WorldWideScience

Sample records for igg subclass autoantibodies

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

    Science.gov (United States)

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

    2008-10-01

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

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

    NARCIS (Netherlands)

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

    1991-01-01

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

  3. Serum IgG subclasses in autoimmune diseases.

    Science.gov (United States)

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

    2015-01-01

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

  4. IgG Subclass Staining in Routine Renal Biopsy Material.

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

    Wahn, Volker; von Bernuth, Horst

    2017-09-01

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

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

    Science.gov (United States)

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

    1982-01-01

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

  7. 肿瘤相关膜性肾病:抗足细胞自身抗体与肾组织IgG亚型的检测%Tumor associated membranous nephropathy:analysis of Anti-PLA2R autoantibodies and IgG subclass depositions on glomeruli

    Institute of Scientific and Technical Information of China (English)

    李世军; 秦卫松; 张明超; 郑春霞; 左科; 陈惠萍; 吴燕; 刘志红

    2011-01-01

    . The anti-PLA2R (M-type phospholipase A2 receptor) autoantibodies in serum were detected and the glomerular IgG subclass deposits were observed. Results:10 cases were diagnosed as cancer of various types, including carcinomas of lung (5 cases), stomach (2 cases), colon ( 1 case), larynx ( 1 case), and tongue (1 case). All of those patients presented proteinuria and edema; 8 patients showed nephrotic syndrome. The serum Anti-PLA2R autoantibodies were detected in 3 cases (30%), and lgGl deposits was the dominant IgG on the glomeruli in 8 cases (80%). However, the glomerular IF intensities of IgG4 deposits were the same as lgG1 in 2 cases with AntiPLA2R autoantibodies. During follow-up, in seven patients without Anti-PLA2R autoantibodies, the complete remission of the proteinuria was observed in 2 patients associated with tumor remission; 3 patients died of cancer; the other 2 patients had persistent proteinuria. While in three patients with Anti-PLA2R autoantibodies, they had persistent or relapse of proteinuria. Conclusion :The clinical and pathologic features of tumor-associated MN were not significantly different from idiopathic MN. Most of patients had no Anti-PLA2R autoantibodies and had glomerular IgG1 deposits, which indicated that the pathogenesis of tumor-associated MN differs from that of idiopathic MN. The patient with Anti-PLA2R autoantibodies and glomerular IgG4 deposits may suggest the coincidence of tumor and idiopathic MN.

  8. The isotype and IgG subclass distribution of anti-carbamylated protein antibodies in rheumatoid arthritis patients.

    Science.gov (United States)

    van Delft, Myrthe A M; Verheul, Marije K; Burgers, Leonie E; Derksen, Veerle F A M; van der Helm-van Mil, Annette H M; van der Woude, Diane; Huizinga, Tom W J; Toes, René E M; Trouw, Leendert A

    2017-08-15

    Anti-carbamylated protein (anti-CarP) antibodies have recently been reported to occur in around 45% of rheumatoid arthritis (RA) patients and to have prognostic and diagnostic properties. At present, the breadth and molecular make-up of the anti-CarP antibody response is ill defined. To understand the anti-CarP antibody immune response and potential immune effector mechanisms it can recruit, we determined the anti-CarP antibody isotype and IgG-subclass usage in RA patients. Anti-CarP antibody IgM, IgA, and IgG or IgG subclasses were detected by enzyme-linked immunosorbent assay (ELISA) in sera from 373 unselected RA patients and 196 healthy controls. An additional 114 anti-citrullinated protein antibody (ACPA) and anti-CarP IgG double-positive patients were selected to study the concomitant presence of both antibody systems. Anti-CarP IgG was present in around 45% of the patients and comprised all anti-CarP IgG subclasses. The presence of anti-CarP IgG1 particularly associates with radiological damage. Anti-CarP IgM was detected in 16% of RA patients, even in anti-CarP IgG-positive individuals, and is indicative of an actively ongoing immune response. Around 45% of the patients were positive for IgA which included ACPA-positive cases but also 24% of the ACPA-negative cases. In ACPA and anti-CarP double-positive patients, the distribution and number of isotypes and IgG subclasses was similar for both autoantibodies at the group level, but substantial variation was observed within individual patient samples. In RA, the anti-CarP antibody response uses a broad spectrum of isotypes and seems to be an actively ongoing immune reaction. Furthermore, the anti-CarP and ACPA autoantibody responses seems to be differentially regulated.

  9. Biophysical and Functional Characterization of Rhesus Macaque IgG Subclasses

    Science.gov (United States)

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

    2016-01-01

    Antibodies raised in Indian rhesus macaques [Macaca mulatta (MM)] in many preclinical vaccine studies are often evaluated in vitro for titer, antigen-recognition breadth, neutralization potency, and/or effector function, and in vivo for potential associations with protection. However, despite reliance on this key animal model in translation of promising candidate vaccines for evaluation in first in man studies, little is known about the properties of MM immunoglobulin G (IgG) subclasses and how they may compare to human IgG subclasses. Here, we evaluate the binding of MM IgG1, IgG2, IgG3, and IgG4 to human Fc gamma receptors (FcγR) and their ability to elicit the effector functions of human FcγR-bearing cells, and unlike in humans, find a notable absence of subclasses with dramatically silent Fc regions. Biophysical, in vitro, and in vivo characterization revealed MM IgG1 exhibited the greatest effector function activity followed by IgG2 and then IgG3/4. These findings in rhesus are in contrast with the canonical understanding that IgG1 and IgG3 dominate effector function in humans, indicating that subclass-switching profiles observed in rhesus studies may not strictly recapitulate those observed in human vaccine studies. PMID:28018355

  10. Biophysical and Functional Characterization of Rhesus Macaque IgG Subclasses

    Directory of Open Access Journals (Sweden)

    Austin W. Boesch

    2016-12-01

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

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

    Science.gov (United States)

    Boctor, F N; Peter, J B

    1990-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Angel Guevara E.

    1995-08-01

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

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

    Science.gov (United States)

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

    2014-09-15

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

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

    DEFF Research Database (Denmark)

    Tian, Xinsheng; Vestergaard, Bente; Thorolfsson, Matthias

    2015-01-01

    with identical variable regions, were thoroughly analysed by the ensemble optimization method. The extended analysis of the optimized ensembles through shape clustering reveals distinct subclass-specific conformational preferences, which provide new insights for understanding the variations in physical......IgG subclass-specific differences in biological function and in vitro stability are often referred to variations in the conformational flexibility, while this flexibility has rarely been characterized. Here, small-angle X-ray scattering data from IgG1, IgG2 and IgG4 antibodies, which were designed...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-01-01

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

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

    Science.gov (United States)

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

    2014-08-01

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

  17. 不典型膜性肾病患者血清M型磷脂酶A2受体抗体及肾组织IgG亚型分布的研究%Anti-PLA2R autoantibodies in serum and IgG subclass deposits on glomeruli in undetermined atypical membranous nephropathy

    Institute of Scientific and Technical Information of China (English)

    陈幸; 蔡美顺; 王梅

    2014-01-01

    型阳性率最低(均为5%).SMN组中,IgG1亚型阳性率最高(76.9%),IgG4亚型阳性率最低(30.8%).UAMN组IgG1、IgG3亚型阳性率与IMN及SMN组比较差异均无统计学,IgG2亚型阳性率表现出与SMN组差异有统计学意义(30.0%比69.2%,P<0.05),IgG4亚型阳性率与IMN组差异有统计学意义(20%比60%,P<0.05).SMN组IgG1、IgG2和IgG3亚型的阳性率均显著高于IMN组(分别为76.9%、69.2%、46.2%比15%、5%、5%,均P<0.01).IMN组IgG4亚型在肾小球沉积的阳性率高于SMN及UAMN组,但仅与UAMN组差异具统计学意义(P=0.0225).UAMN组显示出了与IMN及SMN组的不同,更类似于SMN组特点.结论 UAMN组患者抗PLA2R自身抗体检测均为阴性,肾组织以IgG1亚型沉积为主,表现了类似SMN的特点,但在临床指标上又显示了与SMN的不同.因此要加强临床的长期随访,深入对这一类疾病的研究.%Objective To investigate the characteristic of autoantibodies of M-type phospholipase A2 receptor (PLA2R) in serum and the glomerular IgG subclass deposits in undetermined atypical membranous nephropathy (MN) patients.Methods From Feb 2004 to Nov 2011,53 cases diagnosed as MN by kidney puneture biopsy in our hospital were included into the study.There were 20 undetermined atypical membranous nephropathy (UAMN),20 idiopathic membranous nephropathy (IMN) and 13 secondary membranous nephropathy (SMN) which were composed of lupus membranous nephropathy (LMN) and HBV related membranous nephropathy (HBV-MN).Clinlical and pathological characteristics were analyzed.The autoantibodies of PLA2R in serum were detected and the glomerular IgG subclass deposits were observed.Results (1) The average age underwent renal biopsy was (37.9±3.8) years of UAMN,(50.1±3.0) years of IMN and (49.5±4.5) years of SMN.The difference in onset average age at disease was significant between UAMN and IMN (P =0.0178).The female/male ratio (F/M) in UAMN,IMN and SMN was 0.8∶ 1,0.7∶1 and 0.6∶ 1(P > 0

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

    Science.gov (United States)

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

    1988-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Visciano Maria Luisa

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Latha G

    2005-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Fernanda S. NASCIMENTO

    2015-10-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Xinsheng Tian

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    1986-08-01

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

  7. Retrospective Study of Phospholipase A2 Receptor and IgG Subclasses in Glomerular Deposits in Chinese Patients with Membranous Nephropathy.

    Directory of Open Access Journals (Sweden)

    Hong-Rui Dong

    Full Text Available The research work in the past years showed that detection of phospholipase A2 receptor (PLA2R antigen and its dominant IgG4 autoantibody in glomerular deposits of patients with membranous nephropathy (MN was useful for the differentiation between primary MN (PMN and secondary MN (SMN, but so far such research data from large Chinese patient series is little. Here, we are going to report a research work in a Chinese cohort.This study enrolled 179 patients with PMN, 40 patients with membranous lupus nephritis (LN-MN, 26 patients with hepatitis B virus-associated MN (HBV-MN, 2 patients with malignancy-associated MN (M-MN and one patient with IgG4-related MN (IgG4-MN. PLA2R and IgG subclasses in glomerular deposits of these patients were examined by immunofluorescence and/or immunohistochemical staining, and the potential value of the above examinations for differential diagnosis of PMN and SMN was evaluated.Glomerular PLA2R deposition was present in 92.2% patients with PMN and 7.7% patients with HBV-MN, but none of the patients with LN-MN. Predominant/codominant IgG4 deposition was found in 93.3% patients with PMN and 11.5% patients with HBV-MN, but none of the patients with LN-MN. The two M-MN patients both had glomerular PLA2R and predominant/codominant IgG4 deposition. The one IgG4-MN patient had deeply staining IgG4 but no PLA2R in glomeruli.The glomerular PLA2R and predominant/codominant IgG4 deposition is frequently observed in Chinese patients with PMN. Immunofluorescence and immunohistochemical staining of renal biopsy tissue for detection of glomerular PLA2R and IgG subclasses deposition can help to distinguish PMN from LN-MN and most of HBV-MN.

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

    DEFF Research Database (Denmark)

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

    1996-01-01

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

  9. 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....

  10. Anti-PLA2R autoantibodies in serum and Ig G subclass deposits on glomeruli in undetermined atypical membranous nephropathy

    Institute of Scientific and Technical Information of China (English)

    陈幸

    2014-01-01

    Objective To investigate the characteristic of autoantibodies of M-type phospholipase A2 receptor(PLA2R)in serum and the glomerular Ig G subclass deposits in undetermined atypical membranous nephropathy(MN)patients.Methods From Feb 2004 to Nov 2011,53 cases diagnosed as MN by kidney puncture biopsy in our hospital were included into the study.There were 20

  11. Influence of IgG Subclass on Human Antimannan Antibody-Mediated Resistance to Hematogenously Disseminated Candidiasis in Mice.

    Science.gov (United States)

    Nishiya, Casey T; Boxx, Gayle M; Robison, Kerry; Itatani, Carol; Kozel, Thomas R; Zhang, Mason X

    2015-11-16

    Candida albicans is a yeast-like pathogen and can cause life-threatening systemic candidiasis. Its cell surface is enriched with mannan that is resistant to complement activation. Previously, we developed the recombinant human IgG1 antimannan antibody M1g1. M1g1 was found to promote complement activation and phagocytosis and protect mice from systemic candidiasis. Here, we evaluate the influence of IgG subclass on antimannan antibody-mediated protection. Three IgG subclass variants of M1g1 were constructed: M1g2, M1g3, and M1g4. The IgG subclass identity for each variant was confirmed with DNA sequence and subclass-specific antibodies. These variants contain identical M1 Fabs and exhibited similar binding affinities for C. albicans yeast and purified mannan. Yeast cells and hyphae recovered from the kidney of antibody-treated mice with systemic candidiasis showed uniform binding of each variant, indicating constitutive expression of the M1 epitope and antibody opsonization in the kidney. All variants promoted deposition of both murine and human C3 onto the yeast cell surface, with M1g4 showing delayed activation, as determined by flow cytometry and immunofluorescence microscopy. M1g4-mediated complement activation was found to be associated with its M1 Fab that activates the alternative pathway in an Fc-independent manner. Treatment with each subclass variant extended the survival of mice with systemic candidiasis (P candidiasis is influenced by its IgG subclass.

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

    Science.gov (United States)

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

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Maria A. Araújo

    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

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

    Directory of Open Access Journals (Sweden)

    Neil M. Gude BSc, MSc, PhD

    2013-10-01

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

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

    NARCIS (Netherlands)

    Jaarsma, AS; Muis, N; DeGraaf, SSN

    1996-01-01

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

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

    Science.gov (United States)

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

    2000-01-01

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

  17. 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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Daniela Kao

    2015-12-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2000-01-01

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

  2. 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, ...

  3. 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 ...

  4. IgA and/or IgG subclass deficiency in children with recurrent respiratory infections and its relationship with chronic pulmonary damage.

    Science.gov (United States)

    Ozkan, H; Atlihan, F; Genel, F; Targan, S; Gunvar, T

    2005-01-01

    Most patients with IgA and/or IgG subclass deficiency are asymptomatic but some may suffer from frequent mainly respiratory infections. The aim of our study was to determine the frequency of IgA and/or IgG subclass deficiencies and the rate of chronic pulmonary damage secondary to recurrent pulmonary infections in these children. Serum IgA and IgG subclass levels were measured in 225 children aged 6 months to 6 years with recurrent sinopulmonary infections (44 with recurrent upper respiratory tract infections, 100 with recurrent pulmonary infections and 81 with recurrent bronchiolitis). In order to determine chronic pulmonary damage due to recurrent infections in patients with recurrent pulmonary infections CT scans of thorax were also obtained. The overall frequency of antibody defects was found to be 19.1%. IgA deficiency was observed in 9.3%, IgG subclass deficiency in 8.4% and IgA + IgG subclass deficiency in 1.4%. The prevalance of IgA and/or IgG subclass deficiency was 25% in patients with recurrent upper respiratory tract infections, 22% in patients with recurrent pulmonary infections and 12.3% in patients with recurrent bronchiolitis (p>0.05). Chronic pulmonary damage in lungs was determined radiologically in 17 of 100 cases with recurrent pulmonary infection. In IgG subclass deficiencies sequel changes, although not statistically significant, were observed five times more frequently than that of IgA deficiencies. CT scans revealed pulmonary sequels in 5 of the 22 (22.7%) patients with recurrent pulmonary infections and immunodeficiency (bronchiectasis in 2 patients with IgG3 deficiency, fibrotic changes in one with IgA deficiency and in one with IgG3 deficiency, bronchiolitis obliterans in one with IgG2 + IgG3 deficiency). On the other hand, pulmonary sequels were observed in 12 patients (15.4%) with normal immunoglobulin levels. Eight of them were bronchiolitis obliterans, 2 of them were atelectasia and 1 of them was bronchiectasia. We therefore suggest

  5. IgG antibody subclass responses determined by immunoblot in infants' sera following vaccination with a meningococcal recombinant hexavalent PorA OMV vaccine.

    Science.gov (United States)

    Martin, S; Sadler, F; Borrow, R; Dawson, M; Fox, A; Cartwright, K

    2001-08-14

    The introduction of meningococcal serogroup C conjugate vaccines into the UK immunisation schedule has led to the decline of serogroup C disease in those vaccinated but there is no imminent vaccine solution for serogroup B disease. The PorA outer membrane protein (OMP) is a potential serogroup B vaccine candidate and an outer membrane vesicle (OMV) vaccine containing six different PorA OMPs (each representing a different serosubtype) has been evaluated in phase II trials with encouraging results. Little is known about the IgG subclass response to the various antigens contained within this vaccine. These responses are important due to the different half-lives and complement fixing abilities of these antibodies. In this study, immunoblotting was undertaken with infants' sera following either three or four doses of vaccine, and OMVs from six isogenic meningococcal strains differing only in their PorA serosubtype. Following either three or four doses of the vaccine, IgG(3) and IgG(1) subclass antibodies were induced to all six of the isogenic strains, although sera collected after four doses of vaccine showed stronger antibody levels. IgG(3) was found in more sera than IgG(1). For both sets of sera, the two isogenic strains expressing P1.5,2 and P1.5(c),10 induced stronger IgG subclass antibody responses than the other four meningococcal strains. The recombinant hexavalent PorA OMV vaccine stimulates both IgG(1) and IgG(3) subclass antibodies, the subclasses that are most effective in activating the complement system.

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

    Science.gov (United States)

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

    2016-10-20

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

  7. [Distribution of IgG subclasses of TgAb and TPOAb in sera from patients with Graves' disease, Graves' disease plus Hashimoto's thyroiditis and Hashimoto's thyrotoxicosis].

    Science.gov (United States)

    Yuan, Shanshan; Yu, Nan; Gao, Ying; Huang, Wei; He, Yifan; Dong, Bin; Lu, Guizhi; Li, Maorong; Cai, Xiaopin; Peng, Dingqiong; Wang, Yunhong; Li, Ting; Huang, Youyuan; Gao, Yanming; Guo, Xiaohui; Shi, Bingyin

    2014-01-14

    To evaluate the distribution of IgG subclasses of TgAb and TPOAb in sera from patients with Graves' disease (GD), Graves' disease plus Hashimoto's thyroiditis (GH) and Hashimoto's thyrotoxicosis. Patients with GD (n = 33), GH (n = 31) or Hashimoto's thyrotoxicosis (n = 18) diagnosed by fine needle aspiration cytology at Department of Endocrinology of Peking University First Hospital, Beijing Haidian Hospital, China-Japan Friendship Hospital and Civil Aviation General Hospital during the period from January 2010 to May 2013 were enrolled. All of them had TgAb and TPOAb. The total serum IgG and IgG subclasses of TgAb and TPOAb were detected by antigen-specific enzyme-linked immunosorbent assay (ELISA). The prevalence and relative amount of IgG subclasses were calculated and compared among three groups. The levels of TRAb in GD group (21.80(7.53, 40) U/L) were significantly higher than those in GH (7.30(3.10, 25.40) U/L) (P = 0.000) and Hashimoto's thyrotoxicosis groups (4.90(1.69, 16.43) U/L) (P = 0.003). And no significant differences were found in the levels of TgAb and TPOAb. The prevalence of TgAb IgG3 subclass in Hashimoto's thyrotoxicosis group (66.7%) was higher than GD group (35.5%) and GH group (36.4%) and the difference was close to significance (P = 0.066). There were significant differences of relative amount of TgAb IgG2 and TgAb IgG4 among three groups (P = 0.039 and 0.013), and GD patients had higher relative amounts of TgAb IgG2 (0.59(0.34, 0.94)) and TgAb IgG4 (0.57(0.28, 0.97)) than GH patients (TgAb IgG2, 0.31(0.23, 0.34); TgAb IgG4, 0.26(0.09, 0.48)) or patients with Hashimoto's thyrotoxicosis (TgAb IgG2, 0.32(0.24, 0.83); TgAb IgG4, 0.33(0.10, 0.65)) (for TgAb IgG2, P = 0.009 and 0.167; for TgAb IgG4, P = 0.005 and 0.041 respectively). No significant difference was found in the prevalence of each TPOAb IgG subclass. The difference of relative amount of TPOAb IgG2 among three groups was close to significance (P = 0.069). And the relative amount

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

    Science.gov (United States)

    Weaver, Rupert; Reiling, Linda; Feng, Gaoqian; Drew, Damien R.; Mueller, Ivo; Siba, Peter M.; Tsuboi, Takafumi; Richards, Jack S.; Fowkes, Freya J. I.; Beeson, James G.

    2016-01-01

    Understanding the targets and mechanisms of human immunity to malaria is important for advancing the development of highly efficacious vaccines and serological tools for malaria surveillance. The PfRH5 and PfRipr proteins form a complex on the surface of P. falciparum merozoites that is essential for invasion of erythrocytes and are vaccine candidates. We determined IgG subclass responses to these proteins among malaria-exposed individuals in Papua New Guinea and their association with protection from malaria in a longitudinal cohort of children. Cytophilic subclasses, IgG1 and IgG3, were predominant with limited IgG2 and IgG4, and IgG subclass-specific responses were higher in older children and those with active infection. High IgG3 to PfRH5 and PfRipr were significantly and strongly associated with reduced risk of malaria after adjusting for potential confounding factors, whereas associations for IgG1 responses were generally weaker and not statistically significant. Results further indicated that malaria exposure leads to the co-acquisition of IgG1 and IgG3 to PfRH5 and PfRipr, as well as to other PfRH invasion ligands, PfRH2 and PfRH4. These findings suggest that IgG3 responses to PfRH5 and PfRipr may play a significant role in mediating naturally-acquired immunity and support their potential as vaccine candidates and their use as antibody biomarkers of immunity. PMID:27604417

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

    Directory of Open Access Journals (Sweden)

    Kristina Kakalacheva

    2016-02-01

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

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

    Science.gov (United States)

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

    2015-03-15

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

  11. 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...... then gradually develop into protective response dominated by cytophilic IgG1 and IgG3 antibodies. METHODS: Naturally occurring IgG antibodies against P. falciparum blood-stage antigens were analysed from plasma samples collected from four groups of individuals differing in age and level of exposure to P....... falciparum infections. Western Blot profiling of blood-stage parasite antigens displaying reactivity with individual plasma samples in terms of their subclass specificities was conducted. Parasite antigens detected by IgG were grouped based on their apparent molecular sizes resolved by SDS-PAGE as high...

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

    Science.gov (United States)

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

    1990-01-01

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

  13. 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.

