapy on five consecutive days. The eluents from the IA columns were collected and prepared for cell culture. Cardiomyocytes from neonatal rats (NRCM) were incubated with increasing DCM-immunoglobulin-G (IgG) concentrations for 48 h. Polyclonal IgG (Venimmun N), which was used to restore IgG plasma levels in DCM patients after the IA therapy was additionally used for control cell culture purposes. Results: Elevated serum levels of VEGF decreased significantly after IA (Serum VEGF (ng/ml); DCM pre-IA: 45 ± 9.1 vs. DCM post–IA: 29 ± 6.7; P < 0.05). In cell culture, pretreatment of NRCM by DCM-IgG induced VEGF expression in a time and dose dependent manner. Biologically active VEGF that was secreted by NRCM significantly increased BNP mRNA levels in control cardiomyocytes and induced cell-proliferation of cultured cardiac fibroblast (Fibroblast proliferation; NRCM medium/HC-IgG: 1 ± 0.0 vs. NRCM medium/DCM-IgG 100 ng/ml: 5.6 ± 0.9; P < 0.05). Conclusion: The present study extends the knowledge about the possible link between autoimmune signaling in DCM and VEGF induction. Whether this observation plays a considerable role in cardiac remodeling during DCM development needs to be further elucidated. - Highlights: • Mechanisms of remodeling in dilated cardiomyopathy (DCM) are not fully understood. • Autoantibodies have been identified as major predisposing factors

  9. Mass spectrometry detection of G3m and IGHG3 alleles and follow-up of differential mother and neonate IgG3.

    Directory of Open Access Journals (Sweden)

    Célia Dechavanne

    Full Text Available Mass spectrometry (MS analysis for detection of immunoglobulins (IG of the human IgG3 subclass is described that relies on polymorphic amino acids of the heavy gamma3 chains. IgG3 is the most polymorphic human IgG subclass with thirteen G3m allotypes located on the constant CH2 and CH3 domains of the gamma3 chain, the combination of which leads to six major G3m alleles. Amino acid changes resulting of extensive sequencing previously led to the definition of 19 IGHG3 alleles that have been correlated to the G3m alleles. As a proof of concept, MS proteotypic peptides were defined which encompass discriminatory amino acids for the identification of the G3m and IGHG3 alleles. Plasma samples originating from ten individuals either homozygous or heterozygous for different G3m alleles, and including one mother and her baby (drawn sequentially from birth to 9 months of age, were analyzed. Total IgG3 were purified using affinity chromatography and then digested by a combination of AspN and trypsin proteases, and peptides of interest were detected by mass spectrometry. The sensitivity of the method was assessed by mixing variable amounts of two plasma samples bearing distinct G3m allotypes. A label-free approach using the high-performance liquid chromatography (HPLC retention time of peptides and their MS mass analyzer peak intensity gave semi-quantitative information. Quantification was realized by selected reaction monitoring (SRM using synthetic peptides as internal standards. The possibility offered by this new methodology to detect and quantify neo-synthesized IgG in newborns will improve knowledge on the first acquisition of antibodies in infants and constitutes a promising diagnostic tool for vertically-transmitted diseases.

  10. Efficacy of D- red blood cell transfusion and rituximab therapy in autoimmune hemolytic anemia with anti-D and panreactive autoantibodies arising after hematopoietic stem cell transplant.

    Science.gov (United States)

    Minakawa, Keiji; Ohto, Hitoshi; Yasuda, Hiroyasu; Saito, Shunichi; Kawabata, Kinuyo; Ogawa, Kazuei; Nollet, Kenneth E; Ikeda, Kazuhiko

    2018-04-17

    Autoimmune hemolytic anemia (AIHA) is caused by autoantibodies to red blood cells (RBCs), which can be panreactive and/or specific to Rh/other blood group antigens. We report a severe case of AIHA after bone marrow transplantation (BMT) due to autoanti-D triggered by reactivation of Epstein-Barr virus (EBV) infection. A combined strategy of D- RBC transfusion and administration of anti-CD20 monoclonal antibody (MoAb) resolved the hemolysis. A 33-year-old male underwent allogeneic BMT from an ABO-identical and HLA-matched unrelated male donor. Five months later, while having mild chronic graft-versus-host disease, he manifested AIHA, with a hemoglobin (Hb) level of 5.1 g/dL on AIHA Day 2 (Posttransplant Day 156) and was refractory to D+ RBCs, with a Hb level of 2.4 g/dL on AIHA Day 6. Anti-D-like autoantibodies (titer 1280, subclass immunoglobulin G 1 , monocyte monolayer assay 28.7%) and panreactive (titer 40) were identified. Changing the RBC transfusion strategy to D- increased his Hb level to 6.7 g/dL on Day 10. Administration of anti-CD20 MoAb mitigated EBV-related B-cell proliferation and reduced anti-D autoantibody titer to 320 by Day 16 with normalized Hb concentration after 6 months. In severe AIHA, when standard treatment and regular RBC transfusions are ineffective, transfusion of RBCs lacking the target antigen(s) of autoantibodies and administration of anti-CD20 MoAb should be considered. © 2018 AABB.

  11. Autoantibodies in Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Lifang Wen

    2018-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD, the fourth leading cause of death worldwide, is characterized by irreversible airflow limitation based on obstructive bronchiolitis, emphysema, and chronic pulmonary inflammation. Inhaled toxic gases and particles, e.g., cigarette smoke, are major etiologic factors for COPD, while the pathogenesis of the disease is only partially understood. Over the past decade, an increasing body of evidence has been accumulated for a link between COPD and autoimmunity. Studies with clinical samples have demonstrated that autoantibodies are present in sera of COPD patients and some of these antibodies correlate with specific disease phenotypes. Furthermore, evidence from animal models of COPD has shown that autoimmunity against pulmonary antigens occur during disease development and is capable of mediating COPD-like symptoms. The idea that autoimmunity could contribute to the development of COPD provides a new angle to understand the pathogenesis of the disease. In this review article, we provide an advanced overview in this field and critically discuss the role of autoantibodies in the pathogenesis of COPD.

  12. Dietary fatty acids were not independently associated with lipoprotein subclasses in elderly women.

    Science.gov (United States)

    Alaghehband, Fatemeh Ramezan; Lankinen, Maria; Värri, Miika; Sirola, Joonas; Kröger, Heikki; Erkkilä, Arja T

    2017-07-01

    Dietary fatty acids are known to affect serum lipoproteins; however, little is known about the associations between consumption of dietary fatty acids and lipoprotein subclasses. In this study, we hypothesized that there is an association between dietary fatty acids and lipoprotein subclasses and investigated the cross-sectional association of dietary fat intake with subclasses of lipoproteins in elderly women. Altogether, 547 women (aged ≥65 years) who were part of OSTPRE cohort participated. Dietary intake was assessed by 3-day food records, lifestyle, and health information obtained through self-administrated questionnaires, and lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy. To analyze the associations between fatty acids and lipoprotein subclasses, we used Pearson and Spearman correlation coefficients and the analysis of covariance (ANCOVA) test with, adjustment for physical activity, body mass index, age, smoking status, and intake of lipid-lowering drugs. There were significant correlations between saturated fatty acids (SFA; % of energy) and concentrations of large, medium, and small low-density lipoproteins (LDL); total cholesterol in large, medium, and small LDL; and phospholipids in large, medium, and small LDL, after correction for multiple testing. After adjustment for covariates, the higher intake of SFA was associated with smaller size of LDL particles (P = .04, ANCOVA) and lower amount of triglycerides in small very low-density lipoproteins (P = .046, ANCOVA). However, these associations did not remain significant after correction for multiple testing. In conclusion, high intake of SFA may be associated with the size of LDL particles, but the results do not support significant, independent associations between dietary fatty acids and lipoprotein subclasses. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Generating and Purifying Fab Fragments from Human and Mouse IgG Using the Bacterial Enzymes IdeS, SpeB and Kgp.

    Science.gov (United States)

    Sjögren, Jonathan; Andersson, Linda; Mejàre, Malin; Olsson, Fredrik

    2017-01-01

    Fab fragments are valuable research tools in various areas of science including applications in imaging, binding studies, removal of Fc-mediated effector functions, mass spectrometry, infection biology, and many others. The enzymatic tools for the generation of Fab fragments have been discovered through basic research within the field of molecular bacterial pathogenesis. Today, these enzymes are widely applied as research tools and in this chapter, we describe methodologies based on bacterial enzymes to generate Fab fragments from both human and mouse IgG. For all human IgG subclasses, the IdeS enzyme from Streptococcus pyogenes has been applied to generate F(ab')2 fragments that subsequently can be reduced under mild conditions to generate a homogenous pool of Fab' fragments. The enzyme Kgp from Porphyromonas gingivalis has been applied to generate intact Fab fragments from human IgG1 and the Fab fragments can be purified using a CH1-specific affinity resin. The SpeB protease, also from S. pyogenes, is able to digest mouse IgGs and has been applied to digest antibodies and Fab fragments can be purified on light chain affinity resins. In this chapter, we describe methodologies that can be used to obtain Fab fragments from human and mouse IgG using bacterial proteases.

  14. IgG4 anti-phospholipase A2 receptor might activate lectin and alternative complement pathway meanwhile in idiopathic membranous nephropathy: an inspiration from a cross-sectional study.

    Science.gov (United States)

    Yang, Yang; Wang, Chao; Jin, Liping; He, Fagui; Li, Changchun; Gao, Qingman; Chen, Guanglei; He, Zhijun; Song, Minghui; Zhou, Zhuliang; Shan, Fujun; Qi, Ka; Ma, Lu

    2016-08-01

    The deposition of IgG4 of antibodies against phospholipase A2 receptor (anti-PLA2R) is predominating in the kidneys of patients with idiopathic membranous nephropathy, while its predictive value has not been determined. It was a retrospective study, and 438 patients were included. Serum samples of two time points [before intervention (baseline) and after 1.5-year treatment (endpoint)] were detected for total and IgG4 anti-PLA2R. IgG4 IgG4 subclass and the achievement of CR; (3) bi-negativity of IgG4 has a high accuracy of predicting CR compared with total antibodies; (4) in patients of bi-positivity, those achieving CR showed lower MASP-1/2, MBL, C3a, C5a, FB, Ba and Bb than patients failing to achieve CR; (5) the titers of endpoint and decrease in Ba and Bb were associated with improvement of 24 h-UP in those of bi-positivity; and (6) the decrease in Ba was a significant factor for achieving CR in those of bi-positivity. Continuous IgG4 negativity was a useful tool to predict the achievement of CR; however, in patients of continuous IgG4 positivity, those with lower activation of lectin and alternative pathways would still more probably achieve CR.

  15. Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system.

    Directory of Open Access Journals (Sweden)

    Mark A Little

    Full Text Available Evidence is lacking for direct pathogenicity of human anti-proteinase-3 (PR3 antibodies in development of systemic vasculitis and granulomatosis with polyangiitis (GPA, Wegener's granulomatosis. Progress in study of these antibodies in rodents has been hampered by lack of PR3 expression on murine neutrophils, and by different Fc-receptor affinities for IgG across species. Therefore, we tested whether human anti-PR3 antibodies can induce acute vasculitis in mice with a human immune system. Chimeric mice were generated by injecting human haematopoietic stem cells into irradiated NOD-scid-IL2Rγ⁻/⁻ mice. Matched chimera mice were treated with human IgG from patients with: anti-PR3 positive renal and lung vasculitis; patients with non-vasculitic renal disease; or healthy controls. Six-days later, 39% of anti-PR3 treated mice had haematuria, compared with none of controls. There was punctate bleeding on the surface of lungs of anti-PR3 treated animals, with histological evidence of vasculitis and haemorrhage. Anti-PR3 treated mice had mild pauci-immune proliferative glomerulonephritis, with infiltration of human and mouse leukocytes. In 3 mice (17% more severe glomerular injury was present. There were no glomerular changes in controls. Human IgG from patients with anti-PR3 autoantibodies is therefore pathogenic. This model of anti-PR3 antibody-mediated vasculitis may be useful in dissecting mechanisms of microvascular injury.

  16. Anti-proteinase 3 anti-neutrophil cytoplasm autoantibodies recapitulate systemic vasculitis in mice with a humanized immune system.

    LENUS (Irish Health Repository)

    Little, Mark A

    2012-01-01

    Evidence is lacking for direct pathogenicity of human anti-proteinase-3 (PR3) antibodies in development of systemic vasculitis and granulomatosis with polyangiitis (GPA, Wegener\\'s granulomatosis). Progress in study of these antibodies in rodents has been hampered by lack of PR3 expression on murine neutrophils, and by different Fc-receptor affinities for IgG across species. Therefore, we tested whether human anti-PR3 antibodies can induce acute vasculitis in mice with a human immune system. Chimeric mice were generated by injecting human haematopoietic stem cells into irradiated NOD-scid-IL2Rγ⁻\\/⁻ mice. Matched chimera mice were treated with human IgG from patients with: anti-PR3 positive renal and lung vasculitis; patients with non-vasculitic renal disease; or healthy controls. Six-days later, 39% of anti-PR3 treated mice had haematuria, compared with none of controls. There was punctate bleeding on the surface of lungs of anti-PR3 treated animals, with histological evidence of vasculitis and haemorrhage. Anti-PR3 treated mice had mild pauci-immune proliferative glomerulonephritis, with infiltration of human and mouse leukocytes. In 3 mice (17%) more severe glomerular injury was present. There were no glomerular changes in controls. Human IgG from patients with anti-PR3 autoantibodies is therefore pathogenic. This model of anti-PR3 antibody-mediated vasculitis may be useful in dissecting mechanisms of microvascular injury.

  17. On the role of IgG4 in inflammatory conditions: lessons for IgG4-related disease

    NARCIS (Netherlands)

    Trampert, David C.; Hubers, Lowiek M.; van de Graaf, Stan F. J.; Beuers, Ulrich

    2017-01-01

    The pathophysiology of immunoglobulin G4-related disease (IgG4-RD) and its most common manifestations, IgG4-associated (sclerosing) cholangitis and autoimmune pancreatitis, remains largely unknown, but IgG4 is presumably involved. IgG4 is a promiscuous antibody, which could be directly pathogenic,

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

    Science.gov (United States)

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

    2015-01-01

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

  19. GPIHBP1 autoantibodies in a patient with unexplained chylomicronemia

    DEFF Research Database (Denmark)

    Hu, Xuchen; Dallinga-Thie, Geesje M.; Hovingh, G. Kees

    2017-01-01

    into the frequency of the GPIHBP1 autoantibody syndrome in patients with unexplained chylomicronemia. Methods We used enzyme-linked immunosorbent assays to screen for GPIHBP1 autoantibodies in 33 patients with unexplained chylomicronemia and then used Western blots and immunocytochemistry studies to characterize....... The patient had no history of autoimmune disease, but his plasma was positive for antinuclear antibodies. Conclusions One of 33 patients with unexplained chylomicronemia had the GPIHBP1 autoantibody syndrome. Additional studies in large lipid clinics will be helpful for better defining the frequency...

  20. Cholangiocarcinoma with respect to IgG4 Reaction

    Directory of Open Access Journals (Sweden)

    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.

  1. Large scale aggregate microarray analysis reveals three distinct molecular subclasses of human preeclampsia.

    Science.gov (United States)

    Leavey, Katherine; Bainbridge, Shannon A; Cox, Brian J

    2015-01-01

    Preeclampsia (PE) is a life-threatening hypertensive pathology of pregnancy affecting 3-5% of all pregnancies. To date, PE has no cure, early detection markers, or effective treatments short of the removal of what is thought to be the causative organ, the placenta, which may necessitate a preterm delivery. Additionally, numerous small placental microarray studies attempting to identify "PE-specific" genes have yielded inconsistent results. We therefore hypothesize that preeclampsia is a multifactorial disease encompassing several pathology subclasses, and that large cohort placental gene expression analysis will reveal these groups. To address our hypothesis, we utilized known bioinformatic methods to aggregate 7 microarray data sets across multiple platforms in order to generate a large data set of 173 patient samples, including 77 with preeclampsia. Unsupervised clustering of these patient samples revealed three distinct molecular subclasses of PE. This included a "canonical" PE subclass demonstrating elevated expression of known PE markers and genes associated with poor oxygenation and increased secretion, as well as two other subclasses potentially representing a poor maternal response to pregnancy and an immunological presentation of preeclampsia. Our analysis sheds new light on the heterogeneity of PE patients, and offers up additional avenues for future investigation. Hopefully, our subclassification of preeclampsia based on molecular diversity will finally lead to the development of robust diagnostics and patient-based treatments for this disorder.

  2. Colony-stimulating factor (CSF) radioimmunoassay: detection of a CSF subclass stimulating macrophage production

    International Nuclear Information System (INIS)

    Stanley, E.R.

    1979-01-01

    Colony-stimulating factors (CSFs) stimulate the differentiation of immature precursor cells to mature granulocytes and macrophages. Purified 125 I-labeled murine L cell CSF has been used to develop a radioimmunoassay (RIA) that detects a subclass of CSFs that stimulates macrophage production. Murine CSF preparations that contain this subclass of CSF compete for all of the CSF binding sites on anti-L cell CSF antibody. With the exception of mouse serum, which can contain inhibitors of the bioassay, there is complete correspondence between activities determined by RIA and those determined by bioassay. The RIA is slightly more sensitive than the bioassay, detecting approximately 0.3 fmol of purified L cell CSF. It can also detect this subclass of CSF in chickens, rats, and humans. In the mouse, the subclass is distinguished from other CSFs by a murine cell bioassay dose-response curve in which 90% of the response occurs over a 10-fold (rather than a 100-fold) increase in concentration, by stimulating the formations of colonies contaning a high proportion of mononuclear (rather than granulocytic) cells, and by certain physical characteristics

  3. Fekete-Szegö Inequalities of a Subclass of Multivalent Analytic Functions

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    Selvaraj C.

    2016-07-01

    Full Text Available The main object of this paper is to study Fekete-Szegö problem for a certain subclass of p - valent analytic functions. Fekete-Szegö inequality of several classes are obtained as special cases from our results. Applications of the result are also obtained on the class defined by convolution.

  4. On certain subclasses of multivalent functions associated with an extended fractional differintegral operator

    Science.gov (United States)

    Patel, J.; Mishra, A. K.

    2007-08-01

    In the present paper an extended fractional differintegral operator , suitable for the study of multivalent functions is introduced. Various mapping properties and inclusion relationships between certain subclasses of multivalent functions are investigated by applying the techniques of differential subordination. Relevant connections of the definitions and results presented in this paper with those obtained in several earlier works on the subject are also pointed out.

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

    Science.gov (United States)

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

    2016-08-01

    Immunoglobulin G4-related disease (IgG4-RD) is a systemic disease involving many organs; it includes IgG4-related sclerosing cholangitis and inflammatory pseudotumor in the hepatobiliary system. Two types of hepatic parenchymal involvement have been reported in IgG4-RD: IgG4-related autoimmune hepatitis (AIH) and IgG4-hepatopathy. Moreover, only three cases of IgG4-related AIH have been reported. Immunoglobulin G4-related AIH is clinicopathologically similar to AIH, except for an elevated serum IgG4 level and heavy infiltration of IgG4-positive plasma cells in the liver tissue. Interestingly, IgG4-related AIH can be complicated by well-known IgG4-RD(s). Immunoglobulin G4-hepatopathy, which includes various histopathological lesions encountered in the liver of patients with type I autoimmune pancreatitis, is classified into five histological categories: portal inflammation, large bile duct damage, portal sclerosis, lobular hepatitis, and cholestasis. Immunoglobulin G4-hepatopathy is currently a collective term covering hepatic lesions primarily or secondarily related to IgG4-related sclerosing cholangitis and type 1 autoimmune pancreatitis. In conclusion, the liver is not immune to IgG4-RD, and at least two types of hepatic involvement in IgG4-RD have been reported: IgG4-related AIH and IgG4-hepatopathy. Additional studies are required to clarify their precise clinical significance with respect to IgG4-RD and inherent liver diseases. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  6. A Unique Report: Development of Super Anti-Human IgG Monoclone with Optical Density Over Than 3

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    Leili Aghebati Maleki

    2013-08-01

    Full Text Available Purpose: Monoclonal antibodies and related conjugates are key reagents used in biomedical researches as well as, in treatment, purification and diagnosis of infectious and non- infectious diseases. Methods: Balb/c mice were immunized with purified human IgG. Spleen cells of the most immune mouse were fused with SP2/0 in the presence of Poly Ethylene Glycol (PEG. Supernatant of hybridoma cells was screened for detection of antibody by ELISA. Then, the sample was assessed for cross-reactivity with IgM & IgA by ELISA and confirmed by immunoblotting. The subclasses of the selected mAbs were determined. The best clone was injected intraperitoneally to some pristane-injected mice. Anti-IgG mAb was purified from the animals' ascitic fluid by Ion exchange chromatography and then, mAb was conjugated with HRP. Results: In the present study, over than 50 clones were obtained that 1 clone had optical density over than 3. We named this clone as supermonoclone which was selected for limiting dilution. The result of the immunoblotting, showed sharp band in IgG position and did not show any band in IgM&IgA position. Conclusion: Based on the findings of this study, the conjugated monoclonal antibody could have application in diagnosis of infectious diseases like Toxoplasmosis, Rubella and IgG class of other infectious and non- infectious diseases.

  7. A Unique Report: Development of Super Anti-Human IgG Monoclone with Optical Density Over Than 3

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    Aghebati Maleki, Leili; Baradaran, Behzad; Abdolalizadeh, Jalal; Ezzatifar, Fatemeh; Majidi, Jafar

    2013-01-01

    Purpose: Monoclonal antibodies and related conjugates are key reagents used in biomedical researches as well as, in treatment, purification and diagnosis of infectious and non- infectious diseases. Methods: Balb/c mice were immunized with purified human IgG. Spleen cells of the most immune mouse were fused with SP2/0 in the presence of Poly Ethylene Glycol (PEG). Supernatant of hybridoma cells was screened for detection of antibody by ELISA. Then, the sample was assessed for cross-reactivity with IgM & IgA by ELISA and confirmed by immunoblotting. The subclasses of the selected mAbs were determined. The best clone was injected intraperitoneally to some pristane-injected mice. Anti-IgG mAb was purified from the animals' ascitic fluid by Ion exchange chromatography and then, mAb was conjugated with HRP. Results: In the present study, over than 50 clones were obtained that 1 clone had optical density over than 3. We named this clone as supermonoclone which was selected for limiting dilution. The result of the immunoblotting, showed sharp band in IgG position and did not show any band in IgM&IgA position. Conclusion: Based on the findings of this study, the conjugated monoclonal antibody could have application in diagnosis of infectious diseases like Toxoplasmosis, Rubella and IgG class of other infectious and non- infectious diseases. PMID:24312857

  8. Clinical and Pathological Roles of Ro/SSA Autoantibody System

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    Ryusuke Yoshimi

    2012-01-01

    Full Text Available Anti-Ro/SSA antibodies are among the most frequently detected autoantibodies against extractable nuclear antigens and have been associated with systemic lupus erythematosus (SLE and Sjögren's syndrome (SS. Although the presence of these autoantibodies is one of the criteria for the diagnosis and classification of SS, they are also sometimes seen in other systemic autoimmune diseases. In the last few decades, the knowledge of the prevalence of anti-Ro/SSA antibodies in various autoimmune diseases and symptoms has been expanded, and the clinical importance of these antibodies is increasing. Nonetheless, the pathological role of the antibodies is still poorly understood. In this paper, we summarize the milestones of the anti-Ro/SSA autoantibody system and provide new insights into the association between the autoantibodies and the pathogenesis of autoimmune diseases.

  9. Increases in IgE, Eosinophils, and Mast Cells Can be Used in Diagnosis and to Predict Relapse of IgG4-Related Disease.

    Science.gov (United States)

    Culver, Emma L; Sadler, Ross; Bateman, Adrian C; Makuch, Mateusz; Cargill, Tamsin; Ferry, Berne; Aalberse, Rob; Barnes, Eleanor; Rispens, Theo

    2017-09-01

    IgG subclass 4-related disease (IgG4-RD) is characterized by increased serum levels of IgG4 and infiltration of biliary, pancreatic, and other tissues by IgG4-positive plasma cells. We assessed the prevalence of allergy and/or atopy, serum, and tissue IgE antibodies, and blood and tissue eosinophils in patients with IgG4-RD. We investigated the association between serum IgE and diagnosis and relapse of this disease. We performed a prospective study of 48 patients with IgG4-RD, 42 patients with an increased serum level of IgG4 with other inflammatory and autoimmune conditions (disease control subjects), and 51 healthy individuals (healthy control subjects) recruited from Oxford, United Kingdom from March 2010 through March 2014, and followed for a median of 41 months (range, 3-73 months). Serum levels of immunoglobulin were measured at diagnosis, during steroid treatment, and at disease relapse for patients with IgG4-RD; levels at diagnosis were compared with baseline levels of control subjects. Allergen-specific IgEs were measured using the IgE ImmunoCAP. Levels and distribution of IgG4 and IgE antibodies in lymphoid, biliary, and pancreatic tissues from patients with IgG4-RD and disease control subjects were measured by immunohistochemistry. We analyzed data using the Spearman rank correlation and receiver operating characteristic curves. Serum levels of IgG4 increased to 1.4 g/L or more, and IgE increased to 125 kIU/L or more, in 81% and 54% of patients with IgG4-RD, respectively, compared with 6% and 16% of healthy control subjects (P IgG4-RD versus 9% of healthy control subjects (P = .004). Of patients with IgG4-RD, 63% had a history of allergy and 40% had a history of atopy with an IgE-specific response; these values were 60% and 53% in patients with increased serum levels of IgE (P 480 kIU/L distinguished patients with IgG4-RD from disease control subjects with 86% specificity, 36% sensitivity, and a likelihood ratio of 3.2. Level of IgE at diagnosis >380 k

  10. IgG4-related kidney disease – an update

    Science.gov (United States)

    Kawano, Mitsuhiro; Saeki, Takako

    2015-01-01

    Purpose of review IgG4-related disease (IgG4-RD) is a recently recognized systemic inflammatory disorder that can affect most organs/tissues such as sarcoidosis. The kidney is a frequently affected organ with tubulointerstitial nephritis (TIN), the representative lesion of IgG4-RD. This review focuses on the latest knowledge of IgG4-related kidney disease (IgG4-RKD). Recent findings A wide range of renal manifestations of IgG4-RD, that is TIN, membranous glomerulonephritis (MGN) and other glomerular lesions, and pyelitis, are collectively referred to as IgG4-RKD. Clinically, decreased renal function, or characteristic imaging findings such as multiple low-density lesions on contrast-enhanced computed tomography or diffuse thickening of the renal pelvic wall, are typical presenting features. Although a rapid response to corticosteroid therapy is a very important feature of IgG4-TIN, in cases in which renal function is moderately to severely decreased before therapy, only partial recovery of renal function is obtained. Summary TIN with characteristic imaging findings is a typical manifestation of IgG4-RKD in the interstitium, while MGN is a representative manifestation of the glomerular lesions. Although IgG4 is a central feature of IgG4-RD, the recent discovery of IgG4-negative IgG4-RD raises questions about the causative role of the IgG4 molecule in this context. PMID:25594543

  11. Peroxynitrite modified DNA presents better epitopes for anti-DNA autoantibodies in diabetes type 1 patients.

    Science.gov (United States)

    Tripathi, Prashant; Moinuddin; Dixit, Kiran; Mir, Abdul Rouf; Habib, Safia; Alam, Khursheed; Ali, Asif

    2014-07-01

    Peroxynitrite (ONOO(-)), formed by the reaction between nitric oxide (NO) and superoxide (O2(-)), has been implicated in the etiology of numerous disease processes. Peroxynitrite interacts with DNA via direct oxidative reactions or via indirect radical-mediated mechanism. It can inflict both oxidative and nitrosative damages on DNA bases, generating abasic sites, resulting in the single strand breaks. Plasmid pUC 18 isolated from Escherichiacoli was modified with peroxynitrite, generated by quenched flow process. Modifications incurred in plasmid DNA were characterized by ultraviolet and fluorescence spectroscopy, circular dichroism, HPLC and melting temperature studies. Binding characteristics and specificity of antibodies from diabetes patients were analyzed by direct binding and inhibition ELISA. Peroxynitrite modification of pUC 18 plasmid resulted in the formation of strand breaks and base modification. The major compound formed when peroxynitrite reacted with DNA was 8-nitroguanine, a specific marker for peroxynitrite induced DNA damage in inflamed tissues. The concentration of 8-nitroguanine was found to be 3.8 μM. Sera from diabetes type 1 patients from different age groups were studied for their binding to native and peroxynitrite modified plasmid. Direct binding and competitive-inhibition ELISA results showed higher recognition of peroxynitrite modified plasmid, as compared to the native form, by auto-antibodies present in diabetes patients. The preferential recognition of modified plasmid by diabetes autoantibodies was further reiterated by gel shift assay. Experimentally induced anti-peroxynitrite-modified plasmid IgG was used as a probe to detect nitrosative lesions in the DNA isolated from diabetes patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Anti-signal recognition particle autoantibody ELISA validation and clinical associations.

    Science.gov (United States)

    Aggarwal, Rohit; Oddis, Chester V; Goudeau, Danielle; Fertig, Noreen; Metes, Ilinca; Stephens, Chad; Qi, Zengbiao; Koontz, Diane; Levesque, Marc C

    2015-07-01

    The aim of this study was to develop and validate a quantitative anti-signal recognition particle (SRP) autoantibody serum ELISA in patients with myositis and longitudinal association with myositis disease activity. We developed a serum ELISA using recombinant purified full-length human SRP coated on ELISA plates and a secondary antibody that bound human IgG to detect anti-SRP binding. Protein immunoprecipitation was used as the gold standard for the presence of anti-SRP. Serum samples from three groups were analysed: SRP(+) myositis subjects by immunoprecipitation, SRP(-) myositis subjects by immunoprecipitation and non-myositis controls. The ELISA's sensitivity, specificity, positive predictive value and negative predictive value were evaluated. Percentage agreement and test-retest reliability were assessed. Serial samples from seven SRP immunoprecipitation-positive subjects were also tested, along with serum muscle enzymes and manual muscle testing. Using immunoprecipitation, we identified 26 SRP(+) myositis patients and 77 SRP(-) controls (including 38 patients with necrotizing myopathy). Non-myositis control patients included SLE (n = 4) and SSc (n = 7) patients. Anti-SRP positivity by ELISA showed strong agreement (97.1%) with immunoprecipitation (κ = 0.94). The sensitivity, specificity, positive predictive value, and negative predictive value of the anti-SRP ELISA were 88, 100, 100 and 96, respectively. The area under the curve was 0.94, and test-retest reliability was strong (r = 0.91, P < 0.001). Serial samples showed that anti-SRP levels paralleled changes in muscle enzymes and manual muscle testing. We developed a quantitative ELISA for detecting serum anti-SRP autoantibodies and validated the assay in myositis. Longitudinal assessment of SRP levels by ELISA may be a useful biomarker for disease activity. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions

  13. Rapid induction of autoantibodies during ARDS and septic shock

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    Meduri G Umberto

    2010-10-01

    Full Text Available Abstract Background Little is known about the induction of humoral responses directed against human autoantigens during acute inflammation. We utilized a highly sensitive antibody profiling technology to study autoantibodies in patients with acute respiratory distress syndrome (ARDS and severe sepsis, conditions characterized by intensive immune activation leading to multiple organ dysfunction. Methods Using Luciferase Immunoprecipitation Systems (LIPS, a cohort of control, ARDS and sepsis patients were tested for antibodies to a panel of autoantigens. Autoantibody titers greater than the mean plus 3 SD of the 24 control samples were used to identify seropositive samples. Available longitudinal samples from different seropositive ARDS and sepsis patient samples, starting from within the first two days after admission to the intensive care, were then analyzed for changes in autoantibody over time. Results From screening patient plasma, 57% of ARDS and 46% of septic patients without ARDS demonstrated at least one statistically significant elevated autoantibody compared to the controls. Frequent high titer antibodies were detected against a spectrum of autoantigens including potassium channel regulator, gastric ATPase, glutamic decarboxylase-65 and several cytokines. Analysis of serial samples revealed that several seropositive patients had low autoantibodies at early time points that often rose precipitously and peaked between days 7-14. Further, the use of therapeutic doses of corticosteroids did not diminish the rise in autoantibody titers. In some cases, the patient autoantibody titers remained elevated through the last serum sample collected. Conclusion The rapid induction of autoantibodies in ARDS and severe sepsis suggests that ongoing systemic inflammation and associated tissue destruction mediate the break in tolerance against these self proteins.