  14. FcγRIIa (CD32 polymorphism and anti-malarial IgG subclass pattern among Fulani and sympatric ethnic groups living in eastern Sudan

    Directory of Open Access Journals (Sweden)

    Balogun Halima A

    2009-03-01

    Full Text Available Abstract Background A SNP at position 131, in the FcγRIIa gene, affects the binding of the different IgG subclasses and may influence the clinical variation seen in patients with falciparum malaria. This study confirms and extends previous findings, analysing the FcγRIIa (CD32 polymorphism in relation to the IgG subclass distribution seen among two sympatric tribes living in eastern Sudan, characterized by marked differences in susceptibility to Plasmodium falciparum malaria. Methods Two hundred and fifty Fulani subjects living in an area of meso-endemic P. falciparum malaria infection were genotyped for the FcγRIIa-131 polymorphism. For comparison, 101 non-Fulani donors – (Masaleit, Hausa and Four – living in the same study area, were genotyped. The levels of plasma antibodies (IgG and subclasses to four malaria antigens (AMA-1, MSP 2 – 3D7 & FC27, Pf332-C231 were measured using indirect enzyme-linked immunosorbent assays. Results The FcγRIIa-H/H131 genotype was found to be significantly more prevalent in the Fulani as compared to the non-Fulani ethnic groups (36.0% for Fulani versus 17.8% for non-Fulani, adjusted OR 3.10, 95% CI 1.61–5.97, P value Conclusion The FcγRIIa-H/H131 genotype and H131 allele is at higher frequency in the Fulani ethnic group. The H/H131 genotype was consistently associated with higher levels of anti-malarial IgG2 and IgG3 antibodies, while the R/R131 genotype was associated with higher levels of IgG1 antibodies.

  15. 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.

  16. Impact of the IL-4 -590 C/T transition on the levels of Plasmodium falciparum specific IgE, IgG, IgG subclasses and total IgE in two sympatric ethnic groups living in Mali.

    Science.gov (United States)

    Vafa, Manijeh; Maiga, Bakary; Israelsson, Elisabeth; Dolo, Amagana; Doumbo, Ogobara K; Troye-Blomberg, Marita

    2009-01-01

    This study aimed to examine the effect of IL-4 -590 T/C polymorphism on the levels of malaria-specific IgE, IgG, IgG (1-4) subclasses as well as total IgE in the Fulani and their sympatric ethnic group, the Dogon, in Mali. Asymptomatic individuals, of the Fulani and the Dogon ethnic groups, were included in the study. IL-4 is involved in the regulation of IgE and IgG4 subclass. In line with this we found that within the Fulani, the T allele was associated with increased levels of total and anti-malarial IgE (P=0.02 and P=0.04, respectively). The Fulani T allele carriers had slightly higher levels of malarial specific IgG4 as compared to those with the CC genotype (P=0.08). No such differences were observed amongst the Dogon individuals. Taken together, these data indicate that the impact of IL-4 -590 variants on antibody levels may vary in different ethnic populations, and that this might affect the Ig-class and subclass distributions.

  17. The role of IgG subclass of mouse monoclonal antibodies in antibody-dependent enhancement of feline infectious peritonitis virus infection of feline macrophages.

    Science.gov (United States)

    Hohdatsu, T; Tokunaga, J; Koyama, H

    1994-01-01

    Antibody-dependent enhancement (ADE) of feline infectious peritonitis virus (FIPV) infection was studied in feline alveolar macrophages and human monocyte cell line U937 using mouse neutralizing monoclonal antibodies (MAbs) directed to the spike protein of FIPV. Even among the MAbs that have been shown to recognize the same antigenic site, IgG 2a MAbs enhanced FIPV infection strongly, whereas IgG 1 MAbs did not. These IgG 2a MAbs enhanced the infection even when macrophages pretreated with the MAb were washed and then inoculated with the virus. Immunofluorescence flow cytometric analysis of the macrophages treated with each of the MAbs showed that the IgG 2a MAbs but not the IgG 1 MAbs bound to feline alveolar macrophages. Treatment of the IgG 2a MAb with protein A decreased the binding to the macrophages and, in parallel, diminished the ADE activity. Although no infection was observed by inoculation of FIPV to human monocyte cell line U937 cells, FIPV complexed with either the IgG 2a MAb or the IgG 1 MAb caused infection in U937 cells which are shown to express Fc gamma receptor (Fc gamma R) I and II that can bind mouse IgG 2a and IgG 1, respectively. These results suggest that the enhancing activity of MAb is closely correlated with IgG subclass and that the correlation is involved in binding of MAb to Fc gamma R on feline macrophage.

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

    Science.gov (United States)

    Suzuki, Lisandra Akemi; Rossi, Cláudio Lúcio

    2013-02-01

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

  19. 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.

  20. Specific IgG Antibodies (Total and Subclasses against Saffron Pollen: A Study of Their Correlation with Specific IgE and Immediate Skin Reactions

    Directory of Open Access Journals (Sweden)

    Abdol-Reza Varasteh

    2007-12-01

    Full Text Available Saffron (Zaaferan, botanical name Crocus sativus, is the most expensive spice in the world. It is derived from the dried stigma and pistil of the purple saffron crocus flowers. Iran is the largest saffron producer accounting for more than 80% of the world's production. Saffron contains an aeroallergen that causes reactive respiratory allergic reactions in atopic subjects. IgG antibody to allergens in the serum of allergic patients is not routinely measured. In this study in order to find out more about mechanism of allergy against saffron pollen, specific antibodies (IgE and IgG, total and subclasses in atopic subjects were assayed. We used an ELISA assay for measuring specific IgE and IgG against saffron pollen extract in the sera of 38 atopic subjects (test group and 20 non allergic subjects (control group. The optical densities were compared between allergic subjects and non-allergic individuals. The prick test with saffron pollen extract was used to evaluate the cutaneous and specific antibody responses in the allergic subjects. The correlation was determined by statistical analysis. Specific saffron pollen IgE and IgG subclasses were found significantly higher in the allergic subjects than the control group. The immediate skin reaction was found positive in 70% of the test group. We report here, the existence of a positive correlation between specific IgE and skin reaction by prick test in atopic subjects (R=0.433. A negative correlation between specific IgE and IgG4 subclass was also found (R=-0.576. These data may be useful to understand the mechanism of allergy to saffron and may help in clarifying clinical manifestations and to prevent IgE production as well as therapeutic application.

  1. Differences in Fcgamma receptor IIa genotypes and IgG subclass pattern of anti-malarial antibodies between sympatric ethnic groups in Mali.

    Science.gov (United States)

    Israelsson, Elisabeth; Vafa, Manijeh; Maiga, Bakary; Lysén, Anna; Iriemenam, Nnaemeka C; Dolo, Amagana; Doumbo, Ogobara K; Troye-Blomberg, Marita; Berzins, Klavs

    2008-09-15

    The Ig Fc receptor family is an important link between the humoral and cellular immune systems. The association of a dimorphism in amino acid 131 (R/H) of the FcgammaRIIa with malaria severity, the R-allele being associated with a milder disease outcome, led to the investigation of the possible impact of this polymorphism in the interethnic difference in malaria susceptibility seen between the Fulani and Dogon in Mali. Plasma from individuals from Mali (164 Fulani and 164 Dogon) were analysed for malaria-reactive and total IgG subclass antibodies using ELISA, and the same individuals were also genotyped for the FcgammaRIIa R131H polymorphism using RFLP-PCR. Statistical analyses of the IgG subclass levels were done by unpaired t-test and ANOVA, and genotype differences were tested by chi2-test. While the two ethnic groups showed a similar frequency of the FcgammaRIIa 131 R/H heterozygote genotype, 131R/R dominated over the 131 H/H genotype in the Dogon whereas the Fulani presented a similar frequency of the two homozygote genotypes. The two alleles were evenly distributed in the Fulani, while the Dogon were clearly biased towards the R-allele. The Fulani showed higher levels of anti-malarial IgG1, -2 and -3 antibodies, with a higher proportion of IgG2, than the Dogon. In the Fulani, H-allele carriers had higher anti-malarial IgG2 levels than R/R homozygotes, while in the Dogon, the R-allele carriers showed the higher IgG2 levels. For anti-malarial IgG3, the R-allele carriers in the Fulani had higher levels than the H/H homozygotes. Taken together, the results showed marked interethnic differences in FcgammaRIIa R131H genotypes. Furthermore, the results indicate that the FcgammaRIIa R131H genotype may influence the IgG subclass responses related to protection against malaria, and that IgG2 may be of importance in this context.

  2. Differences in Fcgamma receptor IIa genotypes and IgG subclass pattern of anti-malarial antibodies between sympatric ethnic groups in Mali

    Directory of Open Access Journals (Sweden)

    Dolo Amagana

    2008-09-01

    Full Text Available Abstract Background The Ig Fc receptor family is an important link between the humoral and cellular immune systems. The association of a dimorphism in amino acid 131 (R/H of the FcγRIIa with malaria severity, the R-allele being associated with a milder disease outcome, led to the investigation of the possible impact of this polymorphism in the interethnic difference in malaria susceptibility seen between the Fulani and Dogon in Mali. Methods Plasma from individuals from Mali (164 Fulani and 164 Dogon were analysed for malaria-reactive and total IgG subclass antibodies using ELISA, and the same individuals were also genotyped for the FcγRIIa R131H polymorphism using RFLP-PCR. Statistical analyses of the IgG subclass levels were done by unpaired t-test and ANOVA, and genotype differences were tested by χ2-test. Results While the two ethnic groups showed a similar frequency of the FcγRIIa 131 R/H heterozygote genotype, 131R/R dominated over the 131 H/H genotype in the Dogon whereas the Fulani presented a similar frequency of the two homozygote genotypes. The two alleles were evenly distributed in the Fulani, while the Dogon were clearly biased towards the R-allele. The Fulani showed higher levels of anti-malarial IgG1, -2 and -3 antibodies, with a higher proportion of IgG2, than the Dogon. In the Fulani, H-allele carriers had higher anti-malarial IgG2 levels than R/R homozygotes, while in the Dogon, the R-allele carriers showed the higher IgG2 levels. For anti-malarial IgG3, the R-allele carriers in the Fulani had higher levels than the H/H homozygotes. Conclusion Taken together, the results showed marked interethnic differences in FcγRIIa R131H genotypes. Furthermore, the results indicate that the FcγRIIa R131H genotype may influence the IgG subclass responses related to protection against malaria, and that IgG2 may be of importance in this context.

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  4. [Autoantibodies].

    Science.gov (United States)

    Ishihara, Yasushi

    2005-06-01

    The autoantibody test gives significant information for diagnosis of autoimmune diseases. Since the finding of the LE-cell in 1948, dozens of autoantibodies have been found. Anti nuclear antibody (ANA) is the essential test for the screening of autoantibodies. Indirect immunofluorescence (IIF) is the conventional method for the detection of ANA. IIF can detect a wide spectrum of ANA and gives abundant information obtained from a staining pattern. However under the recent circumstances of using advanced fluorescent microscopes and reagents we often have difficulty interpreting positive results seen in normal individuals and in detailed staining patterns. ELISA (enzyme-linked immunosorbent assay), detecting disease specific autoantibodies alone, is one solution. Some antibodies such as anti-DNA or anti-ENA (extractable nuclear antigen) have a strong relation to specific diseases. These autoantibodies have been detected by IIF, RIA (radioimmunoassay) or DID (double immune diffusion). With the progress of molecular biology many autoantigens have been characterized. Now ELISA is a typical way to detect autoantibodies because purified or recombinant antigens are easily available. Though RF (rheumatoid factor) is the historical autoantibody detected in RA patients, the specificity to RA is low. The new anti-CCP is promising from its high specificity and sensitivity. Now we can choose various kind of autoantibody tests, not only conventional ones but also newly developed ones. For diagnosis and treatment of autoimmune diseases, understanding of both clinical significance and methodology is important.

  5. Validation and evaluation of VapA-specific IgG and IgG subclass enzyme-linked immunosorbent assays (ELISAs) to identify foals with Rhodococcus equi pneumonia.

    Science.gov (United States)

    Sanz, M G; Oliveira, A F; Loynachan, A; Page, A; Svansson, V; Giguère, S; Horohov, D W

    2016-01-01

    Rhodococcus equi (Rhodococcus hoagii/Prescottella equi) is a common cause of foal pneumonia, but its diagnosis remains a challenge for equine veterinarians. While the VapA-specific (virulence-associated protein A) immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) has low sensitivity and specificity for detecting pneumonic foals, little is known about VapA-specific IgG subclasses. To evaluate the performance of VapA-specific ELISA for IgG and its subclasses IgGa, IgGb and IgG(T) in the early diagnosis of pneumonia caused by R. equi. Assay validation followed by assessment of diagnostic performance using archived samples from animals of known status. Serum samples from exposed (n = 125) and nonexposed adult horses (n = 10) and from experimentally challenged and naturally infected foals were used for ELISA validation. Post mortem and tissue culture records of the last 24 years from the Institute for Experimental Pathology at the University of Iceland in Keldur, Iceland laboratory were evaluated to confirm the absence of R. equi cases in Iceland. The diagnostic performance of VapA-specific IgG and its subclasses was evaluated using banked serum samples from pneumonic (n = 21) and healthy foals (n = 80). To evaluate each IgG assay, a cut-off value was selected based on receiver operating characteristic curve analysis and used to calculate sensitivity and specificity. The intra- and interassay coefficients of variation were calculated for each ELISA. Using sera from Iceland, where R. equi infection has not been reported, the VapA-specific IgG ELISA differentiated exposed from nonexposed horses. When used to identify infected foals, VapA-specific IgG, IgGa and IgGb had no diagnostic value. In contrast, IgG(T) had high sensitivity and specificity. Horses from Iceland are not exposed to VapA(+) R. equi and can serve as negative controls. VapA-specific IgG subclasses, with the exception of IgG(T), are poor predictors of disease. Further

  6. Complement deposition induced by binding of anti-contactin-1 auto-antibodies is modified by immunoglobulins.

    Science.gov (United States)

    Appeltshauser, Luise; Weishaupt, Andreas; Sommer, Claudia; Doppler, Kathrin

    2017-01-01

    Inflammatory neuropathies associated with auto-antibodies against paranodal proteins like contactin-1 are reported to respond poorly to treatment with intravenous immunoglobulins (IVIG). A reason might be that IVIG interacts with the complement pathway and these auto-antibodies often belong to the IgG4 subclass that does not activate complement. However, some patients do show a response to IVIG, especially at the beginning of the disease. This corresponds with the finding of coexisting IgG subclasses IgG1, IgG2 and IgG3. We therefore aimed to investigate complement deposition and activation by samples of three patients with anti-contactin-1 IgG auto-antibodies of different subclasses as a potential predictor for response to IVIG. Complement deposition and activation was measured by cell binding and ELISA based assays, and the effect of IVIG on complement deposition was assessed by addition of different concentrations of IVIG. Binding of anti-contactin-1 auto-antibodies of all three patients induced complement deposition and activation with the strongest effect shown by the serum of a patient with predominance of IgG3 auto-antibodies. IVIG led to a reduction of complement deposition in a dose-dependent manner, but did not reduce binding of auto-antibodies to contactin-1. We conclude that complement deposition may contribute to the pathophysiology of anti-contactin-1 associated neuropathy, particularly in patients with predominance of the IgG3 subclass. The proportion of different auto-antibody subclasses may be a predictor for the response to IVIG in patients with auto-antibodies against paranodal proteins. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. IgG antibody subclasses, tumor necrosis factor and IFN-gamma levels in patients with type II lepra reaction on thalidomide treatment.

    Science.gov (United States)

    Partida-Sanchez, S; Favila-Castillo, L; Pedraza-Sanchez, S; Gomez-Melgar, M; Saul, A; Estrada-Parra, S; Estrada-Garcia, I

    1998-05-01

    A group of 9 Mexican lepromatous leprosy patients was studied at the beginning of a type II reaction (erythema nodosum leprosum, ENL) and after 1 or 2 months of thalidomide treatment. ENL patients at the onset of the reaction had slightly higher amounts of anti-Mycobacterium leprae IgG1 and IgG2 antibodies, compared to similar lepromatous patients that did not develop ENL. Neither these antibody levels nor IgM and the other IgG subclasses were importantly modified after thalidomide treatment. Serum TNF was significantly higher in the patients that developed ENL compared to those that did not develop the reaction. TNF levels were slightly decreased after 1 month of thalidomide treatment and significantly decreased after 2 months of treatment. Serum IFN-gamma was significantly lower in patients at the onset of ENL and was increased after 1 and 2 months of thalidomide treatment.

  8. 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.

  9. IgG subclass concentrations in certified reference material 470 and reference values for children and adults determined with the binding site reagents.

    Science.gov (United States)

    Schauer, Uwe; Stemberg, Frank; Rieger, Christian H L; Borte, Michael; Schubert, Simone; Riedel, Frank; Herz, Udo; Renz, Harald; Wick, Manfred; Carr-Smith, Hugh D; Bradwell, Arthur R; Herzog, Wilhelm

    2003-11-01

    There is currently no international reference preparation for IgG subclass (IgGSc) quantification. This situation has led to calibration differences among assays and a variety of reference interval values with consequential difficulties in comparing results. We therefore evaluated IgGSc concentrations in Certified Reference Material 470 (CRM 470). Pure, polyclonal IgG1, -2, -3, and -4 were prepared from a large serum pool for use as primary standards. The IgG mass in each preparation was calculated from amino-acid analysis data. IgGSc concentrations were assessed in CRM 470 by nephelometry with modern analytical techniques, using these reference preparations. Subsequently, IgGSc concentrations were measured in 380 healthy individuals (250 males and 130 females), and age-dependent reference intervals were established. IgGSc concentrations in CRM 470 were as follows: IgG1, 5028 mg/L; IgG2, 3418 mg/L; IgG3, 579 mg/L, and IgG4, 381 mg/L, with a total IgG concentration of 9406 mg/L, 2.83% below the certified total IgG value of 9680 mg/L. Age-dependent percentile curves for the four IgGSc were constructed using a Box-Cox transformation. Maximum median values were as follows: IgG1, 6.02 g/L at 11 years; IgG2, 3.45 g/L at 31 years; IgG3, 0.63 g/L at 17 years; and IgG4, 0.48 g/L at 14 years. No significant sex-related differences were observed. The correlation between the summation of individual IgGSc and separate measurements of total IgG concentrations was good and supports the accuracy of the results. The results are based on The Binding Site assays and should not be considered appropriate for other assays unless so demonstrated.

  10. Plasma IgG autoantibody against actin-related protein 3 in liver fluke Opisthorchis viverrini infection.

    Science.gov (United States)

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

    2015-07-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    INTRODUCTION: Spondyloarthritis (SpA), an interrelated group of rheumatic diseases, has been suggested to be triggered by bacterial infections prior to the development of an autoimmune response that causes inflammation of the spinal and peripheral joints. Because human heat shock protein 60 (HSP60...... and patient follow-up. In this study, we have focused on these parameters in a cohort of axial SpA patients with a well-established set of clinical characteristics, including MRI changes and human leukocyte antigen B27. METHODS: IgG subclass antibodies (IgG1, IgG2, IgG3 and IgG4) against recombinant HSP60...... of three reactive arthritis-related bacteria; human HSP60; and the microorganisms Chlamydia trachomatis and C. pneumoniae were determined by ELISA. Serum samples collected from 2004 to 2006 and in 2010 and 2011 from 39 axial SpA patients were analyzed and compared with samples from 39 healthy controls...

  12. 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.

  13. Circulating IgG autoantibodies to IgE in atopic syndromes.

    Science.gov (United States)

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

    1986-04-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  15. Epitopes, avidity and IgG subclasses of tyrosine hydroxylase autoantibodies in vitiligo and alopecia areata patients.

    Science.gov (United States)

    Rahoma, S F E; Sandhu, H K; McDonagh, A J G; Gawkrodger, D J; Weetman, A P; Kemp, E H

    2012-07-01

    We previously detected antibodies against tyrosine hydroxylase (TH) in 23% of patients with nonsegmental vitiligo and in 19% of patients with alopecia areata (AA). To identify TH epitopes recognized by TH antibodies in patients with vitiligo and AA. Recombinant plasmids containing defined fragments of TH cDNA were constructed. The cloned TH cDNA fragments were subsequently translated in vitro to produce a series of [(35) S]-labelled TH protein fragments which were then used in radioimmunoassays to analyse the immunoreactivity of sera from 18 TH antibody-positive patients with vitiligo and so initially define TH epitope domains. Further localization of TH epitopes was investigated by antibody absorption experiments using synthetic TH peptides and nonradiolabelled, in vitro-expressed TH protein fragments. Antibody binding to identified epitopes was confirmed in TH peptide enzyme-linked immunosorbent assays. Analysis of the results obtained indicated the presence of two major antibody-binding sites on TH between amino acids 1 and 14 (epitope 1-14) and between amino acids 61 and 80 (epitope 61-80). Of 18 patients with vitiligo and six with AA, 17 (94%) and five (83%), respectively, had antibodies against epitope 1-14. In addition, 11/18 (61%) vitiligo and 2/6 (33%) AA patient sera displayed immunoreactivity against epitope 61-80. Two major binding sites for human TH antibodies are located at the N-terminus of the protein. The humoral immune response to TH in vitiligo and AA is heterogeneous in nature in that patients may have antibodies to more than one TH epitope. TH antibodies from patients with vitiligo or AA can recognize identical epitopes. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

  16. 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

  17. Novel feline autoimmune blistering disease resembling bullous pemphigoid in humans: IgG autoantibodies target the NC16A ectodomain of type XVII collagen (BP180/BPAG2).

    Science.gov (United States)

    Olivry, T; Chan, L S; Xu, L; Chace, P; Dunston, S M; Fahey, M; Marinkovich, M P

    1999-07-01

    In humans and dogs, bullous pemphigoid (BP) is an autoimmune blistering disease associated with the production of basement membrane autoantibodies that target the 180-kd type XVII collagen (BP180, BPAG2) and/or the 230-kd plakin epidermal isoform BPAG1e (BP230). In two adult cats, an acquired dermatosis and stomatitis was diagnosed as BP subsequent to the fulfillment of the following criteria: 1) presence of cutaneous vesicles, erosions, and ulcers; 2) histologic demonstration of subepidermal vesiculation with inflammatory cells, including eosinophils; 3) in vivo deposition of IgG autoantibodies at the epidermal basement membrane zone; and 4) serum IgG autoantibodies targeting a 180-kd epidermal protein identified as type XVII collagen. In both cats, the antigenic epitopes targeted by IgG autoantibodies were shown to be situated in the NC16A ectodomain of type XVII collagen, a situation similar to that of humans and dogs with BP. Feline BP therefore can be considered a clinical, histopathologic, and immunologic homologue of BP in humans and dogs.