  14. Evaluation of classical and novel autoantibodies for the diagnosis of Primary Biliary Cholangitis-Autoimmune Hepatitis Overlap Syndrome (PBC-AIH OS).

    Science.gov (United States)

    Nguyen, Henry H; Shaheen, Abdel Aziz; Baeza, Natalia; Lytvyak, Ellina; Urbanski, Stefan J; Mason, Andrew L; Norman, Gary L; Fritzler, Marvin J; Swain, Mark G

    2018-01-01

    vs 9.9% in PBC alone, P <0.01) was the only autoantibody associated with PBC-AIH OS; a finding consistent with previous reports. Significant elevation in serum ALT (62 IU/L in PBC-AIH OS vs 37 IU/L in PBC alone, P < 0.01), and serum IgG (17.6 g/L in OS vs 12.1 g/L in PBC alone, P <0.01) were observed in patients with PBC-AIH OS receiving medical/immunosuppressive therapy. In a multivariate model, positive anti-dsDNA by CLIFT, ALT and IgG were significant predictors of PBC-AIH OS with an area under the receiver operator curve (AUROC) value of 0.84. Consistent with previous findings, the presence of anti-dsDNA by CLIFT is associated with PBC-AIH OS. Contrary to previous reports, anti-p53 was not associated with PBC-AIH OS. Our comprehensive evaluation of various classical and novel autoantibody biomarkers including Ro52/TRIM21, anti-p53, anti-KLHL-12 and anti-HK-1 were not significantly associated with PBC-AIH OS. Our findings highlight the ongoing need for the research and development of new autoantibody biomarkers to aid in the diagnosis of PBC-AIH OS.

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

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    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.

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

    International Nuclear Information System (INIS)

    Fukuhara, Takataro; Tomiyama, Takashi; Yasuda, Kaneki; Ueda, Yoshihiro; Ozaki, Yoshio; Son, Yonsu; Nomura, Shosaku; Uchida, Kazushige; Okazaki, Kazuichi; Kinashi, Tatsuo

    2015-01-01

    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

  17. Anti-interleukin-1 alpha autoantibodies in humans: Characterization, isotype distribution, and receptor-binding inhibition--higher frequency in Schnitzler's syndrome (urticaria and macroglobulinemia)

    International Nuclear Information System (INIS)

    Saurat, J.H.; Schifferli, J.; Steiger, G.; Dayer, J.M.; Didierjean, L.

    1991-01-01

    Since autoantibodies (Abs) to cytokines may modify their biologic activities, high-affinity binding factors for interleukin-1 alpha (IL-1 alpha BF) were characterized in human sera. IL-1 alpha BF was identified as IgG (1) by sucrose density-gradient centrifugation followed by immunodiffusion autoradiography, (2) by ligand-blotting method, (3) by ligand binding to affinity-immobilized serum IgG, and (4) by IgG affinity purification followed by sucrose density-gradient centrifugation. IL-1 alpha binding activity resided in the F(ab)2 fragment. The apparent equilibrium constant was in the range of IgG found after immunization with conventional antigens (i.e., 10(-9) to 10(-10) mol/L). Anti-IL-1 alpha IgG auto-Abs represented only an extremely small fraction of total IgG (less than 1/10(-5)). Some sera with IL-1 alpha BF and purified IgG thereof were able to inhibit by 96% to 98% the binding of human recombinant IL-1 alpha to its receptor on murine thymoma EL4-6.1 cells, whereas other sera did not. When 125I-labeled anti-IL-1 alpha IgG complexes were injected into rats, they prolonged the plasma half-life of 125I-labeled IL-1 alpha several fold and altered its tissue distribution. The predominant class was IgG (12/19), mainly IgG4 (9/19), but in five of the sera, anti-IL-1 alpha IgA was also detected. In a screening of 271 sera, IL-1 alpha BF was detected in 17/98 normal subjects and was not more frequent in several control groups of patients, except in patients with Schnitzler's syndrome (fever, chronic urticaria, bone pain, and monoclonal IgM paraprotein) (6/9; p less than 0.005). The pathologic significance of these auto-Abs remains to be determined

  18. Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass profiles to DTaP booster vaccination

    NARCIS (Netherlands)

    van der Lee, Saskia; Sanders, Elisabeth A.M.; Berbers, Guy A M; Buisman, Anne-Marie

    2018-01-01

    Introduction Duration of protection against pertussis is shorter in adolescents who have been immunized with acellular pertussis (aP) in infancy compared with adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is related to immune responses elicited by these priming

  19. Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass profiles to DTaP booster vaccination.

    NARCIS (Netherlands)

    van der Lee, Saskia; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

    2018-01-01

    Duration of protection against pertussis is shorter in adolescents who have been immunized with acellular pertussis (aP) in infancy compared with adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is related to immune responses elicited by these priming vaccines. To better

  20. 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.

  1. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium.

    Science.gov (United States)

    Humby, Frances; Bombardieri, Michele; Manzo, Antonio; Kelly, Stephen; Blades, Mark C; Kirkham, Bruce; Spencer, Jo; Pitzalis, Costantino

    2009-01-13

    closely associated with circulating human IgG ACPA in mouse sera. Finally, the survival and proliferation of functional B cell niches was associated with persistent overexpression of genes regulating ectopic lymphoneogenesis. Our demonstration that FDC+ follicular units invariably express AID and are surrounded by ACPA-producing plasma cells provides strong evidence that ectopic lymphoid structures in the RA synovium are functional and support autoantibody production. This concept is further confirmed by evidence of sustained AID expression, B cell proliferation, ongoing CSR, and production of human IgG ACPA from GC+ synovial tissue transplanted into SCID mice, independently of new B cell influx from the systemic circulation. These data identify AID as a potential therapeutic target in RA and suggest that survival of functional synovial B cell niches may profoundly influence chronic inflammation, autoimmunity, and response to B cell-depleting therapies.

  2. Troponin and anti-troponin autoantibody levels in patients with ventricular noncompaction.

    Directory of Open Access Journals (Sweden)

    Hatice Betül Erer

    Full Text Available Ventricular hypertrabeculation/noncompaction is a morphologic and functional anomaly of myocardium characterized by prominent trabeculae accompanied by deep recessus. Dilated cardiomyopathy with left ventricular failure is observed in these patients, while the cause or pathophysiologic nature of this complication is not known. Anti-troponin antibodies are formed against circulating cardiac troponins after an acute coronary event or conditions associated with chronic myocyte necrosis, such as dilated cardiomyopathy. In present study, we aimed to investigate cardiac troponins and anti troponin autoantibodies in ventricular noncompaction/hypertrabeculation patients with/without reduced ejection fraction. A total of 50 patients with ventricular noncompaction and 23 healthy volunteers were included in this study. Noncompaction/hypertrabeculation was diagnosed with two-dimensional echocardiography using appropriate criteria. Depending on ejection fraction, patients were grouped into noncompaction with preserved EF (LVEF >50%, n = 24 and noncompaction with reduced EF (LVEF <35%, n = 26 groups. Troponin I, troponin T, anti-troponin I IgM and anti-troponin T IgM were measured with sandwich immunoassay method using a commercially available kit. Patients with noncompaction had significantly higher troponin I (28.98±9.21 ng/ml in NCNE group and 28.11±10.42 ng/ml in NCLE group, troponin T (22.17±6.97 pg/ml in NCNE group and 22.78±7.76 pg/ml in NCLE group and antitroponin I IgM (1.92±0.43 µg/ml in NCNE group and 1.79±0.36 µg/ml in NCLE group levels compared to control group, while antitroponin T IgM and IgG were only elevated in patients with noncompaction and reduced EF (15.81±6.52 µg/ml for IgM and 16.46±6.25 µg/ml for IgG. Elevated cardiac troponins and anti-troponin I autoantibodies were observed in patients with noncompaction preceding the decline in systolic function and could indicate ongoing myocardial damage in these patients.

  3. Troponin and Anti-Troponin Autoantibody Levels in Patients with Ventricular Noncompaction

    Science.gov (United States)

    Erer, Hatice Betül; Güvenç, Tolga Sinan; Kemik, Ahu Sarbay; Yılmaz, Hale Yaka; Kul, Şeref; Altay, Servet; Sayar, Nurten; Kaya, Yüksel; Eren, Mehmet

    2013-01-01

    Ventricular hypertrabeculation/noncompaction is a morphologic and functional anomaly of myocardium characterized by prominent trabeculae accompanied by deep recessus. Dilated cardiomyopathy with left ventricular failure is observed in these patients, while the cause or pathophysiologic nature of this complication is not known. Anti-troponin antibodies are formed against circulating cardiac troponins after an acute coronary event or conditions associated with chronic myocyte necrosis, such as dilated cardiomyopathy. In present study, we aimed to investigate cardiac troponins and anti troponin autoantibodies in ventricular noncompaction/hypertrabeculation patients with/without reduced ejection fraction. A total of 50 patients with ventricular noncompaction and 23 healthy volunteers were included in this study. Noncompaction/hypertrabeculation was diagnosed with two-dimensional echocardiography using appropriate criteria. Depending on ejection fraction, patients were grouped into noncompaction with preserved EF (LVEF >50%, n = 24) and noncompaction with reduced EF (LVEF <35%, n = 26) groups. Troponin I, troponin T, anti-troponin I IgM and anti-troponin T IgM were measured with sandwich immunoassay method using a commercially available kit. Patients with noncompaction had significantly higher troponin I (28.98±9.21 ng/ml in NCNE group and 28.11±10.42 ng/ml in NCLE group), troponin T (22.17±6.97 pg/ml in NCNE group and 22.78±7.76 pg/ml in NCLE group) and antitroponin I IgM (1.92±0.43 µg/ml in NCNE group and 1.79±0.36 µg/ml in NCLE group) levels compared to control group, while antitroponin T IgM and IgG were only elevated in patients with noncompaction and reduced EF (15.81±6.52 µg/ml for IgM and 16.46±6.25 µg/ml for IgG). Elevated cardiac troponins and anti-troponin I autoantibodies were observed in patients with noncompaction preceding the decline in systolic function and could indicate ongoing myocardial damage in these patients. PMID:23469039

  4. LKM3 autoantibodies in hepatitis C cirrhosis: a further phenomenon of the HCV-induced autoimmunity.

    Science.gov (United States)

    Csepregi, A; Nemesánszky, E; Luettig, B; Obermayer-Straub, P; Manns, M P

    2001-03-01

    Chronic hepatitis C is frequently associated with laboratory markers-including LKM1 autoantibodies--of autoimmunity. A 62-yr-old woman with hepatitis C cirrhosis presented autoantibodies against liver and kidney microsomal proteins. By further evaluation of autoantibodies using ELISA and immunoblotting LKM1 and LKM3 autoantibodies could be revealed. The target antigen of LKM3 autoantibodies proved to be UGT-1.1 isoenzyme. In the absence of chronic hepatitis D infection or autoimmune hepatitis type 2, this is the first case that reports the occurrence of LKM3 autoantibodies in HCV-induced chronic liver disease.

  5. Proteins oxidation and autoantibodies' reactivity against hydrogen peroxide and malondialdehyde -oxidized thyroid antigens in patients' plasmas with Graves' disease and Hashimoto Thyroiditis.

    Science.gov (United States)

    Mseddi, Malek; Ben Mansour, Riadh; Gargouri, Bochra; Mnif, Fatma; El Ghawi, Samir; Hammami, Boutheina; Ghorbel, Abdelmonem; Abid, Mohamed; Lassoued, Saloua

    2017-06-25

    The aim of this study was to evaluate proteins oxidation in plasmas of two autoimmune thyroid diseases (AITD): Graves' disease (GD) and Hashimoto Thyroiditis (HT), and to determine whether oxidative modification of thyroid antigens (T.Ag) enhanced the reactivity of autoantibodies in plasmas of AITD patients compared with the reactivity towards native T.Ag. Carbonyl and thiol groups and MDA-protein adducts were assessed spectrophotometric methods in plasmas of 74 AITD patients and 65 healthy controls. The reactivities immunoglobulin (Ig)G autoantibodies towards malondialdéhyde (MDA)-modified T.Ag, hydrogen peroxide (H 2 O 2 )-modified T.Ag, native T.Ag and native derm were checked by enzyme-linked immunosorbent assay (ELISA). Evaluation of oxidized proteins exhibited high levels of MDA bound to proteins and carbonyl groups, as well as reduced thiol level in plasmas of AITD patients by comparison to healthy controls (p thyroid stimulating hormone level in HT patients in the other (r = 0.65, p < 0.001). The data suggest that high production of H 2 O 2 probably occurred during hormone synthesis could contribute to protein oxidation in AITD and to create neoepitopes responsible for autoantibody reactivity's to H 2 O 2 -oxidized T.Ag enhancement. These results provide support to the involvement of oxidative stress in AITD development and/or exacerbation. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Non-immune binding of human IgG to M-related proteins confers resistance to phagocytosis of group A streptococci in blood.

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    Harry S Courtney

    Full Text Available The non-immune binding of immunoglobulins by bacteria is thought to contribute to the pathogenesis of infections. M-related proteins (Mrp are group A streptococcal (GAS receptors for immunoglobulins, but it is not known if this binding has any impact on virulence. To further investigate the binding of immunoglobulins to Mrp, we engineered mutants of an M type 4 strain of GAS by inactivating the genes for mrp, emm, enn, sof, and sfbX and tested these mutants in IgG-binding assays. Inactivation of mrp dramatically decreased the binding of human IgG, whereas inactivation of emm, enn, sof, and sfbx had only minor effects, indicating that Mrp is a major IgG-binding protein. Binding of human immunoglobulins to a purified, recombinant form of Mrp indicated that it selectively binds to the Fc domain of human IgG, but not IgA or IgM and that it preferentially bound subclasses IgG₁>IgG₄>IgG₂>IgG₃. Recombinant proteins encompassing different regions of Mrp were engineered and used to map its IgG-binding domain to its A-repeat region and a recombinant protein with 3 A-repeats was a better inhibitor of IgG binding than one with a single A-repeat. A GAS mutant expressing Mrp with an in-frame deletion of DNA encoding the A-repeats had a dramatically reduced ability to bind human IgG and to grow in human blood. Mrp exhibited host specificity in binding IgG; human IgG was the best inhibitor of the binding of IgG followed by pig, horse, monkey, and rabbit IgG. IgG from goat, mouse, rat, cow, donkey, chicken, and guinea pig were poor inhibitors of binding. These findings indicate that Mrp preferentially binds human IgG and that this binding contributes to the ability of GAS to resist phagocytosis and may be a factor in the restriction of GAS infections to the human host.

  7. Autoantibodies in infectious mononucleosis have specificity for the glycine-alanine repeating region of the Epstein-Barr virus nuclear antigen

    Science.gov (United States)

    1987-01-01

    Viruses have been postulated to be involved in the induction of autoantibodies by: autoimmunization with tissue proteins released by virally induced tissue damage; immunization with virally encoded antigens bearing molecular similarities to normal tissue proteins; or nonspecific (polyclonal) B cell stimulation by the infection. Infectious mononucleosis (IM) is an experiment of nature that provides the opportunity for examining these possibilities. We show here that IgM antibodies produced in this disease react with at least nine normal tissue proteins, in addition to the virally encoded Epstein-Barr nuclear antigen (EBNA-1). The antibodies are generated to configurations in the glycine-alanine repeat region of EBNA-1 and are crossreactive with the normal tissue proteins through similar configurations, as demonstrated by the effectiveness of a synthetic glycine-alanine peptide in inhibiting the reactions. The antibodies are absent in preillness sera and gradually disappear over a period of months after illness, being replaced by IgG anti-EBNA-1 antibodies that do not crossreact with the normal tissue proteins but that are still inhibited by the glycine-alanine peptide. These findings are most easily explained by either a molecular mimicry model of IgM autoantibody production or by the polyclonal activation of a germline gene for a crossreactive antibody. It also indicates a selection of highly specific, non-crossreactive anti-EBNA-1 antibodies during IgM to IgG isotype switching. PMID:2435830

  8. IgG4-related Disease of the Genitourinary Tract

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    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

  9. Inhibition of complement activation by IgG4 antibodies

    NARCIS (Netherlands)

    van der Zee, J. S.; van Swieten, P.; Aalberse, R. C.

    1986-01-01

    Prolonged exposure to antigens may result in high IgG4 antibody titres as was shown in a previous paper (Aalberse et al., 1983b). In novice bee keepers, a shift in the IgG1/IgG4 ratio of the response against phospholipase-A (PLA; a major component of bee venom) occurred. This resulted in an

  10. Brief Communication: Maternal Plasma Autoantibodies Screening in Fetal Down Syndrome

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    Karol Charkiewicz

    2016-01-01

    Full Text Available Imbalance in the metabolites levels which can potentially be related to certain fetal chromosomal abnormalities can stimulate mother’s immune response to produce autoantibodies directed against proteins. The aim of the study was to determine the concentration of 9000 autoantibodies in maternal plasma to detect fetal Down syndrome. Method. We performed 190 amniocenteses and found 10 patients with confirmed fetal Down syndrome (15th–18th weeks of gestation. For the purpose of our control we chose 11 women without confirmed chromosomal aberration. To assess the expression of autoantibodies in the blood plasma, we used a protein microarray, which allows for simultaneous determination of 9000 proteins per sample. Results. We revealed 213 statistically significant autoantibodies, whose expression decreased or increased in the study group with fetal Down syndrome. The second step was to create a classifier of Down syndrome pregnancy, which includes 14 antibodies. The predictive value of the classifier (specificity and sensitivity is 100%, classification errors, 0%, cross-validation errors, 0%. Conclusion. Our findings suggest that the autoantibodies may play a role in the pathophysiology of Down syndrome pregnancy. Defining their potential as biochemical markers of Down syndrome pregnancy requires further investigation on larger group of patients.

  11. The plant lectin wheat germ agglutinin inhibits the binding of pemphigus foliaceus autoantibodies to desmoglein 1 in a majority of patients and prevents pathomechanisms of pemphigus foliaceus in vitro and in vivo.

    Science.gov (United States)

    Ortiz-Urda, Susana; Elbe-Bürger, Adelheid; Smolle, Josef; Marquart, Yvonne; Chudnovsky, Yakov; Ridky, Todd W; Bernstein, Pamela; Wolff, Klaus; Rappersberger, Klemens

    2003-12-01

    Pemphigus foliaceus (PF) is a life-threatening autoimmune blistering skin disease caused by pathogenic IgG autoantibodies against desmoglein 1 (dg1), a desmosomal cadherin-type adhesion glycoprotein. Using lectins and glycosidases, we have shown that dg1 displays an N-glycosylation pattern of the complex triantennary type. We have found that lectins and glycosidases interfere with N-bound sugar residues on the amino-terminal ectodomain of dg1 and completely abolish, in vitro, the antigenicity of dg1 in most of the patients' sera. Moreover, in an ex vivo model using punch biopsies from normal human skin, we demonstrate that preincubation of the epidermis in wheat germ agglutinin (WGA) prevents PF autoantibody binding, acantholysis, and subcorneal blistering. In addition, we show that topical treatment with WGA inhibits PF autoantibody binding to keratinocytes in both newborn BALB/c mice and in organotypic human epidermis grafted onto the back of SCID mice. The epidermis of these pretreated animals displays a regular morphology, whereas control animals develop the immunopathologic phenotype of PF. These findings suggest that WGA may interfere with autoantibody binding to dg1, preventing experimental PF without affecting the adhesive function of dg1. Our observations may provide a new approach to the therapy of PF.

  12. Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies

    International Nuclear Information System (INIS)

    Stagnaro-Green, A.; Roman, S.H.; Cobin, R.H.; El-Harazy, E.; Alvarez-Marfany, M.; Davies, T.F.

    1990-01-01

    The authors screened 552 women who presented to their obstetrician in the first trimester of pregnancy using highly sensitive enzyme-linked immunosorbent assays for the presence of thyroglobulin and thyroidperoxidase autoantibodies and found an incidence of positivity of 19.6%. The tendency to secrete detectable levels of thyroid autoantibodies was significantly correlated with an increased rate of miscarriage. Thyroid autoantibody-positive women miscarried at a rate of 17%, compared with 8.4% for the autoantibody-negative women. Individual levels of thyroglobulin and thyroidperoxidase autoantibodies were similarly related to this increased miscarriage rate, with no evidence of autoantibody specificity in the relationship. Furthermore, the increase in miscarriages could not be explained by differences in thyroid hormone levels, the presence of cardiolipin autoantibodies, maternal age, gestational age at the time of maternal entry into the study, or previous obstetric history. They conclude that thyroid autoantibodies are an independent marker of at-risk pregnancy

  13. FcGammaRIIa polymorphism and anti-malaria specific IgG and IgG subclass responses in populations differing in susceptibility to malaria in Burkina Faso

    DEFF Research Database (Denmark)

    Cherif, Mariama K; Sanou, Guillaume S; Maiga, Boubakar

    2012-01-01

    Fc¿RIIa is known to be polymorphic; and certain variants err associated with differt susceptibilities to malaria. Studies involving the Fulani ethnic group reported an ethnic difference in Fc¿RIIa-R131H genotype frequencies between the Fulani and other sympatric groups. No previous studies have a...

  14. Evidence of a common regulation of IgE and IgG-subclass antibodies in humans during immunotherapy

    DEFF Research Database (Denmark)

    Søndergaard, I; Poulsen, L K; Osterballe, O

    1992-01-01

    Based on a 3-year prospective study of 20 pollen-allergic patients, where a detailed analysis of the IgE, IgG1 and IgG4 immune response was performed, we propose that a common regulatory mechanism exists between the IgE and IgG1 synthesis and between IgE and IgG4 synthesis during immunotherapy. I...

  15. Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen.

    Science.gov (United States)

    Ponomarenko, Natalia A; Durova, Oxana M; Vorobiev, Ivan I; Belogurov, Alexey A; Kurkova, Inna N; Petrenko, Alexander G; Telegin, Georgy B; Suchkov, Sergey V; Kiselev, Sergey L; Lagarkova, Maria A; Govorun, Vadim M; Serebryakova, Marina V; Avalle, Bérangère; Tornatore, Pete; Karavanov, Alexander; Morse, Herbert C; Thomas, Daniel; Friboulet, Alain; Gabibov, Alexander G

    2006-01-10

    Autoantibody-mediated tissue destruction is among the main features of organ-specific autoimmunity. This report describes "an antibody enzyme" (abzyme) contribution to the site-specific degradation of a neural antigen. We detected proteolytic activity toward myelin basic protein (MBP) in the fraction of antibodies purified from the sera of humans with multiple sclerosis (MS) and mice with induced experimental allergic encephalomyelitis. Chromatography and zymography data demonstrated that the proteolytic activity of this preparation was exclusively associated with the antibodies. No activity was found in the IgG fraction of healthy donors. The human and murine abzymes efficiently cleaved MBP but not other protein substrates tested. The sites of MBP cleavage determined by mass spectrometry were localized within immunodominant regions of MBP. The abzymes could also cleave recombinant substrates containing encephalytogenic MBP(85-101) peptide. An established MS therapeutic Copaxone appeared to be a specific abzyme inhibitor. Thus, the discovered epitope-specific antibody-mediated degradation of MBP suggests a mechanistic explanation of the slow development of neurodegeneration associated with MS.

  16. Detection of Serum IgG4 Levels in Patients with IgG4-Related Disease and Other Disorders

    Science.gov (United States)

    Wang, Chenqiong; Wu, Xuefen; Miao, Ye; Xiong, Hui; Bai, Lin; Dong, Lingli

    2015-01-01

    Objective 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. Methods 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. Results 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. Conclusion 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. PMID:25885536

  17. IgG4-Related Disease of Bilateral Temporal Bones.

    Science.gov (United States)

    Li, Lilun; Ward, Bryan; Cocks, Margaret; Kheradmand, Amir; Francis, Howard W

    2017-03-01

    IgG4-related disease (IgG4-RD) is an idiopathic inflammatory condition that causes pseudotumor formation in single or multiple organs, including those of the head and neck. Temporal bone involvement is rare, with only 3 cases of unilateral temporal bone IgG4-RD described in the literature. We report the first known case of IgG4-RD of bilateral temporal bones and describe its clinical presentation, diagnosis, and treatment. The patient was a 52-year-old man with latent tuberculosis (TB) who presented with a 10-year history of bilateral profound hearing loss and vestibular dysfunction. Computed tomography and magnetic resonance imaging demonstrated bilateral labyrinthine destruction with invasion of the posterior fossa. Immunoglobulin level testing showed elevated total serum IgG levels with normal IgG4 levels. Bilateral mastoidectomies were performed, with biopsy samples demonstrating IgG4 staining with IgG4-positive plasma cells up to 40/HPF (high power field) on the right and 20/HPF on the left, consistent with bilateral IgG4-RD. IgG4-RD of bilateral temporal bones presents with chronic and progressive bilateral hearing loss and vestibular dysfunction. Clinical presentation and radiologic findings are nonspecific, and definitive diagnosis must be made with histopathology and immunostaining. Corticosteroids are therapeutic, but surgical resection may be necessary for temporal bone IgG4-RD to improve long-term remission.

  18. Detection of autoantibodies against reactive oxygen species modified glutamic acid decarboxylase-65 in type 1 diabetes associated complications

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    Mashal Subhash N

    2011-03-01

    Full Text Available Abstract Background Autoantibodies against glutamate decarboxylase-65 (GAD65Abs are thought to be a major immunological tool involved in pathogenic autoimmunity development in various diseases. GAD65Abs are a sensitive and specific marker for type 1 diabetes (T1D. These autoantibodies can also be found in 6-10% of patients classified with type 2 diabetes (T2D, as well as in 1-2% of the healthy population. The latter individuals are at low risk of developing T1D because the prevalence rate of GAD65Abs is only about 0.3%. It has, therefore, been suggested that the antibody binding to GAD65 in these three different GAD65Ab-positive phenotypes differ with respect to epitope specificity. The specificity of reactive oxygen species modified GAD65 (ROS-GAD65 is already well established in the T1D. However, its association in secondary complications of T1D has not yet been ascertained. Hence this study focuses on identification of autoantibodies against ROS-GAD65 (ROS-GAD65Abs and quantitative assays in T1D associated complications. Results From the cohort of samples, serum autoantibodies from T1D retinopathic and nephropathic patients showed high recognition of ROS-GAD65 as compared to native GAD65 (N-GAD65. Uncomplicated T1D subjects also exhibited reactivity towards ROS-GAD65. However, this was found to be less as compared to the binding recorded from complicated subjects. These results were further proven by competitive ELISA estimations. The apparent association constants (AAC indicate greater affinity of IgG from retinopathic T1D patients (1.90 × 10-6 M followed by nephropathic (1.81 × 10-6 M and uncomplicated (3.11 × 10-7 M T1D patients for ROS-GAD65 compared to N-GAD65. Conclusion Increased oxidative stress and blood glucose levels with extended duration of disease in complicated T1D could be responsible for the gradual formation and/or exposing cryptic epitopes on GAD65 that induce increased production of ROS-GAD65Abs. Hence regulation of ROS

  19. MS2 VLP-based delivery of microRNA-146a inhibits autoantibody production in lupus-prone mice

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    Pan Y

    2012-12-01

    Full Text Available Yang Pan,1,2 Tingting Jia,1,2 Yuan Zhang,1,2 Kuo Zhang,1 Rui Zhang,1 Jinming Li,1 Lunan Wang11National Center for Clinical Laboratories, Beijing Hospital of the Ministry of Health, Beijing, People’s Republic of China; 2Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaBackground: Systemic lupus erythematosus (SLE is a chronic autoimmune disease characterized by the presence of pathogenic autoantibodies. Recent studies suggest that microRNAs (miRNAs play an essential role in immunoregulation and may be involved in the pathogenesis of SLE. Therefore, it was of interest to investigate the potential therapeutic application of miRNAs in SLE, a concept that has not been thoroughly investigated thus far. Virus-like particles (VLPs are a type of recombinant nanoparticle enveloped by certain proteins derived from the outer coat of a virus. Herein, we describe a novel miRNA-delivery approach via bacteriophage MS2 VLPs and investigate the therapeutic effects of miR-146a, a well-studied and SLE-related miRNA, in BXSB lupus-prone mice.Methods: VLPs containing miR-146a, and the control VLPs, were prepared using an Escherichia coli expression system and then administered to lupus-prone mice over a 12-day period. We performed an enzyme-linked immunosorbent assay to evaluate the anti-dsDNA antibody, autoantibody to nuclear antigen (ANA, total IgG and total IgM levels in serum. The expression of miR-146a was analyzed by qRT-PCR. SLE-related cytokines as well as some toll-like receptor signaling pathway molecules were also measured.Results: Treatment with MS2-miR146a VLP showed profound effects on lupus-prone BXSB mice, including an increased level of mature miR-146a, which led to a significant reduction in the expression of autoantibodies and total IgG. Remarkably, these mice also exhibited reduced levels of proinflammatorycytokines, including IFN-Interferon-α (IFN-α, Interleukin-1β (Il-1

  20. Anti-LC1 autoantibodies in patients with chronic hepatitis C virus infection.

    Science.gov (United States)

    Béland, Kathie; Lapierre, Pascal; Marceau, Gabriel; Alvarez, Fernando

    2004-03-01

    Various autoantibodies have been reported in patients chronically infected by hepatitis C virus. 2% to 10% of theses patients have anti-liver-kidney microsome type 1 (anti-LKM1) autoantibodies. In type 2 autoimmune hepatitis, anti-LKM1 autoantibodies are frequently associated with anti-liver-cytosol type 1 (anti-LC1) autoantibodies. To determine the prevalence of anti-LC1 autoantibodies in a hepatitis C-positive population and characterize their reactivity. 146 patients suffering from liver diseases, of which 99 were chronically infected by hepatitis C virus, were tested by Western blotting and immunoprecipitation to detect and characterize anti-LC1 autoantibodies. 12% of this hepatitis C population had anti-LC1 autoantibodies. LC1 positivity by Western blotting was 30% of LC1+ sera. Epitopes were found throughout the protein but linear epitopes were situated in the 395-541 amino acid region of formiminotransferase cyclodeaminase. Three putative conformational epitopes were identified by phage display. Anti-LC1 autoantibodies are as prevalent as anti-LKM1 autoantibodies in patients infected with hepatitis C virus and their production is not dependent of anti-LKM1 autoantibodies formation. Autoantibody reactivity against the anti-LC1 antigen is different in hepatitis C than in type 2 autoimmune hepatitis. Anti-LC1 autoantibodies can now be regarded as a serological marker of autoimmunity in chronic hepatitis C infection.

  1. IgG4 Aortitis: A Case Report.

    Science.gov (United States)

    Marketkar, Shivali; LeGolvan, Mark

    2017-04-03

    IgG4 aortitis is one of the entities seen in the spectrum of IgG4-related disease (IgG4-RD). It is characterized by serologic (elevated serum IgG4) and histologic features including a lymphoplasmacytic infiltrate with increased numbers of IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. Some studies have described a correlation between infections and IgG4 aortitis. We describe a patient with an aneurysm of the infrarenal descending abdominal aorta with features of IgG4-RD, as well as culture evidence of Streptococcus sanguis. [Full article available at http://rimed.org/rimedicaljournal-2017-04.asp].

  2. IgG4-related disease in autoimmune lymphoproliferative syndrome.

    Science.gov (United States)

    van de Ven, Annick A J M; Seidl, Maximilian; Drendel, Vanessa; Schmitt-Graeff, Annette; Voll, Reinhard E; Rensing-Ehl, Anne; Speckmann, Carsten; Ehl, Stephan; Warnatz, Klaus; Kollert, Florian

    2017-07-01

    A patient with autoimmune lymphoproliferative disorder (ALPS) developed IgG4-related disease. In retrospect, he had high levels of serum IgG4 for several years prior to presenting with IgG4-related pancreatitis. These high IgG4 levels were masked by hypergammaglobulinemia, a common feature of ALPS. We next screened 18 ALPS patients; four of them displayed increased levels of IgG4. Hence, IgG4-related disease should be considered in ALPS patients, especially in those manifesting lymphocytic organ infiltration or excessive hypergammaglobulinaemia. Screening of IgG4-related disease patients for ALPS-associated mutations would provide further information on whether this disease could be a late-onset atypical presentation of ALPS. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Nonorgan-specific autoantibodies in HIV-infected patients in the HAART era.