  18. Renal Transplant Patients Biopsied for Cause and Tested for C4d, DSA, and IgG Subclasses and C1q: Which Humoral Markers Improve Diagnosis and Outcomes?

    Science.gov (United States)

    Cicciarelli, James C.; Chang, Youngil; Koss, Michael; Hacke, Katrin; Kasahara, Noriyuki; Burns, Kevin M.; Min, David I.; Naraghi, Robert; Shah, Tariq

    2017-01-01

    The association between donor specific antibodies (DSA) and renal transplant rejection has been generally established, but there are cases when a DSA is present without rejection. We examined 73 renal transplant recipients biopsied for transplant dysfunction with DSA test results available: 23 patients diffusely positive for C4d (C4d+), 25 patients focally positive for C4d, and 25 patients negative for C4d (C4d−). We performed C1q and IgG subclass testing in our DSA+ and C4d+ patient group. Graft outcomes were determined for the C4d+ group. All 23 C4d+ patients had IgG DSA with an average of 12,500 MFI (cumulative DSA MFI). The C4d− patients had average DSA less than 500 MFI. Among the patients with C4d+ biopsies, 100% had IgG DSA, 70% had C1q+ DSA, and 83% had complement fixing IgG subclass antibodies. Interestingly, IgG4 was seen in 10 of the 23 recipients' sera, but always along with complement fixing IgG1, and we have previously seen excellent function in patients when IgG4 DSA exists alone. Cumulative DSA above 10,000 MFI were associated with C4d deposition and complement fixation. There was no significant correlation between graft loss and C1q positivity, and IgG subclass analysis seemed to be a better correlate for complement fixing antibodies in the C4d+ patient group.

  19. 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

    either at low concentration (interaction parameter (kD) obtained from dynamic light scattering, DLS) or at high concentration (solution storage modulus (G') from ultrasonic shear rheology). We also developed a novel method for the determination of PPI using the apparent radius of the protein at either...... 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...... differently with respect to increase in ionic strength. Two mAbs (A and B) showed little or no effect of increasing ionic strength, whereas mAb-C showed a remarkable decrease in attractive PPI and viscosity. Previous studies have mainly investigated mAbs of the IgG1 and IgG2 subclass. We show here...

  20. 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

    2013-02-01

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

  1. 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

  2. Effect of Continuous B Cell Depletion With Rituximab on Pathogenic Autoantibodies and Total IgG Levels in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

    Science.gov (United States)

    Cortazar, Frank B; Pendergraft, William F; Wenger, Julia; Owens, Charles T; Laliberte, Karen; Niles, John L

    2017-05-01

    To evaluate the effect of rituximab on pathogenic autoantibodies and total Ig levels, and to identify serious adverse events in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) treated with continuous B cell depletion. We conducted a retrospective analysis of 239 patients with AAV treated with rituximab-induced continuous B cell depletion. Two treatment cohorts were analyzed: an induction group (n = 52) and a maintenance group (n = 237). Changes in ANCA titers and total Ig levels over time were evaluated using mixed-effects models. Risk factors for serious infections during maintenance treatment were evaluated using Poisson regression. During induction, IgG levels fell at a mean rate of 6% per month (95% confidence interval [95% CI] 4, 8%), while ANCA levels declined at a mean rate of 47% per month (95% CI 42, 52%) and 48% per month (95% CI 42, 54%) for patients with antimyeloperoxidase (anti-MPO) antibodies and those with anti-proteinase 3 (anti-PR3) antibodies, respectively. During maintenance treatment, with a median duration of 2.4 years (interquartile range 1.5, 4.0 years), IgG levels declined a mean of 0.6% per year (95% CI -0.2, 1.4%). New significant hypogammaglobulinemia (IgG level of <400 mg/dl) during maintenance treatment occurred in 4.6% of the patients, all of whom were in the lowest baseline IgG quartile. Serious infections during maintenance therapy occurred at a rate of 0.85 per 10 patient-years (95% CI 0.66, 1.1) and were independently associated with an IgG level of <400 mg/dl. B cell-targeted therapy causes a preferential decline in ANCA titers relative to total IgG levels. Despite prolonged maintenance therapy with rituximab, IgG levels remain essentially constant. Serious infections were rare. © 2016, American College of Rheumatology.

  3. Natural autoantibodies, IgG antibodies to tetanus toxoid and CD5+ B cells in patients with Mediterranean visceral leishmaniasis. The Leishmania Study Group.

    Science.gov (United States)

    Louzir, H; Belal-Kacemi, L; Sassi, A; Laouini, D; Ben Ismail, R; Dellagi, K

    1994-03-01

    Natural autoantibodies (NaAb) and IgG antibodies to tetanus toxoid (TT) were analysed in the sera of 38 children with active visceral leishmaniasis (VL) previously vaccinated with TT and in 30 healthy controls matched for sex and age. Patients exhibited high levels of NaAb to a panel of self antigens (tubulin, myosin, myoglobin, actin) contrasting to a low level of IgG to TT. Analysis of the circulating B cells in 26 untreated patients showed a low percentage of CD5+ per total B cells (3-66%, mean 36.6%) compared with 14 normal controls (17.8-66.6%, mean 52.7%) (P < 0.001). Evaluation of these parameters after antimonial therapy showed a significant decrease of the level of the NaAb (P < 0.0005), and a spontaneous increase of the level of the IgG to TT without any vaccine boosting (P < 0.01). In contrast, there was a significant increase in CD5+ B cells (P < 0.0005). This result suggests that CD5+ B cells may be sequestrated in parasitized lymphoid organs and may be released after remission. These findings show that the polyclonal B cell activation that occurs during active VL involves mainly B cells bearing NaAb and are in favour of a functional dichotomy of B cells.

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

    Directory of Open Access Journals (Sweden)

    Christoph Fickentscher

    2015-01-01

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

  5. High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients.

    Science.gov (United States)

    Hecker, Michael; Fitzner, Brit; Wendt, Matthias; Lorenz, Peter; Flechtner, Kristin; Steinbeck, Felix; Schröder, Ina; Thiesen, Hans-Jürgen; Zettl, Uwe Klaus

    2016-04-01

    Intrathecal immunoglobulin G (IgG) synthesis and oligoclonal IgG bands in cerebrospinal fluid (CSF) are hallmarks of multiple sclerosis (MS), but the antigen specificities remain enigmatic. Our study is the first investigating the autoantibody repertoire in paired serum and CSF samples from patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and other neurological diseases by the use of high-density peptide microarrays. Protein sequences of 45 presumed MS autoantigens (e.g.MOG, MBP, and MAG) were represented on the microarrays by overlapping 15mer peptides. IgG reactivities were screened against a total of 3991 peptides, including also selected viral epitopes. The measured antibody reactivities were highly individual but correlated for matched serum and CSF samples. We found 54 peptides to be recognized significantly more often by serum or CSF antibodies from MS patients compared with controls (pvalues <0.05). The results for RRMS and PPMS clearly overlapped. However, PPMS patients presented a broader peptide-antibody signature. The highest signals were detected for a peptide mapping to a region of the Epstein-Barr virus protein EBNA1 (amino acids 392-411), which is homologous to the N-terminal part of human crystallin alpha-B. Our data confirmed several known MS-associated antigens and epitopes, and they delivered additional potential linear epitopes, which await further validation. The peripheral and intrathecal humoral immune response in MS is polyspecific and includes antibodies that are also found in serum of patients with other diseases. Further studies are required to assess the pathogenic relevance of autoreactive and anti-EBNA1 antibodies as well as their combinatorial value as biomarkers for MS. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. High-Density Peptide Microarray Analysis of IgG Autoantibody Reactivities in Serum and Cerebrospinal Fluid of Multiple Sclerosis Patients*

    Science.gov (United States)

    Hecker, Michael; Fitzner, Brit; Wendt, Matthias; Lorenz, Peter; Flechtner, Kristin; Steinbeck, Felix; Schröder, Ina; Thiesen, Hans-Jürgen; Zettl, Uwe Klaus

    2016-01-01

    Intrathecal immunoglobulin G (IgG) synthesis and oligoclonal IgG bands in cerebrospinal fluid (CSF) are hallmarks of multiple sclerosis (MS), but the antigen specificities remain enigmatic. Our study is the first investigating the autoantibody repertoire in paired serum and CSF samples from patients with relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and other neurological diseases by the use of high-density peptide microarrays. Protein sequences of 45 presumed MS autoantigens (e.g. MOG, MBP, and MAG) were represented on the microarrays by overlapping 15mer peptides. IgG reactivities were screened against a total of 3991 peptides, including also selected viral epitopes. The measured antibody reactivities were highly individual but correlated for matched serum and CSF samples. We found 54 peptides to be recognized significantly more often by serum or CSF antibodies from MS patients compared with controls (p values <0.05). The results for RRMS and PPMS clearly overlapped. However, PPMS patients presented a broader peptide-antibody signature. The highest signals were detected for a peptide mapping to a region of the Epstein-Barr virus protein EBNA1 (amino acids 392–411), which is homologous to the N-terminal part of human crystallin alpha-B. Our data confirmed several known MS-associated antigens and epitopes, and they delivered additional potential linear epitopes, which await further validation. The peripheral and intrathecal humoral immune response in MS is polyspecific and includes antibodies that are also found in serum of patients with other diseases. Further studies are required to assess the pathogenic relevance of autoreactive and anti-EBNA1 antibodies as well as their combinatorial value as biomarkers for MS. PMID:26831522

  7. Genetic homogeneity but IgG subclass-dependent clinical variability of alloimmune membranous nephropathy with anti-neutral endopeptidase antibodies.

    Science.gov (United States)

    Vivarelli, Marina; Emma, Francesco; Pellé, Thimothée; Gerken, Christopher; Pedicelli, Stefania; Diomedi-Camassei, Francesca; Klaus, Günter; Waldegger, Siegfried; Ronco, Pierre; Debiec, Hanna

    2015-03-01

    Alloimmune antenatal membranous nephropathy (MN) during pregnancy results from antibodies produced by a neutral endopeptidase (NEP)-deficient mother. Here we report two recent cases that provide clues to the severity of renal disease. Mothers of the two children had circulating antibodies against NEP showing the characteristic species-dependent pattern by immunofluorescence on kidney slices. A German mother produced predominantly anti-NEP IgG4 accompanied by a low amount of IgG1. Her child recovered renal function within a few weeks. In sharp contrast, an Italian mother mainly produced complement-fixing anti-NEP IgG1, which also inhibits NEP enzymatic activity, whereas anti-NEP IgG4 has a weak inhibitory potency. Her child was dialyzed for several weeks. A kidney biopsy performed at 12 days of age showed MN, ischemic glomeruli, and arteriolar and tubular lesions. A second biopsy performed at 12 weeks of age showed aggravation with an increased number of collapsed capillary tufts. Both mothers were homozygous for the truncating deletion mutation 466delC and were thus NEP deficient. The 466delC mutation, identified in three previously described families, suggests a founder effect. Because of the potential severity of alloimmune antenatal MN, it is essential to identify families at risk by the detection of anti-NEP antibodies and NEP antigen in urine. On the basis of the five families identified to date, we propose an algorithm for the diagnosis of the disease and the prevention of complications.

  8. IgG Autoantibodies against β2-Glycoprotein I Complexed with a Lipid Ligand Derived from Oxidized Low-Density Lipoprotein are Associated with Arterial Thrombosis in Antiphospholipid Syndrome

    Directory of Open Access Journals (Sweden)

    Daniel Lopez

    2003-01-01

    Full Text Available We recently reported [J. Lipid Res. 42 (2001, 697; 43 (2002, 1486; 44 (2003, 716] that β2-glycoprotein I (β2GPI forms complexes with oxidized LDL (oxLDL and autoantibodies against these complexes are present in patients with SLE and antiphospholipid syndrome (APS. The relationship of β2GPI/oxLDL complexes and IgG autoantibodies against β2GPI complexed with oxLig-1 (an oxLDL-derived ligand with clinical manifestations of APS was studied in 150 APS and SLE patients. The β2GPI/oxLDL levels of APS patients were similar to those of SLE patients without APS, but they were significantly higher than healthy individuals. There was no difference in the complex levels among the patients with arterial, venous thrombosis, or pregnancy morbidity. IgG anti-β2GPI/oxLig-1 levels of APS were significantly higher than those of SLE without APS and healthy individuals. Further, antibody levels of APS patients with arterial thrombosis were significantly higher than those patients with venous thrombosis and pregnancy morbidity. Thus, oxidation of LDL leads the complex formation with β2GPI in SLE and APS patients. In contrast, anti-β2GPI/oxLig-1 autoantibodies were generated only in APS and were strongly associated with arterial thrombosis. These results suggest that autoantibodies against β2GPI/oxLDL complexes are etiologically important in the development of atherosclerosis in APS.

  9. Identification of human IgG1 variant with enhanced FcRn binding and without increased binding to rheumatoid factor autoantibody

    Science.gov (United States)

    Maeda, Atsuhiko; Iwayanagi, Yuki; Haraya, Kenta; Tachibana, Tatsuhiko; Nakamura, Genki; Nambu, Takeru; Esaki, Keiko; Hattori, Kunihiro; Igawa, Tomoyuki

    2017-01-01

    ABSTRACT Various studies have demonstrated that Fc engineering to enhance neonatal Fc receptor (FcRn) binding is effective for elongating half-life or increasing cellular uptake of IgG. A previous study has shown that a N434H mutation to enhance FcRn binding resulted in increased binding to rheumatoid factor (RF) autoantibody, which is not desirable for therapeutic use in autoimmune disease. In this study, we first showed that all the existing Fc variants with enhanced FcRn binding also show increased RF binding, and then identified specific mutations that could be introduced to those Fc variants to reduce the RF binding. Furthermore, we generated novel Fc variants that do not increase RF binding and show half-lives of 45 d in cynomolgus monkey, which is longer than those of previously reported Fc variants. In addition, we generated novel Fc variants with antigen sweeping activity that do not increase RF binding. We expect that these novel Fc variants will be useful as antibody therapeutics against autoimmune diseases. PMID:28387635

  10. 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

    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......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...... 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...

  11. Immunoglobulin G subclasses in older persons with Down syndrome.

    Science.gov (United States)

    Mehta, P D; Dalton, A J; Mehta, S P; Percy, M E; Sersen, E A; Wisniewski, H M

    1993-07-01

    IgG subclasses were measured in sera from 33 persons with Down syndrome (DS) (mean age 55 +/- 7 years) and 33 age- and sex-matched control individuals using a mouse monoclonal antibody based sandwich enzyme linked immunosorbent assay. Significantly higher levels of IgG1 and IgG3 and lower levels of IgG2 and IgG4 subclasses were found in the DS group compared to the control individuals. The higher levels of IgG1 and IgG3 subclasses found in DS persons were consistent with those seen in patients with autoimmune diseases and chronic viral infections; the lower levels of IgG2 and IgG4 subclasses were consistent with those seen in patients with recurrent infections. Our findings are similar to those reported in children with DS. We speculate that the subclass levels may have little or no relationship to the development of brain lesions typical of Alzheimer disease in older persons with DS. There were no significant differences between the levels of IgG subclasses of persons with DS showing signs of dementia of the Alzheimer type compared to those without such manifestations.

  12. 伴甲状腺抗体阳性的荨麻疹患者血清白介素13、总IgG及IgG3水平检测%Detection of IL-13, IgG and IgG3 in serum of patients with urticaria containing anti-thyreoid autoantibodies

    Institute of Scientific and Technical Information of China (English)

    李莉敏; 廖文俊; 李承新; 高天文

    2011-01-01

    目的:观察伴有器官特异性自身抗体的荨麻疹患者血清中白介素(IL)-13、总IgG及IgG3的水平.方法:用ELISA方法检测24例伴有器官特异性自身抗体的荨麻疹患者、24例慢性荨麻疹患者及24例健康对照者血清IL-13的水平;用散射比浊方法检测30例伴有器官特异性自身抗体的荨麻疹患者和20例健康对照血清总IgG及IgG3水平.结果:自身免疫性荨麻疹患者血清中IL-13明显高于慢性荨麻疹组及健康对照组,总IgG及IgG3的水平亦高于健康对照组,差异具有统计学意义(P < 0.05).结论:IL-13及IgG3可能参与了自身免疫性荨麻疹的发病过程.%Objective: To detect the levels of IL-13, IgG and IgG3 in serum of patients with urticaria containing organ specific auto-antibodies.Methods: The sera were collected from patients with urticaria containing organ specific auto-antibodies (24 cases), chronic idiopathic urticaria (24 cases) and healthy donors (24 cases).IL-13, IgG and IgG3 in serums were detected respectively by enzyme linked immunosorbent assay (ELISA) technique and rate nephelometry technique.Results:The serum concentration of IL-13 in patients with urticaria containing organ specific auto-antibodies was significantly increased than those in normal controls and chronic idiopathic urticaria.The serum levels of IgG and IgG3 in patients with urticaria containing organ specific auto-antibodies was significantly higher than those in normal controls.Conclusion: IL-13 and IgG3 may contribute to the progression of urticaria with organ specific auto-antibodies.

  13. Proteolysis breaks tolerance toward intact α345(IV) collagen, eliciting novel anti-glomerular basement membrane 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

    2013-02-15

    Goodpasture disease is an autoimmune kidney disease mediated by autoantibodies against noncollagenous domain 1 (NC1) monomers of α3(IV) collagen that bind to the glomerular basement membrane (GBM), usually causing rapidly progressive glomerulonephritis (GN). We identified a novel type of human IgG4-restricted anti-GBM autoantibodies associated with mild nonprogressive GN, which specifically targeted α345NC1 hexamers but not α3NC1 monomers. The mechanisms eliciting these anti-GBM autoantibodies were investigated in mouse models recapitulating this phenotype. Wild-type and FcγRIIB(-/-) mice immunized with autologous murine GBM NC1 hexamers produced mouse IgG1-restricted autoantibodies specific for α345NC1 hexamers, which bound to the GBM in vivo but did not cause GN. 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 Abs specific for α345NC1 hexamers, which were not subclass restricted. As heterologous Ag in COL4A3-humanized mice, murine GBM NC1 hexamers elicited mouse IgG1, IgG2a, and IgG2b autoantibodies specific for α345NC1 hexamers and induced anti-GBM Ab GN. These findings indicate that tolerance toward autologous intact α345(IV) collagen is established in hosts expressing this Ag, even though autoreactive B cells specific for α345NC1 hexamers are not purged from their repertoire. Proteolysis selectively breaches this tolerance by generating autoimmunogenic α345NC1 hexamers. This provides a mechanism eliciting autoantibodies specific for α345NC1 hexamers, which are restricted to noninflammatory IgG subclasses and are nonnephritogenic. In Alport syndrome, lack of tolerance toward α345(IV) collagen promotes production of alloantibodies to α345NC1 hexamers, including proinflammatory IgG subclasses that mediate posttransplant anti-GBM nephritis.

  14. 甲状腺球蛋白抗体IgG亚型在桥本甲状腺炎中的分布及意义%Distribufion and significance of IgG subclasses of serum antithyroglobulin antibody in Hashimoto thyroiditis

    Institute of Scientific and Technical Information of China (English)

    李茂蓉; 郭晓蕙; 高莹; 高燕明; 卢桂芝; 惠岩; 王淑凤; 施秉银; 滕卫平

    2008-01-01

    目的 探讨血清甲状腺球蛋白抗体(TgAb)IgG亚型在桥本甲状腺炎中的分布及意义.方法 收集112例TgAb滴度升高的桥本甲状腺炎患者的血清,按甲状腺功能分为甲状腺功能减低(甲减)组、亚临床甲状腺功能减低(亚甲减)组和甲状腺功能正常组(功能正常组).采用抗原特异性ELISA方法 检测TgAb各IgG亚型阳性率及其滴度.结果 TgAb各IgG亚型阳性率分别为IgG190.2%、IgG2 58.0%、IgG3 19.6%、IgG4 87.5%.甲减组及亚甲减组IgG1亚型滴度的几何均数均高于功能正常组(分别为1:450.8,1:245.5,1:8.7,P<0.01);甲减组与亚甲减组IgG2亚型滴度的几何均数均高于功能正常组(1:37.3,1:3.2,1:0.2,分别为P<0.01和P<0.05),并且甲减组IgG2亚型滴度的几何均数高于亚甲减组(P<0.05).结论 桥本甲状腺炎TgAb亚型主要由IgG1、IgG2、IgG4组成.高滴度IgG1、IgG2可能与甲状腺功能损伤有关.%objective To evaluate the distribution and significance of IgG subclasses of antithyroglobulin antibody in sera from patients with Hashimoto thyroiditis.Methods Sera from 112 patients with Hashimoto thyroiditis were collected and patients were divided into 3 groups,i.e.hypothyroidism,subclinical hypothyroidism and euthyroidism.Antigen specific ELISA was used to detect the distribution of IgG subclasses of antithyroglobulin antibody.Results The positive rates of IgG subclasses of TgAb were IgG1 90.2%,IgG2 58.0%,IgG3 19.6%and IgG4 87.5%respectively.The mean geometric titers of IgG1 in sera from patients with hypothyroidism and subclinical hypothyroidism were 1:450.8 and 1:245.5 respectively,both being significantly higher than that with euthyroidism(1:8.7,P<0.01).The mean geometric titers of IgG2 in sera from patients with hypothyroidism and subclinical hypothyroidism were 1:37.3 and 1:3.2 respectively,both being also significantly higher than that with euthyroidism(1:0.2,P<0.01 and P<0.05 respectively)and that with hypothyroidism was

  15. Collagen-induced arthritis in Biozzi mice. Joint involvement is not correlated with collagen II IgG2a autoantibodies nor restricted to only H-2q and H-2r.

    Science.gov (United States)

    Bouvet, J P; Couderc, J; Bouthillier, Y; Franc, B; Decreusefond, C; Mouton, D

    1989-09-01

    High (H) and low (L) immune responder "Biozzi" mice, obtained by four different selections, were investigated for their ability to develop collagen-induced arthritis. Both LI and LII lines--characterized by their low antibody responses to a wide variety of Ag--developed arthritis though they do not bear the susceptible H-2q and H-2r haplotypes. Out of the two lines (HI and HII) selected for their high antibody responses and bearing H-2q, only one (HI) developed arthritis. Both the lines with amplified high or low antibody responses (HG and LG), and the lines differing in the levels of cell-mediated immunity (Hpha and Lpha), failed to develop arthritis. Collagen II autoantibodies were found in all the lines: the responses being high (HI and HG), low (LI, LII and LG), or intermediate (HII, Hpha and Lpha). The level of IgG2a autoantibodies, presumed to be the most pathogenic, was low in two (HI and LII) of the three arthritic lines, and was high in the unaffected HG line. These results show that this arthritis is not solely restricted to H-2q and H-2r haplotypes, and argue against a correlation between collagen autoantibody levels and disease incidence.

  16. 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...

  17. Induction of T regulatory cells by the superagonistic anti-CD28 antibody D665 leads to decreased pathogenic IgG autoantibodies against desmoglein 3 in a HLA-transgenic mouse model of pemphigus vulgaris.

    Science.gov (United States)

    Schmidt, Thomas; Willenborg, Sebastian; Hünig, Thomas; Deeg, Cornelia A; Sonderstrup, Grete; Hertl, Michael; Eming, Rüdiger

    2016-04-01

    Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune disease of the skin and mucous membranes. Its pathogenesis is based on IgG autoantibodies that target the desmosomal cadherins, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1) and induce intra-epidermal loss of adhesion. Although the PV pathogenesis is well-understood, therapeutic options are still limited to immunosuppressive drugs, particularly corticosteroids, which are associated with significant side effects. Dsg3-reactive T regulatory cells (Treg) have been previously identified in PV and healthy carriers of PV-associated HLA class II alleles. Ex vivo, Dsg3-specific Treg cells down-regulated the activation of pathogenic Dsg3-specific T-helper (Th) 2 cells. In this study, in a HLA-DRB1*04:02 transgenic mouse model of PV, peripheral Treg cells were modulated by the use of Treg-depleting or expanding monoclonal antibodies, respectively. Our findings show that, in vivo, although not statistically significant, Treg cells exert a clear down-regulatory effect on the Dsg3-driven T-cell response and, accordingly, the formation of Dsg3-specific IgG antibodies. These observations confirm the powerful immune regulatory functions of Treg cells and identify Treg cells as potential therapeutic modulators in PV.

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

    Science.gov (United States)

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

    2013-12-01

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

  19. 抗BP180NC16A IgG亚型检测方法的建立以及在大疱性类天疱疮中的意义%Development of a method to detect anti-BP180NC16A IgG subclasses and the significance of antiBP180NC16A IgG in bullous pemphigoid

    Institute of Scientific and Technical Information of China (English)

    左亚刚; LIU Zhi

    2012-01-01

    目的 建立抗BP180NC16A IgG亚型的检测方法,并探讨其在大疱性类天疱疮(BP)中的意义.方法 原核表达GST-NC16A融合蛋白,并采用亲和层析法纯化.优化ELISA关键环节,建立抗BP180NC16A IgG各亚型的ELISA检测方法,并对10例未经治疗的BP、5例妊娠疱疹、1例成人线状IgA大疱性皮病、2例天疱疮患者血清分别进行检测.结果 通过方阵测定法确定GST-NC16A融合蛋白的包被浓度为500 μg/L,包被条件为4℃12h,血清稀释倍数为1∶100,酶标二抗为1∶2000,孵育条件为37℃1h,底物反应条件37℃20 min.10例大疱性类天疱疮患者10例IgG1阳性,9例IgG2阳性,5例IgG3阳性,9例IgG4阳性.2例寻常型天疱疮、1例成人线状IgA大疱性皮病均阴性.5例妊娠疱疹所有亚型均阳性,以IgG1和IgG3亚型为主.结论 抗BPI80NCI6A ELISA检测法特异性强、重复性好,是检测BP和妊娠疱疹患者抗BP180NC 16A抗体亚型的半定量方法.%Objective To develop an assay to quantitatively detect anti-BP180NC16A IgG subclasses and to assess the significance of anti-BP180NC16A lgG in bullous pemphigoid (BP).Methods The Glutathione S-transferase (GST)-BPI80NC16A fusion protein was expressed in E.coli system and purified by affinity chromatography.An improved enzyme-linked immunoabsorbent assay (ELISA) was developed and used to detect anti-BP180NCI6A IgG subclasses in serum samples from 10 patients with BP,5 patients with pemphigoid gestationis (PG),1 patient with linear IgA bullous dermatosis (LIBD) and 2 patients with pemphigus.Results The optimal condition for the ELISA was determined by cross assay as follows:the concentration of GSTBP180NC16A fusion protein for coating,500 μg/L; the condition for coating,4 ℃ for 12 hours; the dilution ratio of sera and secondary antibody,1∶ 100 and 1 ∶ 2000 respectively; the condition for incubation,37 ℃ for 1 hour;,the condition for the enzyme-substrate reaction,37 ℃ for 20 minutes.Of the 10 patients with BP

  20. 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

  1. 血乙肝病毒抗原阴性的乙肝病毒相关性肾炎患者肾组织IgG亚型特点%Renal IgG subclasses in hepatitis-related nephropathy patient with negative plasma hepatitis B antigen

    Institute of Scientific and Technical Information of China (English)

    马丹娜; 刘海静; 邹万忠; 郑丹侠

    2016-01-01

    目的 分析血乙肝病毒抗原阴性的乙肝病毒相关性肾炎(以下简称乙肝肾)肾组织IgG亚型特点.方法 选取经肾活检病理诊断的乙肝肾患者(血乙肝抗原阴性)14例为乙肝肾组,特发性膜性肾病组18例为膜性肾病组.肾活检组织HBsAg及HBcAg采用间接免疫荧光法,IgG,IgG1、2、3、4均用直接免疫荧光法进行染色检测.结果 乙肝肾组中IgG1、2、3、4各亚型沉积率分别为100% (14/14),78.6%(11/14),78.6%(11/14),100% (14/14);膜性肾病组中IgG1、2、3、4亚型沉积率分别为88.9%(16/18),5.6%(1/18),5.6%(1/18),83.3%(15/18).乙肝肾组的肾IgG2阳性率78.6%、IgG3阳性率78.6%,明显高于膜性肾病组的5.6%与5.6%,差异有统计学意义(P=0.000);而肾IgG1和IgG4阳性率与膜性肾病组差异无统计学意义(P均>0.05).结论 肾IgG2和IgG3沉积率在乙肝肾组明显高于膜性肾病组,在诊断时或有帮助意义.%Objective To analyze the renal IgG subclasses in special patients whose renal HBsAg and HBcAg are positive, but plasma HBsAg, HBeAg, and HBcAg are negative.Methods Renal IgG subclasses were compared between 14 cases hepatitis-related nephropathy patients(diagnosed by renal biopsy pathology,whose blood hepatitis B antigens were negative) and 18 cases idiopathic membranous nephropathy patients.HBcAg and HBsAg were detected by indirect immunofluorescence assay, IgG, IgG1, 2, 3, 4 were stained by immunofluorescence.Results Renal IgG1-4 deposits were 100% (14/14), 78.6% (11/14), 78.6% (11/14), 100%(14/14) separately in hepatitis B-related nephropathy group, and renal IgG1-4 deposits were 88.9% (16/18), 5.6% (1/18), 5.6% (1/18), and 83.3% (15/18) in idiopathic membranous nephropathy group.Renal IgG2 and IgG3 deposit more in hepatitis B-related nephropathy group than in idiopathic membranous nephropathy group (78.6% vs 5.6% ,78.6% vs 5.6%;P =0.000) , but no significant difference in IgG1 and IgG4 deposit

  2. 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...

  3. Analysis of a subclass-restricted HIV-1 gp41 epitope by omission peptides.

    Science.gov (United States)

    Mathiesen, T; Chiodi, F; Broliden, P A; Albert, J; Houghten, R A; Utter, G; Wahren, B; Norrby, E

    1989-01-01

    To define the amino acids involved in IgG subclass reactivity to two overlapping HIV-1 gp41 (E34/32; amino acid positions 582-613) peptides, sera from 18 HIV-infected individuals were studied. Peptides mimicking E34 but with single amino acid deletions or glycine substitutions were used to define the amino acid residues necessary for antibody binding. Two dominating immunogenic epitopes, containing highly hydrophilic amino acids, were found on the original peptide. Further analysis was undertaken with two corresponding omission sets of dodecapeptides representing halves of the complete E34 plus a terminal cystein peptide. The subclass reactivities usually differed between the patients with regard to the epitopes with which the different IgG subclasses reacted and also to the importance of different amino acids in antibody binding. The 600 glycine and the 601 lysine were involved in the binding of all IgG1, 2 and 4 and most IgG3. The development of E34/32-reactive IgM and IgG subclasses showed different patterns in four patients with primary HIV infections, contradicting the existence of a general pattern for the development of IgG subclasses to this peptide. The findings suggest that different progenitor clones are selected for synthesis of the different subclasses. PMID:2472353

  4. Pathologies Associated with Serum IgG4 Elevation

    Directory of Open Access Journals (Sweden)

    Mikael Ebbo

    2012-01-01

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

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    ESCOBAR-PÉREZ XIOMARA

    2000-01-01

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

  7. Autoantibodies in anti-p200 pemphigoid stain skin lacking laminin 5 and type VII collagen

    NARCIS (Netherlands)

    Zillikens, D; Ishiko, A; Jonkman, MF; Chimanovitch, [No Value; Shimizu, H; Hashimoto, T; Brocker, EB

    2000-01-01

    We report the case of a patient with a widespread bullous skin disease and linear deposits of IgG and C3 at the dermal-epidermal junction using direct immunofluorescence microscopy. Indirect immunofluorescence analysis demonstrated circulating IgG autoantibodies that stained, like autoantibodies to

  8. Autoantibodies in anti-p200 pemphigoid stain skin lacking laminin 5 and type VII collagen

    NARCIS (Netherlands)

    Zillikens, D; Ishiko, A; Jonkman, MF; Chimanovitch, [No Value; Shimizu, H; Hashimoto, T; Brocker, EB

    2000-01-01

    We report the case of a patient with a widespread bullous skin disease and linear deposits of IgG and C3 at the dermal-epidermal junction using direct immunofluorescence microscopy. Indirect immunofluorescence analysis demonstrated circulating IgG autoantibodies that stained, like autoantibodies to

  9. Anti-aquaporin-1 autoantibodies in patients with neuromyelitis optica spectrum disorders.

    Directory of Open Access Journals (Sweden)

    John S Tzartos

    Full Text Available Autoantibodies against aquaporin-4 (AQP4, a water channel in CNS astrocytes, are detected in ∼50-80% of patients with neuromyelitis optica spectrum disorders (NMOsd, characterized by longitudinally extensive transverse myelitis (LETM and/or optic neuritis. Although these autoantibodies present an invaluable biomarker for NMOsd and for the differential diagnosis of multiple sclerosis (MS, diagnosis of anti-AQP4-seronegative NMOsd remains challenging. We hypothesized that seronegative NMOsd patients might have autoantibodies against aquaporin-1 (AQP1, another water channel in CNS astrocytes. We initially developed a radioimmunoprecipitation assay to search for anti-AQP1 antibodies in sera from 632 individuals. Anti-AQP1 or anti-AQP4 autoantibodies were detected in 16.7% and 12%, respectively, of 348 patients with suspected NMOsd. Anti-AQP1 specificity was confirmed by competition, protein immunoblotting and ELISA assays, whereas epitope localization was studied by immunoadsorption on intact cells expressing AQP1 and peptide mapping experiments. Most anti-AQP1 autoantibodies were of the complement-activating IgG1 subclass and the majority bound to the extracellular domain of AQP1, suggesting a possible pathogenic role. Five out of 42 MS patients had anti-AQP1 antibodies, but 2 of them also had spinal cord lesions, while the anti-AQP1 antibodies in the other 3 bound to the cytoplasmic domain of AQP1. Anti-AQP1 antibodies were not detected in 100 healthy individuals or 142 patients with non-demyelinating neuroimmune diseases. Analysis of 17 anti-AQP1+/anti-AQP4- patients with suspected NMOsd showed that 5 had NMO and 11 had LETM. 12/17 of these sera bound predominantly to the extracellular AQP1 loop-Α. Overall, we found that anti-AQP1 autoantibodies are present in a subgroup of patients with chronic demyelination in the CNS and similarities with anti-AQP4-seronegative NMOsd, offering a novel potential biomarker for CNS demyelination disorders.

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

    Directory of Open Access Journals (Sweden)

    Nancy O Duah

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. SIGNIFICANCE: 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.

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

    NARCIS (Netherlands)

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

    1996-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

    The neonatal receptor, FcRn, mediates both serum half-life extension as well as active transport of maternal IgG to the fetus during pregnancy. Therefore, transport efficiency and half-life go hand-in-hand. However, while the half-life of the human IgG2 subclass is comparable to IgG1, the placental

  13. Kinetics of dengue virus-specific serum immunoglobulin classes and subclasses correlate with clinical outcome of infection.

    NARCIS (Netherlands)

    P. Koraka (Penelope); C. Suharti (Catarina); T.E. Setiati (Tatty); A.T.A. Mairuhu; E.C.M. van Gorp (Eric); C.E. Hack (Erik); M. Juffrie; J. Sutaryo; G.M. van der Meer; J. Groen (Jan); A.D.M.E. Osterhaus (Albert)

    2001-01-01

    textabstractThe kinetics of dengue virus (DEN)-specific serum immunoglobulin classes (immunoglobulin M [IgM] and IgA) and subclasses (IgG1 to IgG4) were studied in patients suffering from dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Serum samples from non-DEN f

  14. Kinetics of dengue virus-specific serum immunoglobulin classes and subclasses correlate with clinical outcome of infection.

    NARCIS (Netherlands)

    P. Koraka (Penelope); C. Suharti (Catarina); T.E. Setiati (Tatty); A.T.A. Mairuhu; E.C.M. van Gorp (Eric); C.E. Hack (Erik); M. Juffrie; J. Sutaryo; G.M. van der Meer; J. Groen (Jan); A.D.M.E. Osterhaus (Albert)

    2001-01-01

    textabstractThe kinetics of dengue virus (DEN)-specific serum immunoglobulin classes (immunoglobulin M [IgM] and IgA) and subclasses (IgG1 to IgG4) were studied in patients suffering from dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Serum samples from non-DEN

  15. 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.

  16. Incidence of Autoantibodies to C1Q Complement Component in Women with Miscarriages and Autoantibodies to Phospholipids and Chorionic Gonadotropin.

    Science.gov (United States)

    Menzhinskaya, I V; Van'ko, L V; Kashentseva, M M; Kiryushchenkov, P A; Sukhikh, G T

    2015-12-01

    Autoantibodies to C1q complement component are often detected in patients with autoimmune diseases. The complement system is involved in the pathophysiology of gestosis. The incidence of anti-C1q autoantibodies was studied in women with miscarriages and autoantibodies to phospholipids and chorionic gonadotropin. Serum C3 and C4 complement components and anti-C1Q autoantibodies (IgG) were measured by ELISA. The median levels of C3 and C4 in patients with miscarriages were lower than in healthy women. Anti-C1q autoantibodies were more often found in the patients than in controls; patients with autoantibodies to phospholipids formed a risk group. Median levels of anti-C1q autoantibodies were higher in the patients with autoantibodies to phospholipids and chorionic gonadotropin than in healthy women. Hence, activation of the complement system and hyperproduction of anti-C1q autoantibodies were unfolding in patients with miscarriages, mainly in the patients with autoantibodies to phospholipids.

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

    OpenAIRE

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

    2000-01-01

    An IgG subclass deficiency is often associated with bacterial infections. We studied four pediatric patients suffering from meningoencephalitis, two of them due to Streptococcus pneumoniae and two due to Haemophilus influenzae type b. Simultaneous diagnostic serum and cerebrospinal fluid samples were taken during income. The four subclasses of IgG and albumin were quantified in both biologic fluids by radial immunodiffusion. Very low levels of seric IgG2 with non detectable cerebrospinal flui...

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

    Science.gov (United States)

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

    2014-11-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  20. IgG abnormality in narcolepsy and idiopathic hypersomnia.

    Directory of Open Access Journals (Sweden)

    Susumu Tanaka

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

  1. Alternative Pathway Dysregulation and the Conundrum of Complement Activation by IgG4 Immune Complexes in Membranous Nephropathy

    Science.gov (United States)

    Borza, Dorin-Bogdan

    2016-01-01

    Membranous nephropathy (MN), a major cause of nephrotic syndrome, is a non-inflammatory immune kidney disease mediated by IgG antibodies that form glomerular subepithelial immune complexes. In primary MN, autoantibodies target proteins expressed on the podocyte surface, often phospholipase A2 receptor (PLA2R1). Pathology is driven by complement activation, leading to podocyte injury and proteinuria. This article overviews the mechanisms of complement activation and regulation in MN, addressing the paradox that anti-PLA2R1 and other antibodies causing primary MN are predominantly (but not exclusively) IgG4, an IgG subclass that does not fix complement. Besides immune complexes, alterations of the glomerular basement membrane (GBM) in MN may lead to impaired regulation of the alternative pathway (AP). The AP amplifies complement activation on surfaces insufficiently protected by complement regulatory proteins. Whereas podocytes are protected by cell-bound regulators, the GBM must recruit plasma factor H, which inhibits the AP on host surfaces carrying certain polyanions, such as heparan sulfate (HS) chains. Because HS chains present in the normal GBM are lost in MN, we posit that the local complement regulation by factor H may be impaired as a result. Thus, the loss of GBM HS in MN creates a micro-environment that promotes local amplification of complement activation, which in turn may be initiated via the classical or lectin pathways by subsets of IgG in immune complexes. A detailed understanding of the mechanisms of complement activation and dysregulation in MN is important for designing more effective therapies. PMID:27199983

  2. In vitro functional test of two subclasses of an anti-RhD antibody produced by transient expression in COS cells

    DEFF Research Database (Denmark)

    Nielsen, Leif Kofoed; Norderhaug, Lars; Sandlie, Inger;

    2006-01-01

    that other sources of anti-RhD will be needed. One such source is recombinant human antibodies. Here we describe the construction of plasmids encoding two subclasses (IgG1 and IgG3) of an anti-RhD antibody, their transient expression in COS cells, and subsequent functional characterization of the antibodies...

  3. 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.

  4. 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...

  5. Autoantibody standardization in The Netherlands.

    NARCIS (Netherlands)

    Damoiseaux, J.; Tervaert, J.W.; Derksen, R.; Hamann, D.; Hooijkaas, H.; Klasen, I.S.; Kallenberg, C.; Limburg, P.; Smeenk, R.

    2009-01-01

    Several initiatives have been undertaken, independent of the European Autoantibody Standardization Initiative (EASI), to standardize autoantibodies in The Netherlands. The Dutch EASI team has made an inventory of which initiatives on autoantibody standardization are already available and what future

  6. Acute changes in lipoprotein subclasses during exercise.

    Science.gov (United States)

    Søndergaard, Esben; Poulsen, Marianne K; Jensen, Michael D; Nielsen, Søren

    2014-01-01

    Lipids are important substrates for oxidation in the basal fasting state and during exercise. Studies have demonstrated beneficial changes in lipoprotein subclass composition the day after an exercise bout. However, the acute effect of exercise on TG concentration and lipoprotein subclass composition remains unclear. Sixteen lean, healthy individuals (8 men and 8 women) were recruited (age 20-30 years, BMILipoprotein subclass composition was measured with (1)H NMR spectroscopy. During exercise, LDL and HDL particle concentration increased significantly (plipoprotein subclass composition. These changes are similar to the effects of exercise training. © 2013.

  7. A Subclass of Ockham Algebras

    Institute of Scientific and Technical Information of China (English)

    Jie FANG; Zhong Ju SUN

    2012-01-01

    Here we introduce a subclass of the class of Ockham algebras (L; f) for which L satisfies the property that for every x ∈ L,there exists n ≥ 0 such that fn(x) and fn+1(x) are complementary.We characterize the structure of the lattice of congruences on such an algebra (L; f).We show that the lattice of compact congruences on L is a dual Stone lattice,and in particular,that the lattice Con L of congruences on L is boolean if and only if L is finite boolean.We also show that L is congruence coherent if and only if it is boolean.Finally,we give a sufficient and necessary condition to have the subdirectly irreducible chains.

  8. A proper subclass of Maclane's class

    Directory of Open Access Journals (Sweden)

    May Hamdan

    1999-01-01

    paper, we define a subclass ℛ of consisting of those functions that have asymptotic values at a dense subset of the unit circle reached along rectifiable asymptotic paths. We also show that the class ℛ is a proper subclass of by constructing a function f∈ that admits no asymptotic paths of finite length.

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

    NARCIS (Netherlands)

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

    2002-01-01

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

  10. Detection of pemphigus autoantibodies by IIF and ELISA tests in patients with pemphigus vulgaris and foliaceus and in healthy relatives

    NARCIS (Netherlands)

    Torzecka, Jolanta Dorota; Narbutt, Joanna; Sysa-Jedrzejowska, Anna; Waszczykowska, Elzbieta; Lukamowicz, Jolanta; Pas, Hendri H.

    2003-01-01

    BACKGROUND: Pemphigus is a life-threatening, autoimmune blistering disease, mediated by IgG autoantibodies. The aim of our study was to assess the usefulness of a new enzyme-linked immunosorbent assay (ELISA) in detecting circulating pemphigus autoantibodies, and to compare its sensitivity and speci

  11. 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.

  12. Distribution of IgG subclass of anti-myeloperoxidase antibodies in sera from patients with propylthiouracil induced vasculitis%抗髓过氧化物酶抗体IgG亚型在丙基硫氧嘧啶引起的小血管炎中的分布及其意义

    Institute of Scientific and Technical Information of China (English)

    高莹; 赵明辉; 郭晓蕙; 张颖; 王海燕

    2004-01-01

    目的观察丙基硫氧嘧啶(PTU)引起的抗中性粒细胞胞浆抗体(ANCA)相关小血管炎患者活动期和缓解期血清中抗MPO抗体IgG亚型的分布并探讨其意义.方法以12例PTU引起的ANCA相关小血管炎患者为研究对象,收集患者未治疗的活动期血清,其中10例同时具有缓解期的血清,应用抗原特异性ELISA法检测抗MPO抗体总IgG及各IgG亚型的滴度,比较其与原发性小血管炎中抗MPO抗体IgG亚型分布的异同.结果与原发性血管炎不同,所有PTU引起的ANCA相关小血管炎患者血清中均未检测到IgG3亚型.其他亚型在活动期的检测结果分别为IgG1(12/12例,100%),IgG2(8/12例,66.7%),IgG4(7/12例,58.3%);缓解期各亚型的检测结果分别为IgG1(9/10例,90%),IgG2(4/10例,40%),IgG4(2/10例,20%).与原发性小血管炎缓解期中IgG4仍保持较高水平的现象不同,经停用PTU及应用免疫抑制治疗病情缓解后,IgG4亚型的滴度显著下降甚至转阴.结论 PTU引起的抗MPO抗体IgG亚型的分布与原发性小血管炎并不一致.高滴度的ANCA可能与PTU的反复抗原刺激有关.