    Science.gov (United States)

    Iordache, Laura; Bengoufa, Djaouida; Taulera, Olivier; Rami, Agathe; Lascoux-Combe, Caroline; Day, Nesrine; Parrinello, Maguy; Sellier, Pierre-Olivier; Molina, Jean-Michel; Mahr, Alfred

    2017-03-01

    Nonorgan-specific autoantibodies (AAbs) are used for diagnosing autoimmune diseases but can also be detected in other conditions. We carried out a cross-sectional study with the aim to screen HIV1-infected patients in the era of highly active antiretroviral therapy (HAART) for AAbs and to analyze the association of their presence with hypergammaglobulinemia and immunovirological status.Blood samples from HIV1-infected patients without major concomitant illnesses followed in 2 hospitals in Paris, France were tested for immunovirological status, serum immunoglobulin G (IgG) level, antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA), anti-extractable nuclear antigens (anti-ENAs), anticardiolipin (aCL), anti-β2glycoprotein1 (anti-β2GP1), and antineutrophil cytoplasmic antibodies (ANCAs). Clinically relevant AAbs were defined as ANAs with titers ≥1:160, anti-dsDNA or anti-ENA antibodies; aCL or anti-β2GP1 antibodies with a level ≥40 U/ml; and ANCAs reacting with proteinase 3 or myeloperoxidase.We included 92 patients (mean age 47 years, men 55%, sub-Saharan African background 55%, HAART 85%, mean CD4 lymphocyte count 611/mm, viral load < 40 copies/mL 74%). At least 1 AAb was detected in 45% of patients, mostly ANAs (33%) and ANCAs (13%); 12% had ≥1 clinically relevant AAb. Above-normal IgG levels were found in 71% of patients. We found an inverse association between the presence of ≥1 AAb and CD4 lymphocyte count (P = 0.03) and between above-normal IgG levels and duration of virological control (P = 0.02) and non-sub-Saharan African background (P = 0.001).In sum, in HIV1-infected patients without any major concomitant illness in the HAART era, the prevalence of AAbs remains high but AAb patterns leading to high suspicion of autoimmune diseases are rather uncommon. AAb presence is associated with reduced CD4 lymphocyte count but not hypergammaglobulinemia.

  4. The Immunome of Colon Cancer: Functional In Silico Analysis of Antigenic Proteins Deduced from IgG Microarray Profiling

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    Johana A. Luna Coronell

    2018-02-01

    Full Text Available Characterization of the colon cancer immunome and its autoantibody signature from differentially-reactive antigens (DIRAGs could provide insights into aberrant cellular mechanisms or enriched networks associated with diseases. The purpose of this study was to characterize the antibody profile of plasma samples from 32 colorectal cancer (CRC patients and 32 controls using proteins isolated from 15,417 human cDNA expression clones on microarrays. 671 unique DIRAGs were identified and 632 were more highly reactive in CRC samples. Bioinformatics analyses reveal that compared to control samples, the immunoproteomic IgG profiling of CRC samples is mainly associated with cell death, survival, and proliferation pathways, especially proteins involved in EIF2 and mTOR signaling. Ribosomal proteins (e.g., RPL7, RPL22, and RPL27A and CRC-related genes such as APC, AXIN1, E2F4, MSH2, PMS2, and TP53 were highly enriched. In addition, differential pathways were observed between the CRC and control samples. Furthermore, 103 DIRAGs were reported in the SEREX antigen database, demonstrating our ability to identify known and new reactive antigens. We also found an overlap of 7 antigens with 48 “CRC genes.” These data indicate that immunomics profiling on protein microarrays is able to reveal the complexity of immune responses in cancerous diseases and faithfully reflects the underlying pathology. Keywords: Autoantibody tumor biomarker, Cancer immunology, Colorectal cancer, Immunomics, Protein microarray

  5. Modulation of natural IgM autoantibodies to oxidative stress-related neo-epitopes on apoptotic cells in newborns of mothers with anti-Ro autoimmunity.

    Science.gov (United States)

    Grönwall, Caroline; Clancy, Robert M; Getu, Lelise; Lloyd, Katy A; Siegel, Don L; Reed, Joanne H; Buyon, Jill P; Silverman, Gregg J

    2016-09-01

    At birth, the human immune system already contains substantial levels of polymeric IgM, that include autoantibodies to neo-epitopes on apoptotic cells (ACs) that are proposed to play homeostatic and anti-inflammatory roles. Yet the biologic origins and developmental regulation of these naturally arising antibodies remain poorly understood. Herein, we report that levels of IgM-antibodies to malondialdehyde (MDA) protein adducts, a common type of in vivo generated oxidative stress-related neoepitope, directly correlate with the relative binding of neonatal-IgM to ACs. Levels of IgM to phosphorylcholine (PC), a natural antibody prevalent in adults, were relatively scant in cord blood, while there was significantly greater relative representation of IgM anti-MDA antibodies in newborns compared to adults. To investigate the potential interrelationships between neonatal IgM with pathogenic IgG-autoantibodies, we studied 103 newborns born to autoimmune mothers with IgG anti-Ro (i.e., 70 with neonatal lupus and 33 without neonatal lupus). In these subjects the mean levels of IgM anti-Ro60 were significantly higher than in the newborns from non-autoimmune mothers. In contrast, levels of IgM anti-MDA in IgG anti-Ro exposed neonates were significantly lower than in neonates from non-autoimmune mothers. The presence or absence of neonatal lupus did not appear to influence the total levels of IgM in the anti-Ro exposed newborns. Taken together, our studies provide evidence that the immune development of the natural IgM-repertoire may be affected, and become imprinted by, the transfer of maternal IgG into the fetus. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. [IgG4 immunohistochemistry in Riedle thyroiditis].

    Science.gov (United States)

    Wang, S; Luo, Y F; Cao, J L; Zhang, H; Shi, X H; Liang, Z Y; Feng, R E

    2017-03-08

    Objective: To observe the histopathological changes and immunohistochemical expression of IgG4 in Riedle thyroiditis (RT) and to study the relationship between RT and IgG4-related diseases (IgG4-RD). Methods: A total of 5 RT patients were collected from the Department of Pathology, Peking Union Medical College Hospital during April 2012 to August 2014. The clinical and immunohistochemical features were analyzed in the 5 patients. Histopathologic analysis was performed on hematoxylin and eosin-stained sections. Results: There were one male and four female patients, aged 52 to 78 years (median 59 years). Five cases were characterized by multiple nodules of thyroid, which increased year by year. All patients were found to have surrounding tissue compression symptoms and signs. Two female patients were found to have hypothyroidism. The serum concentration of IgG was elevated in 2 cases, and the serum concentration of IgG was not tested before operation in the remaining patients. By ultrasound, all presented as low echo or medium low echo. Strong echo occasionally appeared in hypoechoic nodules. Microscopically, fibrous tissue hyperplasia was infiltrated with varying numbers of lymphocytes and plasma cells. The occlusion of phlebitis was found in 4 cases and eosinophils were found in 3 cases. IgG4 counts and IgG4/IgG ratios in 5 cases were 20/HPF, 16%; 60/HPF, 82%; 22/HPF, 28%; 400/HPF, 266% and 33/HPF, 71%, respectively. Conclusions: With the similar pathological manifestations between RT and IgG4-RD, immunohistochemical staining shows that the number of IgG4 positive plasma cells and IgG4/IgG ratio of RT are increased in varying degrees. Some cases meet the diagnostic criteria of IgG4-RD, and speculate that some cases of RT belong to IgG4-RD.

  7. Immunoregulation by naturally occurring and disease-associated autoantibodies

    DEFF Research Database (Denmark)

    Nielsen, Claus H; Bendtzen, Klaus

    2012-01-01

    The role of naturally occurring autoantibodies (NAbs) in homeostasis and in disease manifestations is poorly understood. In the present chapter, we review how NAbs may interfere with the cytokine network and how NAbs, through formation of complement-activating immune complexes with soluble self......-antigens, may promote the uptake and presentation of self-molecules by antigen-presenting cells. Both naturally occurring and disease-associated autoantibodies against a variety of cytokines have been reported, including NAbs against interleukin (IL)-1α, IL-6, IL-8, IL-10, granulocyte-macrophage colony...

  8. Autoantibodies against GPIHBP1 as a Cause of Hypertriglyceridemia

    DEFF Research Database (Denmark)

    Beigneux, Anne P; Miyashita, Kazuya; Ploug, Michael

    2017-01-01

    lipoprotein lipase from reaching the capillary lumen. Patients with GPIHBP1 deficiency have low plasma levels of lipoprotein lipase, impaired intravascular hydrolysis of triglycerides, and severe hypertriglyceridemia (chylomicronemia). During the characterization of a monoclonal antibody-based immunoassay......-rich lipoproteins and causing severe hypertriglyceridemia. (Funded by the National Heart, Lung, and Blood Institute and the Leducq Foundation.)........ Three of the six patients had systemic lupus erythematosus. One of these patients who had GPIHBP1 autoantibodies delivered a baby with plasma containing maternal GPIHBP1 autoantibodies; the infant had severe but transient chylomicronemia. Two of the patients with chylomicronemia and GPIHBP1...

  9. The myositis autoantibody phenotypes of the juvenile idiopathic inflammatory myopathies.

    Science.gov (United States)

    Rider, Lisa G; Shah, Mona; Mamyrova, Gulnara; Huber, Adam M; Rice, Madeline Murguia; Targoff, Ira N; Miller, Frederick W

    2013-07-01

    The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. In follow-up to our study defining the major clinical subgroup phenotypes of JIIM, we compared demographics, clinical features, laboratory measures, and outcomes among myositis-specific autoantibody (MSA) subgroups, as well as with published data on adult idiopathic inflammatory myopathy patients enrolled in a separate natural history study. In the present study, of 430 patients enrolled in a nationwide registry study who had serum tested for myositis autoantibodies, 374 had either a single specific MSA (n = 253) or no identified MSA (n = 121) and were the subject of the present report. Following univariate analysis, we used random forest classification and exact logistic regression modeling to compare autoantibody subgroups. Anti-p155/140 autoantibodies were the most frequent subgroup, present in 32% of patients with juvenile dermatomyositis (JDM) or overlap myositis with JDM, followed by anti-MJ autoantibodies, which were seen in 20% of JIIM patients, primarily in JDM. Other MSAs, including anti-synthetase, anti-signal recognition particle (SRP), and anti-Mi-2, were present in only 10% of JIIM patients. Features that characterized the anti-p155/140 autoantibody subgroup included Gottron papules, malar rash, "shawl-sign" rash, photosensitivity, cuticular overgrowth, lowest creatine kinase (CK) levels, and a predominantly chronic illness course. The features that differed for patients with anti-MJ antibodies included muscle cramps, dysphonia, intermediate CK levels, a high frequency of hospitalization, and a monocyclic disease course. Patients with anti-synthetase antibodies had higher frequencies of interstitial lung disease, arthralgia, and "mechanic's hands," and had an older age at diagnosis. The anti-SRP group, which had exclusively juvenile polymyositis, was characterized by high

  10. Anti-M(3) muscarinic cholinergic autoantibodies from patients with primary Sjögren's syndrome trigger production of matrix metalloproteinase-3 (MMP-3) and prostaglandin E(2) (PGE(2)) from the submandibular glands.

    Science.gov (United States)

    Reina, Silvia; Sterin-Borda, Leonor; Passafaro, Daniela; Borda, Enri

    2011-05-01

    We demonstrated that serum immunoglobulin G (IgG) from patients with primary Sjögren's syndrome (pSS), interacting with the second extracellular loop of human glandular M(3) muscarinic acetylcholine receptors (M(3) mAChR), trigger the production of matrix metalloproteinase-3 (MMP-3) and prostaglandin E(2) (PGE(2)). Enzyme-linked immunosorbent assays (ELISAs) were performed in the presence of M(3) mAChR synthetic peptide as antigen to detect in serum the autoantibodies. Further, MMP-3 and PGE(2) production were determined in the presence of anti-M(3) mAChR autoantibodies. An association was observed between serum and anti-M(3) mAChR autoantibodies and serum levels of MMP-3 and PGE(2) in pSS patients. Thus, we established that serum anti-M(3) mAChR autoantibodies, MMP-3 and PGE(2) may be considered to be early markers of pSS associated with inflammation. Affinity-purified anti-M(3) mAChR peptide IgG from pSS patients, whilst stimulating salivary-gland M(3) mAChR, causes an increase in the level of MMP-3 and PGE(2) as a result of the activation of phospholipase A(2) (PLA(2)) and cyclooxygenase-2 (COX-2) (but not COX-1). These results provide a novel insight into the role that cholinoceptor antibodies play in the development of glandular inflammation. This is the first report showing that an antibody interacting with glandular mAChR can induce the production of pro-inflammatory mediators (MMP-3/PGE(2)). Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Uncoupling the widespread occurrence of anti-NMDAR1 autoantibodies from neuropsychiatric disease in a novel autoimmune model.

    Science.gov (United States)

    Pan, Hong; Oliveira, Bárbara; Saher, Gesine; Dere, Ekrem; Tapken, Daniel; Mitjans, Marina; Seidel, Jan; Wesolowski, Janina; Wakhloo, Debia; Klein-Schmidt, Christina; Ronnenberg, Anja; Schwabe, Kerstin; Trippe, Ralf; Mätz-Rensing, Kerstin; Berghoff, Stefan; Al-Krinawe, Yazeed; Martens, Henrik; Begemann, Martin; Stöcker, Winfried; Kaup, Franz-Josef; Mischke, Reinhard; Boretius, Susann; Nave, Klaus-Armin; Krauss, Joachim K; Hollmann, Michael; Lühder, Fred; Ehrenreich, Hannelore

    2018-02-09

    Autoantibodies of the IgG class against N-methyl-D-aspartate-receptor subunit-NR1 (NMDAR1-AB) were considered pathognomonic for anti-NMDAR encephalitis. This view has been challenged by the age-dependent seroprevalence (up to >20%) of functional NMDAR1-AB of all immunoglobulin classes found in >5000 individuals, healthy or affected by different diseases. These findings question a merely encephalitogenic role of NMDAR1-AB. Here, we show that NMDAR1-AB belong to the normal autoimmune repertoire of dogs, cats, rats, mice, baboons, and rhesus macaques, and are functional in the NMDAR1 internalization assay based on human IPSC-derived cortical neurons. The age dependence of seroprevalence is lost in nonhuman primates in captivity and in human migrants, raising the intriguing possibility that chronic life stress may be related to NMDAR1-AB formation, predominantly of the IgA class. Active immunization of ApoE -/- and ApoE +/+ mice against four peptides of the extracellular NMDAR1 domain or ovalbumin (control) leads to high circulating levels of specific AB. After 4 weeks, the endogenously formed NMDAR1-AB (IgG) induce psychosis-like symptoms upon MK-801 challenge in ApoE -/- mice, characterized by an open blood-brain barrier, but not in their ApoE +/+ littermates, which are indistinguishable from ovalbumin controls. Importantly, NMDAR1-AB do not induce any sign of inflammation in the brain. Immunohistochemical staining for microglial activation markers and T lymphocytes in the hippocampus yields comparable results in ApoE -/- and ApoE +/+ mice, irrespective of immunization against NMDAR1 or ovalbumin. These data suggest that NMDAR1-AB of the IgG class shape behavioral phenotypes upon access to the brain but do not cause brain inflammation on their own.

  12. Purification of polyclonal IgG specific for Camelid’s antibodies and their recombinant nanobodies

    Directory of Open Access Journals (Sweden)

    Haddad Muhammad

    2016-01-01

    Full Text Available Camelid’ s heavy-chain antibody (HCAb consists of only two heavy chains and lacks the two light chains together with the CH1 domain usually found in conventional immunoglobulins. A recombinant single antigen-binding entity, named VHH (or Nanobody® was generated by reengineering the variable domains from HCAb. This study focuses on the detection of camelid´s immunoglobulins as well as their derivative nanobodies using a universal anti-camel antibody produced in rabbit (rIgG. Starting from a crude rabbit serum, a standard stock of rIgG (1 mg/ml was prepared after purification by affinity chromatography using protein-A column. As expected, rIgG was able to detect camel antibodies in ELISA and immunoblotting, and its reactivity was equal against all different camel IgG subclasses, which were purified from serum by differential affinity chromatography on protein-G and -A. Interestingly, rIgG also recognized nanobodies since they were originally part of camel HCAbs, providing an alternative method to detect the corpus of these recombinant proteins rather than targeting their artificial tags. These data suggest that the anti-camel rIgG described here could be efficiently applied at different stages of nanobody technology, including the quantitation of the issued nanobodies and their detection when bound to target antigens.

  13. Association among Dietary Flavonoids, Flavonoid Subclasses and Ovarian Cancer Risk: A Meta-Analysis

    Science.gov (United States)

    You, Ruxu; Yang, Yu; Liao, Jing; Chen, Dongsheng; Yu, Lixiu

    2016-01-01

    Background Previous studies have indicated that intake of dietary flavonoids or flavonoid subclasses is associated with the ovarian cancer risk, but presented controversial results. Therefore, we conducted a meta-analysis to derive a more precise estimation of these associations. Methods We performed a search in PubMed, Google Scholar and ISI Web of Science from their inception to April 25, 2015 to select studies on the association among dietary flavonoids, flavonoid subclasses and ovarian cancer risk. The information was extracted by two independent authors. We assessed the heterogeneity, sensitivity, publication bias and quality of the articles. A random-effects model was used to calculate the pooled risk estimates. Results Five cohort studies and seven case-control studies were included in the final meta-analysis. We observed that intake of dietary flavonoids can decrease ovarian cancer risk, which was demonstrated by pooled RR (RR = 0.82, 95% CI = 0.68–0.98). In a subgroup analysis by flavonoid subtypes, the ovarian cancer risk was also decreased for isoflavones (RR = 0.67, 95% CI = 0.50–0.92) and flavonols (RR = 0.68, 95% CI = 0.58–0.80). While there was no compelling evidence that consumption of flavones (RR = 0.86, 95% CI = 0.71–1.03) could decrease ovarian cancer risk, which revealed part sources of heterogeneity. The sensitivity analysis indicated stable results, and no publication bias was observed based on the results of Funnel plot analysis and Egger’s test (p = 0.26). Conclusions This meta-analysis suggested that consumption of dietary flavonoids and subtypes (isoflavones, flavonols) has a protective effect against ovarian cancer with a reduced risk of ovarian cancer except for flavones consumption. Nevertheless, further investigations on a larger population covering more flavonoid subclasses are warranted. PMID:26960146

  14. Effect of pistachio consumption on plasma lipoprotein subclasses in pre-diabetic subjects.

    Science.gov (United States)

    Hernández-Alonso, P; Salas-Salvadó, J; Baldrich-Mora, M; Mallol, R; Correig, X; Bulló, M

    2015-04-01

    Nuts have been demonstrated to improve several cardiovascular risk factors and the lipid profile in diabetic and pre-diabetic subjects. However, analysis of conventional serum lipid profiles does not completely explain the atherogenic risk associated with pre-diabetes. We therefore investigated whether chronic consumption of pistachio modifies the lipoprotein subclasses to a healthier profile in pre-diabetic subjects. Randomized cross-over clinical trial in 54 subjects with pre-diabetes. Subjects consumed a pistachio-supplemented diet (PD, 50% carbohydrates, 33% fat, including 57 g/d of pistachios daily) and a control diet (CD, 55% carbohydrates, 30% fat) for 4 months each, separated by a 2-week wash-out. Diets were isocaloric and matched for protein, fiber and saturated fatty acids. Nuclear magnetic resonance (NMR) was performed to determine changes in plasma lipoprotein subclasses. Small low-density lipoprotein particles (sLDL-P) significantly decreased after pistachio consumption compared to the nut-free diet (P = 0.023). The non-high-density lipoprotein particles (non-HDL-P i.e. VLDL-P plus LDL-P) significantly decreased under the PD compared to CD (P = 0.041). The percentage of sHDL-P increased by 2.23% after the PD compared with a reduction of 0.08% after the CD (P = 0.014). Consequently, the overall size of HDL-P significantly decreased in the PD (P = 0.007). Chronic pistachio consumption could modify the lipoprotein particle size and subclass concentrations independently of changes in total plasma lipid profile, which may help to explain the decreased risk of cardiovascular disease and mortality associated with those individuals who frequently consumed nuts. This study is registered at www.clinicaltrials.gov as NCT01441921. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. 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.

  16. A solid dietary fat containing fish oil redistributes lipoprotein subclasses without increasing oxidative stress in men

    DEFF Research Database (Denmark)

    Tholstrup, T.; Hellgren, Lars; Petersen, M.

    2004-01-01

    , a solid dietary fat containing (n-3) PUFA decreased plasma TAG, VLDL, and IDL cholesterol, and redistributed lipoprotein subclasses in LDL and HDL, with a higher concentration of the larger and less atherogenic subfractions. These changes took place without an increase in oxidative stress as measured...... of F than O fat (P oxidation measured as the ratio of plasma isoprostanes F-2 to arachidonic acid and urinary isoprostanes, whereas the vitamin E activity/plasma total lipids ratio was higher after intake of F than O (P = 0.008). In conclusion...

  17. Effects of dietary saturated fat on LDL subclasses and apolipoprotein CIII in men

    OpenAIRE

    Faghihnia, Nastaran; Mangravite, Lara M.; Chiu, Sally; Bergeron, Nathalie; Krauss, Ronald M.

    2012-01-01

    Background/Objectives Small dense LDL particles and apolipoprotein (apo) CIII are risk factors for cardiovascular disease (CVD) that can be modulated by diet, but there is little information regarding the effects of dietary saturated fat on their plasma levels. We tested the effects of high vs. low saturated fat intake in the context of a high beef protein diet on levels and composition of LDL subclasses and on apoCIII levels in plasma and LDL. Subjects/Methods Following consumption of a base...

  18. Quantitation of autoantibodies in systemic autoimmune diseases : clinically useful?

    NARCIS (Netherlands)

    Kallenberg, C. G. M.; Stegeman, C. A.; Bootsma, H.; Biji, M.; Limburg, P. C.

    2006-01-01

    Serial assessment of levels of autoantibodies has been proposed as being clinically useful in certain systemic autoimmune diseases. In particular, attention has been given to anti-dsDNA antibodies in systemic lupus erythematosus (SLE) and ANCA in the ANCA-associated vasculitides (AAV). Much

  19. Clinical utility of autoantibodies and biologic markers in rheumatoid ...

    African Journals Online (AJOL)

    Objective: To review the current and emerging auto-antibodies and biologic markers in rheumatoid arthritis. Data source: Published original research work and reviews were searched in English related to pathophysiology, diagnosis and auto antibodies in rheumatoid arthritis. Study design: Only articles that emphasis on ...

  20. Autoantibody Profiling in Lupus Patients using Synthetic Nucleic Acids

    DEFF Research Database (Denmark)

    Klecka, Martin; Thybo, Christina; Macaubas, Claudia

    2018-01-01

    Autoantibodies to nuclear components of cells (antinuclear antibodies, ANA), including DNA (a-DNA), are widely used in the diagnosis and subtyping of certain autoimmune diseases, including systemic lupus erythematosus (SLE). Despite clinical use over decades, precise, reproducible measurement of a...

  1. Measurement of antiacetylcholine receptor auto-antibodies in ...

    African Journals Online (AJOL)

    Two different acetylcholine receptor (AChR) preparations derived from amputated human muscle (AChRAMP) and from the human rhabdomyosarcoma cell line TE671 (AChRTE67,) were compared in radio-immunoprecipitation assays for the detection of AChR auto-antibodies in serum specimens from 20 patients with ...

  2. Antinuclear human autoantibodies as markers in Nicotiana tabacum pollen tubes

    Directory of Open Access Journals (Sweden)

    C. Poggialini

    2014-01-01

    Full Text Available In the present paper we report on the use of antinuclear human autoantibodies as specific markers in Nicotiana tabacum pollen tubes. The antibodies have been tested by fluorescence techniques using a confocal laser scanning microscope. All the antibodies showed specifc labelling pattern and the results, although preliminary in nature, could open new perspectives of research.

  3. IgG4 plasma cell myeloma: new insights into the pathogenesis of IgG4-related disease.

    Science.gov (United States)

    Geyer, Julia T; Niesvizky, Ruben; Jayabalan, David S; Mathew, Susan; Subramaniyam, Shivakumar; Geyer, Alexander I; Orazi, Attilio; Ely, Scott A

    2014-03-01

    IgG4-related disease is a newly described systemic fibroinflammatory process, characterized by increase in IgG4-positive plasma cells. Its pathogenesis, including the role of IgG4, remains poorly understood. Plasma cell myeloma is typically associated with a large monoclonal serum spike, which is frequently of IgG isotype. We sought to identify and characterize a subset of IgG4-secreting myeloma, as it may provide a biological model of disease with high serum levels of IgG4. Six out of 158 bone marrow biopsies (4%) from patients with IgG myeloma expressed IgG4. Four patients were men and two were women, with a mean age of 64 (range 53-87) years. Imaging showed fullness of pancreatic head (1), small non-metabolic lymphadenopathy (1), and bone lytic lesions (6). Two patients developed necrotizing fasciitis. All had elevated serum M-protein (mean 2.4, range 0.5-4.2 g/dl), and none had definite signs or symptoms of IgG4-related disease. Four myelomas had plasmablastic morphology. Four had kappa and two had lambda light chain expression. Three cases expressed CD56. Two patients had a complex karyotype. In conclusion, the frequency of IgG4 myeloma correlates with the normal distribution of IgG4 isoform. The patients with IgG4 myeloma appear to have a high rate of plasmablastic morphology and could be predisposed to necrotizing fasciitis. Despite high serum levels of IgG4, none had evidence of IgG4-related disease. These findings suggest that the increased number of IgG4-positive plasma cells is not the primary etiologic agent in IgG4-related disease. Elevated serum levels of IgG4 is not sufficient to produce the typical disease presentation and should not be considered diagnostic of IgG4-related disease.

  4. Falsely low immunoglobulin (Ig)G4 in routine analysis: how not to miss IgG4 disease.

    Science.gov (United States)

    Egner, W; Swallow, K; Lock, R J; Patel, D

    2016-10-01

    Immunoglobulin (Ig)G4 disease can have apparently 'normal' levels of IgG4 due to antigen excess conditions. IgG4 measurement therefore appears falsely low. UK National External Quality Assurance Scheme (UK NEQAS) data and other reports have suggested that this problem occurred despite pre-existing antigen excess detection steps. To determine the clinical relevance of the problem, we examined the prevalence and characteristics of prozoning in our laboratory and patient cohorts. We establish that the prevalence of raised IgG4 in routine IgG4 analysis is low (IgG4 samples in our patients. This may explain the previous reports of low sensitivity of raised IgG4 for IgG4RD, and predictive values should be re-evaluated in this disease using modified prozone-resistant protocols. All laboratories providing IgG4 measurements should verify that their assays are fit for the clinical quality requirement of detection raised IgG4 levels and must verify the upper limit of their reference ranges and freedom from prozoning. © 2016 British Society for Immunology.

  5. Monovalent IgG4 molecules

    Science.gov (United States)

    Wilkinson, Ian C.; Fowler, Susan B.; Machiesky, LeeAnn; Miller, Kenneth; Hayes, David B.; Adib, Morshed; Her, Cheng; Borrok, M. Jack; Tsui, Ping; Burrell, Matthew; Corkill, Dominic J.; Witt, Susanne; Lowe, David C.; Webster, Carl I.

    2013-01-01

    Antibodies have become the fastest growing class of biological therapeutics, in part due to their exquisite specificity and ability to modulate protein-protein interactions with a high biological potency. The relatively large size and bivalency of antibodies, however, limits their use as therapeutics in certain circumstances. Antibody fragments, such as single-chain variable fragments and antigen binding-fragments, have emerged as viable alternatives, but without further modifications these monovalent formats have reduced terminal serum half-lives because of their small size and lack of an Fc domain, which is required for FcRn-mediated recycling. Using rational engineering of the IgG4 Fc domain to disrupt key interactions at the CH3-CH3 interface, we identified a number of point mutations that abolish Fc dimerization and created half-antibodies, a novel monovalent antibody format that retains a monomeric Fc domain. Introduction of these mutations into an IgG1 framework also led to the creation of half-antibodies. These half-antibodies were shown to be soluble, thermodynamically stable and monomeric, characteristics that are favorable for use as therapeutic proteins. Despite significantly reduced FcRn binding in vitro, which suggests that avidity gains in a dimeric Fc are critical to optimal FcRn binding, this format demonstrated an increased terminal serum half-life compared with that expected for most alternative antibody fragments. PMID:23567207

  6. Comparison of clinical and laboratory characteristics in children with type 1 diabetes according to pancreatic autoantibodies

    Directory of Open Access Journals (Sweden)

    Ji Hae Choi

    2010-03-01

    Full Text Available Purpose:The purpose of this study was to determine whether there is any difference in the clinical and laboratory characteristics of patients with autoantibody-positive and patients with autoantibody-negative type 1 diabetes at initial presentation. Methods:We analyzed 96 patients under 18 years of age with newly diagnosed type 1 diabetes. One or both of the pancreatic autoantibodies-glutamic acid decarboxylase autoantibodies (GADA and insulin autoantibody (IAA-were measured in all patients, and we reviewed clinical and laboratory characteristics according to the presence of these autoantibodies. Results:GADA was examined in 48 of 87 patients, and 55.2% of patients were positive. IAA was checked in 88 patients, and 39.8% were positive. Both GADA and IAA were measured in 83 patients, and 22.8% had both antibodies. The patients who had one or both autoantibodies (autoantibody-positive group were younger than those not having any autoantibody (autoantibody-negative group. The autoantibody-positive group had lower BMI, corrected sodium level, and serum effective osmolarity, compared to the autoantibody-negative group (P&lt;0.05. Similar differences were found between the GADA-positive and GADA-negative groups. However, there were no significant differences between the IAA- positive and IAA-negative groups. Conclusion:The prevalence of pancreatic autoantibodies was significantly higher in the under-6 years age group than in the other age groups. These findings suggest that measurement of autoantibodies at the initial diagnosis of diabetes is very useful for detecting immune-mediated type 1 diabetes and providing intensive insulin therapy, especially in younger children.

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

    Directory of Open Access Journals (Sweden)

    Robert Schwenk

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

  8. Rheumatic Disease Autoantibodies in Patients with Autoimmune Thyroid Diseases.

    Science.gov (United States)

    Nisihara, Renato; Pigosso, Yasmine; Prado, Nathalia; Utiyama, Shirley R R; Carvalho, Gisah; Skare, Thelma

    2018-06-04

    Patients with autoimmune thyroid diseases (ATD) such as Graves' disease (GD) and Hashimoto thyroiditis (HT) may have non-organ specific autoantibodies such as ANA (antinuclear antibodies) and RF (rheumatoid factor). To study the prevalence of rheumatic autoantibodies in a group of ATD patients without known rheumatic diseases and to evaluate its association with the patients' epidemiological and treatment profile. To follow positive non-organ specific autoantibody-positive ATD individuals to investigate whether they will develop a rheumatic disorder. A sample of 154 ATD patients (70 HT and 84 GD; mean age 45.3 ± 14.2) had determination of ANA by immunofluorescence, using hep-2 cells as substrate, extractable nuclear antigen (ENA) profile by ELISA kits and RF by latex agglutination. Epidemiological and treatment profile were obtained through chart review. These patients were followed for the mean period of five years, between 2010 to 2015. Positive ANA was found in 17.5% (27/154) of the patients: anti-Ro/SS-A in 4/154 (2.5%); anti-RNP in 4/154 (2.5%) and anti-La/SS-B in 3/154 (1.9%). None had anti-Sm antibodies. RF was detected in 12/154 (7.7%) of ATD patients and was more common in older individuals (p = 0.007). There was a positive association between the presence of RF and ANA (p = 0.03; OR = 3.89; 95% CI = 1.1-13.3). None of the patients with positive autoantibodies developed clinical rheumatic diseases during the period of observation. We found rheumatic autoantibodies in 17.5% of ATD patients without rheumatic diseases. None of them were associated with the appearance of clinical rheumatic disorder during the period of five years. ©2018The Author(s). Published by S. Karger AG, Basel.

  9. Diagnostic Utility of Auto-Antibodies in Inflammatory Muscle Diseases.

    Science.gov (United States)

    Allenbach, Y; Benveniste, O

    2015-01-01

    To date, there are four main groups of idiopathic inflammatory myopathies (IIM): polymyositis (PM), dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM) and sporadic inclusion body myositis; based on clinical presentation and muscle pathology. Nevertheless, important phenotypical differences (either muscular and/or extra-muscular manifestations) within a group persist. In recent years, the titration of different myositis-specific (or associated) auto-antibodies as a diagnostic tool has increased. This is an important step forward since it may facilitate, at a viable cost, the differential diagnosis between IIM and other myopathies. We have now routine access to assays for the detection of different antibodies. For example, IMNM are related to the presence of anti-SRP or anti-HMGCR. PM is associated with anti-synthetase antibodies (anti-Jo-1, PL-7, PL-12, OJ, and EJ) and DM with anti-Mi-2, anti-SAE, anti-TIF-1-γ and anti-NXP2 (both associated with cancer) or anti-MDA5 antibodies (associated with interstitial lung disease). Today, over 30 myositis specific and associated antibodies have been characterised, and all groups of myositis may present one of those auto-antibodies. Most of them allow identification of homogenous patient groups, more precisely than the classical international classifications of myositis. This implies that classification criteria could be modified accordingly, since these auto-antibodies delineate groups of patients suffering from myositis with consistent clinical phenotype (muscular and extra-muscular manifestations), common prognostic (cancer association, presence of interstitial lung disease, mortality and risk of relapse) and treatment responses. Nevertheless, since numerous auto-antibodies have been recently characterised, the exact prevalence of myositis specific antibodies remains to be documented, and research of new auto-antibodies in the remaining seronegative group is still needed.

  10. Overview of IgG4 - Related Disease.

    Science.gov (United States)

    Opriţă, R; Opriţă, B; Berceanu, D; Diaconescu, I B

    2017-01-01

    Rationale (hypothesis): IgG4-related disease (IgG4-RD) is a pathological entity recently recognized by the medical world that can affect any organ or system. However, there is insufficient data about this disease in medical literature. Aim (objective): A more extensive clarification of the IgG4 molecule, the diversified aspects of IgG4-related disease, and the response of this disease to treatment, will provide a crucial understanding of the immune system and other diseases now known to be associated with IgG4. The MEDLINE online medical database was used, and, after a comprehensive review of medical articles regarding IgG4-RD, published after 2003, using the search words "IgG4- related disease" and "IgG4 molecule", we have described the clinical, pathological and therapeutic features of IgG4-RD, as well as the presence of the IgG4 molecule in the evolution, diagnosis and management of this syndrome. We characterized the potential disease mechanisms and discussed early observations related to treatment. Given the response to immunosuppressive therapy, it is hypothesized that IgG4-related disease is most likely an autoimmune disease. Therefore, IgG4-related disease is a fibro-inflammatory condition that can affect any organ and can lead to the formation of pseudotumoral lesions requiring differential diagnosis with various malignancies. Positive diagnostic criteria are histopathological and require at least two features out of the following three: dense limphoplasmocitary infiltrate, storiform fibrosis, obliterative phlebitis.

  11. Flavonoids, Flavonoid Subclasses, and Esophageal Cancer Risk: A Meta-Analysis of Epidemiologic Studies.

    Science.gov (United States)

    Cui, Lingling; Liu, Xinxin; Tian, Yalan; Xie, Chen; Li, Qianwen; Cui, Han; Sun, Changqing

    2016-06-08

    Flavonoids have been suggested to play a chemopreventive role in carcinogenesis. However, the epidemiologic studies assessing dietary intake of flavonoids and esophageal cancer risk have yielded inconsistent results. This study was designed to examine the association between flavonoids, each flavonoid subclass, and the risk of esophageal cancer with a meta-analysis approach. We searched for all relevant studies with a prospective cohort or case-control study design published from January 1990 to April 2016, using PUBMED, EMBASE, and Web of Science. Pooled odds ratios (ORs) were calculated using fixed or random-effect models. In total, seven articles including 2629 cases and 481,193 non-cases were selected for the meta-analysis. Comparing the highest-intake patients with the lowest-intake patients for total flavonoids and for each flavonoid subclass, we found that anthocyanidins (OR = 0.60, 95% CI: 0.49-0.74), flavanones (OR = 0.65, 95% CI: 0.49-0.86), and flavones (OR = 0.78, 95% CI 0.64-0.95) were inversely associated with the risk of esophageal cancer. However, total flavonoids showed marginal association with esophageal cancer risk (OR = 0.78, 95% CI: 0.59-1.04). In conclusion, our study suggested that dietary intake of total flavonoids, anthocyanidins, flavanones, and flavones might reduce the risk of esophageal cancer.

  12. Differences in immunoglobulin subclasses between dye exclusion and 51Cr release complement-dependent lymphocytotoxicity assays

    International Nuclear Information System (INIS)

    McConnachie, P.R.; Denegri, J.F.; Lower, F.E.; Torry, D.S.; McIntyre, J.A.

    1986-01-01

    Paradoxical differences previously noted between lymphocytotoxicity detected by dye exclusion at room temperature (CDCE) or by 51 Cr release (CDC 51 Cr) at 37 0 C in maternal antipaternal complement-dependent lymphocytotoxicity have suggested that CDCE and CDC 51 Cr at 37 0 C, but not at 20 degrees C, may detect different immunological antibody-antigen interactions. Reactions in the two test systems against the same target cells were compared in sera from known immune dialysis patients, secondary aborting women, and refractory platelet recipients before and after heat treatment of sera, absorption with solid-phase heparin, anti-light-chain augmentation, and the addition of murine monoclonal anti-IgG subclass antibodies. The results demonstrate significant differences between the two tests using the same target and sera. Further, the results imply the presence of an inhibitor and an inhibitor of inhibitor in sera. The involvement of different immunoglobulin subclasses was shown in the two tests. These data demonstrate the necessity for further study of the nature of the differences in the mechanisms of these clinically important antibody-detecting systems

  13. Low density lipoprotein subclasses and response to a low-fat diet in healthy men

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, R.M.; Dreon, D.M. [Lawrence Berkeley Lab., CA (United States). Life Sciences Div.

    1994-11-01

    Lipid and lipoprotein response to reduced dietary fat intake was investigated in relation to differences in distribution of LDL subclasses among 105 healthy men consuming high-fat (46%) and low-fat (24%) diets in random order for six weeks each. On high-fat, 87 subjects had predominantly large, buoyant LDL as measured by gradient gel electrophoresis and confirmed by analytic ultracentrifugation (pattern A), while the remainder had primarily smaller, denser LDL (pattern B). On low-fat, 36 men changed from pattern A to B. Compared with the 51 men in the stable A group, men in the stable B group (n = 18) had a three-fold greater reduction in LDL cholesterol and significantly greater reductions in plasma apoB and mass of intermediate (LDL II) and small (LDL III) LDL subtractions measured by analytic ultracentrifugation. In both stable A and change groups, reductions in LDL-cholesterol were not accompanied by reduced plasma apoB, consistent with the observation of a shift in LDL particle mass from larger, lipid-enriched (LDL I and II) to smaller, lipid-depleted (LDL III and IV) subfractions, without significant change in particle number. Genetic and environmental factors influencing LDL subclass distributions thus may also contribute substantially to interindividual variation in response to a low-fat diet.

  14. IgG4-Associated Cholangitis Can Mimic Hilar Cholangiocarcinoma.

    Science.gov (United States)

    Zaydfudim, Victor M; Wang, Andrew Y; de Lange, Eduard E; Zhao, Zimin; Moskaluk, Christopher A; Bauer, Todd W; Adams, Reid B

    2015-07-01

    IgG4-associated cholangitis can mimic hilar cholangiocarcinoma. Previously reported patients with IgG4-associated cholangitis mimicking cholangiocarcinoma had elevated serum IgG4 levels and long-segment biliary strictures. However, in the absence of other diagnostic criteria for malignancy, IgG4-associated cholangitis should remain a consideration among patients with normal serum IgG4 and a hilar mass suspicious for cholangiocarcinoma. The presence of a hilar mass and a malignant-appearing biliary stricture in two patients with normal serum IgG4 prompted further evaluation and subsequent concomitant liver and bile duct resection and reconstruction. The diagnosis of IgG4-associated cholangitis was established during the pathologic evaluation of the resected specimens. IgG4-associated cholangitis is a known imitator of hilar cholangiocarcinoma and should be considered in the differential diagnosis even among serologically IgG4-negative patients with a hilar mass prior to operative resection.

  15. Intrathoracic Manifestations of IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Sian Yik Lim

    2016-10-01

    Full Text Available Intrathoracic involvement with IgG4-related disease (IgG4-RD is frequently overlooked in IgG4-related disease patients. In this article we review the intrathoracic findings of IgG4-RD which are variable and protean. IgG4-related disease has been reported to affect the lung parenchyma, pleura, mediastinal/hilar lymph nodes, vasculature, and pericardium within the thorax. Mediastinal and hilar lymphadenopathy is the most common intrathoracic manifestation of IgG4-RD. Four main patterns of pulmonary disease have been described, including the solid nodular type, the bronchovascular type, the alveolar interstitial type, and the round shaped ground glass type. When feasible, a biopsy should be obtained to confirm the diagnosis. Most lesions show characteristic pathologic findings of IgG4-RD: dense lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. While this helps establish the diagnosis, the interpretation of pathology findings in the clinical context is key in making an accurate diagnosis. Mimickers of IgG4-RD should be ruled out, before making a diagnosis. The intrathoracic findings of IgG4-RD can be treated effectively with prednisone, but may require additional immunosuppressive therapies, including rituximab.

  16. Diagnosis of IgG4-related sclerosing cholangitis

    Science.gov (United States)

    Nakazawa, Takahiro; Naitoh, Itaru; Hayashi, Kazuki; Miyabe, Katsuyuki; Simizu, Shuya; Joh, Takashi

    2013-01-01

    IgG4-related sclerosing cholangitis (IgG4-SC) is often associated with autoimmune pancreatitis. However, the diffuse cholangiographic abnormalities observed in IgG4-SC may resemble those observed in primary sclerosing cholangitis (PSC), and the presence of segmental stenosis suggests cholangiocarcinoma (CC). IgG4-SC responds well to steroid therapy, whereas PSC is only effectively treated with liver transplantation and CC requires surgical intervention. Since IgG4-SC was first described, it has become a third distinct clinical entity of sclerosing cholangitis. The aim of this review was to introduce the diagnostic methods for IgG4-SC. IgG4-SC should be carefully diagnosed based on a combination of characteristic clinical, serological, morphological, and histopathological features after cholangiographic classification and targeting of a disease for differential diagnosis. When intrapancreatic stenosis is detected, pancreatic cancer or CC should be ruled out. If multiple intrahepatic stenoses are evident, PSC should be distinguished on the basis of cholangiographic findings and liver biopsy with IgG4 immunostaining. Associated inflammatory bowel disease is suggestive of PSC. If stenosis is demonstrated in the hepatic hilar region, CC should be discriminated by ultrasonography, intraductal ultrasonography, bile duct biopsy, and a higher cutoff serum IgG4 level of 182 mg/dL. PMID:24282356

  17. The Use of Electrochemiluminescence Assays to Predict Autoantibody and Glycemic Progression Toward Type 1 Diabetes in Individuals with Single Autoantibodies.

    Science.gov (United States)

    Sosenko, Jay M; Yu, Liping; Skyler, Jay S; Krischer, Jeffrey P; Gottlieb, Peter A; Boulware, David; Miao, Dongmei; Palmer, Jerry P; Steck, Andrea K

    2017-03-01

    Electrochemiluminescence (ECL) assays have shown promise for enhancing the prediction of type 1 diabetes (T1D) with autoantibodies. We thus studied relatives of T1D patients to determine whether ECL assays can be used to refine risk assessments for T1D among individuals either positive for single GADA or single mIAA autoantibodies. TrialNet Pathway to Prevention (PTP) study participants with either GADA or mIAA single autoantibodies were tested for ECL positivity during their participation in the TrialNet PTP study. Those ECL positive (ECL + ) were compared with those ECL negative (ECL - ) for conversion to multiple autoantibodies, 6-month glycemic progression (PS6M), and the progression to T1D. The progression to multiple autoantibodies was significantly higher for those GADA/ECL + (n = 107) than those GADA/ECL - (n = 78) (P = 0.001) and for those mIAA/ECL + (n = 24) than those mIAA/ECL - (n = 63) (P < 0.001). The hazard ratios with 95% confidence intervals were 3.42 (1.58-7.39; P < 0.01) for GADA and 8.15 (3.02-22.00; P < 0.001) for mIAA. GADA/ECL + and mIAA/ECL + participants had significantly higher PS6M values than their ECL - counterparts (P = 0.001 for GADA and P = 0.009 for mIAA). Of those GADA/ECL + , 14% progressed to T1D; of those mIAA/ECL + , 17% progressed to T1D. Only 1 individual (positive for GADA) of the 141 who was ECL - progressed to T1D (median follow-up: 5 years). ECL measurements appear to have utility for natural history studies and prevention trials of individuals with single autoantibodies. Those ECL + are at appreciable risk for developing multiple autoantibodies and for glycemic progression toward T1D, whereas those ECL - are at very low risk.

  18. Detection of IgG1 and IgG4 subtypes reactive against potato apyrase in schistosomiasis patients

    Directory of Open Access Journals (Sweden)

    Priscila de Faria-Pinto

    2010-07-01

    Full Text Available In this paper, we showed for the first time that the conserved domains within Schistosoma mansoni ATP diphosphohydrolase isoforms, shared with potato apyrase, possess epitopes for the IgG1 and IgG4 subtypes, as 24 (80% of the 30 schistosomiasis patients were seropositive for this vegetable protein. The analyses for each patient cured (n = 14 after treatment (AT with praziquantel revealed variable IgG1 and IgG4 reactivity against potato apyrase. Different antigenic epitopes shared between the vegetable and parasite proteins could be involved in susceptibility or resistance to S. mansoni AT with praziquantel and these possibilities should be explored.

  19. Use of Dried Capillary Blood Sampling for Islet Autoantibody Screening in Relatives: A Feasibility Study.

    Science.gov (United States)

    Bingley, Polly J; Rafkin, Lisa E; Matheson, Della; Steck, Andrea K; Yu, Liping; Henderson, Courtney; Beam, Craig A; Boulware, David C

    2015-12-01

    Islet autoantibody testing provides the basis for assessment of risk of progression to type 1 diabetes. We set out to determine the feasibility and acceptability of dried capillary blood spot-based screening to identify islet autoantibody-positive relatives potentially eligible for inclusion in prevention trials. Dried blood spot (DBS) and venous samples were collected from 229 relatives participating in the TrialNet Pathway to Prevention Study. Both samples were tested for glutamic acid decarboxylase, islet antigen 2, and zinc transporter 8 autoantibodies, and venous samples were additionally tested for insulin autoantibodies and islet cell antibodies. We defined multiple autoantibody positive as two or more autoantibodies in venous serum and DBS screen positive if one or more autoantibodies were detected. Participant questionnaires compared the sample collection methods. Of 44 relatives who were multiple autoantibody positive in venous samples, 42 (95.5%) were DBS screen positive, and DBS accurately detected 145 of 147 autoantibody-negative relatives (98.6%). Capillary blood sampling was perceived as more painful than venous blood draw, but 60% of participants would prefer initial screening using home fingerstick with clinic visits only required if autoantibodies were found. Capillary blood sampling could facilitate screening for type 1 diabetes prevention studies.

  20. Diagnosis and Treatment of IgG4-Related Disease.

    Science.gov (United States)

    Kamisawa, Terumi; Okazaki, Kazuichi

    2017-01-01

    It is critical to differentiate IgG4-related disease (IgG4-RD) from malignant tumor and similar disease of the affected organ to apply appropriate therapy and avoid unnecessary surgery. IgG4-RD is diagnosed on combination of typical radiological findings; elevation of serum IgG4 levels; histopathological findings of abundant infiltration of IgG4-positive plasma cells and lymphocytes, storiform fibrosis , and obliterative phlebitis ; association with other IgG4-related diseases; and response to steroids. Histopathological approach is particularly recommended. Systemic glucocorticoids are currently the first-line approach for IgG4-RD, and the indications are symptoms. The initial recommended dose of oral prednisolone for induction of remission is 0.6 mg/kg/day, administered for 2-4 weeks. This dose is gradually tapered to a maintenance dose of 2.5-5 mg/day over a period of 2-3 months. As IgG4-RD sometimes relapses after steroids, maintenance therapy is usually performed in Japan. However, as IgG4-RD patients are typically elderly and are at high risk of developing steroid-related complications, cessation of the medication should be attempted at least within 3 years. For relapsed IgG4-RD, re-administration or dose up of steroid is effective, but the addition of immunomodulatory drugs such as azathioprine has been considered to be appropriate. B cell depletion with rituximab (an anti-CD20 antibody) is effective, even in many patients in whom treatment with immunomodulatory drugs was unsuccessful. The short-term clinical, morphological, and functional outcomes of most IgG4-RD patients treated with steroid therapy are good, but the long-term outcomes are less clear due to several unknown factors such as relapse, developed fibrosis, and associated malignancy.

  1. The autoimmune IgG4 -associated endocrine pathology

    Directory of Open Access Journals (Sweden)

    Marina Yu. Yukina

    2017-11-01

    Full Text Available Immunoglobulin G4-associated diseases (IgG4-AD arethe group of chronic progressive autoimmune fibro-inflammatory pathology of various organs and tissues, characterized by their enlargement and abundant infiltration of immunoglobulin G4-positive plasma cells, as well as an increase in the level of serum immunoglobulin G4 (IgG4.In most patients, the disease is characterized by a mild course.However, there is evidence of a high incidence of malignancies in patients with IgG4-AD.Among endocrine IgG4-associated pathologies, pancreatitis with outcome in diabetes mellitus, hypophysitis and thyroiditis are described. Laboratory examination usually reveals an increased level of IgG4. However, the concentration of IgG4 could not be used as the only diagnostic criterion.The possibility of plasmablastsdetermining as a marker of the disease is discussed.Among the imaging techniques CT, MRI and 18F-FDG-PET/CT are used.However, the most informative method of diagnosis is biopsy. Randomized clinical trials to determine clear recommendations for the treatment of IgG4-AD were not conducted.In most cases, glucocorticoids are prescribed, and immunosuppressive therapy is sometimes used.According to the results of recent studies, the genetically engineered drug rituximab is relatively effective in inducing remission of the disease.Given the high recurrence rate and the risk of malignancy, patients with IgG4-AD require careful long-term follow-up. Thus, the review describes the clinical manifestations of IgG4-AD, examines the possibilities of their diagnosis and presents the existing methods of treatment.However, given the fact that IgG4-AD became a separate group of autoimmune pathology less than 20 years ago, there are insufficient data on these diseases. Researches related to epidemiology, pathophysiology, diagnosis and effective treatment of IgG4-AD are actual.

  2. Autoantibody profile in individuals with chronic hepatitis C.

    Science.gov (United States)

    Marconcini, Maíra Luciana; Fayad, Leonardo; Shiozawa, Maria Beatriz Cacese; Dantas-Correa, Esther Buzaglo; Lucca Schiavon, Leonardo de; Narciso-Schiavon, Janaína Luz

    2013-01-01

    Autoantibodies are often produced during infection with chronic hepatitis C virus (HCV), but it remains controversial whether they influence the biochemical profile and histological features of this disease. Therefore, this current study sought to describe these autoantibodies and evaluate their impact on the clinical and histological presentation of hepatitis C. This cross-sectional analytical study assessed patients with HCV (RNA+) from October 2011 to July 2012. This study included 66 patients, with a mean age of 53.2±10.5 years. Of these patients, 60.6% were male, and 54.3% presented with genotype 1. Non-organ-specific autoantibodies (NOSA) were detected in 24% of the patients; of these, 7.6% were anti-mitochondrial antibodies (AMA+), 26.7% were anti-smooth muscle antibodies (SMA+) and 6.8% were liver kidney microsomal type 1 antibodies (LKM1+). With respect to the thyroid autoantibodies, 7.4% were anti-peroxidase (ATPO+) antibodies, and none were anti-thyroglobulin (ATG+) antibodies. Regarding celiac disease autoantibodies, 5.8% were endomysial antibodies (EMA+), and no transglutaminase (TTG+) antibodies were detected. Cryoglobulins were found in 2.1% of patients. When NOSA+ individuals were compared to patients without the presence of NOSAs, they exhibited higher median alkaline phosphatase (0.7 vs. 0.6 xULN; p=0.041), lower median platelet counts (141,500.0 vs. 180,500.0/mm 3 ; p=0.036), lower mean prothrombin activity (72.6±11.5% vs. 82.2±16.0%; p=0.012) and an increased prevalence of significant fibrosis (E≥2) (45.5% vs. 18.2%; p=0.012). There was also a tendency for a greater proportion of NOSA+ cases to have marked periportal activity (APP≥3) (44.5% vs. 15.6%; p=0.087). In addition to the high prevalence of autoantibodies associated with HCV infection, it was observed that NOSA positivity was associated with a more severe histological and biochemical profile of hepatitis C infection.

  3. Autoantibody profile in individuals with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Maíra Luciana Marconcini

    2013-04-01

    Full Text Available Introduction Autoantibodies are often produced during infection with chronic hepatitis C virus (HCV, but it remains controversial whether they influence the biochemical profile and histological features of this disease. Therefore, this current study sought to describe these autoantibodies and evaluate their impact on the clinical and histological presentation of hepatitis C. Methods This cross-sectional analytical study assessed patients with HCV (RNA+ from October 2011 to July 2012. Results This study included 66 patients, with a mean age of 53.2±10.5 years. Of these patients, 60.6% were male, and 54.3% presented with genotype 1. Non-organ-specific autoantibodies (NOSA were detected in 24% of the patients; of these, 7.6% were anti-mitochondrial antibodies (AMA+, 26.7% were anti-smooth muscle antibodies (SMA+ and 6.8% were liver kidney microsomal type 1 antibodies (LKM1+. With respect to the thyroid autoantibodies, 7.4% were anti-peroxidase (ATPO+ antibodies, and none were anti-thyroglobulin (ATG+ antibodies. Regarding celiac disease autoantibodies, 5.8% were endomysial antibodies (EMA+, and no transglutaminase (TTG+ antibodies were detected. Cryoglobulins were found in 2.1% of patients. When NOSA+ individuals were compared to patients without the presence of NOSAs, they exhibited higher median alkaline phosphatase (0.7 vs. 0.6 xULN; p=0.041, lower median platelet counts (141,500.0 vs. 180,500.0/mm 3 ; p=0.036, lower mean prothrombin activity (72.6±11.5% vs. 82.2±16.0%; p=0.012 and an increased prevalence of significant fibrosis (E≥2 (45.5% vs. 18.2%; p=0.012. There was also a tendency for a greater proportion of NOSA+ cases to have marked periportal activity (APP≥3 (44.5% vs. 15.6%; p=0.087. Conclusions In addition to the high prevalence of autoantibodies associated with HCV infection, it was observed that NOSA positivity was associated with a more severe histological and biochemical profile of hepatitis C infection.

  4. A condition closely mimicking IgG4-related disease despite the absence of serum IgG4 elevation and IgG4-positive plasma cell infiltration.

    Science.gov (United States)

    Hara, Satoshi; Kawano, Mitsuhiro; Mizushima, Ichiro; Yamada, Kazunori; Fujita, Kentaro; Harada, Kenichi; Matsumura, Masami; Yamagishi, Masakazu; Sato, Yasuharu; Yamaguchi, Yutaka; Nakanuma, Yasuni; Nagata, Michio

    2016-09-01

    We describe a 74-year-old Japanese man with systemic fibroinflammatory conditions closely resembling those of immunoglobulin G4-related disease (IgG4-RD). Radiology and histology showed characteristics of IgG4-related tubulointerstitial nephritis, despite normal serum IgG4 value and scanty IgG4-positive plasma cell infiltration in each organ. This case suggests that a condition closely mimicking IgG4-RD may develop without IgG4-positive plasma cells and those exceptional cases should also be taken into account in the differential diagnosis of IgG4-RD.

  5. Flexibility and conformational change of IgG molecule

    International Nuclear Information System (INIS)

    Alpert, Y.; Ostanevich, Yu.M.

    1982-12-01

    The dynamic behaviour of pig anti-Dnp-immunoglobulin (IgG) investigated by the neutron spin echo technique gave evidence of internal motion of a biological macromolecule. It is suggested that this motion belongs to the wobbling of the Fab parts of the investigated IgG molecule around its so called hinge region. (author)

  6. The emerging mysteries of IgG4-related disease

    NARCIS (Netherlands)

    Smit, Wouter; Barnes, Eleanor

    2014-01-01

    IgG4-related disease (IgG4-RD) is increasingly recognised in Western societies as a multi-system, inflammatory, fibrosing disease of unknown aetiology that typically, though not exclusively, presents in older men. The clinical manifestations are diverse and almost any organ may be affected. The

  7. Seropositivity and determinants of immunoglobulin-G (IgG ...

    African Journals Online (AJOL)

    Background: This study is the first documented prevalence of IgG antibody against HSV-1&-2 in Port Harcourt, Nigeria and thus provides baseline data for future in-depth studies on HSV infection in South-South, Nigeria. Objective: This study determined the seropositivity and determinants of serum IgG antibody against ...

  8. The Histopathology of IgG4-Related Disease.

    Science.gov (United States)

    Avincsal, Mehmet Ozgur; Zen, Yoh

    2017-01-01

    IgG4-related disease is a multi-organ immune-mediated chronic fibroinflammatory condition characterized by elevated serum IgG4 concentrations, tumefaction, and tissue infiltration by IgG4-positive plasma cells. The exact etiology of IgG4-related disease remains unclear with no known role of the IgG4 molecule itself being identified. Although the pancreas and salivary glands are the main organs affected, the involvement of other organs has also been reported. This multi-organ disease mimics a large number of malignant, infectious, and inflammatory disorders; therefore, a prompt differential diagnosis is important for selecting the right therapeutic strategy. Early steroid therapy assists in preventing tissue fibrosis, parenchymal extinction, and severe functional impairments in the affected organs. The definitive and prompt diagnosis of IgG4-related disease requires both histopathological confirmation and clinicopathological correlations. A histopathological examination is mandatory to exclude neoplastic or inflammatory conditions that mimic IgG4-related disease. The histological changes that occur are basically similar in any organ manifestation, with several site-specific findings being recognized. This chapter summarizes general rules for the pathological examination of IgG4-related disease, as well as the histopathological features and differential diagnoses of major organ manifestations.

  9. Current Concept of IgG4-Related Disease.

    Science.gov (United States)

    Okazaki, Kazuichi; Umehara, Hisanori

    2017-01-01

    IgG4-related disease (IgG4-RD) is a fibroinflammatory disease of unknown etiology, which is characterized by a tendency to form tumefactive lesions, increased serum levels of IgG4, and massive infiltration of IgG4-positive plasma cells with storiform fibrosis and/or obliterative phlebitis. Patients with IgG4-RD have frequently multiorgan involvements such as the pancreas, biliary tree, salivary glands, periorbital tissues, kidneys, lungs, lymph nodes, and retroperitoneum. IgG4-RD mainly affects middle-aged to elderly men except for involvement in lachrymal and salivary glands, so-called Mikulicz's disease. The clinical manifestations of IgG4-RD depend on individually involved organs and respond well to steroid, but the prognosis still remains unclear. Some patients develop serious complications such as obstructive jaundice due to hepatic, gallbladder, or pancreatic lesions; hydronephrosis due to retroperitoneal fibrosis; or respiratory symptoms due to pulmonary lesions. Nomenclatures of individual organ manifestation of IgG4-RD have been internationally consented.

  10. 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.

  11. Persistent Lymphadenopathy due to IgG4-Related Disease

    Science.gov (United States)

    2012-10-01

    capsid IgM negative), CMV (IgM negative, IgG negative), parvovirus B19 (IgM negative, IgG negative), Hepatitis (HBs Ag negative, HBc Ab negative, HBs...lymphadenopathy). Figure 2: Hematoxylin and eosin stain of a resected lymph node, 2x magnification. This preparation shows nonspecific reactive follicular

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

    NARCIS (Netherlands)

    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

  13. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium.

    Directory of Open Access Journals (Sweden)

    Frances Humby

    2009-01-01

    were closely associated with circulating human IgG ACPA in mouse sera. Finally, the survival and proliferation of functional B cell niches was associated with persistent overexpression of genes regulating ectopic lymphoneogenesis.Our demonstration that FDC+ follicular units invariably express AID and are surrounded by ACPA-producing plasma cells provides strong evidence that ectopic lymphoid structures in the RA synovium are functional and support autoantibody production. This concept is further confirmed by evidence of sustained AID expression, B cell proliferation, ongoing CSR, and production of human IgG ACPA from GC+ synovial tissue transplanted into SCID mice, independently of new B cell influx from the systemic circulation. These data identify AID as a potential therapeutic target in RA and suggest that survival of functional synovial B cell niches may profoundly influence chronic inflammation, autoimmunity, and response to B cell-depleting therapies.

  14. Clinical features of IgG4-related rhinosinusitis.

    Science.gov (United States)

    Hanaoka, Machiko; Kammisawa, Terumi; Koizumi, Satomi; Kuruma, Sawako; Chiba, Kazuro; Kikuyama, Masataka; Shirakura, Satoshi; Sugimoto, Taro; Hishima, Tsunekazu

    2017-09-01

    IgG4-related disease is a systemic disease that affects various organs of the body. Aim of this study is to elucidate the clinical characteristics of IgG4-related rhinosinusitis. Clinical features, laboratory findings, radiological and endoscopic findings, associated disease, treatment and prognosis were retrospectively examined in 10 patients with IgG4-related rhinosinusitis. The age was 59.1±11.3 years old and male-to-female ratio was 1:1. The chief nasal complaints were hyposmia (n=4), nasal obstruction (n=3), and nothing (n=3). Serum IgG4 levels were elevated in all patients and the value was 740.4±472.4mg/dl. Other IgG4-related diseases were associated in all 10 patients, including IgG4-related sialadenitis (n=6), IgG4-related dacryoadenitis (n=5), and autoimmune pancreatitis (n=5). Imaging findings on CT/MRI were obstruction of the way of elimination (n=10), thickening of the sinus mucous membrane (n=10), and fluid in the sinus (n=6). All of the cases had bilateral findings. Nasal endoscopic findings were chiefly deviated nasal septum (n=5), polyps (n=4), edema of the mucous membrane (n=3). Histologically, abundant infiltration of IgG4 positive plasma cell and lymphocyte and an elevated IgG4+/IgG+ cell ration was detected in all 8 patients and 5 patients, respectively. Endoscopic sinus surgery was performed in 8 patients. Eight patients were treated with steroid therapy for other associated IgG4-related diseases. Symptoms improved in all 6 patients after an initial treatment (endoscopic surgery (n=5) and steroids (n=1)), but one patient suffered relapse. IgG4-related rhinosinusitis is a distinct entity of IgG4-related disease, and is associated in patients with multiple IgG4-related diseases. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

  15. Riedel's thyroiditis association with IgG4-related disease.

    Science.gov (United States)

    Stan, Marius N; Sonawane, Vikram; Sebo, Thomas J; Thapa, Prabin; Bahn, Rebecca S

    2017-03-01

    IgG4-positive (+) plasma cells have been reported in both Riedel's thyroiditis (RT) and Hashimoto's thyroiditis (HT). These cells are the hallmark of IgG4-related disease (IgG4-RD). We sought to determine whether RT is part of IgG4-RD spectrum. This was a case-control study performed at a tertiary medical centre. We included RT cases from the period 1958 to 2008 that had sufficient paraffin-embedded tissue for IgG4 immunostaining. Controls were patients with HT, age and gender matched, with similar pathology criteria. The main outcome measures were the intensity of the IgG4 staining and the clinical and histological correlates with IgG4-RD. Six pairs of RT and HT were analysed. The mean age was 44·7 years. In both groups, 5/6 cases had positive IgG4 staining. The mean number of IgG4 + cells/ HPF, normalized to the degree of inflammation, was 3·2 ± 3·0 SD (RT) vs 0·9 ± 0·7 (HT), P = 0·15, for fibrotic areas and 2·1 ± 2·3 SD vs 1·0 ± 0·8 (P = 0·39) for areas with lymphoid aggregates. We found the number of IgG4 +  cells in RT to be inversely correlated with the duration of disease (P = 0·046). Three RT cases had associated comorbidities from the IgG4-RD spectrum while none of the HT cases had such conditions. Riedel's thyroiditis is a component of IgG4-RD with the density of the IgG4 +  lymphocytic infiltrate being time dependent. In this small study, we did not identify differences in IgG4 infiltration between RT and HT, minimizing the utility of this marker in RT diagnosis. © 2016 John Wiley & Sons Ltd.