  13. Pathogenicity of autoantibodies in anti-p200 pemphigoid.

    Directory of Open Access Journals (Sweden)

    Katerina Vafia

    Full Text Available Recently, the C-terminus of laminin γ1 has been identified as target antigen in anti-p200 pemphigoid and the disease was renamed as anti-laminin γ1 pemphigoid. However, the pathogenic relevance of these autoantibodies has not yet been demonstrated. Therefore, we employed an ex vivo model of autoantibody-mediated leukocyte-dependent neutrophil activation and dermal-epidermal separation (DES using cryosections of human skin. We showed that anti-p200 pemphigoid sera (n = 7 induced DES in a time-dependent manner, in contrast to sera from healthy controls. Furthermore, laminin γ1-specific IgG and serum depleted from anti-laminin γ1 reactivity were generated using the recombinant C-terminus of laminin γ1 (LAMC1-term; amino acids 1364 to 1609. Interestingly, both fractions labeled the dermal-epidermal-junction (DEJ by indirect immunofluorescence microscopy on human foreskin and recognized a 200 kDa protein by immunoblotting with dermal extract. Human and rabbit IgG against LAMC1-cterm failed to attract neutrophils at the DEJ and to induce DES. In contrast, patient serum depleted from LAMC1-cterm reactivity led to the same extent of DES as non-depleted IgG. Repeated injection of rabbit anti-murine LAMC1-cterm IgG into both neonatal and adult C57BL/6mice as well as repetitive immunization of various mouse strains with murine LAMC1-cterm failed to induce macro- and microscopic lesions. In all mice, circulating anti-LAMC1-cterm antibodies were present, but only in some mice, IgG deposits were seen at the DEJ. We conclude that autoantibodies in anti-p200 pemphigoid sera are pathogenic while pathogenicity is not mediated by autoantibodies against laminin γ1. Further studies are needed to identify the pathogenically relevant autoantigen in anti-p200 pemphigoid.

  14. 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.

  15. Detecting Violence in Video using Subclasses

    OpenAIRE

    Li, Xirong; Huo, Yujia; Xu, Jieping; Jin, Qin

    2016-01-01

    This paper attacks the challenging problem of violence detection in videos. Different from existing works focusing on combining multi-modal features, we go one step further by adding and exploiting subclasses visually related to violence. We enrich the MediaEval 2015 violence dataset by \\emph{manually} labeling violence videos with respect to the subclasses. Such fine-grained annotations not only help understand what have impeded previous efforts on learning to fuse the multi-modal features, ...

  16. Intestinal inflammation influences α-MSH reactive autoantibodies: relevance to food intake and body weight.

    Science.gov (United States)

    Coquerel, Quentin; Sinno, Maria Hamze; Boukhettala, Nabile; Coëffier, Moïse; Terashi, Mutsumi; Bole-Feysot, Christine; Breuillé, Denis; Déchelotte, Pierre; Fetissov, Sergueï O

    2012-01-01

    Autoantibodies reacting with alpha-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, are involved in regulation of feeding. In this work we studied if intestinal inflammation (mucositis) may influence α-MSH autoantibodies production relevant to food intake and body weight. Mucositis and anorexia were produced in Sprague-Dawley rats by methotrexate (MTX, 2.5mg/kg/day, for three days, subcutaneously). Plasma levels of total IgG and of α-MSH autoantibodies were measured during and after MTX-induced mucositis and were compared with pair-fed and ad libitum-fed controls. Effects of intraperitoneal injections of rabbit anti-α-MSH IgG (3 or 10 μg/day/rat) on MTX-induced anorexia and on plasma α-MSH peptide concentration were separately studied. Here we show that in MTX rats, intestinal mucositis and anorexia were accompanied by decreased plasma levels of both total IgG and of α-MSH autoantibodies while refeeding was characterized by their elevated levels. In spite of similar food intake in MTX and pair-fed rats, recovery of body weight was delayed by at least 1 week in the MTX group. During refeeding and body weight deficit in MTX rats, α-MSH IgG autoantibody levels correlated negatively with food to water intake ratios. Injections of anti-α-MSH IgG induced a dose-dependent attenuation of food intake and body weight regain in MTX-treated rats accompanied by increased concentrations of α-MSH peptide which correlated positively with plasma levels of α-MSH autoantibodies. These data show that intestinal inflammation, independently from food restriction, affects general humoral immune response which may influence food intake and body weight control via modulation of α-MSH plasma concentration by α-MSH reactive autoantibodies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. A study of type-1 diabetes associated autoantibodies in schizophrenia.

    Science.gov (United States)

    Hallford, Philomena; Clair, David St; Halley, Lorna; Mustard, Colette; Wei, Jun

    2016-10-01

    Epidemiological studies revealed an association between type-1 diabetes (T1D) and schizophrenia but the findings reported to date have been controversial. To clarify the inconsistency across studies, T1D-associated autoantibodies were examined in plasma samples collected from 272 patients with schizophrenia and 276 control subjects. An in-house enzyme-linked immunosorbent assay (ELISA) was developed using three linear peptide antigens, one of which was derived from glutamic acid decarboxylase (GAD) and two were derived from insulinoma-associated antigen 2 (IA2). Mann-Whitney U test showed a significant decrease in the levels of plasma IgG against the IA2b antigen in schizophrenia patients as compared to control subjects (Z=-3.54, p=0.0007), while no significant difference was found between these two groups either in anti-IA2a IgG levels (Z=-1.62, p=0.105) or in anti-GAD IgG levels (Z=-1.63, p=0.104). Linear regression analysis indicated no association of antipsychotic medication with the levels of plasma IgG against IA2a, IA2b or GAD, while the levels of plasma IgG for these 3 peptide antigens were significantly correlated with each other. Binary logistic regression showed that neither the DQ2.5 variant nor the DQ8 variant was associated with circulating levels of 3 T1D-associated autoantibodies in both the patient group and the control group. The coefficient of variation was 10.7% for anti-IA2a IgG assay, 10.1% for anti-IA2b IgG assay and 10.7% for anti-GAD IgG assay. The present work suggests that T1D-associated antibodies are unlikely to confer risk of schizophrenia and that the in-house ELISA developed with linear peptide antigens is highly reproducible.

  18. IgG4-RELATED DISEASE. CLINICAL NOTES

    Directory of Open Access Journals (Sweden)

    Vladimir Ivanovich Vasilyev

    2013-01-01

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

  19. Bullous pemphigoid autoantibodies directly induce blister formation without complement activation.

    Science.gov (United States)

    Ujiie, Hideyuki; Sasaoka, Tetsumasa; Izumi, Kentaro; Nishie, Wataru; Shinkuma, Satoru; Natsuga, Ken; Nakamura, Hideki; Shibaki, Akihiko; Shimizu, Hiroshi

    2014-11-01

    Complement activation and subsequent recruitment of inflammatory cells at the dermal/epidermal junction are thought to be essential for blister formation in bullous pemphigoid (BP), an autoimmune blistering disease induced by autoantibodies against type XVII collagen (COL17); however, this theory does not fully explain the pathological features of BP. Recently, the involvement of complement-independent pathways has been proposed. To directly address the question of the necessity of the complement activation in blister formation, we generated C3-deficient COL17-humanized mice. First, we show that passive transfer of autoantibodies from BP patients induced blister formation in neonatal C3-deficient COL17-humanized mice without complement activation. By using newly generated human and murine mAbs against the pathogenic noncollagenous 16A domain of COL17 with high (human IgG1, murine IgG2), low (murine IgG1), or no (human IgG4) complement activation abilities, we demonstrate that the deposition of Abs, and not complements, is relevant to the induction of blister formation in neonatal and adult mice. Notably, passive transfer of BP autoantibodies reduced the amount of COL17 in lesional mice skin, as observed in cultured normal human keratinocytes treated with the same Abs. Moreover, the COL17 depletion was associated with a ubiquitin/proteasome pathway. In conclusion, the COL17 depletion induced by BP autoantibodies, and not complement activation, is essential for the blister formation under our experimental system. Copyright © 2014 by The American Association of Immunologists, Inc.

  20. Characterization of autoantibodies to vasoactive intestinal peptide in asthma.

    Science.gov (United States)

    Paul, S; Said, S I; Thompson, A B; Volle, D J; Agrawal, D K; Foda, H; de la Rocha, S

    1989-07-01

    Vasoactive intestinal peptide (VIP) is a potent relaxant of the airway smooth muscle. In this study, VIP-binding autoantibodies were observed in the plasma of 18% asthma patients and 16% healthy subjects. Immunoprecipitation studies and chromatography on DEAE-cellulose and immobilized protein G indicated that the plasma VIP-binding activity was largely due to IgG antibodies. Saturation analysis of VIP binding by the plasmas suggested the presence of one or two classes of autoantibodies, distinguished by their apparent equilibrium affinity constants (Ka). The autoantibodies from asthma patients exhibited a larger VIP-binding affinity compared to those from healthy subjects (Ka 7.8 x 10(9) M-1 and 0.13 x 10(9) M-1, respectively; P less than 0.005). The antibodies were specific for VIP, judged by their poor reaction with peptides bearing partial sequence homology with VIP (peptide histidine isoleucine, growth hormone releasing factor and secretin). IgG prepared from the plasma of an antibody-positive asthma patient inhibited the saturable binding of 125I-VIP by receptors in guinea pig lung membranes (by 39-59%; P less than 0.001). These observations are consistent with a role for the VIP autoantibodies in the airway hyperresponsiveness of asthma.

  1. 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

    status, parity, gestational age, and parasite transmission intensity, whereas only the parasite transmission intensity influenced the levels of IgG specific for non-PAM type VSA. For both types of VSA, the responses were dominated by the cytophilic subclass IgG1, followed by IgG3. In pregnant women...... 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......, the levels of VSA(PAM)-specific antibodies either were very low or negative or were very high, whereas the levels of the antibodies specific for non-PAM type VSA were uniformly high. Interestingly, the levels of VSA(PAM)-specific IgG1 increased with increasing gestational age, while the levels...

  2. Autoantibodies in inflammatory arthritis.

    Science.gov (United States)

    Conigliaro, P; Chimenti, M S; Triggianese, P; Sunzini, F; Novelli, L; Perricone, C; Perricone, R

    2016-07-01

    Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone with joint destruction. The lack of immunological tolerance in RA represents the first step toward the development of autoimmunity. Susceptible individuals, under the influence of environmental factors, such as tobacco smoke, and silica exposure, develop autoimmune phenomena that result in the presence of autoantibodies. HLA and non-HLA haplotypes play a major role in determining the development of specific autoantibodies differentiating anti-citrullinated antibodies (ACPA)-positive and negative RA patients. Rheumatoid factor (RF) and ACPA are the serological markers for RA, and during the preclinical immunological phase, autoantibody titers increase with a progressive spread of ACPA antigens repertoire. The presence of ACPA represents an independent risk factor for developing RA in patients with undifferentiated arthritis or arthralgia. Moreover, anti-CarP antibodies have been identified in patients with RA as well as in individuals before the onset of clinical symptoms of RA. Several autoantibodies mainly targeting post-translational modified proteins have been investigated as possible biomarkers to improve the early diagnosis, prognosis and response to therapy in RA patients. Psoriatic arthritis (PsA) is distinguished from RA by infrequent positivity for RF and ACPA, together with other distinctive clinical features. Actually, specific autoantibodies have not been described. Recently, anti-CarP antibodies have been reported in sera from PsA patients with active disease. Further investigations on autoantibodies showing high specificity and sensibility as well as relevant correlation with disease severity, progression, and response to therapy are awaited in inflammatory arthritides.

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  4. Autoantibodies in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Paweł Żebryk

    2015-05-01

    Full Text Available Systemic sclerosis (SSc is a rare connective tissue disorder, which leads to progressive fibrosis of many organs. Its course is characterized by the presence of two classical autoantibodies: anti-topoisomerase I (ATA, Scl-70 and anti-centromere (ACA. In recent years, the presence of antibodies against a wider range of antigens was demonstrated, namely: RNA polymerase III, fibrillarin, NOR90, Th/To, PM-Scl-100, PM-Scl-75, Ku, PDGFR, but their clinical significance is relatively little known and until recently the methods of their assessment were available only in specialized laboratories. More and more reports in the literature indicate existence of links between the presence of selected autoantibodies with clinical correlations i.e. anti-RNA polymerase III with scleroderma renal crisis or anti-Ku and myositis, arthritis and joint contractures. The importance of autoantibodies in the diagnostic process was underlined by their inclusion into the new ACR/EULAR 2013 classification criteria for systemic sclerosis. This work reviews the current knowledge on the clinical significance of autoantibodies in systemic sclerosis.

  5. In vitro functional characterization of feline IgGs.

    Science.gov (United States)

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

    2014-04-15

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

  6. 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.

  7. Autoantigen Microarray for High-throughput Autoantibody Profiling in Systemic Lupus Erythematosus

    Institute of Scientific and Technical Information of China (English)

    Honglin Zhu; Hui Luo; Mei Yan; Xiaoxia Zuo; Quan-Zhen Li

    2015-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technology has emerged as a powerful tool for the identification of biomarkers in SLE and other autoimmune diseases. Proteomic microarray has the capacity to hold large number of self-antigens on a solid surface and serve as a high-throughput screening method for the determination of autoantibody specificities. The autoantigen arrays carrying a wide variety of self-antigens, such as cell nuclear components (nucleic acids and associated proteins), cytoplas-mic proteins, phospholipid proteins, cell matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific proteins, have been used for screening of autoantibody specificities associated with different manifestations of SLE. Arrays containing synthetic peptides and molecular modified proteins are also being utilized for identification of autoantibodies targeting to special antigenic epi-topes. Different isotypes of autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes, can be detected simultaneously with multi-color labeled secondary antibodies. Serum and plasma are the most common biologic materials for autoantibody detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and saliva can also be a source of autoantibody detection.

  8. On Certain Subclasses of Analytic Functions Defined by Differential Subordination

    Directory of Open Access Journals (Sweden)

    Hesam Mahzoon

    2011-01-01

    Full Text Available We introduce and study certain subclasses of analytic functions which are defined by differential subordination. Coefficient inequalities, some properties of neighborhoods, distortion and covering theorems, radius of starlikeness, and convexity for these subclasses are given.

  9. Autoantibody Production in Rabbits

    Science.gov (United States)

    Asherson, G. L.; Rose, M. Elaine

    1963-01-01

    The finding that the serum of apparently healthy rabbits fixed complement with rabbit liver and kidney has been confirmed. Experimental infection of rabbits with Eimeria stiedae, the cause of hepatic coccidiosis, led to a rise in the titre of serum complement-fixing factors. The rise was statistically significant 14, 21 and 28 days after infection. The factors were regarded as antibodies because they behaved as macroglobulins on diethylaminoethyl—cellulose chromatography and sucrose gradient centrifugation, and as autoantibodies because they fixed complement with the kidney of the rabbits in which they occurred. The antibody reacted with widely distributed antigen(s) with high activity in brain and low activity in skeletal muscle. The possibility that coccidial infection may be responsible for the natural autoantibody of rabbits is discussed. PMID:13965167

  10. Purification of human immunoglobulin G autoantibodies to tumor necrosis factor using affinity chromatography and magnetic separation.

    Science.gov (United States)

    Sennikov, S V; Golikova, E A; Kireev, F D; Lopatnikova, J A

    2013-04-30

    Autoantibodies to cytokines are important biological effector molecules that can regulate cytokine activities. The aim of the study was to develop a protocol to purify autoantibodies to tumor necrosis factor from human serum, for use as a calibration material to determine the absolute content of autoantibodies to tumor necrosis factor by enzyme-linked immunosorbent assay. The proposed protocol includes a set of affinity chromatography methods, namely, Bio-Gel P6DG sorbent to remove albumin from serum, Protein G Sepharose 4 Fast Flow to obtain a total immunoglobulin G fraction of serum immunoglobulins, and Affi-Gel 15 to obtain specifically antibodies to tumor necrosis factor. The addition of a magnetic separation procedure to the protocol eliminated contaminant tumor necrosis factor from the fraction of autoantibodies to tumor necrosis factor. The protocol generated a pure fraction of autoantibodies to tumor necrosis factor, and enabled us to determine the absolute concentrations of different subclasses of immunoglobulin G autoantibodies to tumor necrosis factor in apparently healthy donors.

  11. IgA autoantibodies in the pemphigoids and linear IgA bullous dermatosis

    NARCIS (Netherlands)

    Horvath, Barbara; Niedermeier, Andrea; Podstawa, Eva; Mueller, Ralf; Hunzelmann, Nicolas; Karpati, Sarolta; Hertl, Michael

    2010-01-01

    Background: Patients with bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and pemphigoid gestationis (PG) have IgG antibodies against BP180 and BP230, components of the hemidesmosomes. Patients with linear IgA bullous dermatosis (LABD) have IgA autoantibodies against a 97/120-kDa protein w

  12. 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......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.......04). Blocking of folate binding to FR was similar among cases and controls (p = 0.54). The results did not change when stratifying into the cleft subgroups, nor when only isolated oral cleft cases were considered. In conclusion, high maternal autoantibody levels and blocking of folate binding to FRalpha...

  13. Autoantigen Microarray for High-throughput Autoantibody Profiling in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Honglin Zhu

    2015-08-01

    Full Text Available Systemic lupus erythematosus (SLE is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technology has emerged as a powerful tool for the identification of biomarkers in SLE and other autoimmune diseases. Proteomic microarray has the capacity to hold large number of self-antigens on a solid surface and serve as a high-throughput screening method for the determination of autoantibody specificities. The autoantigen arrays carrying a wide variety of self-antigens, such as cell nuclear components (nucleic acids and associated proteins, cytoplasmic proteins, phospholipid proteins, cell matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific proteins, have been used for screening of autoantibody specificities associated with different manifestations of SLE. Arrays containing synthetic peptides and molecular modified proteins are also being utilized for identification of autoantibodies targeting to special antigenic epitopes. Different isotypes of autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes, can be detected simultaneously with multi-color labeled secondary antibodies. Serum and plasma are the most common biologic materials for autoantibody detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and saliva can also be a source of autoantibody detection. Proteomic microarray as a multiplexed high-throughput screening platform is playing an increasingly-important role in autoantibody diagnostics. In this article, we highlight the use of autoantigen microarrays for autoantibody exploration in SLE.

  14. Autoantigen Microarray for High-throughput Autoantibody Profiling in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Zhu, Honglin; Luo, Hui; Yan, Mei; Zuo, Xiaoxia; Li, Quan-Zhen

    2015-08-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technology has emerged as a powerful tool for the identification of biomarkers in SLE and other autoimmune diseases. Proteomic microarray has the capacity to hold large number of self-antigens on a solid surface and serve as a high-throughput screening method for the determination of autoantibody specificities. The autoantigen arrays carrying a wide variety of self-antigens, such as cell nuclear components (nucleic acids and associated proteins), cytoplasmic proteins, phospholipid proteins, cell matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific proteins, have been used for screening of autoantibody specificities associated with different manifestations of SLE. Arrays containing synthetic peptides and molecular modified proteins are also being utilized for identification of autoantibodies targeting to special antigenic epitopes. Different isotypes of autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes, can be detected simultaneously with multi-color labeled secondary antibodies. Serum and plasma are the most common biologic materials for autoantibody detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and saliva can also be a source of autoantibody detection. Proteomic microarray as a multiplexed high-throughput screening platform is playing an increasingly-important role in autoantibody diagnostics. In this article, we highlight the use of autoantigen microarrays for autoantibody exploration in SLE.

  15. Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

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

    2009-01-01

    BACKGROUND: Plasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control. METHODS: In this study, 216 individuals from...... on susceptibility to uncomplicated P. falciparum malaria and antigen-dependent influence on total IgG and IgG subclasses....

  16. 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

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

    Science.gov (United States)

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

    1998-08-01

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

  18. Characterization Analysis of Human Anti-Ferritin Autoantibodies

    Directory of Open Access Journals (Sweden)

    Shusaku Higashi

    2014-03-01

    Full Text Available Anti-ferritin autoantibodies are found in many animals. Human ferritin-binding proteins (FBPs were partially purified from human serum by ion-exchange chromatography and immobilized metal affinity chromatography with Zn2+. Crude FBPs were immunocoprecipitated with canine liver ferritin followed by the addition of anti-ferritin antibodies. Immunoglobulins in the immunocoprecipitate were detected with antibodies specific for human IgG, IgM or IgA heavy chains, and immunoglobulins IgG, IgM and IgA to bind to expressed recombinant human H and L chain homopolymers were also found. A portion of human serum proteins bound to zinc ions immobilized on beads were released upon the addition of canine liver ferritin, and the released protein was identified as IgM antibody. Additionally, the released proteins recognized peptide sequence (DPHLCDF commonly found in amino acid sequences of mammalian ferritin H and L subunits. These results suggest that human serum contains anti-ferritin autoantibodies (IgG, IgM and IgA which bind zinc ions and preferentially bind ferritin over both the H and L subunits, and that a portion of, but not all, the IgM antibodies bound to ferritin with higher affinity than to zinc ions and may recognize the common sequence found in mammalian ferritin H and L subunits.

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

    Directory of Open Access Journals (Sweden)

    Sergey E Sedykh

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

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

    Science.gov (United States)

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

    2008-12-01

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

  1. 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.

  2. Administration of commercial Rhodococcus equi specific hyperimmune plasma results in variable amounts of IgG against pathogenic bacteria in foals.

    Science.gov (United States)

    Sanz, M G; Oliveira, A F; Page, A; Horohov, D W

    2014-11-15

    Rhodococcus equi is the most common cause of pneumonia in young foals. A vaccine is not available and the use of R equi-specific hyperimmune plasma (HIP) is common. Despite its widespread use, the efficacy of HIP in preventing disease remains controversial. The objectives of this study were (1) to evaluate the virulence associate protein A (VapA)-specific IgG and IgG subclasses in commercially available R equi HIP and (2) to evaluate serum VapA-specific IgG and IgG subclasses in foals following administration of commercial R equi HIP. Three different lots from four commercial R equi HIP were sampled. VapA-specific IgG and IgG subclasses were evaluated in all samples using an ELISA. Serum was collected from newborn foals either after commercial R equi HIP was administered (n=97) or not (n=70). Serum was also collected from each mare. Administration of HIP significantly (P<0.001) increased VapA-specific IgGs in recipient foals, however, there was a marked variation in VapA-specific IgGs in foals receiving the same product. VapA-specific IgGs were significantly different (P<0.001) between products and varied between lots, with coefficients of variation ranging from 17 to 123 per cent. These results may explain previously reported disparities in HIP efficacy. British Veterinary Association.

  3. Autoantibodies in Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Daniel S. Smyk

    2012-01-01

    Full Text Available Autoimmune pancreatitis (AIP was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-γ-globulinaemia, and antinuclear antibody (ANA positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis.

  4. Catalytic autoantibodies against myelin basic protein (MBP) isolated from serum of autistic children impair in vitro models of synaptic plasticity in rat hippocampus.

    Science.gov (United States)

    Gonzalez-Gronow, Mario; Cuchacovich, Miguel; Francos, Rina; Cuchacovich, Stephanie; Blanco, Angel; Sandoval, Rodrigo; Gomez, Cristian Farias; Valenzuela, Javier A; Ray, Rupa; Pizzo, Salvatore V

    2015-10-15

    Autoantibodies from autistic spectrum disorder (ASD) patients react with multiple proteins expressed in the brain. One such autoantibody targets myelin basic protein (MBP). ASD patients have autoantibodies to MBP of both the IgG and IgA classes in high titers, but no autoantibodies of the IgM class. IgA autoantibodies act as serine proteinases and degrade MBP in vitro. They also induce a decrease in long-term potentiation in the hippocampi of rats either perfused with or previously inoculated with this IgA. Because this class of autoantibody causes myelin sheath destruction in multiple sclerosis (MS), we hypothesized a similar pathological role for them in ASD.

  5. Relevance of anti-C1q autoantibodies to lupus nephritis.

    Science.gov (United States)

    Tsirogianni, Alexandra; Pipi, Elena; Soufleros, Kostantinos

    2009-09-01

    The first component of the classical pathway of the complement system (C1q) is considered to have a crucial role in the clearance of immune complexes (ICs) as well as in the removal of waste material originating from apoptotic cells. A prolonged exposure of C1q epitopes to the immune system could eventually lead to an autoimmune response against itself. Although autoantibodies against C1q are found in several diseases, their clinical interest originates from their strong association to active lupus nephritis (LN). Several studies indicate that anti-C1q autoantibodies could serve as a reliable serologic marker in the assessment of LN activity compared to other immunological tests. Additionally, it was suggested that anti-C1q autoantibodies could play a role in LN pathogenesis. Their potential pathogenic actions likely depend on genetic background, titers, Ig classes and subclasses, and specific epitopes of anti-C1q autoantibodies as well as C1q availability and allocation. It is still unclear which different types of anti-C1q autoantibodies dominate in each case and if their upregulation is pathogenic, an epiphenomenon of aberrant tissue damage, or compensatory to an uncontrolled immune response.

  6. 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.

  7. Autoantibodies in cryptogenic fibrosing alveolitis

    Science.gov (United States)

    Singh, Suveer; du Bois, Ron

    2001-01-01

    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. PMID:11686865

  8. Autoantibodies in autoimmune liver diseases.

    Science.gov (United States)

    Sener, Asli Gamze

    2015-11-01

    Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by clinical, histological, and immunological features, generally including circulating autoantibodies and a high total serum and/or gamma globulin. Liver-related autoantibodies are very significant for the correct diagnosis and classification of autoimmune liver diseases (AILD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis types in adults and children. This article intends to review recent studies that investigate autoantibodies in autoimmune liver diseases from a microbiological perspective.

  9. TSH RECEPTOR AUTOANTIBODIES

    Science.gov (United States)

    Michalek, Krzysztof; Morshed, Syed A.; Latif, Rauf; Davies, Terry F.

    2009-01-01

    Thyrotropin receptor autoantibodies (TSHR-Abs) of the stimulating variety are the hallmark of Graves’ disease. The presence of immune defects leading to synthesis of TSHR-Abs causes hyperthyroidism and is associated with other extrathyroidal manifestations. Further characterization of these antibodies has now been made possible by the generation of monoclonal antibodies with this unique stimulating capacity as well as similar TSHR-Abs not associated with hyperthyroidism. Their present classification divides TSHR-Abs into stimulating, blocking (competing with TSH binding) and neutral (no signaling). Recent studies using monoclonal TSHR-Abs has revealed that stimulating and blocking antibodies bind to the receptor using mostly conformational epitopes, whilst neutral antibodies utilize exclusively linear peptides. Subtle differences in epitopes for stimulating and blocking antibodies account for the diversity of their biological actions. Recently non-classical signaling elicited by neutral antibodies has also been described, raising the need for a new classification of TSHR-Abs. PMID:19332151

  10. The sactibiotic subclass of bacteriocins: an update.

    Science.gov (United States)

    Mathur, Harsh; Rea, Mary C; Cotter, Paul D; Hill, Colin; Ross, R Paul

    2015-01-01

    The sactibiotics are a recently designated subclass of bacteriocins that contain characteristic cysteine sulphur to α -carbon linkages mediated through post-translational modifications. They are a relatively small subclass of bacteriocins compared to the most thoroughly studied lantibiotics. The sactibiotics that have been extensively studied thus far are thuricin CD, subtilosin A, thurincin H, and propionicin F. Despite their recent discovery, there have already been significant advances made in the study of sactibiotics, most notably the discovery of the narrow spectrum anti-Clostridium difficile sactibiotic, thuricin CD. In addition, scientists have gained insights into the mechanisms of action of the sactibiotic subtilosin A, which targets Listeria monocytogenes,Gardnerella vaginalis, and other pathogens. Also, the development of heterologous host systems and homologous expression and site-directed mutagenesis systems for the sactibiotic thurincin H have opened up many opportunities for further studies on this sactibiotic. These and other recent studies concerning the molecular biology, 3D structural elucidation, mode of action, self-protection mechanisms, and antimicrobial spectrum of the sactibiotic subgroup of bacteriocins are discussed in this review.

  11. [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

  12. Autoantibody Profile in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Marvin J Fritzler

    2010-02-01

    Full Text Available Systemic sclerosis is a generalized disorder of connective tissue clinically characterized by thickening and fibrosis of the skin and by distinctive forms of involvement of internal organs. One of the hallmarks of systemic sclerosis is the presence of serum autoantibodies against a variety of nuclear and cytoplasmic antigens. The primary purpose of this study was to identify the autoantibodies profile in the scleroderma sera and the secondary goal was to determine the correlation and discrepancy of autoantibody profile. Autoantibody profile was determined in 118 samples stored in the Advanced Diagnostic Laboratory at the University of Calgary. 78 sera were provided from Canadian and 40 sera were provided from Ukraine. We used the following techniques to identify autoantibodies profile in scleroderma patients: 1. Antinuclear antibody (ANA by indirect immunofluorescence on human epithelial cell substrate 2. Detection and identification of specific autoantibodies by Innolia strip assay 3. Detection and identification of specific autoantibodies against extractable nuclear antigens. 111 out of 118 patients showed positive ANA results by indirect immunofluorescence and 7 patients had negative ANA results. Anti-ENA analyses by Inolia were positive in 84 patients, while by western blotting 81 patients showed positive results. In this study, we compared the results of anti-ENA antibody by Innolia with SLR technique. A significant correlation was found between anti-SCl-70 antibodies (P=0.000 and anti- RNP antibodies (P=0.001 and JO-1 antibodies (P=0.014. Thus, we may propose that SLR and Innolia techniques could be used for the detection of autoantibody in systemic sclerosis.

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

    Directory of Open Access Journals (Sweden)

    Sadeq Eivazi

    2015-03-01

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

  14. The in vitro biological activity of the HLA-DR-binding clinical IgG4 antibody 1D09C3 is a consequence of the disruption of cell aggregates and can be abrogated by Fab arm exchange.

    NARCIS (Netherlands)

    Hansen, K.; Ruttekolk, I.R.R.; Glauner, H.B.; Becker, F.; Brock, R.E.; Hannus, S.

    2009-01-01

    Antibodies of the IgG4 subclass, directed against cell surface antigens have received attention as therapeutic molecules due to their poor induction of the complement system. The MHC class II-directed IgG4 antibody 1D09C3 has been explored for the treatment of lymphomas. The mechanism-of-action is s

  15. Analyzing neuroimaging data with subclasses: A shrinkage approach.

    Science.gov (United States)

    Höhne, Johannes; Bartz, Daniel; Hebart, Martin N; Müller, Klaus-Robert; Blankertz, Benjamin

    2016-01-01

    Among the numerous methods used to analyze neuroimaging data, Linear Discriminant Analysis (LDA) is commonly applied for binary classification problems. LDAs popularity derives from its simplicity and its competitive classification performance, which has been reported for various types of neuroimaging data. Yet the standard LDA approach proves less than optimal for binary classification problems when additional label information (i.e. subclass labels) is present. Subclass labels allow to model structure in the data, which can be used to facilitate the classification task. In this paper, we illustrate how neuroimaging data exhibit subclass labels that may contain valuable information. We also show that the standard LDA classifier is unable to exploit subclass labels. We introduce a novel method that allows subclass labels to be incorporated efficiently into the classifier. The novel method, which we call Relevance Subclass LDA (RSLDA), computes an individual classification hyperplane for each subclass. It is based on regularized estimators of the subclass mean and uses other subclasses as regularization targets. We demonstrate the applicability and performance of our method on data drawn from two different neuroimaging modalities: (I) EEG data from brain-computer interfacing with event-related potentials, and (II) fMRI data in response to different levels of visual motion. We show that RSLDA outperforms the standard LDA approach for both types of datasets. These findings illustrate the benefits of exploiting subclass structure in neuroimaging data. Finally, we show that our classifier also outputs regularization profiles, enabling researchers to interpret the subclass structure in a meaningful way. RSLDA therefore yields increased classification accuracy as well as a better interpretation of neuroimaging data. Since both results are highly favorable, we suggest to apply RSLDA for various classification problems within neuroimaging and beyond. Copyright © 2015

  16. Pemphigus vulgaris autoantibody profiling by proteomic technique.

    Directory of Open Access Journals (Sweden)

    Mina Kalantari-Dehaghi

    Full Text Available Pemphigus vulgaris (PV is a mucocutaneous blistering disease characterized by IgG autoantibodies against the stratified squamous epithelium. Current understanding of PV pathophysiology does not explain the mechanism of acantholysis in patients lacking desmoglein antibodies, which justifies a search for novel targets of pemphigus autoimmunity. We tested 264 pemphigus and 138 normal control sera on the multiplexed protein array platform containing 701 human genes encompassing many known keratinocyte cell-surface molecules and members of protein families targeted by organ-non-specific PV antibodies. The top 10 antigens recognized by the majority of test patients' sera were proteins encoded by the DSC1, DSC3, ATP2C1, PKP3, CHRM3, COL21A1, ANXA8L1, CD88 and CHRNE genes. The most common combinations of target antigens included at least one of the adhesion molecules DSC1, DSC3 or PKP3 and/or the acetylcholine receptor CHRM3 or CHRNE with or without the MHC class II antigen DRA. To identify the PV antibodies most specific to the disease process, we sorted the data based on the ratio of patient to control frequencies of antigen recognition. The frequency of antigen recognition by patients that exceeded that of control by 10 and more times were the molecules encoded by the CD33, GP1BA, CHRND, SLC36A4, CD1B, CD32, CDH8, CDH9, PMP22 and HLA-E genes as well as mitochondrial proteins encoded by the NDUFS1, CYB5B, SOD2, PDHA1 and FH genes. The highest specificity to PV showed combinations of autoantibodies to the calcium pump encoded by ATP2C1 with C5a receptor plus DSC1 or DSC3 or HLA-DRA. The results identified new targets of pemphigus autoimmunity. Novel autoantibody signatures may help explain individual variations in disease severity and treatment response, and serve as sensitive and specific biomarkers for new diagnostic assays in PV patients.

  17. Distinguishing immunorelated haemocytopenia from idiopathic cytopenia of undetermined significance (ICUS): a bone marrow abnormality mediated by autoantibodies

    Science.gov (United States)

    Fu, R; Liu, H; Wang, Y; Liu, H; He, H; Chen, J; Wang, H; Yu, H; Ding, K; Huang, L; Wang, H; Xing, L; Song, J; Li, L; Shao, Z

    2014-01-01

    In recent years we have observed that some patients with idiopathic cytopenia of undetermined significance (ICUS) responded well to corticosteroid and high-dose intravenous immunoglobulin treatment, indicating that some cytopenia in ICUS might be mediated by autoantibodies. In this study, we analysed 166 ICUS cases retrospectively, some of which were autoantibodies detected on haemopoietic cells in bone marrow (BM) by BM mononuclear cell (BMMNC)-Coombs test, flow cytometry (FCM), Western blot and immunofluorescence (IF). We found that 25·9% (43 of 166) of the cases had autoantibodies positive verified with BMMNC-Coombs test or FCM analysis, 72·1% (31 of 43) of whom had immunoglobulin (Ig)G autoantibody positive by Western blot. IgG could be detected in the erythroblastic islands on the BM smear of nine (32·1%, nine of 28) ICUS patients with autoantibodies by IF. Of these 43 patients, the median percentage of reticulocytes was 1·79%. More than half the patients had hyper-BM cellularity with a higher percentage of nucleated erythroid cells in the sternum. Total response rates to immunosuppressive therapy at 6, 12, 24 and > 36 months were 46·5% (20 of 43), 75% (30 of 40), 77·4% (24 of 31) and 66·7% (16 of 24), respectively. We termed this group of ICUS cases with autoantibodies as immunorelated haemocytopenia (or BMMNC-Coombs test-positive haemocytopenia). PMID:24730511

  18. On Certain Subclass of Meromorphic Close-to-Convex Functions

    Directory of Open Access Journals (Sweden)

    Goyal S.P.

    2013-05-01

    Full Text Available In this paper we introduce and investigate a certain subclass of functions which are analytic in the punctured unit disk and meromorphically close-to-convex. The sub-ordination property, inclusion relationship, coefficient inequalities, distortion theorem and a sufficient condition for our subclass of functions are derived. The results presented here would provide extensions of those given in earlier works.

  19. 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

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

    Science.gov (United States)

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

    2015-01-01

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

  1. The Frequency Distribution of Celiac Autoantibodies in Alopecia Areata

    Science.gov (United States)

    Mokhtari, Fatemeh; Panjehpour, Tayebeh; Naeini, Farahnaz Fatemi; Hosseini, Sayed Mohsen; Nilforoushzadeh, Mohammad Ali; Matin, Marzieh

    2016-01-01

    Background: Alopecia areata (AA) is a noncicatricial (nonscarring) alopecia. The association between AA and celiac disease (CD) is debatable. Several studies declare the relationship between AA and CD as measurement of celiac autoantibodies (anti-gliadin IgA and anti-gliadin IgG), but a few studies consider anti-tissue transglutaminase IgA. The aim of this study was to evaluate the frequency distribution of celiac autoantibodies (all of them) in patients with AA compared with controls. Methods: This study is a case–control study. Thirty-five patients entered in each group. Anti-gliadin IgA, anti-gliadin IgG, and anti-tissue transglutaminase IgA were tested in all patients. Samples were examined in ELISA method with binding site's kits, and the result was reported as positive/negative. Finally, the frequency distribution of autoantibodies was examined. Results: The age average did not show a significant difference between two groups (P = 0.62). In addition, there was no significant difference between the two groups based on gender (P = 0.15). The prevalence of antibody in case and control groups was 2.85% and 0%, respectively. There was no significant difference between the two groups (P = 0.31). Conclusions: There may be a relationship between CD and AA, but the absence of statistical association between AA and CD does not mean that there is no relationship between gluten and AA in certain patients. Thus, we have shown here that the biological tests to search for CD do not bring information and proof enough, and it is why we recommend another approach to disclose gluten intolerance in AA patients. PMID:27833723

  2. Human IgG1 monoclonal antibody against human collagen 17 noncollagenous 16A domain induces blisters via complement activation in experimental bullous pemphigoid model.

    Science.gov (United States)

    Li, Qiang; Ujiie, Hideyuki; Shibaki, Akihiko; Wang, Gang; Moriuchi, Reine; Qiao, Hong-jiang; Morioka, Hiroshi; Shinkuma, Satoru; Natsuga, Ken; Long, Heather A; Nishie, Wataru; Shimizu, Hiroshi

    2010-12-15

    Bullous pemphigoid (BP) is an autoimmune blistering disease caused by IgG autoantibodies targeting the noncollagenous 16A (NC16A) domain of human collagen 17 (hCOL17), which triggers blister formation via complement activation. Previous in vitro analysis demonstrated that IgG1 autoantibodies showed much stronger pathogenic activity than IgG4 autoantibodies; however, the exact pathogenic role of IgG1 autoantibodies has not been fully demonstrated in vivo. We constructed a recombinant IgG1 mAb against hCOL17 NC16A from BP patients. In COL17-humanized mice, this mAb effectively reproduced a BP phenotype that included subepidermal blisters, deposition of IgG1, C1q and C3, neutrophil infiltration, and mast cell degranulation. Subsequently, alanine substitutions at various C1q binding sites were separately introduced to the Fc region of the IgG1 mAb. Among these mutated mAbs, the one that was mutated at the P331 residue completely failed to activate the complement in vitro and drastically lost pathogenic activity in COL17-humanized mice. These findings indicate that P331 is a key residue required for complement activation and that IgG1-dependent complement activation is essential for blister formation in BP. This study is, to our knowledge, the first direct evidence that IgG1 Abs to hCOL17 NC16A can induce blister formation in vivo, and it raises the possibility that IgG1 mAbs with Fc modification may be used to block pathogenic epitopes in autoimmune diseases.

  3. Autoimmune disease and multiple autoantibodies in 42 patients with RASopathies.

    Science.gov (United States)

    Quaio, Caio R D C; Carvalho, Jozélio F; da Silva, Clovis A; Bueno, Cleonice; Brasil, Amanda S; Pereira, Alexandre C; Jorge, Alexander A L; Malaquias, Alexsandra C; Kim, Chong A; Bertola, Débora R

    2012-05-01

    The association of RASopathies [Noonan syndrome (NS) and Noonan-related syndromes] and autoimmune disorders has been reported sporadically. However, a concomitant evaluation of autoimmune diseases and an assessment of multiple autoantibodies in a large population of patients with molecularly confirmed RASopathy have not been performed. The clinical and laboratory features were analyzed in 42 RASopathy patients, the majority of whom had NS and five individuals had Noonan-related disorders. The following autoantibodies were measured: Anti-nuclear antibodies, anti-double stranded DNA, anti-SS-A/Ro, anti-SS-B/La, anti-Sm, anti-RNP, anti-Scl-70, anti-Jo-1, anti-ribosomal P, IgG and IgM anticardiolipin (aCL), thyroid, anti-smooth muscle, anti-endomysial (AE), anti-liver cytosolic protein type 1 (LC1), anti-parietal cell (APC), anti-mitochondrial (AM) antibodies, anti-liver-kidney microsome type 1 antibodies (LKM-1), and lupus anticoagulant. Six patients (14%) fulfilled the clinical criteria for autoimmune diseases [systemic lupus erythematous, polyendocrinopathy (autoimmune thyroiditis and celiac disease), primary antiphospholipid syndrome (PAPS), autoimmune hepatitis, vitiligo, and autoimmune thyroiditis]. Autoimmune antibodies were observed in 52% of the patients. Remarkably, three (7%) of the patients had specific gastrointestinal and liver autoantibodies without clinical findings. Autoimmune diseases and autoantibodies were frequently present in patients with RASopathies. Until a final conclusion of the real incidence of autoimmunity in Rasopathy is drawn, the physicians should be alerted to the possibility of this association and the need for a fast diagnosis, proper referral to a specialist and ultimately, adequate treatment.

  4. Autoantibodies in primary sclerosing cholangitis

    Institute of Scientific and Technical Information of China (English)

    Johannes Roksund Hov; Kirsten Muri Boberg; Tom H Karlsen

    2008-01-01

    The aetiology of primary sclerosing cholangitis (PSC)is not known and controversy exists as to whether PSC should be denominated an autoimmune disease.A large number of autoantibodies have been detected in PSC patients,but the specificity of these antibodies is generally low,and the frequencies vary largely between different studies.The presence of autoantibodies in PSC may be the result of a nonspecific dysregulation of the immune system,but the literature in PSC points to the possible presence of specific antibody targets in the biliary epithelium and in neutrophil granulocytes.The present review aims to give an overview of the studies of autoantibodies in PSC,with a particular emphasis on the prevalence,clinical relevance and possible pathogenetic importance of each individual marker.

  5. Prevalence of collagen VII-specific autoantibodies in patients with autoimmune and inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Licarete Emilia

    2012-04-01

    Full Text Available Abstract Background Autoimmunity to collagen VII is typically associated with the skin blistering disease epidermolysis bullosa acquisita (EBA, but also occurs occasionally in patients with systemic lupus erythematosus or inflammatory bowel disease. The aim of our present study was to develop an accurate immunoassay for assessing the presence of autoantibodies against collagen VII in large cohorts of patients and healthy donors. Methods Based on in silico antigenic analysis and previous wetlab epitope mapping data, we designed a chimeric collagen VII construct containing all collagen VII epitopes with higher antigenicity. ELISA was performed with sera from patients with EBA (n = 50, Crohn's disease (CD, n = 50, ulcerative colitis (UC, n = 50, bullous pemphigoid (BP, n = 76, and pemphigus vulgaris (PV, n = 42 and healthy donors (n = 245. Results By ELISA, the receiver operating characteristics analysis yielded an area under the curve of 0.98 (95% CI: 0.9638-1.005, allowing to set the cut-off at 0.32 OD at a calculated specificity of 98% and a sensitivity of 94%. Running the optimized test showed that serum IgG autoantibodies from 47 EBA (94%; 95% CI: 87.41%-100%, 2 CD (4%; 95% CI: 0%-9.43%, 8 UC (16%; 95% CI: 5.8%-26%, 2 BP (2.63%; 95% CI: 0%-6.23%, and 4 PV (9.52%; 95% CI: 0%-18.4% patients as well as from 4 (1.63%; 95% CI: 0%-3.21% healthy donors reacted with the chimeric protein. Further analysis revealed that in 34%, 37%, 16% and 100% of sera autoantibodies of IgG1, IgG2, IgG3, and IgG4 isotype, respectively, recognized the recombinant autoantigen. Conclusions Using a chimeric protein, we developed a new sensitive and specific ELISA to detect collagen specific antibodies. Our results show a low prevalence of collagen VII-specific autoantibodies in inflammatory bowel disease, pemphigus and bullous pemphigoid. Furthermore, we show that the autoimmune response against collagen VII is dominated by IgG4 autoantibodies. The new immunoassay should

  6. Women with rheumatoid arthritis negative for anti-cyclic citrullinated peptide and rheumatoid factor are more likely to improve during pregnancy, whereas in autoantibody-positive women autoantibody levels are not influenced by pregnancy.