  16. The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients.

    Science.gov (United States)

    Sosenko, Jay M; Skyler, Jay S; Palmer, Jerry P; Krischer, Jeffrey P; Yu, Liping; Mahon, Jeffrey; Beam, Craig A; Boulware, David C; Rafkin, Lisa; Schatz, Desmond; Eisenbarth, George

    2013-09-01

    We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D). TrialNet Natural History Study participants (n = 784) were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those positive for at least one autoantibody were subsequently tested for ICA and ZnT8A. An autoantibody risk score (ABRS) was developed from a proportional hazards model that combined autoantibody levels from each autoantibody along with their designations of positivity and negativity. The ABRS was strongly predictive of T1D (hazard ratio [with 95% CI] 2.72 [2.23-3.31], P < 0.001). Receiver operating characteristic curve areas (with 95% CI) for the ABRS revealed good predictability (0.84 [0.78-0.90] at 2 years, 0.81 [0.74-0.89] at 3 years, P < 0.001 for both). The composite of levels from the five autoantibodies was predictive of T1D before and after an adjustment for the positivity or negativity of autoantibodies (P < 0.001). The findings were almost identical when ICA was excluded from the risk score model. The combination of the ABRS and the previously validated Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) predicted T1D more accurately (0.93 [0.88-0.98] at 2 years, 0.91 [0.83-0.99] at 3 years) than either the DPTRS or the ABRS alone (P ≤ 0.01 for all comparisons). These findings show the importance of considering autoantibody levels in assessing the risk of T1D. Moreover, levels of multiple autoantibodies can be incorporated into an ABRS that accurately predicts T1D.

  17. 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.

  18. 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.

  19. 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.

  20. IgG4-related Disease and the Liver.

    Science.gov (United States)

    Chen, Jonathan H; Deshpande, Vikram

    2017-06-01

    Pathologists are likely to encounter IgG4-related disease in several organ systems. This article focuses on helping pathologists diagnose IgG4-related disease in the hepatobiliary system. Missing the diagnosis can result in unnecessary organ damage and/or unnecessary surgical and cancer therapy. In the liver, tumefactive lesion(s) involving the bile ducts with storiform fibrosis and an IgG4-enriched lymphoplasmacytic infiltrate are highly concerning for IgG4-related disease. The recent identification of oligoclonal populations of T cells and B cells in IgG4-related disease may lead to molecular tests, new therapeutics, and a greater mechanistic understanding of the disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Thyroid autoantibodies and differentiated thyroid cancer: revue of 662 cases

    International Nuclear Information System (INIS)

    Izembart, M.; Dagousset, F.; Chevalier, A.; Hassid, V.; Leger, A.; Barritault, L.; Clerc, J.

    1999-01-01

    The incidence of thyroid autoantibodies is clearly increased in patients with differentiated thyroid cancer. The aim of this study was to re-evaluate frequency and evolution of anti-thyroglobulin and anti-microsomal (anti-peroxidase) autoantibodies in 662 patients with thyroid carcinoma treated with 131 radioiodine. Ours results obtained with 'classical' methods confirmed others earlier reports. When using more sensitive methods to detect thyroglobulin antibodies we obtained an increase in positive results and a more frequent association with anti-microsomal antibodies. Antibodies became undetectable with a variable period, ranging from a few months to 13 years in one case. If we suppose that the disappearance of antibodies is linked to the thyroid tissue disappearance, thyroid cancer follow up ought to include anti-thyroglobulin and anti-peroxidase antibodies, both directed against thyroid antigens. A decrease of both antibodies seems to indicate a favorable prognostic factor whereas an increase may suggest relapse. (author)

  2. A rapid, accurate and robust particle-based assay for the simultaneous screening of plasma samples for the presence of five different anti-cytokine autoantibodies

    DEFF Research Database (Denmark)

    Guldager, Daniel Kring Rasmussen; von Stemann, Jakob Hjorth; Larsen, Rune

    2015-01-01

    suitable for larger screenings. Based on confirmed antibody binding characteristics and the resultant reactivity in this multiplex assay, a classification of the c-aAb levels was suggested. The screening results of the recipients who received blood transfusions indicate that more studies are needed...... plasma samples and pooled normal immunoglobulin preparations were used to validate the assay. Plasma samples from 98 transfusion recipients, half of whom presented with febrile reactions, were tested by the assay. RESULTS: The assay detected specific and saturable immunoglobulin G (IgG) binding to each...... cytokine autoantibodies quantities in the negative plasma samples ranged between 80% and 125%. The analytical intra- and inter-assay variations were 4% and 11%, respectively. Varying c-aAb levels were detectable in the transfusion recipients. There was no difference in c-aAb frequency between the patients...

  3. Extrahepatic Manifestations and Autoantibodies in Patients with Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Takashi Himoto

    2012-01-01

    Full Text Available Patients with chronic hepatitis C virus (HCV infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren’s syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders.

  4. Expression of human FcgammaRIIIa as a GPI-linked molecule on CHO cells to enable measurement of human IgG binding.

    Science.gov (United States)

    Armour, Kathryn L; Smith, Cheryl S; Clark, Michael R

    2010-03-31

    The efficacy of a therapeutic IgG molecule may be as dependent on the optimisation of the constant region to suit its intended indication as on the selection of its variable regions. A crucial effector function to be maximised or minimised is antibody-dependent cell-mediated cytotoxicity by natural killer cells. Traditional assays of ADCC activity suffer from considerable inter-donor and intra-donor variability, which makes the measurement of antibody binding to human FcgammaRIIIa, the key receptor for ADCC, an attractive alternative method of assessment. Here, we describe the development of cell lines and assays for this purpose. The transmembrane receptor, FcgammaRIIIa, requires co-expression with signal transducing subunits to prevent its degradation, unlike the homologous receptor FcgammaRIIIb that is expressed as a GPI-anchored molecule. Therefore, to simplify the production of cell lines as reliable assay components, we expressed FcgammaRIIIa as a GPI-anchored molecule. Separate, stable CHO cell lines that express either the 158F or the higher-affinity 158V allotype of FcgammaRIIIa were isolated using fluorescence-activated cell sorting. The identities of the expressed receptors were confirmed using a panel of monoclonal antibodies that distinguish between subclasses and allotypes of FcgammaRIII and the cell lines were shown to have slightly higher levels of receptor than FcgammaRIII-positive peripheral blood mononuclear cells. Because the affinity of FcgammaRIIIa for IgG is intermediate amongst the receptors that bind IgG, we were able to use these cell lines to develop flow cytometric assays to measure the binding of both complexed and monomeric immunoglobulin. Thus, by choosing the appropriate method, weakly- or strongly-binding IgG can be efficiently compared. We have quantified the difference in the binding of wildtype IgG1 and IgG3 molecules to the two functional allotypes of the receptor and report that the FcgammaRIIIa-158V-antibody interaction is 3

  5. 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. PMID:22531449

  6. Female Infertility and Serum Auto-antibodies: a Systematic Review.

    Science.gov (United States)

    Deroux, Alban; Dumestre-Perard, Chantal; Dunand-Faure, Camille; Bouillet, Laurence; Hoffmann, Pascale

    2017-08-01

    On average, 10 % of infertile couples have unexplained infertility. Auto-immune disease (systemic lupus erythematosus, anti-phospholipid syndrome) accounts for a part of these cases. In the last 20 years, aspecific auto-immunity, defined as positivity of auto-antibodies in blood sample without clinical or biological criteria for defined diseases, has been evoked in a subpopulation of infertile women. A systematic review was performed (PUBMED) using the MESH search terms "infertility" and "auto-immunity" or "reproductive technique" or "assisted reproduction" or "in vitro fertilization" and "auto-immunity." We retained clinical and physiopathological studies that were applicable to the clinician in assuming joint management of both infertility associated with serum auto-antibodies in women. Thyroid auto-immunity which affects thyroid function could be a cause of infertility; even in euthyroidia, the presence of anti-thyroperoxydase antibodies and/or thyroglobulin are related to infertility. The presence of anti-phospholipid (APL) and/or anti-nuclear (ANA) antibodies seems to be more frequent in the population of infertile women; serum auto-antibodies are associated with early ovarian failure, itself responsible for fertility disorders. However, there exist few publications on this topic. The methods of dosage, as well as the clinical criteria of unexplained infertility deserve to be standardized to allow a precise response to the question of the role of serum auto-antibodies in these women. The direct pathogenesis of this auto-immunity is unknown, but therapeutic immunomodulators, prescribed on a case-by-case basis, could favor pregnancy even in cases of unexplained primary or secondary infertility.

  7. Neuromyelitis optica in a young child with positive serum autoantibody

    OpenAIRE

    Loma, Ingrid P.; Asato, Miya R.; Filipink, Robyn A.; Alper, Gulay

    2008-01-01

    Relapsing neuromyelitis optica is rare in children. The identification of highly specific serum autoantibody marker (neuromyelitis optica –immunoglobulin G) differentiates neuromyelitis optica from other demyelinating disorders particularly in clinically challenging cases. We present a child with multiple episodes of transverse myelitis and optic neuritis with positive neuromyelitis optica-immunoglobulin G titers consistent with a diagnosis of relapsing neuromyelitis optica. Serial titers of ...

  8. Antineutrophil cytoplasmic autoantibodies and myeloperoxidase autoantibodies in clinical expression of Churg-Strauss syndrome.

    Science.gov (United States)

    Healy, Bridget; Bibby, Susan; Steele, Richard; Weatherall, Mark; Nelson, Harold; Beasley, Richard

    2013-02-01

    The clinical significance of antineutrophil cytoplasmic antibodies (ANCAs) in the phenotypic expression of Churg-Strauss syndrome (CSS) is uncertain. We sought to investigate the relationship between ANCA status and the clinical expression of CSS in a case series derived from the US Food and Drug Administration's adverse events database. All cases of CSS reported to the US Food and Drug Administration from 1997 to April 2003 were reviewed. Information about basic demographics, suspect medication use, clinical manifestations, histologic findings, ANCA staining patterns, and the presence of antibodies to myeloperoxidase (anti-MPO) or proteinase 3 (anti-PR3) was recorded when available. There were 93 case reports of CSS with sufficient documentation, including ANCA status. There were 38 (40.9%) of 93 cases with positive ANCA results, of which 15 cases reported a positive ELISA, all of which were positive for anti-MPO. ANCA negativity was associated with an increased proportion of cardiac involvement (risk difference [RD], 38.2%; 95% CI, 25.3% to 51.0%), gastrointestinal involvement (RD, 25.5%; 95% CI, 13.9% to 37.0%), pulmonary infiltrates (odds ratio, 4.9; 95% CI, 1.5-16.2), and the outcome of a life-threatening event or death (RD, 30.9%; 95% CI, 18.7% to 43.1%) when compared with anti-MPO-positive cases. ANCA negativity was associated with a decreased proportion of peripheral neuropathy (odds ratio, 0.3; 95% CI, 0.07-0.9). These findings support the hypothesis that the presence or absence of autoantibodies influences the clinical expression and severity of CSS. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  9. IgG4-producing lymphoma arising in a patient with IgG4-related disease.

    Science.gov (United States)

    Igawa, Takuro; Hayashi, Toshiaki; Ishiguro, Kazuya; Maruyama, Yumiko; Takeuchi, Mai; Takata, Katsuyoshi; Yoshino, Tadashi; Sato, Yasuharu

    2016-12-01

    We herein report a case in which an IgG4-producing lymphoma arose in a patient with a previous diagnosis consistent with an IgG4-related disease. A 43-year-old man presented with enlarged cervical lymph nodes and was treated with steroids and radiation for what was initially assumed to be Kimura's disease, although the lesions were later histologically re-diagnosed as IgG4-related lymphadenopathy. Fourteen years later, when the patient was 58-years-old, he presented with retroperitoneal fibrosis and swollen lymph nodes. The suspicious lesions were not histologically examined as the patient did not give consent. However, the serum IgG4 concentration was high (1400 mg/dL) and he was clinically diagnosed with systemic IgG4-related disease. Although steroid administration reduced the size of the lesions, tapering the dose finally resulted in systemic, prominently enlarged lymph nodes. Analysis of the biopsy specimen revealed that these multiple lymph node lesions were marginal zone B cell lymphomas that themselves expressed IgG4. Complete remission was achieved after a total of six courses of chemotherapy including rituximab. This case suggests that the infiltrating IgG4-expressing cells observed in IgG4-related disease can clonally expand to malignant lymphomas.

  10. Analysis of IgG4-positive clones in affected organs of IgG4-related disease.

    Science.gov (United States)

    Kakuchi, Yasushi; Yamada, Kazunori; Ito, Kiyoaki; Hara, Satoshi; Fujii, Hiroshi; Yamagishi, Masakazu; Kawano, Mitsuhiro

    2016-11-01

    We investigated class switch reaction (CSR) in affected organs and evaluated whether the same or genetically related clones exist in IgG4-RD. We studied three patients with IgG4-RD. Total cellular RNA was extracted from salivary glands and peripheral blood and lung tissue. Activation-induced cytidine deaminase (AID) and immunoglobulin heavy chain third complementarity determining region (IgVH-CDR3) of IgM and IgG4 were detected by reverse transcription polymerase chain reaction (RT-PCR). We analyzed the clonal relationship of infiltrating IgG4-positive cells, as compared with IgM. We determined the existence of common clones among organs and patients. AID was expressed in salivary glands of all patients and lung tissue in one. Closely related IgVH-CDR3 sequences in infiltrating IgG4-positive cells were detected in salivary glands and lung tissue. Identical IgVH-CDR3 sequence between IgM and IgG4 in salivary glands was detected in one patient, indicating CSR in salivary glands. Identical IgVH-CDR3 sequences of IgG4-positive cells were detected between salivary glands and peripheral blood in two patients. Four identical sequences of IgVH-CDR3 existed between patients. Interestingly, one of the four sequences was detected in all patients. Our results demonstrate the existence of common antigen(s) shared by patients with IgG4-RD.

  11. Coeliac disease autoantibodies mediate significant inhibition of tissue transglutaminase.

    LENUS (Irish Health Repository)

    Byrne, Greg

    2012-02-01

    The detection of antibodies directed against tissue transglutaminase (tTG) in serum is a sensitive and specific test for suspected coeliac disease. tTG is a ubiquitous, multifunctional enzyme that has been implicated in many important physiological processes as well as the site-specific deamidation of glutamine residues in gluten-derived peptides. This modification of gluten peptides facilitates their binding to HLA-DQ2, which results in amplification of the T-cell response to gluten. The purpose of this study was to investigate the possibility that patient IgA autoantibodies directed against tTG interfere with the crosslinking activity of the enzyme. IgA autoantibodies against tTG were isolated\\/depleted from patient serum and tested for their capacity to interfere with tTG activity in vitro using a sensitive fluorescence-based activity assay. We have demonstrated that autoantibodies cause significant inhibition of tTG-mediated crosslinking at equimolar and 2:1 ratios of antibody to enzyme.

  12. Clinical Significance of Autoantibodies in Some Thyroid Disorders

    International Nuclear Information System (INIS)

    Choi, Sung Kyu; Han, Sang Ho; Kim, Young Ju; Song, Jun Ho; Lee, Man Ho; Chung, Eul Sun; Lee, Sang Jong

    1984-01-01

    Clinical measurement of thyroid autoantibodies in sera of some thyroid disorders have been widely applied since about twenty years ago. We investigated the incidence and titers of both antimicrosomal and antithyroglobulin antibodies in forty eight cases with controls and one hundred and thirty three patients with some form of thyroid disorders. The results were as follows; 1) In controls, antimicrosomal antibodies were positive in 2% but antithyroglobulin antibodies were all negative. 2) In a series of one hundred and thirty three patients with thyroid disease, antimicrosomal antibodies were positive in 44% but antithyroglobulin antibodies were positive in only 15%. 3) The rate disclosing the positive results of antimicrosomal antibodies were 71% in Hashimoto disease, 60% in Graves' disease, and 38% in primary hypothyroidism, respectively. On the other hand, the positive results of antithyroglobulin antibodies showed 21% in Graves' disease, 19% in primary hypothyroidism, and 18% in Hashimoto, disease, respectively. Though there were relatively high rate of both antimicrosomal and antithyroglobulin antibodies in patients with nodular goiter, they were only seven cases in our series. 4) The rate with the extremely high titers of antimicrosomal and antithyroglobulin antibodies (>1 : 160 2 ) was 83% and 67% in Hashimoto's disease, 50% and 67% in primary hypothyroidism, and 41% and 18% in Graves' disease. Accordingly, the thyroid autoantibodies, were commonly found higher positive rate in patients with Hashimoto disease, primary hypothyroidism, and Graves' disease. Among these disorders, the extremely high positive rate of the thyroid autoantibodies was found in patients with Hashimoto's disease.

  13. Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus.

    Science.gov (United States)

    Rasmussen, N S; Nielsen, C T; Houen, G; Jacobsen, S

    2016-12-01

    We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein-Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein-Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients. © The Author(s) 2016.

  14. Recognition of oxidized albumin and thyroid antigens by psoriasis autoantibodies. A possible role of reactive-oxygen-species induced epitopes in chronic plaque psoriasis

    Directory of Open Access Journals (Sweden)

    Hani A. Al-Shobaili

    2015-12-01

    Full Text Available Objectives: To investigate the role of reactive-oxygen-species (ROS induced epitopes on human-serum-albumin (HSA and thyroid antigens in psoriasis autoimmunity. Methods: This study was performed in the College of Medicine, Qassim University, Buraidah, Saudi Arabia between May 2014 and February 2015. The study was designed to explore the role of ROS-induced epitopes in psoriasis autoimmunity. Singlet-oxygen (or ROS-induced epitopes on protein (ROS-epitopes-albumin was characterized by in-vitro and in-vivo. Thyroid antigens were prepared from rabbit thyroid, and thyroglobulin was isolated from thyroid extract. Immunocross-reactions of protein-A purified anti-ROS-epitopes-HSA-immunoglobulin G (IgGs with thyroid antigen, thyroglobulin, and their oxidized forms were determined. Binding characteristics of autoantibodies in chronic plaque psoriasis patients (n=26 against ROS-epitopes-HSA and also with native and oxidized thyroid antigens were screened, and the results were compared with age-matched controls (n=22. Results: The anti-ROS-epitopes-HSA-IgGs showed cross-reactions with thyroid antigen, thyroglobulin and with their oxidized forms. High degree of specific binding by psoriasis IgGs to ROS-epitopes-HSA, ROS-thyroid antigen and ROS-thyroglobulin was observed. Immunoglobulin G from normal-human-controls showed negligible binding with all tested antigens. Moreover, sera from psoriasis patients had higher levels of carbonyl contents compared with control sera. Conclusion: Structural alterations in albumin, thyroid antigens by ROS, generate unique neo-epitopes that might be one of the factors for the induction of autoantibodies in psoriasis.

  15. IgV peptide mapping of native Ro60 autoantibody proteomes in primary Sjögren's syndrome reveals molecular markers of Ro/La diversification.

    Science.gov (United States)

    Wang, Jing J; Al Kindi, Mahmood A; Colella, Alex D; Dykes, Lukah; Jackson, Michael W; Chataway, Tim K; Reed, Joanne H; Gordon, Tom P

    2016-12-01

    We have used high-resolution mass spectrometry to sequence precipitating anti-Ro60 proteomes from sera of patients with primary Sjögren's syndrome and compare immunoglobulin variable-region (IgV) peptide signatures in Ro/La autoantibody subsets. Anti-Ro60 were purified by elution from native Ro60-coated ELISA plates and subjected to combined de novo amino acid sequencing and database matching. Monospecific anti-Ro60 Igs comprised dominant public and minor private sets of IgG1 kappa and lambda restricted heavy and light chains. Specific IgV amino acid substitutions stratified anti-Ro60 from anti-Ro60/La responses, providing a molecular fingerprint of Ro60/La determinant spreading and suggesting that different forms of Ro60 antigen drive these responses. Sequencing of linked anti-Ro52 proteomes from individual patients and comparison with their anti-Ro60 partners revealed sharing of a dominant IGHV3-23/IGKV3-20 paired clonotype but with divergent IgV mutational signatures. In summary, anti-Ro60 IgV peptide mapping provides insights into Ro/La autoantibody diversification and reveals serum-based molecular markers of humoral Ro60 autoimmunity. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Autoantibodies to alfa-fodrin in patients with Hashimoto thyroiditis and Sjögren's syndrome: possible markers for a common secretory disorder.

    Science.gov (United States)

    Szanto, Antonia; Csipo, Istvan; Horvath, Ildiko; Biro, Edit; Szodoray, Peter; Zeher, Margit

    2008-09-01

    Presence of autoantibodies to alfa-fodrin was investigated in patients with Sjögren's syndrome (n = 61), Hashimoto thyroiditis (n = 27), Sjögren's syndrome associated with Hashimoto thyroiditis (n = 31) and in healthy persons (n = 77). In each group, level of alfa-fodrin antibodies was higher than in the controls. There was no significant difference in their presence either between patients with Hashimoto thyroiditis with or without Sjögren's syndrome, or-in IgA isotype-between Sjögren's and Hashimoto thyroiditis patients. Correlation was found between the level of IgG alfa-fodrin and anti-thyroglobulin antibodies. Based on these findings, fodrin can be associated with both endocrine and exocrine glandular secretion. Antibodies to alfa-fodrin might have a role in the pathogenesis of Hashimoto thyroiditis concerning the "final common effectory pathway", secretion. Alfa-fodrin antibodies can be good markers of secretory disorders. Assessment of these autoantibodies might help the diagnosis and follow-up of patients with impaired secretory capability of not only autoimmune origin.

  17. Patients with a new variant of endemic pemphigus foliaceus have autoantibodies against arrector pili muscle, colocalizing with MYZAP, p0071, desmoplakins 1 and 2 and ARVCF.

    Science.gov (United States)

    Abreu-Velez, A M; Valencia-Yepes, C A; Upegui-Zapata, Y A; Upegui-Quiceno, E; Mesa-Herrera, N R; Velazquez-Velez, J E; Howard, M S

    2017-12-01

    We identified a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America, which we term El Bagre-EPF, and observed reactivity to arrector pili muscle (APM), thus we tested for autoimmunity to APM. We took skin biopsies from 30 patients with El Bagre-EPF and 30 healthy controls (HCs) matched by age, sex and occupation, who were all from the endemic area, and tested these using direct immunofluorescence (DIF), confocal microscopy, immunohistochemistry and immunoblotting (IB). Of the 30 patients with El Bagre-EPF, 27 had autoantibodies to APM that colocalized with commercial antibodies to myocardium-enriched zonula occludens-1-associated protein (MYZAP), desmoplakin (DP)1 and DP2, plakophilin 4, and Armadillo repeat gene deleted in velo-cardio-facial syndrome (ARVCF) (P EPF have autoantibodies to APM, colocalizing with the antibodies MYZAP, ARVCF, p0071, DP1 and DP2, suggesting that these molecules are El Bagre-EPF antigens. Further, all of these antigens represent components of cell junctions, indicating that the immune response is directed, at least partially, against cell junctions. The immune response in patients affected by El Bagre-EPF is polyclonal, and it includes B and T lymphocytes, mast cells, IgG, IgA, IgM, IgD, IgE, fibrinogen, albumin, complement/C1q, C3c and C4. © 2017 British Association of Dermatologists.

  18. Radioimmunoassay of IgG and IgM rheumatoid factors reacting with human IgG

    International Nuclear Information System (INIS)

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

    1977-01-01

    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

  19. Pathomorphological characteristic of IgG4-related diseases

    Directory of Open Access Journals (Sweden)

    O. O. Dyadyk

    2016-08-01

    Full Text Available IgG4-related diseases are a relatively new group of diseases of unknown etiology which are characterized by the development of fibrosis of organs with the presence of big amounts of IgG4-positive plasma-cells in the area of the lesions and increased levels of IgG4 in serum. The organs that may be affected are pancreas, salivary gland, and others, clinical cases of kidney damage are described as well. Renal involvement in IgG4-related diseases most often occurs on the type of tubulointerstitial nephritis, with the further development of acute or chronic kidney injury. The clinic may be represented by the pseudotumor of kidney, renal tissue heterogeneity on the results of CT-studies; acute or chronic renal disease; combination with other organ damage (autoimmune pancreatitis, sclerosing cholangitis, sclerosing lymphoplasmacytic cholecystitis, colitis, sialadenitis, retroperitoneal fibrosis, etc.. Laboratory findings include an increased level of IgG4 in the blood serum, hypocomplementemia, eosinophilia. Histologically, there is interstitial inflammation with many plasma cells, interstitial fibrosis, tubular atrophy, thickening of the tubular basement membrane, some cases are a type of membranous glomerulonephritis. The aim of the study is to identify the patients with IgG4-related diseases with renal impairment and widening the pathological database of such patients with renal impairment to determine the classification criteria of this pathological condition. Materials and methods will include the deceased kidney screening, screening of patients with autoimmune and allergic diseases, nephrological patients screening with the lifetime biopsy (in some cases – repeat biopsy with chronic or acute kidney impairment. There will be clinical and pathological comparison in kidney damage and other diseases with the development of criteria for the classification of lesions in the presence of IgG4-positive substrates and further development of practical

  20. Different IgG-subclass distributions after whole-cell and acellular pertussis infant primary vaccinations in healthy and pertussis infected children

    NARCIS (Netherlands)

    Hendrikx, Lotte H.; Schure, Rose-Minke; Ozturk, Kemal; de Rond, Lia G. H.; de Greeff, S. C.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.; Buisman, Anne-Marie

    2011-01-01

    The distribution of IgG-subclasses provides insight in the immunological mechanisms of protection against whooping cough. We investigated the effect of Dutch whole-cell pertussis and acellular pertussis vaccines administered in infancy on the IgG-subclass distributions in healthy children aged 12

  1. Role of Natural Autoantibodies in Ugandans With Rheumatic Heart Disease and HIV

    Directory of Open Access Journals (Sweden)

    Daniel M. Huck

    2016-03-01

    Interpretation: We found that HIV and RHD are associated with alterations in natural autoantibody responses previously linked to an increased risk for atherosclerosis and autoimmune inflammatory disease.

  2. A systematic approach to obtain validated Partial Least Square models for predicting lipoprotein subclasses from serum NMR spectra

    NARCIS (Netherlands)

    Mihaleva, V.V.; van Schalkwijk, D.B.; de Graaf, A.A.; van Duynhoven, J.; van Dorsten, F.A.; Vervoort, J.; Smilde, A.; Westerhuis, J.A.; Jacobs, D.M.

    2014-01-01

    A systematic approach is described for building validated PLS models that predict cholesterol and triglyceride concentrations in lipoprotein subclasses in fasting serum from a normolipidemic, healthy population. The PLS models were built on diffusion-edited 1H NMR spectra and calibrated on

  3. A systematic approach to obtain validated partial least square models for predicting lipoprotein subclasses from serum NMR spectra

    NARCIS (Netherlands)

    Mihaleva, V.V.; Schalkwijk, van D.B.; Graaf, de A.A.; Duynhoven, van J.P.M.; Dorsten, van F.A.; Vervoort, J.J.M.; Smilde, A.K.; Westerhuis, J.A.; Jacobs, D.M.

    2014-01-01

    A systematic approach is described for building validated PLS models that predict cholesterol and triglyceride concentrations in lipoprotein subclasses in fasting serum from a normolipidemic, healthy population. The PLS models were built on diffusion-edited (1)H NMR spectra and calibrated on

  4. A systematic approach to obtain validated partial least square models for predicting lipoprotein subclasses from serum nmr spectra

    NARCIS (Netherlands)

    Mihaleva, V.V.; Schalkwijk, D.B. van; Graaf, A.A. de; Duynhoven, J. van; Dorsten, F.A. van; Vervoort, J.; Smilde, A.; Westerhuis, J.A.; Jacobs, D.M.

    2014-01-01

    A systematic approach is described for building validated PLS models that predict cholesterol and triglyceride concentrations in lipoprotein subclasses in fasting serum from a normolipidemic, healthy population. The PLS models were built on diffusion-edited 1H NMR spectra and calibrated on

  5. Relative stabilities of IgG1 and IgG4 Fab domains: Influence of the light–heavy interchain disulfide bond architecture

    Science.gov (United States)

    Heads, James T; Adams, Ralph; D'Hooghe, Lena E; Page, Matt J T; Humphreys, David P; Popplewell, Andrew G; Lawson, Alastair D; Henry, Alistair J

    2012-01-01

    The stability of therapeutic antibodies is a prime pharmaceutical concern. In this work we examined thermal stability differences between human IgG1 and IgG4 Fab domains containing the same variable regions using the thermofluor assay. It was found that the IgG1 Fab domain is up to 11°C more stable than the IgG4 Fab domain containing the same variable region. We investigated the cause of this difference with the aim of developing a molecule with the enhanced stability of the IgG1 Fab and the biological properties of an IgG4 Fc. We found that replacing the seven residues, which differ between IgG1 CH1 and IgG4 CH1 domains, while retaining the native IgG1 light-heavy interchain disulfide (L–H) bond, did not affect thermal stability. Introducing the IgG1 type L–H interchain disulfide bond (DSB) into the IgG4 Fab resulted in an increase in thermal stability to levels observed in the IgG1 Fab with the same variable region. Conversely, replacement of the IgG1 L–H interchain DSB with the IgG4 type L–H interchain DSB reduced the thermal stability. We utilized the increased stability of the IgG1 Fab and designed a hybrid antibody with an IgG1 CH1 linked to an IgG4 Fc via an IgG1 hinge. This construct has the expected biophysical properties of both the IgG4 Fc and IgG1 Fab domains and may therefore be a pharmaceutically relevant format. PMID:22761163

  6. A Comparative Analysis of Serum IgG4 Levels in Patients With IgG4-Related Disease and Other Disorders.

    Science.gov (United States)

    Wang, Li; Chu, Xinmin; Ma, Yan; Zhang, Min; Wang, Xue; Jin, Li; Tan, Zhen; Li, Xiangpei; Li, Xiaomei

    2017-09-01

    Elevated serum IgG4 levels are an important hallmark for diagnosing IgG4-related disease (IgG4-RD) but can also be found and reported in other diseases. The present study intended to compare the serum IgG4 levels in both IgG4-RD and non-IgG4-RD and determine the serum IgG4 levels in patients with IgG4-RD before and after glucocorticoid therapy. The study included 323 patients from Anhui Medical University Affiliated Provincial Hospital (China) and was conducted from July 2014-January 2016. A total of 25 patients were eventually diagnosed as having IgG4-RD, according to the IgG4-RD diagnostic criteria. Our study also included 108 patients with connective tissue disease, 94 patients with pancreatic lesions, 66 patients with bile duct lesions, 13 patients with carcinoma of the duodenal papilla and 20 control participants. The assay for serum IgG4 detection was peformed using the nephelometric method. Elevated levels of serum IgG4 (>1.35g/L) were detected in all patients with IgG4-RD, and reduced levels of serum IgG4 (IgG4-RD. The serum IgG4 level in patients with IgG4-RD after glucocorticoid therapy was significantly lower than that before glucocorticoid therapy (t = 2.426, P = 0.04). High levels of IgG4 were observed in IgG4-RD. However, a diagnosis of IgG4 disease can not only be dependent on the detection of elevated serum IgG4 levels but also may need clinical manifestations, serology, histopathology and other comprehensive information for verification. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  7. Diagnostic Performance of Serum IgG4 Levels in Patients With IgG4-Related Disease

    Science.gov (United States)

    Yu, Kuang-Hui; Chan, Tien-Ming; Tsai, Ping-Han; Chen, Ching-Hui; Chang, Pi-Yueh

    2015-01-01

    Abstract The aim of this study is to study the clinical features and diagnostic performance of IgG4 in Chinese populations with IgG4-related diseases (IgG4-RDs). The medical records of 2901 adult subjects who underwent serum IgG4 level tests conducted between December 2007 and May 2014 were reviewed. Serum concentrations of IgG4 were measured in 2901 cases, including 161 (5.6%) patients with IgG4-RD and 2740 (94.4%) patients without IgG4-RD (non-IgG4-RD group). The mean age of the IgG4-RD patients was 58.4 ± 16.1 years (range: 21–87), and 48 (29.8%) were women. The mean serum IgG4 level was significantly much higher in IgG4-RD patients than in non-IgG4-RD (1062.6 vs 104.3 mg/dL, P IgG4 >135 mg/dL, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR)+, and LR− were 86%, 77%, 18%, 99%, 3.70, and 0.19, respectively. When the upper limit of normal was doubled for an IgG4 >270 mg/dL, the corresponding data were 75%, 94%, 43%, 98%, 12.79, and 0.26, respectively. For IgG4 >405 mg/dL (tripling the upper limit of normal), the corresponding data were 62%, 98%, 68%, 98%, 37.00, and 0.39, respectively. When calculated according to the manufacturer's package insert cutoff (>201 mg/dL) for the diagnosis of IgG4-RD, the corresponding sensitivity, specificity, PPV, NPV, LR+, and LR− were 80%, 89%, 29%, 99%, 7.00, and 0.23, respectively. For IgG4 >402 mg/dL (>2× the upper limit of the normal range), the corresponding data were 62%, 98%, 68%, 98%, 36.21, and 0.39, respectively. For IgG4 >603 mg/dL (>3× the upper limit of the normal range), the corresponding data were 50%, 99%, 84%, 97%, 90.77 and 0.51, respectively. The optimal cutoff value of serum IgG4 (measured by nephelometry using a Siemens BN ProSpec instrument and Siemens reagent) for the diagnosis of IgG4-RD was 248 mg/dL, the sensitivity and specificity were 77.6% and 92.8%, respectively. The present study demonstrated that 2 or

  8. The implications of autoantibodies to a single islet antigen in relatives with normal glucose tolerance: development of other autoantibodies and progression to type 1 diabetes.

    Science.gov (United States)

    Bingley, Polly J; Boulware, David C; Krischer, Jeffrey P

    2016-03-01

    Autoantibodies directed at single islet autoantigens are associated with lower overall risk of type 1 diabetes than multiple autoantibodies, but individuals with one autoantibody may progress to higher risk categories. We examined the characteristics of this progression in relatives followed prospectively in the TrialNet Pathway to Prevention. The study population comprised 983 relatives who were single autoantibody positive with normal baseline glucose tolerance (median age 16.2 years). Samples were screened for antibodies to GAD, insulinoma-associated antigen 2 (IA-2) and insulin, and all positive samples tested for antibodies to zinc transporter 8 and islet cell antibodies. Antibodies to at least one additional islet autoantigen appeared in 118 of 983 relatives (overall 5 year risk 22%, 95% CI [17.9, 26.1]). At baseline, antibodies to GAD alone (68%) were more frequent than antibodies to insulin (26%) or IA-2 (6%), but all were associated with a similar risk of developing additional autoantibodies. Risk was associated with younger age (p = 0.002) and HLA class II genotype, but was similar in high and intermediate genetic risk groups (p = 0.65). Relatives who became multiple autoantibody positive during the follow-up had increased risk of developing diabetes comparable with the risk in relatives with multiple autoantibodies at study entry. Progression of islet autoimmunity in single autoantibody positive relatives in late childhood/adult life is associated with a predominance of autoantibodies to GAD and a distinct HLA risk profile. This heterogeneity in type 1 diabetes autoimmunity has potentially important implications for disease prevention.

  9. Extrapancreatic findings of IgG4-related disease

    International Nuclear Information System (INIS)

    Tan, T.J.; Ng, Y.L.; Tan, D.; Fong, W.S.; Low, A.S.C.

    2014-01-01

    IgG4-related disease is a systemic fibro-inflammatory condition, which includes autoimmune pancreatitis as part of the disease spectrum. Imaging has been demonstrated to play a major role in the diagnosis of autoimmune pancreatitis. Recognizing the wide spectrum of extrapancreatic manifestations of IgG4-related disease coupled with a high clinical index of suspicion will allow for an accurate and timely diagnosis to be made, thus avoiding unnecessary invasive procedures and ensuring that early effective corticosteroid therapy is commenced. This review aims to serve as a concise reference tool for both clinicians and radiologists in the diagnosis of extrapancreatic IgG4-related disease

  10. Serological blind spots for variants of human IgG3 and IgG4 by a commonly used anti-immunoglobulin reagent.

    Science.gov (United States)

    Howie, Heather L; Delaney, Meghan; Wang, Xiaohong; Er, Lay See; Vidarsson, Gestur; Stegmann, Tamara C; Kapp, Linda; Lebedev, Jenna N; Wu, Yanyun; AuBuchon, James P; Zimring, James C

    2016-12-01

    Human immunoglobulin G (IgG) includes four different subtypes (IgG1, IgG2, IgG3, and IgG4), and it is also now appreciated that there are genetic variations within IgG subtypes (called isoallotypes). Twenty-nine different isoallotypes have been described, with 7, 4, 15, and 3 isoallotypes described for IgG1, IgG2, IgG3, and IgG4, respectively. The reactivity of anti-IgG with different isoallotypes has not been characterized. A novel monoclonal anti-K antibody (PugetSound Monoclonal Antibody 1 [PUMA1]) was isolated and sequenced, and a panel of PUMA1 variants was expressed, consisting of the 29 known IgG isoallotypes. The resulting panel of antibodies was preincubated with K-positive red blood cells (RBCs) and then subjected to testing with currently approved anti-IgG by flow cytometry, solid phase systems, gel cards, and tube testing. A US Food and Drug Administration (FDA)-approved monoclonal anti-IgG (gamma-clone) failed to recognize 2 of 15 IgG3 isoallotypes (IgG3-03 and IgG3-13) and 3 of 3 IgG4 isoallotypes (IgG4-01, IgG4-02, and IgG4-03). In contrast, an FDA-approved rabbit polyclonal anti-IgG recognized each of the known human IgG isoallotypes. These findings demonstrate "blind spots" in isoalloantibody detection by a monoclonal anti-IgG. If a patient has anti-RBC antibodies predominantly of an IgG3 subtype (the IgG3-03 and/or IgG3-13 variety), then it is possible that a clinically significant alloantibody would be missed. IgG-03 and IgG-13 have an estimated frequency of 1% to 3% in Caucasian populations and 20% to 30% in certain African populations. Nonreactivity with IgG4 is a known characteristic of this monoclonal anti-IgG, but IgG4 isoallotypes have not been previously reported. © 2016 AABB.

  11. Histopathological Diagnostic Value of the IgG4+/IgG+ Ratio of Plasmacytic Infiltration for IgG4-Related Diseases

    Science.gov (United States)

    Deng, Chuiwen; Li, Wenli; Chen, Si; Zhang, Wen; Li, Jing; Hu, Chaojun; Wen, Xiaoting; Zhang, Fengchun; Li, Yongzhe

    2015-01-01

    Abstract This article aims to perform a meta-analysis to evaluate the diagnostic value of the immunoglobulin G (IgG)4+/IgG+ ratio of plasmacytic infiltration for IgG4-related diseases. Four databases—EMBASE, ISI Web of Knowledge, PubMed, and the Cochrane Library—were systematically searched. Approximately 200 participants from several studies were included in this research. STATA 11.2 software (Stata Corporation, College Station, TX) and Meta-DiSc 1.4 (Unit of Clinical Biostatistics, Ramon y Cajal Hospital, Madrid, Spain) were used to perform the meta-analysis. Nine studies were included in the meta-analysis. The pooled diagnostic odds ratio was 18.94 [95% confidence interval (CI), 2.89–124.30]. The sensitivity was 58.80% (95% CI, 50.90–66.30) and the specificity was 90.20% (95% CI, 81.20–95.80). The positive and negative likelihood ratios were 3.12 (95% CI, 1.07–9.16) and 0.26 (95% CI, 0.09–0.70), respectively. The area under the curve of the summary receiver-operating characteristic was 0.88. To conclude, the IgG4+/IgG+ ratio of plasmacytic infiltration is modestly effective in diagnosing IgG-related disease. PMID:25738476

  12. Antisperm autoantibodies and infertility Anticuerpos antiespermatozoides e infertilidad

    Directory of Open Access Journals (Sweden)

    Jorge Eliécer Ossa Londoño

    1997-02-01

    Full Text Available Fourteen human infertile couples were studied along with seven fertile control couples in order to determine the presence of antisperm au. toantibodies and to correlate results with their clinical reproductive status, spermogram parameters and the quality of cervical mucus. Immunoglobulins of IgG and IgA isotypes were evaluated on spermatozoa by the direct immunobead technique and in serum and cervical mucus by the indirect method. The following differences were found: Nine of 14 male patients but only 1 of 7 male controls had IgG on spermatozoa (p= 0.042 and OR= 10.8. Seven out of 14 male patiens and 1 of 7 controls were positive for IgA on spermatozoa (p= 0.12. Infertile males had a higher frequency of abnormal spermogram parameters as compared to controls (p= 0.0029 and OR= 3.32. Interestingly, the presence of only IgG in serum appeared to be a "protective factor" against IgG on sperm; only one out of the 16 positive males contradicted this observation. Para determinar la presencia de anticuerpos antiespermatozoides y correlacionarla con la situación reproductiva, el espermograma y la calidad del moco cervical, se estudiaron 7 parejas sanas, con hijos, y 14 infértiles. Se determinaron por las técnicas directa e indirecta de inmunoesferas los anticuerpos de los isotipos IgG e IgA en espermatozoides, suero y moco cervical. En 9 de los 14 hombres infértiles y en 1 de los 7 fértiles se encontraron anticuerpos IgG en la superficie de los espermatozoides (p= 0.042 y una Razón de disparidad [RD] = 10.8 y 8 de éstos también tuvieron IgA en los espermatozoides. El número de pruebas alteradas en el espermograma de los hombres infértiles fue significativamente mayor (p= 0.0029 y RD = 3.32. Tanto en los hombres infértiles como en los fértiles la presencia de sólo IgG en el suero parece ser un "factor de protección" contra IgG en los espermatozoides; de los 16 hombres que presentaron anticuerpos, fuera en el suero o en los espermatozoides, s

  13. Association between anti-thyroid peroxidase and anti-cytokeratin 18 autoantibodies and bronchial asthma in women

    Directory of Open Access Journals (Sweden)

    Hala A. Mohammad

    2016-01-01

    Conclusion: Positive anti-TPO autoantibodies and anti-CK18 autoantibodies in asthmatic patients and their higher level in the non-allergic asthma group may strengthen the presence of a hidden autoimmune phenomenon in non-allergic asthma.

  14. 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

  15. Large vessel involvement by IgG4-related disease

    Science.gov (United States)

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

    2016-01-01

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

  16. 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.

  17. 14-3-3η Autoantibodies: Diagnostic Use in Early Rheumatoid Arthritis

    NARCIS (Netherlands)

    Maksymowych, Walter P.; Boire, Gilles; van Schaardenburg, Dirkjan; Wichuk, Stephanie; Turk, Samina; Boers, Maarten; Siminovitch, Katherine A.; Bykerk, Vivian; Keystone, Ed; Tak, Paul Peter; van Kuijk, Arno W.; Landewé, Robert; van der Heijde, Desiree; Murphy, Mairead; Marotta, Anthony

    2015-01-01

    To describe the expression and diagnostic use of 14-3-3η autoantibodies in early rheumatoid arthritis (RA). 14-3-3η autoantibody levels were measured using an electrochemiluminescent multiplexed assay in 500 subjects (114 disease-modifying antirheumatic drug-naive patients with early RA, 135 with

  18. Autoantibodies persist in relatives to systemic lupus erythematosus patients during 12 years follow-up

    DEFF Research Database (Denmark)

    Langkilde, Henrik; Voss, A; Heegaard, N

    2017-01-01

    BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease with presence of autoantibodies and characteristic multi-organ involvement. Relatives of SLE patients have an increased risk of autoantibody production and autoimmune diseases. METHODS: In 2001, 226 first degree relatives (FDRs...

  19. GAD65 autoantibodies in women with gestational or insulin dependent diabetes mellitus diagnosed during pregnancy

    DEFF Research Database (Denmark)

    Petersen, J S; Dyrberg, Torben Bech; Damm, P

    1996-01-01

    We have studied the presence of GAD65 autoantibodies in women with insulin-dependent diabetes mellitus (IDDM) (n = 28) or gestational diabetes (GDM) (n = 139) diagnosed during pregnancy and investigated the temporal relationship between these autoantibodies and the subsequent recurrence...

  20. Significance of myositis autoantibody in patients with idiopathic interstitial lung disease.

    Science.gov (United States)

    Song, Ju Sun; Hwang, Jiwon; Cha, Hoon-Suk; Jeong, Byeong-Ho; Suh, Gee Young; Chung, Man Pyo; Kang, Eun-Suk

    2015-05-01

    Some patients with interstitial lung disease (ILD) related to connective tissue disease (CTD) have a delayed diagnosis of the underlying CTD when the ILD is categorized as idiopathic. In this study, we evaluated the frequency of myositis autoantibodies in patients diagnosed with idiopathic ILD and investigated the clinical significance stemming from the presence of the antibodies. A total 32 patients diagnosed with idiopathic ILD were enrolled in this study. We analyzed a panel of 11 myositis autoantibody specificities in the patients using a line blot immunoassay. Then, we divided them into myositis autoantibody-positive and -negative groups and compared the clinical features and laboratory data between the two groups. Of the 32 idiopathic ILD patients, 12 patients had myositis autoantibodies encompassing 9 specificities, except for anti-Mi-2 and anti-PM-Scl 100 (12/32, 38%). Anti-synthetase autoantibodies including Jo-1, EJ, OJ, PL-7, and PL-12 were present in 7 patients (7/32, 22%). The group with myositis autoantibodies presented more frequently with the symptom of mechanic's hand and showed abnormal pulmonary function test results with low forced vital capacity, diffusing capacity for carbon monoxide, total lung capacity, and high lactate dehydrogenase values in blood when compared with the group without myositis antibodies. We strongly suggest that patients undergo an evaluation of myositis autoantibodies, if they are diagnosed with idiopathic ILD in the presence of clinical characteristics including mechanic's hand, arthralgia, and autoantibodies which are insufficient to make a diagnosis of a specific CTD category.

  1. Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes

    DEFF Research Database (Denmark)

    Wandall, Hans H; Blixt, Ola; Tarp, Mads A

    2010-01-01

    Autoantibodies to cancer antigens hold promise as biomarkers for early detection of cancer. Proteins that are aberrantly processed in cancer cells are likely to present autoantibody targets. The extracellular mucin MUC1 is overexpressed and aberrantly glycosylated in many cancers; thus, we evalua...

  2. Thyroid Autoantibodies Display both “Original Antigenic Sin” and Epitope Spreading

    OpenAIRE

    McLachlan, Sandra M.; Rapoport, Basil

    2017-01-01

    Evidence for original antigenic sin in spontaneous thyroid autoimmunity is revealed by autoantibody interactions with immunodominant regions on thyroid autoantigens, thyroglobulin (Tg), thyroid peroxidase (TPO), and the thyrotropin receptor (TSHR) A-subunit. In contrast, antibodies induced by immunization of rabbits or mice recognize diverse epitopes. Recognition of immunodominant regions persists despite fluctuations in autoantibody levels following treatment or over time. The enhancement of...

  3. Identification of novel autoantibodies for detection of malignant mesothelioma.

    Directory of Open Access Journals (Sweden)

    Xufei Zhang

    Full Text Available The malignant mesothelioma (MM survival rate has been hampered by the lack of efficient and accurate early detection methods. The immune system may detect the early changes of tumor progression by responding with tumor-associated autoantibody production. Hence, in this study, we translated the humoral immune response to cancer proteins into a potential blood test for MM.A T7 phage MM cDNA library was constructed using MM tumor tissues and biopanned for tumor-associated antigens (TAAs using pooled MM patient and normal serum samples. About 1008 individual phage TAA clones from the biopanned library were subjected to protein microarray construction and tested with 53 MM and 52 control serum samples as a training group. Nine candidate autoantibody markers were selected from the training group using Tclass system and logistic regression statistical analysis, which achieved 94.3% sensitivity and 90.4% specificity with an AUC value of 0.89 in receiver operating characteristic analysis. The classifier was further evaluated with 50 patient and 50 normal serum samples as an independent blind validation, and the sensitivity of 86.0% and the specificity of 86.0% were obtained with an AUC of 0.82. Sequencing and BLASTN analysis of the classifier revealed that five of these nine candidate markers were found to have strong homology to cancer related proteins (PDIA6, MEG3, SDCCAG3, IGHG3, IGHG1.Our results indicated that using a panel of 9 autoantibody markers presented a promising accuracy for MM detection. Although the results need further validation in high-risk groups, they provided the potentials in developing a serum-based assay for MM diagnosis.

  4. Multiplex autoantibody detection for autoimmune liver diseases and autoimmune gastritis.

    Science.gov (United States)

    Vanderlocht, Joris; van der Cruys, Mart; Stals, Frans; Bakker-Jonges, Liesbeth; Damoiseaux, Jan

    2017-09-01

    Autoantibody detection for autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and autoimmune gastritis (AIG) is traditionally performed by IIF on a combination of tissues. Multiplex line/dot blots (LIA/DIA) offer multiple advantages, i.e. automation, objective reading, no interfering reactivities, no coincidental findings. In the current study we evaluated automated DIA (D-Tek) for detecting autoantibodies related to autoimmune diseases of the gastrointestinal tract. We tested samples of the Dutch EQC program and compared the results with the consensus of the participating labs. For the autoimmune liver diseases and AIG, respectively, 64 and 36 samples were tested. For anti-mitochondrial and anti-smooth muscle antibodies a concordance rate of 97% and 88% was observed, respectively. The concordance rate for anti-parietal cell antibodies was 92% when samples without EQC consensus (n=15) were excluded. For antibodies against intrinsic factor a concordance of 96% was observed. For all these antibodies discrepancies were identified that relate to the different test characteristics and the preponderance of IIF utilizing labs in the EQC program. In conclusion, we observed good agreement of the tested DIA blots with the consensus results of the Dutch EQC program. Taken together with the logistic advantages these blots are a good alternative for autoantibody detection in the respective diseases. A large prospective multicenter study is warranted to position these novel tests further in the whole spectrum of assays for the detection of these antibodies in a routine autoimmune laboratory. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. 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.

  6. Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

    Science.gov (United States)

    Harb, Kawssar; Magrinelli, Elia; Nicolas, Céline S; Lukianets, Nikita; Frangeul, Laura; Pietri, Mariel; Sun, Tao; Sandoz, Guillaume; Grammont, Franck; Jabaudon, Denis; Studer, Michèle; Alfano, Christian

    2016-01-01

    During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features. DOI: http://dx.doi.org/10.7554/eLife.09531.001 PMID:26814051

  7. Red cell autoantibodies characterized by competitive inhibition of iodine 125 Rh alloantibody binding and by immunoprecipitation of membrane proteins

    International Nuclear Information System (INIS)

    Pierce, S.W.; Victoria, E.J.; Masouredis, S.P.

    1990-01-01

    The relationship between determinants recognized by warm-type immunoglobulin G red cell autoantibodies and the Rh antigens was characterized by autoantibody competitive inhibition of iodine 125 Rh alloantibody binding and autoantibody immunoprecipitation of iodine 125 red blood cell membrane proteins. The majority of blood donor autoantibody recognized epitopes that are closely related to Rh antigens as determined by competitive inhibition studies. Eighteen of 20 (90%) autoantibodies inhibited anti-Rh(c) binding, 15 inhibited anti-Rh(E), 5 inhibited anti-Rh(D), and only 2 failed to inhibit any of the three Rh alloantibodies tested. Autoantibodies that inhibited anti-Rh(D) also inhibited anti-Rh(c) and anti-Rh(E) and all those that inhibited anti-Rh(E) also inhibited anti-Rh(c). Autoantibodies that inhibited all three Rh alloantibodies immunoprecipitated 30 kd membrane polypeptides, as did two of the three autoantibodies that inhibited only anti-Rh(c) and anti-Rh(E). One autoantibody in this group and two autoantibodies that inhibited only anti-Rh(c), as well as an autoantibody that did not inhibit any of the Rh alloantibodies, immunoprecipitated only a single membrane polypeptide identified as band 3. The majority of normal donor red blood cell autoantibodies inhibited the binding of Rh alloantibodies, which indicates that they either bound to the Rh polypeptides or to epitopes on band 3 that were closely associated with the Rh complex

  8. Decrease in TSH Receptor Autoantibodies during Antithyroid Treatment

    DEFF Research Database (Denmark)

    Christensen, Niels Juel; Habekost, Gurli; Bratholm, Palle

    2011-01-01

    We have previously shown that a long noncoding RNA transcript Heg is negatively correlated with TSH receptor autoantibodies (TRAb) in patients with untreated Graves' disease and with CD14 mRNA in treated patients and controls. Thus patients with high concentrations of Heg RNA have low levels...... of TRAb or CD14 mRNA, respectively. Here we show that an additional factor, gene expression of Cdk1 in mononuclear cells, is positively related to concentrations of TRAb in patients with untreated Graves' disease. Cdk1 mRNA is very important for regulation of cell cycle activity. It is well known...

  9. Folinic acid treatment for schizophrenia associated with folate receptor autoantibodies.

    Science.gov (United States)

    Ramaekers, V T; Thöny, B; Sequeira, J M; Ansseau, M; Philippe, P; Boemer, F; Bours, V; Quadros, E V

    2014-12-01

    Auto-antibodies against folate receptor alpha (FRα) at the choroid plexus that block N(5)-methyltetrahydrofolate (MTHF) transfer to the brain were identified in catatonic schizophrenia. Acoustic hallucinations disappeared following folinic acid treatment. Folate transport to the CNS prevents homocysteine accumulation and delivers one-carbon units for methyl-transfer reactions and synthesis of purines. The guanosine derivative tetrahydrobiopterin acts as common co-factor for the enzymes producing dopamine, serotonin and nitric oxide. Our study selected patients with schizophrenia unresponsive to conventional treatment. Serum from these patients with normal plasma homocysteine, folate and vitamin B12 was tested for FR autoantibodies of the blocking type on serial samples each week. Spinal fluid was analyzed for MTHF and the metabolites of pterins, dopamine and serotonin. The clinical response to folinic acid treatment was evaluated. Fifteen of 18 patients (83.3%) had positive serum FR auto-antibodies compared to only 1 in 30 controls (3.3%) (χ(2)=21.6; pfolate flux to the CNS, which explained low CSF folate values in 6 and normal values in 7 patients. The mean±SD for CSF MTHF was diminished compared to previously established controls (t-test: 3.90; p=0.0002). A positive linear correlation existed between CSF MTHF and biopterin levels. CSF dopamine and serotonin metabolites were low or in the lower normal range. Administration of folinic acid (0.3-1mg/kg/day) to 7 participating patients during at least six months resulted in clinical improvement. Assessment of FR auto-antibodies in serum is recommended for schizophrenic patients. Clinical negative or positive symptoms are speculated to be influenced by the level and evolution of FRα antibody titers which determine folate flux to the brain with up- or down-regulation of brain folate intermediates linked to metabolic processes affecting homocysteine levels, synthesis of tetrahydrobiopterin and neurotransmitters

  10. Novel Association Between Immune-Mediated Susceptibility Loci and Persistent Autoantibody Positivity in Type 1 Diabetes

    DEFF Research Database (Denmark)

    Brorsson, Caroline A; Onengut, Suna; Chen, Wei-Min

    2015-01-01

    Islet autoantibodies detected at disease onset in patients with type 1 diabetes are signs of an autoimmune destruction of the insulin-producing β-cells. To further investigate the genetic determinants of autoantibody positivity, we performed dense immune-focused genotyping on the Immunochip array...... and tested for association with seven disease-specific autoantibodies in a large cross-sectional cohort of 6,160 type 1 diabetes-affected siblings. The genetic association with positivity for GAD autoantibodies (GADAs), IA2 antigen (IA-2A), zinc transporter 8, thyroid peroxidase, gastric parietal cells (PCAs...... and constitute candidates for early screening. Major susceptibility loci for islet autoantibodies are separate from type 1 diabetes risk, which may have consequences for intervention strategies to reduce autoimmunity....

  11. Pathological features of liver tissue in autoantibody-positive chronic hepatitis C patients after plasmaphoresis

    Directory of Open Access Journals (Sweden)

    WU Huili

    2018-02-01

    Full Text Available ObjectiveTo investigate the detection rate and features of autoantibodies in chronic hepatitis C (CHC patients after plasmaphoresis, as well as the liver pathological features of autoantibody-positive CHC patients. MethodsA total of 120 patients who were infected with hepatitis C virus after plasmaphoresis in the Hospital of Dingxi County and Dingxi Hospital of Infectious Diseases from January 1992 to December 1995 were selected as test group; 11 healthy people from the same region were selected as control group. Autoantibody detection was performed for the 120 CHC patients, and liver pathological features were compared between the autoantibody-positive group(n=44 and autoantibody-negative group(n=76 of these patients. The t test was used for comparison of continuous data, and the chi-square test was used for comparison of categorical data. ResultsOf all 120 CHC patients who underwent plasmaphoresis, 44 (36.7% were found to have serum autoantibodies, with antinuclear antibodies as the most common type (21.7%. Compared with the autoantibody-negative group, the autoantibody-positive group had significantly higher scores of focal necrosis inside the hepatic lobules (211±0.88 vs 164±0.88, t=2.349,P=0.021 and ductular reaction inside the portal area (1.86±0.71 vs 1.13±0.66, t=4.217,P<0.001, as well as a significantly higher rate of interlobular bile duct injury (86.4% vs 55.3%, χ2=12.129,P=0.001. There were no significant differences between the two groups in the degree of liver fibrosis and hepatic steatosis (both P>0.05. ConclusionAutoantibody-positive are common in CHC patients after plasmaphoresis, and autoantibody-positive patients tend to have more severe injuries of the liver.

  12. Polymyositis with elevated serum IgG4 levels and abundant IgG4+ plasma cell infiltration: A case report and literature review.

    Science.gov (United States)

    Anan, Ryusuke; Akiyama, Mitsuhiro; Kaneko, Yuko; Kikuchi, Jun; Suzuki, Kazuko; Matsubara, Shiro; Takeuchi, Tsutomu

    2017-12-01

    Polymyositis (PM) is a type of autoimmune, inflammatory myopathy. IgG4-related disease (IgG4-RD) is a recently recognized disease entity characterized by elevated serum IgG4 levels and IgG4 plasma-cell infiltration of various organs. However, several reports have described cases of other diseases that present with those features, suggesting the importance of careful differential diagnosis. Herein, we report the first case of PM with elevated serum IgG4 levels and IgG4 plasma cells in the muscles, mimicking IgG4-RD.A 73-year-old woman visited our hospital because of proximal muscle weakness of both thighs. Her blood test showed high levels of serum creatinine kinase, aldolase, and IgG4. Magnetic resonance imaging of the thighs showed muscle edema. Needle electromyography showed findings typical of myositis. Histological analysis of her left quadriceps revealed infiltration of IgG4 plasma cells as well as CD8 T cells. Scattered necrotic and regenerating muscle fibers with no specific findings for IgG4-RD (storiform fibrosis and obliterative phlebitis) were typical for PM. We diagnosed her condition as PM and treated her with 40 mg/day of prednisolone that decreased levels of muscle enzymes and improved muscle weakness. Our case indicated that PM could present with high serum IgG4 levels and IgG4 plasma-cell infiltration, mimicking IgG4-RD. Although the mechanism of IgG4 elevation in such PM is unclear, our case highlights the necessity to recognize that high serum IgG4 levels and IgG4 plasma-cell infiltration in organs are not specific for IgG4-RD.

  13. The apparent monovalency of human IgG4 is due to bispecificity

    NARCIS (Netherlands)

    Aalberse, R. C.; Schuurman, J.; van Ree, R.

    1999-01-01

    A hypothesis is put forward to explain the apparent monovalency of human IgG4. It is based upon the known instability of the IgG4 hinge. IgG4 is secreted as a regular bivalent antibody, but after secretion interacts with another IgG4 molecule. This interaction results in the exchange of half

  14. 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.

  15. A shark antibody heavy chain encoded by a nonsomatically rearranged VDJ is preferentially expressed in early development and is convergent with mammalian IgG.

    Science.gov (United States)

    Rumfelt, L L; Avila, D; Diaz, M; Bartl, S; McKinney, E C; Flajnik, M F

    2001-02-13

    In most vertebrate embryos and neonates studied to date unique antigen receptors (antibodies and T cell receptors) are expressed that possess a limited immune repertoire. We have isolated a subclass of IgM, IgM(1gj), from the nurse shark Ginglymostoma cirratum that is preferentially expressed in neonates. The variable (V) region gene encoding the heavy (H) chain underwent V-D-J rearrangement in germ cells ("germline-joined"). Such H chain V genes were discovered over 10 years ago in sharks but until now were not shown to be expressed at appreciable levels; we find expression of H(1gj) in primary and secondary lymphoid tissues early in life, but in adults only in primary lymphoid tissue, which is identified in this work as the epigonal organ. H(1gj) chain associates covalently with light (L) chains and is most similar in sequence to IgM H chains, but like mammalian IgG has three rather than the four IgM constant domains; deletion of the ancestral IgM C2 domain thus defines both IgG and IgM(1gj). Because sharks are the members of the oldest vertebrate class known to possess antibodies, unique or specialized antibodies expressed early in ontogeny in sharks and other vertebrates were likely present at the inception of the adaptive immune system.

  16. Use of Autoantibodies to Detect the Onset of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Jérôme Lacombe

    2014-01-01

    Full Text Available The widespread use of screening mammography has resulted in increased detection of early-stage breast disease, particularly for in situ carcinoma and early-stage breast cancer. However, the majority of women with abnormalities noted on screening mammograms are not diagnosed with cancer because of several factors, including radiologist assessment, patient age, breast density, malpractice concerns, and quality control procedures. Although magnetic resonance imaging is a highly sensitive detection tool that has become standard for women at very high risk of developing breast cancer, it lacks sufficient specificity and costeffectiveness for use as a general screening tool. Therefore, there is an important need to improve screening and diagnosis of early-invasive and noninvasive tumors, that is, in situ carcinoma. The great potential for molecular tools to improve breast cancer outcomes based on early diagnosis has driven the search for diagnostic biomarkers. Identification of tumor-specific markers capable of eliciting an immune response in the early stages of tumor development seems to provide an effective approach for early diagnosis. The aim of this review is to describe several autoantibodies identified during breast cancer diagnosis. We will focus on these molecules highlighted in the past two years and discuss the potential future use of autoantibodies as biomarkers of early-stage breast cancer.

  17. Obstetric and vascular APS: same autoantibodies but different diseases?

    Science.gov (United States)

    Meroni, P L; Raschi, E; Grossi, C; Pregnolato, F; Trespidi, L; Acaia, B; Borghi, M O

    2012-06-01

    Beta2 glycoprotein I (β2GPI)-dependent antiphospholipid antibodies (aPLs) are the main pathogenic autoantibody population and at the same time the laboratory diagnostic tool for the antiphospholipid syndrome (APS). These antibodies are responsible for both the vascular and the obstetric manifestations of the syndrome but the pathogenic mechanisms behind these manifestations are not the same. For example, thrombotic events do not appear to play a major role in APS miscarriages and a direct reactivity of β2GPI-dependent aPLs on decidual and trophoblast cells was reported. A local expression of β2GPI on these tissues was reported both in physiological conditions and in APS women, thus explaining the local tropism of the autoantibodies. The two hit hypothesis was suggested to explain why the vascular manifestations of APS may occur only occasionally in spite of the persistent presence of aPLs. This is not apparently the case for the obstetric variant of the syndrome, making the difference even more striking. A different pathogenesis may also provide the rationale for the well-known fact that the vascular and the obstetric manifestations may occur independently although in a minority of cases.

  18. Immunology of IgG4-related disease

    Science.gov (United States)

    Della-Torre, E; Lanzillotta, M; Doglioni, C

    2015-01-01

    Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition that derives its name from the characteristic finding of abundant IgG4+ plasma cells in affected tissues, as well as the presence of elevated serum IgG4 concentrations in many patients. In contrast to fibrotic disorders, such as systemic sclerosis or idiopathic pulmonary fibrosis in which the tissues fibrosis has remained largely intractable to treatment, many IgG4-RD patients appear to have a condition in which the collagen deposition is reversible. The mechanisms underlying this peculiar feature remain unknown, but the remarkable efficacy of B cell depletion in these patients supports an important pathogenic role of B cell/T cell collaboration. In particular, aberrant T helper type 2 (Th2)/regulatory T cells sustained by putative autoreactive B cells have been proposed to drive collagen deposition through the production of profibrotic cytokines, but definitive demonstrations of this hypothesis are lacking. Indeed, a number of unsolved questions need to be addressed in order to fully understand the pathogenesis of IgG4-RD. These include the identification of an antigenic trigger(s), the implications (if any) of IgG4 antibodies for pathophysiology and the precise immunological mechanisms leading to fibrosis. Recent investigations have also raised the possibility that innate immunity might precede adaptive immunity, thus further complicating the pathological scenario. Here, we aim to review the most recent insights on the immunology of IgG4-RD, focusing on the relative contribution of innate and adaptive immune responses to the full pathological phenotype of this fibrotic condition. Clinical, histological and therapeutic features are also addressed. PMID:25865251

  19. [IgG4-related disease - a case report].