    Science.gov (United States)

    de Man, Y A; Bakker-Jonges, L E; Goorbergh, C M Dufour-van den; Tillemans, S P R; Hooijkaas, H; Hazes, J M W; Dolhain, R J E M

    2010-02-01

    To determine whether changes in levels of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) are associated with the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and with the subsequent flare post partum. Disease activity scores from the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) study of 118 patients were available for analysis. Before conception (if applicable), at each trimester and at 6, 12 and 26 weeks post partum, levels of the autoantibodies anti-CCP, IgM-RF, IgG-RF and IgA-RF were determined. Responses in disease activity were classified according to European League Against Rheumatism (EULAR) response criteria during pregnancy and post partum, and associated with the presence or absence of autoantibodies. The median levels of anti-CCP and all subclasses of RF during pregnancy were stable, whereas post partum the levels of anti-CCP, IgM-RF and IgA-RF declined. A significantly higher percentage of women without autoantibodies (negative for anti-CCP and RF) improved compared with women positive for either or both autoantibodies (75% vs 39%, p = 0.01). The occurrence of a flare post partum was comparable between these groups. Improvement of disease activity of RA during pregnancy was not associated with changes in levels of autoantibodies during pregnancy, however, improvement may occur more frequently in the absence of anti-CCP and RF.

  7. A Machine Learning System for Recognizing Subclasses (Demo)

    Energy Technology Data Exchange (ETDEWEB)

    Vatsavai, Raju [ORNL

    2012-01-01

    Thematic information extraction from remote sensing images is a complex task. In this demonstration, we present *Miner machine learning system. In particular, we demonstrate an advanced subclass recognition algorithm that is specifically designed to extract finer classes from aggregate classes.

  8. Fatal autoimmune hemolytic anemia due to immunoglobulin g autoantibody exacerbated by epstein-barr virus.

    Science.gov (United States)

    Fadeyi, Emmanuel A; Simmons, Julie H; Jones, Mary Rose; Palavecino, Elizabeth L; Pomper, Gregory J

    2015-01-01

    Most cases of autoimmune hemolytic anemia (AIHA) are caused by the production of an autoantibody that targets determinants on red blood cells (RBCs). This autoantibody can be immunoglobulin (Ig) G, IgM, or IgA. Some autoantibodies react optimally at 0° to 4°C (ie, cold agglutinin) and usually are clinically insignificant. High-titer cold agglutinins are associated with IgM autoantibody and complement fixation induced by infectious agents, including the Epstein-Barr virus (EBV). This case report describes a 31-year-old man who had jaundice, a hemoglobin of 6.0 gdL, and was diagnosed with a hemolytic crisis of AIHA. He received a total of 11 RBC transfusions during a 15-hour period without sustained response and later died. The direct antiglobulin test results for this patient were positive, whereas the cold-agglutinin-testing results were negative. We detected EBV DNA in blood via polymerase chain reaction (PCR). We report a rare case of AIHA associated with an IgG autoantibody and exacerbated by EBV infection, causing a fatal hemolytic anemia.

  9. Functional Characterization of Autoantibodies against Complement Component C3 in Patients with Lupus Nephritis*

    Science.gov (United States)

    Vasilev, Vasil V.; Noe, Remi; Dragon-Durey, Marie-Agnes; Chauvet, Sophie; Lazarov, Valentin J.; Deliyska, Boriana P.; Fremeaux-Bacchi, Veronique; Dimitrov, Jordan D.; Roumenina, Lubka T.

    2015-01-01

    Lupus nephritis (LN) is a complication of the autoimmune disease systemic lupus erythematosus. Because the complement system plays a critical role in orchestrating inflammatory and immune responses as well as in the clearance of immune complexes, autoreactivity to complement components may have considerable pathological consequences. Autoantibodies against the central complement component C3 have been reported in systemic lupus erythematosus, but their molecular mechanism and functional relevance are not well understood. The objective of this study was to evaluate the frequency and the functional properties of the anti-C3 autoantibodies. Anti-C3 autoantibodies were measured in plasma of 39 LN patients, and identification of their epitopes on the C3 molecule was performed. By using surface plasmon resonance, we analyzed the influence of patient-derived IgG antibodies on the interaction of C3b with Factor B, Factor H, and complement receptor 1. The capacity of these antibodies to dysregulate the C3 convertase on the surface of endothelial cell was measured by flow cytometry. Here we report that the frequency of anti-C3 autoantibodies in LN is ∼30%. They inhibited interactions of the negative complement regulators Factor H and complement receptor 1 with C3b. An enhanced C3 deposition was also observed on human endothelial cells in the presence of C3 autoantibodies. In addition, anti-C3 autoantibody levels correlated with disease activity. In conclusion, the anti-C3 autoantibodies in LN may contribute to the autoimmune pathology by their capacity to overactivate the complement system. PMID:26245903

  10. 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.

  11. Plasma Autoantibodies against Heat Shock Protein 70, Enolase 1 and Ribonuclease/Angiogenin Inhibitor 1 as Potential Biomarkers for Cholangiocarcinoma

    Science.gov (United States)

    Rucksaken, Rucksak; Pairojkul, Chawalit; Pinlaor, Porntip; Khuntikeo, Narong; Roytrakul, Sittiruk; Selmi, Carlo; Pinlaor, Somchai

    2014-01-01

    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. PMID:25058392

  12. Non-specific binding in solid phase immunoassays for autoantibodies correlates with inflammation markers.

    Science.gov (United States)

    Güven, Esin; Duus, Karen; Lydolph, Magnus Christian; Jørgensen, Charlotte Sværke; Laursen, Inga; Houen, Gunnar

    2014-01-31

    Enzyme-linked immunosorbent assay (ELISA) is a validated and sensitive method for detection of human autoantibodies, but may have problems with specificity. Non-specific binding is a well-known problem often observed in tests for autoantibodies, when sera are incubated on plastic surfaces, e.g. an ELISA plate. To understand the mechanisms underlying non-specific immunoglobulin deposition, we here analyse the phenomenon in detail and we propose means of reducing false positive test results caused by non-specific binding. The level of non-specific binding, in sera with suspected autoreactivity, was analysed in non-coated and autoantigen-coated ELISA wells and 4-32% of sera showed a high level of non-specific binding depending on the assay conditions and serum properties. Non-specifically binding sera were found to contain increased concentrations of IgG and other inflammatory mediators. Moreover, non-specific binding could be induced in serum by increasing the concentration of IgG and incubating the serum at 40 °C. This suggests that non-specific binding immunoglobulins can be formed during inflammation with high immunoglobulin levels and elevated temperature. We show that the level of non-specific binding correlates with the IgG concentration and therefore propose that non-specific binding may be interpreted as an informative finding indicative of elevated IgG and inflammation.

  13. Structural characteristics of the variable regions of immunoglobulin genes encoding a pathogenic autoantibody in murine lupus.

    Science.gov (United States)

    Tsao, B P; Ebling, F M; Roman, C; Panosian-Sahakian, N; Calame, K; Hahn, B H

    1990-02-01

    We have studied several monoclonal anti-double-stranded (ds) DNA antibodies for their ability to accelerate lupus nephritis in young NZB X NZW F1 female mice and to induce it in BALB/c mice. Two identified as pathogens in both strains have characteristics previously associated with nephritogenicity: expression of IgG2a isotype and IdGN2 idiotype. Both pathogenic antibodies used the combination of genes from the VHJ558 and VK9 subfamilies. Two weak pathogens failed to accelerate nephritis in young BW mice, but induced lupus nephritis in BALB/c mice. They both express IdGN2; one is cationic and an IgG3, the other is an IgG2a. Additional MAbs (some IgG2a, one IdGN2-positive) did not accelerate or induce nephritis. We have cloned and sequenced the variable regions of the immunoglobulin genes of one pathogenic autoantibody. No unique V, D, or J gene segments and no evidence of unusual mechanisms in generating diversity were used to construct this antibody. These data argue against use of unique abnormal Ig genes by systemic lupus erythematosus individuals to construct pathogenic autoantibody subsets. Instead, the major abnormality may be immunoregulatory.

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

    Science.gov (United States)

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

    2011-03-01

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

  15. The quantity and quality of African children's IgG responses to merozoite surface antigens reflect protection against Plasmodium falciparum malaria.

    NARCIS (Netherlands)

    Courtin, D.; Oesterholt, M.J.A.M.; Huismans, H.; Kusi, K.; Milet, J.; Badaut, C.; Gaye, O.; Roeffen, W.F.G.; Remarque, E.J.; Sauerwein, R.W.; Garcia, A.; Luty, A.J.F.

    2009-01-01

    BACKGROUND: Antibodies, particularly cytophilic IgG subclasses, with specificity for asexual blood stage antigens of Plasmodium falciparum, are thought to play an important role in acquired immunity to malaria. Evaluating such responses in longitudinal sero-epidemiological field studies, allied to i

  16. Measurement of ferritin and anti-ferritin autoantibodies in serum and colostrum of Holstein and Japanese Black cows.

    Science.gov (United States)

    Kanno, Yoshiya; Ohtsuka, Hiromichi; Yoshikawa, Yasunaga; Watanabe, Kiyotaka; Orino, Koichi

    2013-07-01

    Anti-ferritin autoantibody is a ferritin-binding protein commonly found in mammals; it is thought to form an immune complex with ferritin and thereby mediate the rapid clearance of circulating ferritin. The aim of this study is to determine concentrations of ferritin and anti-ferritin autoantibodies (immunoglobulin (Ig)M, IgG and IgA) in serum and colostrum of Holstein (H) and Japanese Black (JB) cows within 24 h of normal calving. Blood and colostrum samples were collected from cows of various ages (2-11 years) and calving number (1-8 live births). Mean ferritin concentrations were higher in colostrum than in serum for both breeds, and higher colostrum ferritin concentrations were found in H than JB cows. IgA antibodies in serum and colostrum from both breeds had negligible ferritin-binding activity. For both breeds, IgM and IgG antibodies had higher ferritin-binding activity in colostrum than in serum. There was a significant correlation between IgM and IgG ferritin-binding activities in serum and colostrum of H and JB cows. These results suggest that ferritin and IgM and IgG autoantibodies are actively transferred from the blood stream to the colostrum at prepartum or early lactation.

  17. 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.

  18. Autoantibodies in Patients with Fasciolosis

    Directory of Open Access Journals (Sweden)

    M Korkmaz

    2009-07-01

    Full Text Available "nBackground: Antiself humoral immune responses have been detected not only in classical autoimmune dis­eases, but autoantibodies have also been found in sera of patients suffering from chronic parasitic dis­eases. We aimed to investigate the role of fasciolosis as a trigger factor of autoimmune reactivity by searching some anti­bodies related to hepatobiliary systems, in patients with fasciolosis. "nMethods: Thirty-two patients (17 males, 15 females with fasciolosis were included in this case-control study. Anti-nuclear antibodies (ANA Screen (antigen mixture of dsDNA, histones, nRNP/Sm, Sm, SS-A, SS-B, Scl-70, Jo-1, ribosomal P-proteins, centromere ELISA and single-antigen ELISAs for detection of some antibodies (dsDNA, Anti-M2, Anti- liver-kidney microsomes type 1 (LKM-1 and Myeloperoxidase (MPO were carried out. "nResults: ANA-screen, M-2, LKM-1, MPO and anti-dsDNA positivity were detected with ELISA in 7, 7, 4, 2 and 2 of 32 patients with fasciolosis, consecutively. No statistically significant difference was de­tected for any of the autoantibodies' frequency between patients with fasciolosis and control group. How­ever, autoantibody positivity rate was significantly higher in patients with fasciolosis (50 % than control group (12.5 %. Absorbance values of all autoantibodies in patients with fasciolosis were statistically sig­nificant higher than controls. "nConclusion: These results lent support to the role of fasciolosis as a trigger factor of autoimmune reactiv­ity by the breakdown of tolerance. In spite of the extensive knowledge that has accumulated, the specific relationship be­tween fasciolosis and autoimmunity is still obscure.

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

    Science.gov (United States)

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

    2014-11-01

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

  20. Mesothelial Cell Autoantibodies Induce Collagen Deposition in vitro & Using a Case Study to Introduce Undergraduates to Bioinformatics

    Science.gov (United States)

    Serve, Kinta M.

    Part I. Pleural fibrosis, a non-malignant, asbestos-related respiratory disease characterized by excessive collagen deposition, is progressive, debilitating, and potentially fatal. Disease severity may be influenced by the type of asbestos fiber inhaled, with Libby amphibole (LA) a seemingly more potent mediator of pleural fibrosis than chrysotile (CH) asbestos. This difference in severity may be due to the reported immunological component associated with LA but not CH related diseases. Here, we report the potential mechanisms by which asbestos-associated mesothelial cell autoantibodies (MCAAs) contribute to pleural fibrosis development. MCAAs are shown to bind cultured human pleural mesothelial cells and induce the deposition of type I collagen proteins in the absence of phenotypic changes typically associated with fibrosis development. However, additional extracellular proteins seem to differentially contribute to LA and CH MCAA-associated collagen deposition. Our data also suggest that IgG subclass distributions differ between LA and CH MCAAs, potentially altering the antibody effector functions. Differences in MCAA mechanisms of action and effector functions may help explain the disparate clinical disease phenotypes noted between LA and CH-exposed populations and may provide insights for development of novel therapeutic strategies. Part II. As scientific research becomes increasingly reliant on computational tools, it is more important than ever before to train students to use these tools. While educators agree that biology students should gain experience with bioinformatics, there exists no consensus as to how to integrate these concepts into the already demanding undergraduate curriculum. The Portal-21 project offers a solution by utilizing on-line learning case studies to allow flexibility for classroom integration. Presented here are the results from two field tests of a case study developed to introduce the common bioinformatics tools pBLAST and PubMed to

  1. 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

  2. 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.

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

    Science.gov (United States)

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

    2014-04-01

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

  4. 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.

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

    Science.gov (United States)

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

    2016-08-03

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Arezou Khosroshahi

    2012-01-01

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

  8. Tumor-infiltrating T cells correlate with NY-ESO-1-specific autoantibodies in ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Katy Milne

    Full Text Available BACKGROUND: Tumor-infiltrating CD8+ T cells are correlated with prolonged progression-free and overall survival in epithelial ovarian cancer (EOC. A significant fraction of EOC patients mount autoantibody responses to various tumor antigens, however the relationship between autoantibodies and tumor-infiltrating T cells has not been investigated in EOC or any other human cancer. We hypothesized that autoantibody and T cell responses may be correlated in EOC and directed toward the same antigens. METHODOLOGY AND PRINCIPAL FINDINGS: We obtained matched serum and tumor tissue from 35 patients with high-grade serous ovarian cancer. Serum samples were assessed by ELISA for autoantibodies to the common tumor antigen NY-ESO-1. Tumor tissue was examined by immunohistochemistry for expression of NY-ESO-1, various T cell markers (CD3, CD4, CD8, CD25, FoxP3, TIA-1 and Granzyme B and other immunological markers (CD20, MHC class I and MHC class II. Lymphocytic infiltrates varied widely among tumors and included cells positive for CD3, CD8, TIA-1, CD25, FoxP3 and CD4. Twenty-six percent (9/35 of patients demonstrated serum IgG autoantibodies to NY-ESO-1, which were positively correlated with expression of NY-ESO-1 antigen by tumor cells (r = 0.57, p = 0.0004. Autoantibodies to NY-ESO-1 were associated with increased tumor-infiltrating CD8+, CD4+ and FoxP3+ cells. In an individual HLA-A2+ patient with autoantibodies to NY-ESO-1, CD8+ T cells isolated from solid tumor and ascites were reactive to NY-ESO-1 by IFN-gamma ELISPOT and MHC class I pentamer staining. CONCLUSION AND SIGNIFICANCE: We demonstrate that tumor-specific autoantibodies and tumor-infiltrating T cells are correlated in human cancer and can be directed against the same target antigen. This implies that autoantibodies may collaborate with tumor-infiltrating T cells to influence clinical outcomes in EOC. Furthermore, serological screening methods may prove useful for identifying clinically relevant

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

    Science.gov (United States)

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

    2017-04-15

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

  10. [Measurement of human thyroid peroxidase autoantibodies by enzyme immunoassay using recombinant human TPO].

    Science.gov (United States)

    Inoue, T; Ishiguro, R; Takenouchi, H; Umeki, K; Matsumoto, K; Yagihashi, S; Kato, H; Kotani, T; Ohtaki, S

    1994-03-01

    An EIA for measuring anti-TPO autoantibodies (rhTPO-EIA) was developed using recombinant human TPO expressed in CHO cells and was compared with MC-HA generally used in laboratory routine work. rhTPO-EIA showed a satisfactory reproducibility in the intra-assay test and did not have an accidental error of lots. Almost equal number of healthy females and males were measured for their IgG binding to TPO to define a normal range of anti-TPO autoantibodies. After setting 20 IU/ml as an upper limit of normal range, sera from patient with thyroid disorders were measured for their anti-TPO autoantibodies. Chronic thyroiditis and Graves' disease were highly positive, while adenoma, thyroid cancer, SLE, and RA were low in their positivity. The positive rate of anti-TPO autoantibodies was compatible to those of previous reports in each disorder. Seventy-two sera from patients with chronic thyroiditis or Graves' disease were measured for their autoantibodies by both rhTPO-EIA and MC-HA and the results were compared between both methods. A correlation coefficient was 0.486. Following absorption with thyroglobulin, sera were measured again and as the results, the correlation coefficient increased to 0.723. Therefore, MC-HA was thought to be influenced in the presence of anti-thyroglobulin autoantibodies. Since rhTPO-EIA is excellent in quality and not affected by anti-thyroglobulin antibodies, it is useful and applicable to clinical diagnosis and observation of thyroid disorders.

  11. 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.

  12. 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.

  13. Lipoprotein subclasses in genetic studies: The Berkeley Data Set

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, R.M.; Williams, P.T.; Blanche, P.J.; Cavanaugh, A.; Holl, L.G. [Lawrence Berkeley Lab., CA (United States); Austin, M.A. [Washington Univ., Seattle, WA (United States). Dept. of Epidemiology

    1992-10-01

    Data from the Berkeley Data Set was used to investigate familial correlations of HDL-subclasses. Analysis of the sibling intraclass correlation coefficient by HDL particle diameter showed that sibling HDL levels were significantly correlated for HDL{sub 2b}, HDL{sub 3a} and HDL{sub 3b} subclasses. The percentage of the offsprings` variance explained by their two parents. Our finding that parents and offspring-have the highest correlation for HDL{sub 2b} is consistent with published reports that show higher heritability estimates for HDL{sub 2} compared with HDL{sub 3}{minus} cholesterol.

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

    Directory of Open Access Journals (Sweden)

    Jesse W. Williams

    2012-01-01

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

  15. Goodpasture syndrome: selective removal of anti-alpha 3 (IV) collagen autoantibodies. A potential therapeutic alternative to plasmapheresis.

    Science.gov (United States)

    Boutaud, A A; Kalluri, R; Kahsai, T Z; Noelken, M E; Hudson, B G

    1996-01-01

    Anti-alpha 3(IV) collagen autoantibodies have been implicated in the pathogenesis of Goodpasture syndrome, an autoimmune disorder causing glomerulonephritis and pulmonary hemorrhage. Currently treatment involves removal of the entire IgG fraction of plasma by plasmapheresis or adsorption to protein A. The present study shows that the anti-alpha 3(IV)NC1 autoantibodies can be removed from plasma specifically and quantitatively by affinity chromatography utilizing either alpha 3 NC1 domain of bovine type IV collagen or recombinant alpha 3 NC1 domain of human type IV collagen immobilized to agarose beads. This study shows the feasibility of using affinity chromatography, as an alternative to plasmapheresis, to exclusively remove the pathogenic autoantibodies from the plasma of patients with Goodpasture syndrome.

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

    Science.gov (United States)

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

    2015-06-01

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

  17. Distinct interethnic differences in immunoglobulin G class/subclass and immunoglobulin M antibody responses to malaria antigens but not in immunoglobulin G responses to nonmalarial antigens in sympatric tribes living in West Africa.

    Science.gov (United States)

    Bolad, A; Farouk, S E; Israelsson, E; Dolo, A; Doumbo, O K; Nebié, I; Maiga, B; Kouriba, B; Luoni, G; Sirima, B S; Modiano, D; Berzins, K; Troye-Blomberg, M

    2005-04-01

    The well-established relative resistance to malaria observed in the Fulani as compared with other sympatric tribes in West Africa has been attributed to their higher levels of serum immunoglobulin (Ig) G antibodies to malarial antigens. In this study, we confirm and extend the previous findings by analyses of the levels of IgM, IgG and IgG subclasses of anti-malarial antibodies in asymptomatic individuals of different sympatric tribes in Burkina Faso (Fulani/Mossi) and Mali (Fulani/Dogon). The Fulani showed significantly higher median concentrations of anti-malarial IgG and IgM antibodies than the sympatric tribes at both locations. Although the overall subclass pattern of antibodies did not differ between the tribes, with IgG1 and IgG3 as dominant, the Fulani showed consistently significantly higher levels of these subclasses as compared with those of the non-Fulani individuals. No significant differences were seen in the levels of total IgG between the tribes, but the Fulani showed significantly higher levels of total IgM than their neighbours in both countries. While the antibody levels to some nonmalarial antigens showed the same pattern of differences seen for antibody levels to malaria antigens, no significant such differences were seen with antibodies to other nonmalarial antigens. In conclusion, our results show that the Fulani in two different countries show higher levels of anti-malarial antibodies than sympatric tribes, and this appears not to be a reflection of a general hyper-reactivity in the Fulani.

  18. 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 compar

  19. Are There Enhanced MBP Autoantibodies in Autism?

    Science.gov (United States)

    Libbey, Jane E.; Coon, Hilary H.; Kirkman, Nikki J.; Sweeten, Thayne L.; Miller, Judith N.; Stevenson, Edward K.; Lainhart, Janet E.; McMahon, William M.; Fujinami, Robert S.

    2008-01-01

    Autoantibodies to central nervous system antigens, such as myelin basic protein (MBP), may play a role in autism. We measured autoantibody titers to MBP in children with autism, both classic onset and regressive onset forms, controls (healthy age- and gender-matched) and individuals with Tourette syndrome via enzyme-linked immunosorbent assays. We…

  20. 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 compar

  1. 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...