    Science.gov (United States)

    Milczarek-Banach, Justyna; Brodzińska, Kinga; Jankowska, Anna; Ambroziak, Urszula; Szczepankiewicz, Benedykt; Nałęcz-Janik, Jolanta; Miśkiewicz, Piotr

    2017-09-29

    Immunoglobulin G4-related disease (IgG4-RD) is a comparatively new condition that may involve more than one organ. The lack of characteristic, pathognomonic clinical symptoms may delay the diagnosis of this disease. The diagnosis is based upon clinical manifestation, elevated serum levels of IgG4 and histopathologic examination with immunohistochemical staining to reveal infiltration of IgG4-positive plasma cells. The first line treatment is oral glucocorticoids. 38-year-old woman with Hashimoto disease, chronic sinusitis and chronic hepatitis of unknown etiology was admitted to the Department of Endocrinology because of moderate eyelids swelling accompanied by redness for 3 years. Graves' orbitopathy and systemic vasculitis were suspected, however both were excluded (negative antibodies results: anty-TSHR, ANCA, ANA). Serologic investigation of Sjögren's syndrome was also negative. In Magnetic Resonance Imaging (MRI) of orbits there were described bilateral mild extension of lateral rectus muscles, normal signal of adipose tissue and bilateral lacrimal glands enlargement. Moreover, increased IgG4 serum levels were detected. The material derived from perinasal sinuses surgery was analyzed in histopathology examination with immunohistochemical staining, which revealed characteristic features of chronic inflammatory process and increased numbers of IgG4 - positive plasma cells (>50 in a large field of view). The diagnosis of IgG4-RD was established. Because of non-effective oral methylprednisolone therapy in the past, the patient was referred to Clinic of Rheumatology for further treatment. After the therapy with methylprednisolone and azathioprine there were observed the significant reduction of symptoms. Because of lack of characteristic symptoms of IgG4- RD, it should be always considered in differential diagnosis of chronic inflammatory diseases of various organs.

  20. Characteristic tubulointerstitial nephritis in IgG4-related disease.

    Science.gov (United States)

    Yamaguchi, Yutaka; Kanetsuna, Yukiko; Honda, Kazuho; Yamanaka, Nobuaki; Kawano, Mitsuhiro; Nagata, Michio

    2012-04-01

    Nephropathy associated with IgG4-related disease is characterized by tubulointerstitial nephritis. To better identify its pathology, the present study analyzed clinicopathologic features of IgG4-related tubulointerstitial nephritis cases from across Japan. Sixteen cases were identified as IgG4-related nephropathy using the criterion of high serum IgG4 levels (>135 mg/dL) with abnormal kidney computed tomography or elevated serum creatinine levels. Male predominance (75%) and advanced age (average, 62.0 years) were noted. Eight cases displayed no autoimmune pancreatitis. Renal computed tomography abnormalities were found in 12 of 13 cases examined. Renal dysfunction was found in 15 of 16 cases at biopsy. Distinctive features of tubulointerstitial lesions included (1) well-demarcated borders between involved and uninvolved areas; (2) involvement of the cortex and medulla, often extending beyond the renal capsule and with occasional extension to retroperitoneal fibrosis; (3) interstitial inflammatory cells comprising predominantly plasma cells and lymphocytes, with a high prevalence of IgG4-positive cells often admixed with fibrosis; (4) peculiar features of interstitial fibrosis resembling a "bird's-eye" pattern comprising fibrosis among inter-plasma cell spaces; and (5) deposits visible by light and immunofluorescent microscopy in the tubular basement membrane, Bowman capsule, and interstitium that are restricted to the involved portion, sparing normal parts. Ultrastructural analysis revealed the presence of myofibroblasts with intracellular/pericellular collagen accompanied by plasma cell accumulation from an early stage. Histology could not discriminate between IgG4-related tubulointerstitial nephritis with and without autoimmune pancreatitis. In conclusion, the distinctive histologic features of IgG4-related tubulointerstitial nephritis can facilitate the differential diagnosis of tubulointerstitial nephritis, even without autoimmune pancreatitis or an abnormal

  1. Do Electrochemiluminescence Assays Improve Prediction of Time to Type 1 Diabetes in Autoantibody-Positive TrialNet Subjects?

    OpenAIRE

    Fouts, Alexandra; Pyle, Laura; Yu, Liping; Miao, Dongmei; Michels, Aaron; Krischer, Jeffrey; Sosenko, Jay; Gottlieb, Peter; Steck, Andrea K.

    2016-01-01

    OBJECTIVE To explore whether electrochemiluminescence (ECL) assays can help improve prediction of time to type 1 diabetes in the TrialNet autoantibody-positive population. RESEARCH DESIGN AND METHODS TrialNet subjects who were positive for one or more autoantibodies (microinsulin autoantibody, GAD65 autoantibody [GADA], IA-2A, and ZnT8A) with available ECL-insulin autoantibody (IAA) and ECL-GADA data at their initial visit were analyzed; after a median follow-up of 24 months, 177 of these 1,2...

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

    Directory of Open Access Journals (Sweden)

    Vasantha Nagendran

    2015-01-01

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

  3. Subtypes of the Type II Pit Pattern Reflect Distinct Molecular Subclasses in the Serrated Neoplastic Pathway.

    Science.gov (United States)

    Aoki, Hironori; Yamamoto, Eiichiro; Yamano, Hiro-O; Sugai, Tamotsu; Kimura, Tomoaki; Tanaka, Yoshihito; Matsushita, Hiro-O; Yoshikawa, Kenjiro; Takagi, Ryo; Harada, Eiji; Nakaoka, Michiko; Yoshida, Yuko; Harada, Taku; Sudo, Gota; Eizuka, Makoto; Yorozu, Akira; Kitajima, Hiroshi; Niinuma, Takeshi; Kai, Masahiro; Nojima, Masanori; Suzuki, Hiromu; Nakase, Hiroshi

    2018-03-15

    Colorectal serrated lesions (SLs) are important premalignant lesions whose clinical and biological features are not fully understood. We aimed to establish accurate colonoscopic diagnosis and treatment of SLs through evaluation of associations among the morphological, pathological, and molecular characteristics of SLs. A total of 388 premalignant and 18 malignant colorectal lesions were studied. Using magnifying colonoscopy, microsurface structures were assessed based on Kudo's pit pattern classification system, and the Type II pit pattern was subcategorized into classical Type II, Type II-Open (Type II-O) and Type II-Long (Type II-L). BRAF/KRAS mutations and DNA methylation of CpG island methylator phenotype (CIMP) markers (MINT1, - 2, - 12, - 31, p16, and MLH1) were analyzed through pyrosequencing. Type II-O was tightly associated with sessile serrated adenoma/polyps (SSA/Ps) with BRAF mutation and CIMP-high. Most lesions with simple Type II or Type II-L were hyperplastic polyps, while mixtures of Type II or Type II-L plus more advanced pit patterns (III/IV) were characteristic of traditional serrated adenomas (TSAs). Type II-positive TSAs frequently exhibited BRAF mutation and CIMP-low, while Type II-L-positive TSAs were tightly associated with KRAS mutation and CIMP-low. Analysis of lesions containing both premalignant and cancerous components suggested Type II-L-positive TSAs may develop into KRAS-mutated/CIMP-low/microsatellite stable cancers, while Type II-O-positive SSA/Ps develop into BRAF-mutated/CIMP-high/microsatellite unstable cancers. These results suggest that Type II subtypes reflect distinct molecular subclasses in the serrated neoplasia pathway and that they could be useful hallmarks for identifying SLs at high risk of developing into CRC.

  4. Taxonomic resolutions based on 18S rRNA genes: a case study of subclass copepoda.

    Directory of Open Access Journals (Sweden)

    Shu Wu

    Full Text Available Biodiversity studies are commonly conducted using 18S rRNA genes. In this study, we compared the inter-species divergence of variable regions (V1-9 within the copepod 18S rRNA gene, and tested their taxonomic resolutions at different taxonomic levels. Our results indicate that the 18S rRNA gene is a good molecular marker for the study of copepod biodiversity, and our conclusions are as follows: 1 18S rRNA genes are highly conserved intra-species (intra-species similarities are close to 100%; and could aid in species-level analyses, but with some limitations; 2 nearly-whole-length sequences and some partial regions (around V2, V4, and V9 of the 18S rRNA gene can be used to discriminate between samples at both the family and order levels (with a success rate of about 80%; 3 compared with other regions, V9 has a higher resolution at the genus level (with an identification success rate of about 80%; and 4 V7 is most divergent in length, and would be a good candidate marker for the phylogenetic study of Acartia species. This study also evaluated the correlation between similarity thresholds and the accuracy of using nuclear 18S rRNA genes for the classification of organisms in the subclass Copepoda. We suggest that sample identification accuracy should be considered when a molecular sequence divergence threshold is used for taxonomic identification, and that the lowest similarity threshold should be determined based on a pre-designated level of acceptable accuracy.

  5. Glycotoxin and Autoantibodies Are Additive Environmentally Determined Predictors of Type 1 Diabetes

    Science.gov (United States)

    Beyan, Huriya; Riese, Harriette; Hawa, Mohammed I.; Beretta, Guisi; Davidson, Howard W.; Hutton, John C.; Burger, Huibert; Schlosser, Michael; Snieder, Harold; Boehm, Bernhard O.; Leslie, R. David

    2012-01-01

    In type 1 diabetes, diabetes-associated autoantibodies, including islet cell antibodies (ICAs), reflect adaptive immunity, while increased serum Nε-carboxymethyl-lysine (CML), an advanced glycation end product, is associated with proinflammation. We assessed whether serum CML and autoantibodies predicted type 1 diabetes and to what extent they were determined by genetic or environmental factors. Of 7,287 unselected schoolchildren screened, 115 were ICA+ and were tested for baseline CML and diabetes autoantibodies and followed (for median 7 years), whereas a random selection (n = 2,102) had CML tested. CML and diabetes autoantibodies were determined in a classic twin study of twin pairs discordant for type 1 diabetes (32 monozygotic, 32 dizygotic pairs). CML was determined by enzyme-linked immunosorbent assay, autoantibodies were determined by radioimmunoprecipitation, ICA was determined by indirect immunofluorescence, and HLA class II genotyping was determined by sequence-specific oligonucleotides. CML was increased in ICA+ and prediabetic schoolchildren and in diabetic and nondiabetic twins (all P < 0.001). Elevated levels of CML in ICA+ children were a persistent, independent predictor of diabetes progression, in addition to autoantibodies and HLA risk. In twins model fitting, familial environment explained 75% of CML variance, and nonshared environment explained all autoantibody variance. Serum CML, a glycotoxin, emerged as an environmentally determined diabetes risk factor, in addition to autoimmunity and HLA genetic risk, and a potential therapeutic target. PMID:22396204

  6. Myositis-specific autoantibodies: an important tool to support diagnosis of myositis.

    Science.gov (United States)

    Betteridge, Z; McHugh, N

    2016-07-01

    The idiopathic inflammatory myopathies are characterized by muscle weakness, skin disease and internal organ involvement. Autoimmunity is known to have a role in myositis pathogenesis, and myositis-specific autoantibodies, targeting important intracellular proteins, are regarded as key biomarkers aiding in the diagnosis of patients. In recent years, a number of novel myositis autoantibodies including anti-TIF1, anti-NXP2, anti-MDA5, anti-SAE, anti-HMGCR and anti-cN1A have been identified in both adult and juvenile patients. These autoantibodies correlate with distinct clinical manifestations and importantly are found in inclusion body, statin-induced, clinically amyopathic and juvenile groups of myositis patients, previously believed to be mainly autoantibody negative. In this review, we will describe the main myositis-specific and myositis-associated autoantibodies and their frequencies and clinical associations across different ages and ethnic groups. We will also discuss preliminary studies investigating correlations between specific myositis autoantibody titres and clinical markers of disease course, collectively demonstrating the utility of myositis autoantibodies as both diagnostic and prognostic markers of disease. © 2015 The Association for the Publication of the Journal of Internal Medicine.

  7. Hybrid IgG4/IgG4 Fc antibodies form upon 'Fab-arm' exchange as demonstrated by SDS-PAGE or size-exclusion chromatography

    NARCIS (Netherlands)

    Rispens, Theo; den Bleker, Tamara H.; Aalberse, Rob C.

    2010-01-01

    Human IgG4 antibodies are dynamic molecules that in vivo exchange half-molecules to become bispecific antibodies. Here we show that IgG4 antibodies and IgG4 Fc fragments similarly exchange resulting in hybrid antibodies (a single Fab + Fc) with a molecular weight of ca. 100 kDa. These antibodies can

  8. Serologic aspects of IgG4 antibodies. II. IgG4 antibodies form small, nonprecipitating immune complexes due to functional monovalency

    NARCIS (Netherlands)

    van der Zee, J. S.; van Swieten, P.; Aalberse, R. C.

    1986-01-01

    Human IgG4 antibodies directed against phospholipase A, the P1 antigen from Dermatophagoïdes pteronyssinus extracts, and cat albumin were found unable to cross-link antigen. Previously, it was demonstrated that IgG4 antibodies, in contrast to IgG1 antibodies, did not cross-link Sepharose-bound

  9. Biochemical Characterization of CPS-1, a Subclass B3 Metallo-β-Lactamase from a Chryseobacterium piscium Soil Isolate

    DEFF Research Database (Denmark)

    Gudeta, Dereje Dadi; Pollini, Simona; Docquier, Jean-Denis

    2016-01-01

    CPS-1 is a subclass B3 metallo-β-lactamase from a Chryseobacterium piscium isolated from soil, showing 68 % amino acid identity to GOB-1 enzyme. CPS-1 was overproduced in Escherichia coli Rosetta (DE3), purified by chromatography and biochemically characterized. This enzyme exhibits a broad spect...... spectrum substrate profile including penicillins, cephalosporins and carbapenems, which overall resembles those of L1, GOB-1 and acquired subclass B3 enzymes AIM-1 and SMB-1....

  10. Immunoradiometric assay for cytomegalovirus-specific IgG antibodies

    International Nuclear Information System (INIS)

    Klapper, P.E.; Cleator, G.M.; Prinja-Wolks, D.; Morris, D.J.

    1990-01-01

    An immunoradiometric assay (radio-immunosorbent test; RIST) for the detection of IgG antibodies to human herpesvirus 4 [human cytomegalovirus (CMV)] has been developed. The technique utilizes CMV antigen passively adsorbed to a polyvinyl microtitration plate and a radiolabelled murine monoclonal anti-human IgG antibody to detect binding of human antibody to the 'solid phase' reagent. The assay was optimized, and its specifity confirmed by testing paired acute and convalescent sera from patients with acute CMV or other human herpesvirus infections. To determine the assay's sensitivity 1433 blood donor sera were examined. The RIST was more sensitive than a standard complement fixation (CFT). Use of a monoclonal anti-human IgG antibody in the RIST reduced non-specific binding to the control uninfected cell antigen such that blood donor sera could be tested in the assay using only a CMV antigen without generating an unacceptable false positive rate. (author). 23 refs.; 1 tab

  11. Degenerated human intervertebral discs contain autoantibodies against extracellular matrix proteins

    Directory of Open Access Journals (Sweden)

    S Capossela

    2014-04-01

    Full Text Available Degeneration of intervertebral discs (IVDs is associated with back pain and elevated levels of inflammatory cells. It has been hypothesised that discogenic pain is a direct result of vascular and neural ingrowth along annulus fissures, which may expose the avascular nucleus pulposus (NP to the systemic circulation and induce an autoimmune reaction. In this study, we confirmed our previous observation of antibodies in human degenerated and post-traumatic IVDs cultured in vitro. We hypothesised that the presence of antibodies was due to an autoimmune reaction against specific proteins of the disc. Furthermore we identified antigens which possibly trigger an autoimmune response in degenerative disc diseases. We demonstrated that degenerated and post-traumatic IVDs contain IgG antibodies against typical extracellular proteins of the disc, particularly proteins of the NP. We identified IgGs against collagen type II and aggrecan, confirming an autoimmune reaction against the normally immune privileged NP. We also found specific IgGs against collagens types I and V, but not against collagen type III. In conclusion, this study confirmed the association between disc degeneration and autoimmunity, and may open the avenue for future studies on developing prognostic, diagnostic and therapy-monitoring markers for degenerative disc diseases.

  12. 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 IgG4+ count, P 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.

  13. Anti-dog IgG secondary antibody successfully detects IgG in a variety of aquatic mammals

    Science.gov (United States)

    Roehl, Katherine; Jankowski, Mark D.; Hofmeister, Erik K.

    2016-01-01

    Serological tests play an important role in the detection of wildlife diseases. However, while there are many commercial assays and reagents available for domestic species, there is a need to develop efficient serological assays for wildlife. In recent years, marine mammals have represented a wildlife group with emerging infectious diseases, such as influenza, brucellosis, and leptospirosis. However, with the exception of disease-agent-specific assays or functional assays, few reports describe the use of antibody detection assays in marine mammals. In an indirect enzyme-linked immunoassay (EIA) or an immunofluorescence assay, antibody is detected using an antitarget species secondary conjugated antibody. The sensitivity of the assay depends on the avidity of the binding reaction between the bound antibody and the detection antibody. A commercial polyclonal antidog IgG conjugated antibody was tested in an EIA for its ability to sensitively detect the IgG of seven marine mammals including sea otter (Enhydra lutris), polar bear (Ursus maritimus), grey seal (Halichoerus grypus), harbor seal (Phoca vitulina), northern elephant seal (Mirounga angustirostris), California sea lion (Zalophus californianus), Pacific walrus (Odobenus rosmarus) and one freshwater mammal: Asian small-clawed otter (Aonyx cinerea). With the exception of Asian small-clawed sea otters, the detection of IgG in these marine mammals either exceeded or was nearly equal to detection of dog IgG. The use of the tested commercial antidog IgG antibody may be a valid approach to the detection of antibody response to disease in sea mammals.

  14. Antibodies to AB blood group antigens mimic anti-salivary duct autoantibodies in patients with limited sicca symptoms.

    Science.gov (United States)

    Goldblatt, F; Beroukas, D; Gillis, D; Cavill, D; Bradwell, A; Rischmueller, M; Gordon, T P

    2000-10-01

    We evaluated the clinical relevance and pathogenic significance of anti-salivary duct autoantibodies (ASDA) in Sjögren's syndrome (SS) and rheumatoid arthritis (RA) by examining (1) their frequency in healthy controls, patients with sicca symptoms, and patients with various autoimmune and infective disorders; (2) their localization by confocal microscopy; and (3) their tissue distribution and cross reactivity with blood group antigens. Indirect immunofluorescence (IF) was performed on commercial cryostat sections of monkey parotid salivary gland. Sections were examined by fluorescence and confocal laser scanning microscopy. Sera giving positive staining on the ducts were tested by IF on a range of monkey tissues and salivary glands from several mammalian species. Blocking experiments were performed with human erythrocytes of different ABO blood groups and AB antigens. We identified 2 distinct ductal staining patterns. The first resembled ASDA described in earlier studies and showed patchy bright staining of the apical (luminal) surfaces of the ducts and staining of apical cytoplasmic vesicles. The other was only observed with anti-mitochondrial antibody positive sera and stained the mitochondrial-rich ductal epithelium in a distinctive punctate pattern. Antibodies staining the apical surface of ducts were detected rarely in patients with antiRo/La autoantibody-positive primary SS (1/76) and RA (1/36) and were found in only 1115 with RA and secondary SS. ASDA were detected in sera from 13/51 (25.5%) of patients referred to our clinic with limited sicca symptoms who were anti-Ro/La antibody-negative and had no typical clinical or laboratory features of classical primary SS. The apical ductal staining pattern was not observed with sera from 63 healthy controls without sicca symptoms or in patients with autoimmune and infective disorders. Twelve of the 13 patients whose sera gave ASDA-like staining were blood group O and one group A. Ductal staining was abolished in

  15. Determination of autoantibodies to annexin XI in systemic autoimmune diseases

    DEFF Research Database (Denmark)

    Jorgensen, C S; Levantino, G; Houen, Gunnar

    2000-01-01

    Annexin XI, a calcyclin-associated protein, has been shown to be identical to a 56,000 Da antigen recognized by antibodies found in sera from patients suffering from systemic autoimmune diseases. In this work hexahistidine-tagged recombinant annexin XI (His6- rAnn XI) was used as antigen in ELISA...... experiments for determination of autoantibodies to annexin XI in sera of patients with systemic rheumatic autoimmune diseases. Immunoblotting with HeLa cell extract and with His6-rAnn XI as antigen was used for confirmation of positive ELISA results. We found eleven anti-annexin XI positive sera (3.9%) out...... of 282 sera from patients with systemic rheumatic diseases. The highest number of annexin XI positive sera were found in primary antiphospholipid syndrome (3/17), and in subacute lupus erythematosus (1/6), while lower frequencies of positive sera were found in patients with systemic sclerosis (5...

  16. Autoantibody Profiling in Lupus Patients using Synthetic Nucleic Acids

    DEFF Research Database (Denmark)

    Klecka, Martin; Thybo, Christina; Macaubas, Claudia

    2018-01-01

    specificity and reproducibility. Applying the ELISA tests to serological studies of pediatric and adult SLE, we identified novel clinical correlations. We also observed preferential recognition of a specific synthetic antigen by antibodies in SLE sera. We determined the probable basis for this finding using...... computational analyses, providing valuable structural information for future development of DNA antigens. Synthetic nucleic acid molecules offer the opportunity to standardize assays and to dissect antibody-antigen interactions.......Autoantibodies to nuclear components of cells (antinuclear antibodies, ANA), including DNA (a-DNA), are widely used in the diagnosis and subtyping of certain autoimmune diseases, including systemic lupus erythematosus (SLE). Despite clinical use over decades, precise, reproducible measurement of a...

  17. Evaluation of anti-Schistosoma mansoni igG antibodies in patients with chronic schistosomiasis mansoni before and after specific treatment Avaliação da presença de anticorpos IgG anti-Schistosoma mansoni no soro de pacientes com esquistossomose mansônica crônica, antes e após tratamento específico

    Directory of Open Access Journals (Sweden)

    Célia Maria V. VENDRAME

    2001-06-01

    observado no caso de anticorpos da subclasse IgG2. Nos imunoblottings efetuados com o emprego de antígeno de verme adulto (AWA, antes do tratamento com oxamniquine, evidenciou-se a presença de banda com 31 kDa em 14 (82% dos 17 pacientes estudados, observando-se seu desaparecimento em três pacientes examinados seis meses após tratamento específico. Quando se utilizou antígeno obtido a partir de ovos de S. mansoni (SEA a mesma banda foi evidenciada em nove pacientes, desaparecendo em quatro casos, após o tratamento.

  18. What is IgG4? A review of the biology of a unique immunoglobulin subtype.

    Science.gov (United States)

    Nirula, Ajay; Glaser, Scott M; Kalled, Susan L; Taylor, Frederick R; Taylora, Frederick R

    2011-01-01

    Recent descriptions of the group of clinical disorders collectively defined as IgG4-related systemic disease (IgG4-RSD) have prompted this review of the unique biology of the IgG4 antibody. This article will discuss IgG4 structure and function, the unique phenomenon of half-antibody exchange, and the implications of IgG4 biology for its proposed role in immunologic diseases. IgG4 antibodies have unique structural and functional properties and undergo 'half-antibody exchange' in vivo, resulting in recombined antibodies composed of two different binding specificities. The production of IgG4 antibodies appears to be driven in part by T helper 2 (Th2) cytokines that mediate allergic responses and IgE production. Although serum IgG4 levels in healthy individuals vary significantly, data from multiple sclerosis (MS) patients suggest tight regulation of individual IgG4 levels over time. IgG4-RSD represents a diverse group of clinical disorders unified by elevated IgG4 levels and specific histopathologic findings. A key unanswered question is whether IgG4, a relatively weak activator of effector cells, is pathogenic in these disorders. IgG4 is a unique antibody biologically and structurally. Increased understanding of its precise role in the clinical syndromes that comprise IgG4-RSD may ultimately elucidate the underlying pathogenesis.

  19. Musculoskeletal manifestations and autoantibodies in children and adolescents with leprosy

    Directory of Open Access Journals (Sweden)

    Luciana Neder

    2014-09-01

    Full Text Available Objective: To evaluate musculoskeletal involvement and autoantibodies in pediatric leprosy patients. Methods: 50 leprosy patients and 47 healthy children and adolescents were assessed according to musculoskeletal manifestations (arthralgia, arthritis, and myalgia, musculoskeletal pain syndromes (juvenile fibromyalgia, benign joint hypermobility syndrome, myofascial syndrome, and tendinitis, and a panel of autoantibodies and cryoglobulins. Health assessment scores and treatment were performed in leprosy patients. Results: At least one musculoskeletal manifestation was observed in 14% of leprosy patients and in none of the controls. Five leprosy patients had asymmetric polyarthritis of small hands joints. Nerve function impairment was observed in 22% of leprosy patients, type 1 leprosy reaction in 18%, and silent neuropathy in 16%. None of the patients and controls presented musculoskeletal pain syndromes, and the frequencies of all antibodies and cyoglobulins were similar in both groups (p > 0.05. Further analysis of leprosy patients demonstrated that the frequencies of nerve function impairment, type 1 leprosy reaction, and silent neuropathy were significantly observed in patients with versus without musculoskeletal manifestations (p = 0.0036, p = 0.0001, and p = 0.309, respectively, as well as multibacillary subtypes in leprosy (86% vs. 42%, p = 0.045. The median of physicians' visual analog scale (VAS, patients' VAS, pain VAS, and Childhood Health Assessment Questionnaire (CHAQ were significantly higher in leprosy patients with musculoskeletal manifestations (p = 0.0001, p = 0.002, p = 0002, and p = 0.001, respectively. Conclusions: This was the first study to identify musculoskeletal manifestations associated with nerve dysfunction in pediatric leprosy patients. Hansen's disease should be included in the differential diagnosis of asymmetric arthritis, especially in endemic regions.

  20. Change of Serum IgG4 in Patients with Ocular Adnexal Marginal Zone B Cell Lymphoma Associated with IgG4-Related Ophthalmic Disease After Treatment.

    Science.gov (United States)

    Wu, Yuan-Hung; Wang, Lei-Chi; Yen, Sang-Hue; Yu, Wei-Kuang; Kao, Shu-Ching; Kau, Hui-Chuan; Tsai, Chieh-Chih; Liu, Catherine Jui-Ling

    2017-09-01

    To investigate the change of serum IgG4 concentrations correlated with clinical evolution in patients with ocular adnexal marginal zone B cell lymphoma associated with IgG4-related ophthalmic disease (IgG4-ROD). Three consecutive patients with histopathologically confirmed ocular adnexal marginal zone B cell lymphoma associated with IgG4-ROD were evaluated. Two patients received radiotherapy and 1 patient received steroid therapy. Treatment outcome was evaluated by clinical symptoms, radiologic examination, and change of serum IgG4 level in these patients. All patients had elevated serum IgG4 before treatment (462, 338, and 780 mg/dL respectively.) The 2 patients who received radiotherapy achieved complete remission and the serum IgG4 decreased to 345 and 92 mg/dL, respectively. The patient who underwent systemic steroid achieved partial remission and the serum IgG4 decrease to 161 mg/dL. Our study showed elevated serum IgG4 in all patients with ocular adnexal marginal zone B cell lymphoma associated with IgG4-ROD. In addition, the elevated serum IgG4 may decrease or keep stable after treatment, accompanied by improvement in clinical symptoms and reduction of lesions.

  1. 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 thyroiditis was diagnosed in 23 of the 24 IgG4-related cases (96 %) and in 13 of 167 (18 %, p > 0.001) non-IgG4-related cases. The single case of IgG4-related Riedel's thyroiditis also showed a higher median IgG4 plasma cell count (56.3 vs. 14.3) and a higher IgG4/IgG ratio (0.5 vs. 0.2) than the four cases of non-IgG4-related Riedel's thyroiditis. Our data suggests the incidence of IgG4-related disease (IgG4-RD) of the thyroid gland in Europe is considerably lower than that observed in other studies. A significant elevation of IgG4-positive plasma cells was only found in a small group of Hashimoto's thyroiditis and then accompanied by intense fibrosis, indicating an association with IgG4-RD. Morphologically, IgG4-RD of the thyroid gland differs from that in other organ systems, exhibiting a dense fibrosis without intense eosinophilia or obliterative phlebitis.

  2. Estimation of polyclonal IgG4 hybrids in normal human serum.

    Science.gov (United States)

    Young, Elizabeth; Lock, Emma; Ward, Douglas G; Cook, Alexander; Harding, Stephen; Wallis, Gregg L F

    2014-07-01

    The in vivo or in vitro formation of IgG4 hybrid molecules, wherein the immunoglobulins have exchanged half molecules, has previously been reported under experimental conditions. Here we estimate the incidence of polyclonal IgG4 hybrids in normal human serum and comment on the existence of IgG4 molecules with different immunoglobulin light chains. Polyclonal IgG4 was purified from pooled or individual donor human sera and sequentially fractionated using light-chain affinity and size exclusion chromatography. Fractions were analysed by SDS-PAGE, immunoblotting, ELISA, immunodiffusion and matrix-assisted laser-desorption mass spectrometry. Polyclonal IgG4 purified from normal serum contained IgG4κ, IgG4λ and IgG4κ/λ molecules. Size exclusion chromatography showed that IgG4 was principally present in monomeric form (150 000 MW). SDS-PAGE, immunoblotting and ELISA showed the purity of the three IgG4 samples. Immunodiffusion, light-chain sandwich ELISA and mass spectrometry demonstrated that both κ and λ light chains were present on only the IgG4κ/λ molecules. The amounts of IgG4κ/λ hybrid molecules ranged from 21 to 33% from the five sera analysed. Based on the molecular weight these molecules were formed of two IgG4 heavy chains plus one κ and one λ light chain. Polyclonal IgG (IgG4-depleted) was similarly fractionated according to light-chain specificity. No evidence of hybrid IgG κ/λ antibodies was observed. These results indicate that hybrid IgG4κ/λ antibodies compose a substantial portion of IgG4 from normal human serum. © 2014 John Wiley & Sons Ltd.

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

    NARCIS (Netherlands)

    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

    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

  4. Simultaneous occurrence of fetal and neonatal alloimmune thrombocytopenia and neonatal neutropenia due to maternal neutrophilic autoantibodies

    DEFF Research Database (Denmark)

    Taaning, Ellen; Jensen, Lise; Varming, Kim

    2012-01-01

    Foetal and neonatal alloimmune thrombocytopenia (FNAIT) and neonatal neutropenia caused by maternal autoantibodies against neutrophils are rare disorders. We describe a newborn with severe thrombocytopenia and intracerebral bleeding caused by maternal anti-HPA-3a alloantibodies and mild neutropenia...

  5. Anti-C1q autoantibodies in patients with neuromyelitis optica spectrum disorders.

    Science.gov (United States)

    Yoshikura, Nobuaki; Kimura, Akio; Hayashi, Yuichi; Inuzuka, Takashi

    2017-09-15

    We examined anti-complement C1q (C1q) autoantibody levels in serum and cerebrospinal fluid (CSF) samples of patients with neuromyelitis optica spectrum disorders (NMOSD). We analyzed the correlations between anti-C1q autoantibody levels and the clinical and other CSF characteristics of NMOSD. Serum and CSF anti-C1q autoantibody levels increased during the acute phase of NMOSD, reverting to the same levels as controls during remission. CSF anti-C1q autoantibody levels during the acute phase correlated with several markers reflecting disease severity, Expanded Disability Status Scale worsening, spinal cord lesion length in cases with myelitis, CSF protein and interleukin-6 levels, and CSF/serum albumin ratios. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Specific removal of autoantibodies by extracorporeal immunoadsorption ameliorates experimental autoimmune myasthenia gravis.

    Science.gov (United States)

    Lazaridis, Konstantinos; Dalianoudis, Ioannis; Baltatzidi, Vasiliki; Tzartos, Socrates J

    2017-11-15

    Myasthenia gravis (MG) is caused by autoantibodies, the majority of which target the muscle acetylcholine receptor (AChR). Plasmapheresis and IgG-immunoadsorption are useful therapy options, but are highly non-specific. Antigen-specific immunoadsorption would remove only the pathogenic autoantibodies, reducing the possibility of side effects while maximizing the benefit. We have extensively characterized such adsorbents, but in vivo studies are missing. We used rats with experimental autoimmune MG to perform antigen-specific immunoadsorptions over three weeks, regularly monitoring symptoms and autoantibody titers. Immunoadsorption was effective, resulting in a marked autoantibody titer decrease while the immunoadsorbed, but not the mock-treated, animals showed a dramatic symptom improvement. Overall, the procedure was found to be efficient, suggesting the subsequent initiation of clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. ORIGINAL ARTICLE RUBELLA IgG ANTIBODY AMONG NIGERIAN ...

    African Journals Online (AJOL)

    boaz

    capable of causing a spectrum of birth defects described as congenital rubella syndrome (CRS). Despite the availability of safe and effective ... designed to determine the prevalence of anti- rubella IgG among pregnant women in order to ..... Vyse A.J., Gay N.J., White J.M., Ramsay. M.E., Brown D.W., Cohen B.J. Evolution.

  8. Astrocytic autoantibody of neuromyelitis optica (NMO-IgG) binds to aquaporin-4 extracellular loops, monomers, tetramers and high order arrays

    Science.gov (United States)

    Iorio, Raffaele; Fryer, James P.; Hinson, Shannon R.; Fallier-Becker, Petra; Wolburg, Hartwig; Pittock, Sean J.; Lennon, Vanda A.

    2012-01-01

    The principal central nervous system (CNS) water channel, aquaporin-4 (AQP4), is confined to astrocytic and ependymal membranes and is the target of a pathogenic autoantibody, neuromyelitis optica (NMO)-IgG. This disease-specific autoantibody unifies a spectrum of relapsing CNS autoimmune inflammatory disorders of which NMO exemplifies the classic phenotype. Multiple sclerosis and other immune-mediated demyelinating disorders of the CNS lack a distinctive biomarker. Two AQP4 isoforms, M1 and M23, exist as homotetrameric and heterotetrameric intramembranous particles (IMPs). Orthogonal arrays of predominantly M23 particles (OAPs) are an ultrastructural characteristic of astrocytic membranes. We used high-titered serum from 32 AQP4-IgG-seropositive patients and 85 controls to investigate the nature and molecular location of AQP4 epitopes that bind NMO-IgG, and the influence of supramolecular structure. NMO-IgG bound to denatured AQP4 monomers (68% of cases), to native tetramers and high order arrays (90% of cases), and to AQP4 in live cell membranes (100% of cases). Disease-specific epitopes reside in extracellular loop C more than in loops A or E. IgG binding to intracellular epitopes lacks disease specificity. These observations predict greater disease specificity and sensitivity for tissue-based and cell-based serological assays employing “native” AQP4 than assays employing denatured AQP4 and fragments. NMO-IgG binds most avidly to plasma membrane surface AQP4 epitopes formed by loop interactions within tetramers and by intermolecular interactions within high order structures. The relative abundance and localization of AQP4 high order arrays in distinct CNS regions may explain the variability in clinical phenotype of NMO spectrum disorders. PMID:22906356

  9. Thyroid Autoantibodies and the Clinical Presentation of Moyamoya Disease: A Prospective Study.

    Science.gov (United States)

    Lanterna, Luigi A; Galliani, Silvia; Zangari, Rosalia; Conti, Luciano; Brembilla, Carlo; Gritti, Paolo; Colleoni, Maria Luisa; Bernucci, Claudio

    2018-05-01

    Moyamoya is a rare cerebrovascular disease characterized by the progressive occlusion of the intracranial carotid artery. Thyroid autoantibodies have been found to be associated with the disease, but their clinical significance has never been studied. The objective of this study was to investigate the relationship between thyroid autoantibodies and the clinical presentation of moyamoya. This is a prospective study including 37 patients with moyamoya disease (MMD) or unilateral moyamoya (uMM). Thyroid function and thyroid autoantibodies (e.g., antithyroperoxidase and antithyroglobulin) were investigated. We studied the effect of gender, age, type of moyamoya (uMM versus MMD), and thyroid autoantibodies on the clinical presentation, dichotomized into aggressive (hemorrhage, major stroke, or frequent transient ischemic attack [TIA]) and nonaggressive presentation (headache, rare TIAs, and incidental diagnosis) according to the criteria of the Research Committee on Spontaneous Occlusion of the Circle of Willis. Of the 37 patients included in the study, the autoantibodies were elevated in 9 (24.3%). An aggressive presentation occurred in 21 patients (hemorrhage in 11, major stroke in 9, frequent TIAs in 1). The autoantibodies were elevated in 8 of the 21 patients (38.09%) with an aggressive presentation and in 1 of those presenting with minor symptoms (6.2%). The presence of elevated autoantibodies was the only variable associated with an aggressive presentation in the multivariate logistic analysis (P = .048). When the serum concentration of the thyroid autoantibodies is increased, the patients have a higher risk of an aggressive presentation. Our results support the hypothesis that activation of immune-mediated processes affects the moyamoya physiopathology. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  10. Autoantibody to MDM2: A Potential Serological Marker of Systemic Lupus Erythematosus

    OpenAIRE

    Liu, Yuan; Dai, Liping; Liu, Weihong; Shi, Guixiu; Zhang, Jianying

    2015-01-01

    Introduction. Systemic lupus erythematosus (SLE) is one of the systemic autoimmune diseases characterized by the polyclonal autoantibody production. The human homologue of the mouse double minute 2 (MDM2) is well known as the negative regulator of p53. MDM2 has been reported to be overexpressed in SLE animal model and to promote SLE. Since abnormally expressed proteins can induce autoimmune response, anti-MDM2 autoantibody was examined in SLE patients. Methods. Anti-MDM2 antibody in sera from...

  11. AUTOANTIBODIES TO GLUTAMIC ACID DECARBOXYLASE AS A PATHOGENETIC MARKER OF TYPE I DIABETES MELLITUS

    OpenAIRE

    N. V. Piven; L. N. Lukhverchyk; A. I. Burakovsky; N. V. Polegenkaya; M. V. Karpovich

    2011-01-01

    Abstract. A new method of enzyme-linked immunosorbent assay (in solid-phase ELISA format) has been developed to determine concentrations of autoantibodies to glutamic acid decarboxylase, as well as an evidencebased methodology is proposed for its medical implications, as a quantitative pathogenetic predictive marker of autoimmune diagnostics in type 1 diabetes mellitus. This technique could be implied for serial production of diagnostic reagent kits, aimed for detection of autoantibodies to g...

  12. The Emerging Importance of Non-HLA Autoantibodies in Kidney Transplant Complications

    OpenAIRE

    Cardinal, Héloise; Dieudé, Mélanie; Hébert, Marie-Josée

    2016-01-01

    Antibodies that are specific to organ donor HLA have been involved in the majority of cases of antibody-mediated rejection in solid organ transplant recipients. However, recent data show that production of non-HLA autoantibodies can occur before transplant in the form of natural autoantibodies. In contrast to HLAs, which are constitutively expressed on the cell surface of the allograft endothelium, autoantigens are usually cryptic. Tissue damage associated with ischemia-reperfusion, vascular ...

  13. Autoantibodies directed to centromere protein F in a patient with BRCA1 gene mutation

    OpenAIRE

    Moghaddas, Fiona; Joshua, Fredrick; Taylor, Roberta; Fritzler, Marvin J.; Toh, Ban Hock

    2016-01-01

    Background Autoantibodies directed to centromere protein F were first reported in 1993 and their association with malignancy has been well documented. Case We present the case of a 48-year-old Caucasian female with a BRCA1 gene mutation associated with bilateral breast cancer. Antinuclear autoantibody immunofluorescence performed for workup of possible inflammatory arthropathy showed a high titre cell cycle related nuclear speckled pattern, with subsequent confirmation by addressable laser be...

  14. Hello from the Other Side: How Autoantibodies Circumvent the Blood–Brain Barrier in Autoimmune Encephalitis

    Directory of Open Access Journals (Sweden)

    Tyler Cutforth

    2017-04-01

    Full Text Available Antibodies against neuronal receptors and synaptic proteins are associated with autoimmune encephalitides (AE that produce movement and psychiatric disorders. In order to exert their pathological effects on neural circuits, autoantibodies against central nervous system (CNS targets must gain access to the brain and spinal cord by crossing the blood–brain barrier (BBB, a tightly regulated gateway formed by endothelial cells lining CNS blood vessels. To date, the pathogenic mechanisms that underlie autoantibody-triggered encephalitic syndromes are poorly understood, and how autoantibodies breach the barrier remains obscure for almost all AE syndromes. The relative importance of cellular versus humoral immune mechanisms for disease pathogenesis also remains largely unexplored. Here, we review the proposed triggers for various autoimmune encephalopathies and their animal models, as well as basic structural features of the BBB and how they differ among various CNS regions, a feature that likely underlies some regional aspects of autoimmune encephalitis pathogenesis. We then discuss the routes that antibodies and immune cells employ to enter the CNS and their implications for AE. Finally, we explore future therapeutic strategies that may either preserve or restore barrier function and thereby limit immune cell and autoantibody infiltration into the CNS. Recent mechanistic insights into CNS autoantibody entry indicate promising future directions for therapeutic intervention beyond current, short-lived therapies that eliminate circulating autoantibodies.

  15. Hello from the Other Side: How Autoantibodies Circumvent the Blood-Brain Barrier in Autoimmune Encephalitis.

    Science.gov (United States)

    Platt, Maryann P; Agalliu, Dritan; Cutforth, Tyler

    2017-01-01

    Antibodies against neuronal receptors and synaptic proteins are associated with autoimmune encephalitides (AE) that produce movement and psychiatric disorders. In order to exert their pathological effects on neural circuits, autoantibodies against central nervous system (CNS) targets must gain access to the brain and spinal cord by crossing the blood-brain barrier (BBB), a tightly regulated gateway formed by endothelial cells lining CNS blood vessels. To date, the pathogenic mechanisms that underlie autoantibody-triggered encephalitic syndromes are poorly understood, and how autoantibodies breach the barrier remains obscure for almost all AE syndromes. The relative importance of cellular versus humoral immune mechanisms for disease pathogenesis also remains largely unexplored. Here, we review the proposed triggers for various autoimmune encephalopathies and their animal models, as well as basic structural features of the BBB and how they differ among various CNS regions, a feature that likely underlies some regional aspects of autoimmune encephalitis pathogenesis. We then discuss the routes that antibodies and immune cells employ to enter the CNS and their implications for AE. Finally, we explore future therapeutic strategies that may either preserve or restore barrier function and thereby limit immune cell and autoantibody infiltration into the CNS. Recent mechanistic insights into CNS autoantibody entry indicate promising future directions for therapeutic intervention beyond current, short-lived therapies that eliminate circulating autoantibodies.

  16. Circulating autoantibodies to phosphorylated α-enolase are a hallmark of pancreatic cancer.

    Science.gov (United States)

    Tomaino, Barbara; Cappello, Paola; Capello, Michela; Fredolini, Claudia; Sperduti, Isabella; Migliorini, Paola; Salacone, Paola; Novarino, Anna; Giacobino, Alice; Ciuffreda, Libero; Alessio, Massimo; Nisticò, Paola; Scarpa, Aldo; Pederzoli, Paolo; Zhou, Weidong; Petricoin Iii, Emanuel F; Liotta, Lance A; Giovarelli, Mirella; Milella, Michele; Novelli, Francesco

    2011-01-07

    Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis and no diagnostic markers have, as of yet, been defined. In PDAC patients, α-enolase (ENOA) is up-regulated and elicits the production of autoantibodies. Here, we analyzed the autoantibody response to post-translational modifications of ENOA in PDAC patients. ENOA isolated from PDAC tissues and cell lines was characterized by two-dimensional electrophoresis (2-DE) Western blot (WB), revealing the expression of six different isoforms (named ENOA1,2,3,4,5,6) whereas only 4 isoforms (ENOA3,4,5,6) were detectable in normal tissues. As assessed by 2-DE WB, 62% of PDAC patients produced autoantibodies to the two more acidic isoforms (ENOA1,2) as opposed to only 4% of controls. Mass spectrometry showed that ENOA1,2 isoforms were phosphorylated on serine 419. ROC analysis demonstrated that autoantibodies to ENOA1,2 usefully complement the diagnostic performance of serum CA19.9 levels, achieving approximately 95% diagnostic accuracy in both advanced and resectable PDAC. Moreover, the presence of autoantibodies against ENOA1,2 correlated with a significantly better clinical outcome in advanced patients treated with standard chemotherapy. In conclusion, our results demonstrate that ENOA phosphorylation is associated with PDAC and induces specific autoantibody production in PDAC patients that may have diagnostic value.

  17. IgG4-related disease of the biliary tract and pancreas: clinical and experimental advances.

    Science.gov (United States)

    Hubers, Lowiek M; Beuers, Ulrich

    2017-07-01

    IgG4-related disease (IgG4-RD) is an immune-mediated disease of unknown cause. It predominantly affects the biliary tract [IgG4-associated cholangitis (IAC)] and pancreas [autoimmune pancreatitis (AIP)] of mostly elderly men. Accurate diagnostic tests are lacking. Patients benefit from predniso(lo)ne treatment. However, disease relapse is often seen. This review will address pathophysiological aspects and advances in diagnostic and therapeutic strategies. The role of IgG1 and IgG4 in the pathophysiology of IgG4-RD was studied in mice which showed more intense organ damage of pancreas and salivary glands when IgG1 rather than IgG4 of patients with IgG4-RD was injected. Coadministration of IgG1+IgG4 led to dampening of IgG1-mediated injury supporting the view that IgG4 exerts immune-dampening effects. IgG4+ B-cell receptor clones identified by next-generation sequencing and the IgG4/IgG RNA ratio in human blood assessed by quantitative PCR were able to accurately distinguish IAC/AIP from primary sclerosing cholangitis or pancreatobiliary malignancies. Long-term treatment with low-dose prednisolone was safe and reduced the number of flare-ups in patients with AIP. Early diagnosis by a novel accurate and easy-to-use qPCR test may prevent life-threatening complications, unnecessary interventions and fatal course because of misdiagnosis. Prednisolone treatment remains the standard of care in patients with IgG4-RD.

  18. IgG4-related sialadenitis and Sjögren's syndrome.

    Science.gov (United States)

    Fragoulis, G E; Zampeli, E; Moutsopoulos, H M

    2017-03-01

    IgG4-related disease (IgG4-RD) has emerged as a new entity in the last decade. It comprises numerous conditions previously thought to be unrelated. Macroscopically, these diseases cause diffuse organ swelling and formation of pseudotumorous masses. Histopathologically, they are characterized by a lymphoplasmacytic infiltrate with increased IgG4+ plasma cells and storiform fibrosis. Despite rapid progress within the last years, our knowledge on these conditions is still fragmented. To date, more than forty organs have been reported to be included in IgG4-RD, and salivary gland involvement is amongst the most common organs affected [IgG4-related sialadenitis (IgG4-RS)]. Interestingly, IgG4-RS shares commonalities with Sjögren's syndrome (SS), like glandular enlargement, sicca symptoms, arthralgias, hypergammaglobulinemia, hypocomplementemia, and circulating antinuclear antibodies. Nonetheless, they differ in that the incidence of anti-Ro and anti-La reactivity is not frequently found in patients with IgG4-RS, their salivary glands are infiltrated by a large number of IgG4+ plasma cells and IgG4-RS symptoms respond promptly to steroids. The aim of this review was to describe the clinical, serological, histopathological and pathophysiological aspects of IgG4-RS in the context of IgG4-RD and highlight the differences between IgG4-RS and SS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Increased IgG on cell-derived plasma microparticles in systemic lupus erythematosus is associated with autoantibodies and complement activation

    DEFF Research Database (Denmark)

    Nielsen, Christoffer T; Østergaard, Ole; Stener, Line

    2012-01-01

    To quantify immunoglobulin and C1q on circulating cell-derived microparticles (MPs) in patients with systemic lupus erythematosus (SLE) and to determine whether immunoglobulin and C1q levels are correlated with clinical and serologic parameters.......To quantify immunoglobulin and C1q on circulating cell-derived microparticles (MPs) in patients with systemic lupus erythematosus (SLE) and to determine whether immunoglobulin and C1q levels are correlated with clinical and serologic parameters....

  20. Role of Natural IgM Autoantibodies (IgM-NAA) and IgM Anti-Leukocyte Antibodies (IgM-ALA) in Regulating Inflammation.

    Science.gov (United States)

    Lobo, Peter I

    2017-01-01

    Natural IgM autoantibodies (IgM-NAA) are rapidly produced to inhibit pathogens and abrogate inflammation mediated by invading microorganisms and host neoantigens. IgM-NAA achieve this difficult task by being polyreactive with low binding affinity but with high avidity, characteristics that allow these antibodies to bind antigenic determinants shared by pathogens and neoantigens. Hence the same clones of natural IgM can bind and mask host neoantigens as well as inhibit microorganisms. In addition, IgM-NAA regulate the inflammatory response via mechanisms involving binding of IgM to apoptotic cells to enhance their removal and binding of IgM to live leukocytes to regulate their function. Secondly, we review how natural IgM prevents autoimmune disorders arising from pathogenic IgG autoantibodies as well as by autoreactive B and T cells that have escaped tolerance mechanisms. Thirdly, using IgM knockout mice, we show that regulatory B and T cells require IgM to effectively regulate inflammation mediated by innate, adaptive and autoimmune mechanisms. It is therefore not surprising why the host positively selects such autoreactive B1 cells that generate protective IgM-NAA, which are also evolutionarily conserved. Fourthly, we show that IgM anti-leukocyte autoantibodies (IgM-ALA) levels and their repertoire can vary in normal humans and disease states and this variation may partly explain the observed differences in the inflammatory response after infection, ischemic injury or after a transplant. Finally we also show how protective IgM-NAA can be rendered pathogenic under non-physiological conditions. IgM-NAA have therapeutic potential. Polyclonal IgM infusions can be used to abrogate ongoing inflammation. Additionally, inflammation arising after ischemic kidney injury, e.g., during high-risk elective cardiac surgery or after allograft transplantation, can be prevented by pre-emptively infusing polyclonal IgM, or DC pretreated ex vivo with IgM, or by increasing in vivo Ig

  1. Autoantibodies to a 140-kd protein in juvenile dermatomyositis are associated with calcinosis.

    LENUS (Irish Health Repository)

    Gunawardena, H

    2009-06-01

    OBJECTIVE: The identification of novel autoantibodies in juvenile dermatomyositis (DM) may have etiologic and clinical implications. The aim of this study was to describe autoantibodies to a 140-kd protein in children recruited to the Juvenile DM National Registry and Repository for UK and Ireland. METHODS: Clinical data and sera were collected from children with juvenile myositis. Sera that recognized a 140-kd protein by immunoprecipitation were identified. The identity of the p140 autoantigen was investigated by immunoprecipitation\\/immunodepletion, using commercial monoclonal antibodies to NXP-2, reference anti-p140, and anti-p155\\/140, the other autoantibody recently described in juvenile DM. DNA samples from 100 Caucasian children with myositis were genotyped for HLA class II haplotype associations and compared with those from 864 randomly selected UK Caucasian control subjects. RESULTS: Sera from 37 (23%) of 162 patients with juvenile myositis were positive for anti-p140 autoantibodies, which were detected exclusively in patients with juvenile DM and not in patients with juvenile DM-overlap syndrome or control subjects. No anti-p140 antibody-positive patients were positive for other recognized autoantibodies. Immunodepletion suggested that the identity of p140 was consistent with NXP-2 (the previously identified MJ autoantigen). In children with anti-p140 antibodies, the association with calcinosis was significant compared with the rest of the cohort (corrected P < 0.005, odds ratio 7.0, 95% confidence interval 3.0-16.1). The clinical features of patients with anti-p140 autoantibodies were different from those of children with anti-p155\\/140 autoantibodies. The presence of HLA-DRB1*08 was a possible risk factor for anti-p140 autoantibody positivity. CONCLUSION: This study has established that anti-p140 autoantibodies represent a major autoantibody subset in juvenile DM. This specificity may identify a further immunogenetic and clinical phenotype within the

  2. Complete stable remission and autoantibody specificity in myasthenia gravis.

    Science.gov (United States)

    Baggi, Fulvio; Andreetta, Francesca; Maggi, Lorenzo; Confalonieri, Paolo; Morandi, Lucia; Salerno, Franco; Bernasconi, Pia; Montomoli, Cristina; Barberis, Massimo; Mantegazza, Renato; Antozzi, Carlo

    2013-01-08

    Patients with myasthenia gravis (MG) are subgrouped as acetylcholine receptor (AChR)-positive, muscle-specific kinase (MuSK)-positive, and AChR/MuSK-negative MG (or double negative [DN]) on the basis of autoantibody assay. We investigated the relationships between autoantibody specificity, main clinical features, and outcome of the disease, in particular the occurrence of complete stable remission (CSR), by means of a retrospective study on a cohort of 677 Italian patients with MG. A total of 517 (76%) patients with AChR-positive MG, 55 (8%) patients with MuSK-positive MG, and 105 (16%) patients with DN MG were included in the study. Kaplan-Meier and Cox proportional hazard regression analyses were used to evaluate associations between baseline characteristics, antibody specificity, and CSR. Clinical stage at onset and at maximal worsening was more severe for MuSK-positive patients: bulbar impairment at maximal worsening was found in 83.6% of MuSK-positive patients compared with 58.6% of AChR-positive patients and 43.8% of DN patients (p CSR was observed in 3.6% of MuSK-positive patients compared with 22.2% of AChR-positive and 21.9% of DN patients. In the whole MG cohort, onset before age 40 (hazard ratio [HR] = 1.96, 95% confidence interval [CI] 1.27-3.02, p = 0.002) and ocular and generalized clinical stages at maximal worsening were associated with CSR (ocular, HR = 8.05, 95% CI 1.88-34.53, p = 0.005; generalized, HR = 3.71, 95% CI 1.16-11.90, p = 0.023; bulbar, HR = 3.16, 95% CI 1.00-10.05, p = 0.051). MuSK antibodies identify a clinically distinguishable, more severe form of MG since the disease onset, with a lower occurrence of CSR. These features should be considered by the clinician in the management of this particular form of MG.

  3. A novel microtiter plate radioimmunoassay of insulin autoantibody

    International Nuclear Information System (INIS)

    Huang Gan; Li Zhangwei; Jin Helai; Wang Xia; Wang Jianping; Zhou Zhiguang

    2009-01-01

    Objective: Insulin autoantibody (IAA) is known to exist in sera of type 1 diabetes mellitus (T1DM) patients and pre-T1DM individuals. The aim of this study was to establish a novel mierotiter plate radioimmunoassay (RIA) for IAA and evaluate its clinical value. Methods: Diluted 125 I-insulin was mixed with 5 μl serum samples in a 96-well microtiter plate and then incubated for 72 h on an orbital plate shaker (4 degree C). The immunocomplexes were transferred to another protein a coated Millipore plate, and then the plate was washed with Tri-Buffered Saline Tween-20 (TBT) buffer. Counts per minute (CPM) was measured with liquid scintillation and luminescence counter. The positive cut-off point of IAA index was defined as ≥0.06 based on the 99-percentile of the distribution in 317 healthy individuals. The specificity and sensitivity of the assay were calculated from the samples provided by the fourth Diabetes Autoantibodies Standardization Program (DASP 2005). The IAA levels were determined in 71 T1DM and 551 newly diagnosed type 2 diabetes (T2DM) patients, and 317 healthy controls. The t test, non-parametric test, χ 2 test and linear correlation analysis were performed on the data using SPSS 11.5 software. The concordance rate was estimated with Kappa value. Results: (1) The optimized testing condition was described as 2 x 10 4 CPM of 125 I-insulin, 5 μl serum sample and slowly horizontal shaking for 72 h. (2) The intra-assay CV was 4.8%-8.9% and inter-assay CV was 6.4%-10.5%. Based on DASP 2005 samples, the specificity and sensitivity of the assay were 97% (97/100) and 50% (25/50), respectively. Ninety-six serum samples with different IAA levels were selected and tested to compare between our new method and a domestic IAA RIA kit. The results showed that the IAA indices from the two methods were positively correlated (r= 0.678, P<0.001). The concordance rate was 72.9% (Kappa value=0.402). There were 25 samples with discordant results, which were positive for

  4. Circulating autoantibodies to recombinant lipocortin-1 in asthma.

    Science.gov (United States)

    Chung, K F; Podgorski, M R; Goulding, N J; Godolphin, J L; Sharland, P R; O'Connor, B; Flower, R J; Barnes, P J

    1991-03-01

    One of the postulated mechanisms of corticosteroid action is through the de novo synthesis and release of lipocortins. We assayed circulating antibodies to lipocortin-1 in sera obtained from normal (n = 67) and asthmatic (n = 57) subjects using an ELISA technique. Asthmatic subjects with a wide range of severity, with the mildest needing only occasional inhaled beta-agonist therapy to the most severe needing maintenance oral corticosteroid treatment, were recruited from our Asthma Clinic and classified into five categories according to the need of therapy. Median values of IgM and IgG lipocortin-1 antibody for normal subjects were 19.3 (interquartile range (r) = 11.0-30.4) and 16.9 (r = 10.54-29.4) ELISA units (EU) ml-1 respectively. These levels were significantly elevated in asthmatic subjects: IgM = 43.9 EU ml-1 (r = 31.7-64.5) and IgG = 29.0 EU ml-1 (r = 21.2-44.7) (P less than 0.001). There was no significant relationship between the levels of lipocortin antibody and the clinical severity of asthma. Asthmatics with significantly raised levels of antibody were found within all five categories of severity. We conclude that the level of this antibody is not related to severity of asthma, to previous or current corticosteroid therapy or to the development of corticosteroid resistance.

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

    Science.gov (United States)

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

    2016-09-01

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

  6. The Emerging Importance of IgG Fab Glycosylation in Immunity

    NARCIS (Netherlands)

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

    2016-01-01

    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

  7. The role of IgG antibodies in allergy and immunotherapy

    NARCIS (Netherlands)

    Aalberse, R.

    2011-01-01

    In specific immunotherapy (SIT), a beneficial response is associated with an increase in allergen-specific IgG(4) . This does not indicate that IgE-producing B cells have switched to IgG(4) production, because in human DNA, IgE is downstream from IgG(4) . Thus, by conventional switching, B cells

  8. Exposure to occupational antigens might predispose to IgG4-related disease

    NARCIS (Netherlands)

    de Buy Wenniger, Lucas J. Maillette; Culver, Emma L.; Beuers, Ulrich

    2014-01-01

    Evidence is mounting that the immune system of patients with IgG4-related disease (IgG4-RD) shows indications of chronic antigenic stimulation. Hypothesizing a possible role for occupational antigenic exposure, we observed in two independent cohorts of patients with IgG4-RD that the majority had had

  9. IgG isotypic antibodies to crude Plasmodium falciparum blood-stage ...

    African Journals Online (AJOL)

    Methods: Levels of IgG (IgG1-IgG4) and IgM to crude P. falciparum blood stage antigen ... dosage influenced P. falciparum-specific isotypic antibody responses to blood stage .... exposed Swedish donors. ..... with adverse pregnancy outcomes.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    alloimmunity, which may be lethal. A novel strategy to control pathogenic antibodies would be administration of a non-destructive IgG antibody blocking antigen binding while retaining binding to FcRn. We report on two human IgG3 antibodies with a hinge deletion and a C131S point mutation (IgG3ΔHinge...

  11. Shared Genetic Basis for Type 1 Diabetes, Islet Autoantibodies, and Autoantibodies Associated With Other Immune-Mediated Diseases in Families With Type 1 Diabetes

    DEFF Research Database (Denmark)

    Brorsson, Caroline Anna; Pociot, Flemming

    2015-01-01

    ) in autoimmune gastritis, transglutaminase (TGA) in celiac disease, and 21-hydroxylase (21-OHA) in autoimmune hypoadrenalism. In addition to the MHC region, we identify SNPs in five susceptibility loci (IFIH1, PTPN22, SH2B3, BACH2, and CTLA4) as significantly associated with more than one autoantibody at a false...

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

    Directory of Open Access Journals (Sweden)

    Satoshi Yoshimura

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

  13. Increasing ICA512 autoantibody titers predict development of abnormal oral glucose tolerance tests.

    Science.gov (United States)

    Sanda, Srinath

    2018-03-01

    Determine if autoantibody titer magnitude and variability predict glucose abnormalities in subjects at risk for type 1 diabetes. Demographic information, longitudinal autoantibody titers, and oral glucose tolerance test (OGTT) data were obtained from the TrialNet Pathway to Prevention study. Subjects (first and second degree relatives of individuals with type 1 diabetes) with at least 2 diabetes autoantibodies were selected for analysis. Autoantibody titer means were calculated for each subject for the duration of study participation and the relationship between titer tertiles and glucose value tertiles from OGTTs (normal, impaired, and diabetes) was assessed with a proportional odds ordinal regression model. A matched pairs analysis was used to examine the relationship between changes in individual autoantibody titers and 120-minute glucose values. Titer variability was quantified using cumulative titer standard deviations. We studied 778 subjects recruited in the TrialNet Pathway to Prevention study between 2006 and 2014. Increased cumulative mean titer values for both ICA512 and GAD65 (estimated increase in proportional odds = 1.61, 95% CI = 1.39, 1.87, P < 1 × 10 -9 and 1.17, 95% CI = 1.03, 1.32, P = .016, respectively) were associated with peak 120-minute glucose values. While fluctuating titer levels were observed in some subjects, no significant relationship between titer standard deviation and glucose values was observed. ICA512 autoantibody titers associate with progressive abnormalities in glucose metabolism in subjects at risk for type 1 diabetes. Fluctuations in autoantibody titers do not correlate with lower rates of progression to clinical disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Flow cytometric immunobead assay for quantitative detection of platelet autoantibodies in immune thrombocytopenia patients.

    Science.gov (United States)

    Zhai, Juping; Ding, Mengyuan; Yang, Tianjie; Zuo, Bin; Weng, Zhen; Zhao, Yunxiao; He, Jun; Wu, Qingyu; Ruan, Changgeng; He, Yang

    2017-10-23

    Platelet autoantibody detection is critical for immune thrombocytopenia (ITP) diagnosis and prognosis. Therefore, we aimed to establish a quantitative flow cytometric immunobead assay (FCIA) for ITP platelet autoantibodies evaluation. Capture microbeads coupled with anti-GPIX, -GPIb, -GPIIb, -GPIIIa and P-selectin antibodies were used to bind the platelet-bound autoantibodies complex generated from plasma samples of 250 ITP patients, 163 non-ITP patients and 243 healthy controls, a fluorescein isothiocyanate (FITC)-conjugated secondary antibody was the detector reagent and mean fluorescence intensity (MFI) signals were recorded by flow cytometry. Intra- and inter-assay variations of the quantitative FCIA assay were assessed. Comparisons of the specificity, sensitivity and accuracy between quantitative and qualitative FCIA or monoclonal antibody immobilization of platelet antigen (MAIPA) assay were performed. Finally, treatment process was monitored by our quantitative FCIA in 8 newly diagnosed ITPs. The coefficient of variations (CV) of the quantitative FCIA assay were respectively 9.4, 3.8, 5.4, 5.1 and 5.8% for anti-GPIX, -GPIb, -GPIIIa, -GPIIb and -P-selectin autoantibodies. Elevated levels of autoantibodies against platelet glycoproteins GPIX, GPIb, GPIIIa, GPIIb and P-selectin were detected by our quantitative FCIA in ITP patients compared to non-ITP patients or healthy controls. The sensitivity, specificity and accuracy of our quantitative assay were respectively 73.13, 81.98 and 78.65% when combining all 5 autoantibodies, while the sensitivity, specificity and accuracy of MAIPA assay were respectively 41.46, 90.41 and 72.81%. A quantitative FCIA assay was established. Reduced levels of platelet autoantibodies could be confirmed by our quantitative FCIA in ITP patients af