  2. A subclass of close-to-convex functions

    Directory of Open Access Journals (Sweden)

    Zheng- Lv Zhang

    2013-03-01

    Full Text Available In this paper, we introduce and investigate an interesting subclass $\\mathcal {J}_\\alpha(h$ of analytic and close-to-convex function in the open unit disk D. several coefficient inequalities, growth, and distortion theorem for this class are proved. The various results presented here would generalize many know results.

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

    Directory of Open Access Journals (Sweden)

    Cinzia Rizzo

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

  4. Autoantibody against Cardiac β1-Adrenoceptor Induces Apoptosis in Cultured Neonatal Rat Cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    Yan GAO; Hui-Rong LIU; Rong-Rui ZHAO; Jian-Ming ZHI

    2006-01-01

    To clarify whether apoptosis is involved in the injury processes induced by autoantibody against cardiac β1-adrenoceptor, we investigated the biological and apoptotic effects of antibodies on cultured neonatal rat cardiomyocytes. Wistar rats were immunized with peptides corresponding to the second extracellular loop of the β1-adrenoceptor to induce the production of anti-β1-adrenoceptor antibodies in the sera.Immunoglobulin (Ig) G in the sera was detected using synthetic antigen enzyme-linked immunosorbent assay and purified using the diethylaminoethyl cellulose ion exchange technique. Apoptosis of cardiomyocytes was evaluated using agarose gel electrophoresis and flow cytometry. Our results showed that the positive serum IgG greatly increased the beating rates of cardiomyocytes and showed an "agonist-like" activity. Furthermore, positive serum IgG induced cardiomyocyte apoptosis after treatment with β1adrenoceptor overstimulation for 48 h. The effects of monoclonal antibody against β1-adrenoceptor were also found to be similar to those of positive serum IgG. It was suggested that the autoantibody could induce cardiomyocyte apoptosis by excessive stimulation of β1-adrenoceptor.

  5. 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.

  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...... regression. Age-7 blood-mercury concentrations were positively associated with titers of multiple neural- and non-neural-specific antibodies, mostly of the IgM isotype. Additionally, prenatal blood-mercury and -PCBs were negatively associated with anti-keratin IgG and prenatal PFOS was negatively associated...

  7. Chronic rejection of a lung transplant is characterized by a profile of specific autoantibodies

    DEFF Research Database (Denmark)

    Hagedorn, Peter; Burton, Christopher M.; Carlsen, Jørn

    2010-01-01

    Obliterative bronchiolitis (OB) continues to be the major limitation to long-term survival after lung transplantation. The specific aetiology and pathogenesis of OB are not well understood. To explore the role of autoreactivity in OB, we spotted 751 different self molecules onto glass slides......, and used these antigen microarrays to profile 48 human serum samples for immunoglobulin G (IgG) and IgM autoantibodies; 27 patients showed no or mild bronchiolitis obliterans syndrome (BOS; a clinical correlate of OB) and 15 patients showed medium to severe BOS. We now report that these BOS grades could...

  8. Chronic rejection of a lung transplant is characterized by a profile of specific autoantibodies

    DEFF Research Database (Denmark)

    Hagedorn, Peter; Burton, Christopher Malcolm; Carlsen, Jørn

    2010-01-01

    SUMMARY: Obliterative bronchiolitis (OB) continues to be the major limitation to long-term survival after lung transplantation. The specific aetiology and pathogenesis of OB are not well understood. To explore the role of autoreactivity in OB, we spotted 751 different self molecules onto glass...... slides, and used these antigen microarrays to profile 48 human serum samples for immunoglobulin G (IgG) and IgM autoantibodies; 27 patients showed no or mild bronchiolitis obliterans syndrome (BOS; a clinical correlate of OB) and 15 patients showed medium to severe BOS. We now report that these BOS...

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

    Science.gov (United States)

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

    2016-10-01

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

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

    Directory of Open Access Journals (Sweden)

    B. Baradaran

    2005-01-01

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

  11. [IgG responses to candidate malaria vaccine antigens in the urban area of Dakar (Senegal): evolution according to age and parasitemia in patients with mild symptoms].

    Science.gov (United States)

    Mbengue, B; Sylla Niang, M; Ndiaye Diallo, R; Diop, G; Thiam, A; Ka, O; Touré, A; Tall, A; Perraut, R; Dièye, A

    2015-03-01

    Malaria remains a major problem in African countries despite substantial decreases in morbidity and mortality due to sustained control programs. Studies for the evaluation of qualitative or quantitative Ab responses to key targets of anti-plasmodium immunity were mostly done in rural endemic setting compared to urban area. In a cohort of 200 patients with mild malaria and living in Dakar, we analyze total and subclasses IgG responses to a panel of P. falciparum blood stage antigens: MSP1p19, MSP3, EB200, GST-5 and R23. A mean age of 15 yrs (4 to 56 yrs) and parasitemia between 0.1 to 17% were found. Levels of IgG anti-MSP3 were higher in patients with low parasitemia (≤1%) and appear negatively correlated to parasite densities (Rho =. 0.54; p= 0.021). This correlation is more significant in children (≤ 15 yrs). In addition, an increase of IgG responses against MSP1p19 is highly observed in adults having a parasitemia less than 1%. In those patients, we find that IgG1 subclasses were predominant (p <0.01). Our study shows an association between Ab responses and parasitemia. This association is dependant to IgG anti-MSP3 in children and IgG anti-MSP1p19 in adults living in urban area.

  12. Autoantibodies against G-Protein-Coupled Receptors Modulate Heart Mast Cells

    Institute of Scientific and Technical Information of China (English)

    Ludmila Okruhlicova; Rosemarie Morwinski; Wolfgang Schulze; Sabine Bartel; Peter Weismann; Narcisa Tribulova; Gerd Wallukat

    2007-01-01

    Mast cells are believed to be involved in myocardial tissue remodelling under pathophysiological conditions. We examined the effects of autoantibodies against G-protein-coupled receptors in sera of patients with heart diseases on myocardial mast cells in the cultured neonatal Sprague-Dawley rat heart cells. Cells collected at day 3 and 10 of the culture were preincubated with autoantibodies against α1-adrenoceptor and angiotensin Ⅱ AT1-receptor,agonist phenylephrine and angiotensin Ⅱ, and control IgG. The pretreated cultured cells were stained for selected mast cell markers tryptase, chymase and TNF-α. The cultured cells were also processed for observation with electron microscopy. The autoantibodies-treatment of the 3-day cultured cells caused both increased intensity of immunofluorescence (p<0.05) and their enlarged diameters of the mast cells when compared to age-matched ones.In contrast, the fluorescence of preincubated 10-day-old mast cells was decreased compared with controls (p<0.01).In control samples, the fluorescence of 10-day-old mast cells was significantly higher than that of 3-day-old ones (p<0.001). Results of electron microscopy examination demonstrated there was an increased granulation of treated 3-day-old mast cells, while a degranulation of mast cells at day 10 of application. The results suggest the modulation effect of the autoantibodies against G-protein-coupled receptors on mast cells, indicating a potential functional link between the autoantibodies against G-protein-coupled receptors and the mast cells in progression of heart disease.

  13. Adaptive stellar spectral subclass classification based on Bayesian SVMs

    Science.gov (United States)

    Du, Changde; Luo, Ali; Yang, Haifeng

    2017-02-01

    Stellar spectral classification is one of the most fundamental tasks in survey astronomy. Many automated classification methods have been applied to spectral data. However, their main limitation is that the model parameters must be tuned repeatedly to deal with different data sets. In this paper, we utilize the Bayesian support vector machines (BSVM) to classify the spectral subclass data. Based on Gibbs sampling, BSVM can infer all model parameters adaptively according to different data sets, which allows us to circumvent the time-consuming cross validation for penalty parameter. We explored different normalization methods for stellar spectral data, and the best one has been suggested in this study. Finally, experimental results on several stellar spectral subclass classification problems show that the BSVM model not only possesses good adaptability but also provides better prediction performance than traditional methods.

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

    Science.gov (United States)

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

    2012-08-01

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

  15. Sub-classes and evolution stability of Wolfram's classesin the total-rule cellular automata

    Institute of Scientific and Technical Information of China (English)

    YAN Guangwu; TIAN Feng; DONG Yinfeng

    2004-01-01

    In this paper, we propose a concept of sub-classes and its evolution stability for the Wolfram's classes. Firstly, we obtain the sub-classes of the Wolfram's class IV, gene-piece of these sub-classes and their existing circumstance. Secondly, we introduce a new concept, the evolution stability, for the Wolfram's classes and sub-classes of Wolfram's class IV. Lastly, we find that Wolfram's classes I, II, and III have the evolution stability, but sub-classes of the Wolfram's class IV have not the evolution stability for the total rule cellular automata.

  16. Combining Unsupervised and Supervised Learning for Discovering Disease Subclasses

    OpenAIRE

    Tucker, A; Bosoni, P; Bellazzi, R.; Nihtyanova, S; Denton, C.

    2016-01-01

    Diseases are often umbrella terms for many subcategories of disease. The identification of these subcategories is vital if we are to develop personalised treatments that are better focussed on individual patients. In this short paper, we explore the use of a combination of unsupervised learning to identify potential subclasses, and supervised learning to build models for better predicting a number of different health outcomes for patients that suffer from systemic sclerosis, a rare chronic co...

  17. 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.

  18. IGG Subclass and Isotype Specific Immunoglobulin Responses to Lassa Fever and Venezuelan Equine Encephalomyelitis: Natural Infection and Immunization

    Science.gov (United States)

    1991-12-30

    VEE virus to invade the central nervous system via the cribriform plate has been documented for nonhuman primates (7,11), and in hamsters VEE virus has...method for arboviruses . PROC SOC EXP BIOL MED 1967; 125:741-747. 11. Danes L, Rychterova V, Kufner J, Hruskova J: The role of the olfactory route on...viruses that generate an initial antibody response with natural infection that does not provide effective immunity. At the same time, in the primate

  19. 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.

  20. Autoantibodies to Posttranslational Modifications in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Agata N. Burska

    2014-01-01

    Full Text Available 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.

  1. 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

  2. Serum cholesterol and triglyceride reference ranges of twenty lipoprotein subclasses for healthy Japanese men and women.

    Science.gov (United States)

    Furusyo, Norihiro; Ai, Masumi; Okazaki, Mitsuyo; Ikezaki, Hiroaki; Ihara, Takeshi; Hayashi, Takeo; Hiramine, Satoshi; Ura, Kazuya; Kohzuma, Takuji; Schaefer, Ernst J; Hayashi, Jun

    2013-12-01

    This epidemiological study was done to generate normal ranges for the cholesterol and triglyceride levels in serum lipoprotein subclasses isolated from healthy adults based on gender and menopausal status. Cholesterol and triglyceride levels in 20 lipoprotein subclasses as separated by high performance liquid chromatography were measured in serum obtained from 825 fasting healthy subjects (267 men, 558 women). For serum cholesterol, 13.7% was found in very low density lipoprotein (VLDL) subclasses, 55.6% in low density lipoprotein (LDL) subclasses, and 30.4% in high density lipoprotein (HDL) subclasses. For serum triglycerides, these values were 52.1%, 27.9%, and 17.4%, respectively. Levels of cholesterol in some VLDL subclasses were inversely correlated with the levels of some HDL subclasses, while for triglycerides, elevated levels in any one subclass were generally strongly associated with elevated levels in all other subclasses. Men had significantly higher large VLDL-cholesterol levels than women (P cholesterol levels than men (P cholesterol levels than men (P triglyceride levels than women (P triglyceride levels than men (P cholesterol levels, and significantly higher all VLDL, LDL, and HDL-triglyceride levels than premenopausal women (P cholesterol and triglyceride subclass levels, as well as significant correlations between values in the various serum lipoprotein subclasses. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Sumii,Hiroshi

    1989-06-01

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

  4. Therapeutic implications of autoantibodies in rheumatoid arthritis

    OpenAIRE

    Aletaha, Daniel; Blüml, Stephan

    2016-01-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by the presence of autoantibodies. Their value for diagnostic/prognostic purposes has been well established. In contrast, their role in established disease and their associations with disease activity is less clear. Moreover, as evidence is accumulating that these autoantibodies are causally involved in certain key aspects of the disease, such as the initiation and perpetuation of joint inflammation or join destruction, ...

  5. An intrinsic B cell defect is required for the production of autoantibodies in the lpr model of murine systemic autoimmunity

    Energy Technology Data Exchange (ETDEWEB)

    Sobel, E.S.; Katagiri, T.; Katagiri, K.; Morris, S.C.; Cohen, P.L.; Eisenberg, R.A. (Univ. of North Carolina, Chapel Hill (USA))

    1991-06-01

    Mice homozygous for the gene lpr develop marked lymphadenopathy and a spectrum of autoantibodies closely resembling that of human systemic lupus erythematosus. The unusual T cell phenotype of the expanded lymphocyte population and the T-dependence of several antibodies in this strain have suggested that primary T cell abnormalities underlie the autoimmune syndrome. Using double chimeras, we now show that expression of the lpr gene in B cells is absolutely necessary for autoantibody production. Combinations of anti-Thy 1.2 + C' treated bone marrow from congenic strains of C57BL/6 mice, differing only at the immunoglobulin heavy chain (Igh) and lpr loci, were transferred into lethally irradiated B6/lpr mice. Double chimerism was documented by allotype-specific surface IgD and IgM immunofluorescence assay of peripheral blood and by allotype-specific enzyme-linked immunosorbent assay for total IgM in serum. Despite the presence of both +/+ and lpr B cells, IgM and IgG2a anti-chromatin as well as IgM anti-IgG were entirely the products of lpr B cells. Total serum IgG2a and IgG1 were also dominated by the lpr phenotype but not to the same extent. A similar experiment using B6/lpr-Igha recipients confirmed these findings. Additional experiments in which B6/lpr recipients were infused with ratios of donor bone marrow favoring B6.C20 +/+ over B6/lpr showed that even though +/+ B cells were overrepresented, autoantibodies were only of the lpr allotype. In addition, in the presence of lpr B cells, normal B cells showed little response to an exogenous, T cell-dependent antigen. The data thus indicate that lpr B cells manifest an intrinsic abnormality which is essential for autoantibody production in the lpr model.

  6. Somatic Mutations Modulate Autoantibodies against Galactose-Deficient IgA1 in IgA Nephropathy.

    Science.gov (United States)

    Huang, Zhi Qiang; Raska, Milan; Stewart, Tyler J; Reily, Colin; King, R Glenn; Crossman, David K; Crowley, Michael R; Hargett, Audra; Zhang, Zhixin; Suzuki, Hitoshi; Hall, Stacy; Wyatt, Robert J; Julian, Bruce A; Renfrow, Matthew B; Gharavi, Ali G; Novak, Jan

    2016-11-01

    Autoantibodies against galactose-deficient IgA1 drive formation of pathogenic immune complexes in IgA nephropathy. IgG autoantibodies against galactose-deficient IgA1 in patients with IgA nephropathy have a specific amino-acid sequence, Y1CS3, in the complementarity-determining region 3 of the heavy chain variable region compared with a Y1CA3 sequence in similar isotype-matched IgG from healthy controls. We previously found that the S3 residue is critical for binding galactose-deficient IgA1. To determine whether this difference is due to a rare germline sequence, we amplified and sequenced the corresponding germline variable region genes from peripheral blood mononuclear cells of seven patients with IgA nephropathy and six healthy controls from whom we had cloned single-cell lines secreting monoclonal IgG specific for galactose-deficient IgA1. Sanger DNA sequencing revealed that complementarity-determining region 3 in the variable region of the germline genes encoded the Y1C(A/V)3 amino-acid sequence. Thus, the A/V>S substitution in the complementarity-determining region 3 of anti-galactose-deficient-IgA1 autoantibodies of the patients with IgA nephropathy is not a rare germline gene variant. Modeling analyses indicated that the S3 hydroxyl group spans the complementarity-determining region 3 loop stem, stabilizing the adjacent β-sheet and stem structure, important features for effective binding to galactose-deficient IgA1. Understanding processes leading to production of the autoantibodies may offer new approaches to treat IgA nephropathy. Copyright © 2016 by the American Society of Nephrology.

  7. Complement deposition in autoimmune hemolytic anemia is a footprint for difficult-to-detect IgM autoantibodies.

    Science.gov (United States)

    Meulenbroek, Elisabeth M; de Haas, Masja; Brouwer, Conny; Folman, Claudia; Zeerleder, Sacha S; Wouters, Diana

    2015-11-01

    In autoimmune hemolytic anemia autoantibodies against erythrocytes lead to increased clearance of the erythrocytes, which in turn results in a potentially fatal hemolytic anemia. Depending on whether IgG or IgM antibodies are involved, response to therapy is different. Proper identification of the isotype of the anti-erythrocyte autoantibodies is, therefore, crucial. However, detection of IgM autoantibodies can be challenging. We, therefore, set out to improve the detection of anti-erythrocyte IgM. Direct detection using a flow cytometry-based approach did not yield satisfactory improvements. Next, we analyzed whether the presence of complement C3 on a patient's erythrocytes could be used for indirect detection of anti-erythrocyte IgM. To this end, we fractionated patients' sera by size exclusion chromatography and tested which fractions yielded complement deposition on erythrocytes. Strikingly, we found that all patients with C3 on their erythrocytes according to standard diagnostic tests had an IgM anti-erythrocyte component that could activate complement, even if no such autoantibody had been detected with any other test. This also included all tested patients with only IgG and C3 on their erythrocytes, who would previously have been classified as having an IgG-only mediated autoimmune hemolytic anemia. Depleting patients' sera of either IgG or IgM and testing the remaining complement activation confirmed this result. In conclusion, complement activation in autoimmune hemolytic anemia is mostly IgM-mediated and the presence of covalent C3 on patients' erythrocytes can be taken as a footprint of the presence of anti-erythrocyte IgM. Based on this finding, we propose a diagnostic workflow that will aid in choosing the optimal treatment strategy.

  8. Autoantibodies in serum and sputum from patients with cystic fibrosis.

    Science.gov (United States)

    Schiøtz, P O; Egeskjold, E M; Høiby, N; Permin, H

    1979-10-01

    Sera from 89 patients with cystic fibrosis (CF) and 88 control persons were examined for the occurrence of rheumatoid factors (RF) of the IgG, IgA and IgM classes by an indirect immunofluorescence method and by the latex fixation slide test. The prevalence of RF-IgG was significantly higher (88%) (p less than 0.0005) among the CF patients than among the control persons (7%), while no difference was found between the two groups with regard to RF of the IgA or IgM classes. Fifty-five of the CF patients had chronic Pseudomonas aeruginosa infection in their lungs and two or more precipitins against these bacteria in their sera determined by crossed immunoelectrophoresis. These CF patients did not differ from the 34 CF patients without chronic P. aeruginosa infection, neither with regard to prevalence nor titer of RFs, but there was a positive correlation between the number of P. aeruginosa precipitins in the 55 chronically infected CF patients and their titers of IgG-RF. Nineteen CF patients were examined also for RFs, antinuclear antibodies (ANA) and anti-DNA antibodies in their sputum sol phase and corresponding sera. RFs were demonstrated in the sputum sol phase from 6 of the patients by the latex fixation test, whereas their sera were negative in this test, possibly indicating a local production of RF. Positive reactions for ANA and anti-DNA antibodies were found in 7 and 10 of the sputa respectively, and in higher titers than in the corresponding sera, also suggesting a local production. Titers of autoantibodies in sputum were low and no difference was found between patients with chronic P. aeruginosa infection and patients without P. aeruginosa infection. The possible role of autoantibodies in the patogenesis of pulmonary tissue damage in CF patients is discussed.

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

    Science.gov (United States)

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

    2013-02-01

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

  10. Autoantibodies against Linear Epitopes of Myeloperoxidase in Anti-Glomerular Basement Membrane Disease.

    Science.gov (United States)

    Li, Jian-Nan; Cui, Zhao; Wang, Jia; Hu, Shui-Yi; Jia, Xiao-Yu; Guan, Zhe; Chen, Min; Xie, Can; Zhao, Ming-Hui

    2016-04-07

    Approximately 20%-30% of patients with anti-glomerular basement membrane disease present coexisting anti-myeloperoxidase (MPO) autoantibodies. We previously showed the recognition of a linear fragment of the MPO heavy chain N-terminus ((1)H, MPO279-409) in plasma from most double-positive patients. Herein, we investigated the frequency of autoantibodies against overlapping (1)H-derived linear peptides in plasma from patients with anti-glomerular basement membrane disease. We synthesized 13 overlapping linear peptides ((1)H-1 to (1)H-13) covering MPO279-409. We retrospectively collected plasma samples from 67 patients with anti-glomerular basement membrane disease from 1996 to 2012, and we screened them for IgG autoantibodies by ELISA using intact human MPO and the overlapping peptides as antigens, and we further investigated the clinical significance. Autoantibody binding to the linear MPO structure was confirmed by Western blotting. We followed up the 67 patients until 2015, with a median follow-up time of 10.0 (2.3-36.0) months, and 56 ESRD events occurred among the 67 patients with follow-up data. Plasma from 23.9% (16) of the patients recognized intact human MPO, whereas 62.7% (42) plasma samples recognized MPO279-409 linear peptides. Of the 13 linear peptides, (1)H-4 (44.8%, 30 patients) and (1)H-12 (40.3%, 27 patients) exhibited the highest recognition frequencies. Patients with autoantibodies against (1)H-11 or (1)H-12 (MPO371-400) were older (46.1±18.8 versus 34.1±16.6 years; P<0.01), had higher serum creatinine upon diagnosis (median 7.8 mg/dl, interquartile range 4.9-12.6 mg/dl versus median 5.4 mg/dl, interquartile range 2.4-7.3 mg/dl; P=0.02), and had a higher probability of progressing to ESRD; however, multivariate Cox regression analysis showed that (1)H-11 or 12 reaction was not an independent risk factor for renal failure (hazard ratio, 1.2; 95% confidence interval, 0.8 to 2.8; P=0.19). Autoantibodies against linear peptides of MPO can be

  11. Structure of full-length human anti-PD1 therapeutic IgG4 antibody pembrolizumab.

    Science.gov (United States)

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

    2015-12-01

    Immunoglobulin G4 antibodies exhibit unusual properties with important biological consequences. We report the structure of the human full-length IgG4 S228P anti-PD1 antibody pembrolizumab, solved to 2.3-Å resolution. Pembrolizumab is a compact molecule, consistent with the presence of a short hinge region. The Fc domain is glycosylated at the CH2 domain on both chains, but one CH2 domain is rotated 120° with respect to the conformation observed in all reported structures to date, and its glycan chain faces the solvent. We speculate that this new conformation is driven by the shorter hinge. The structure suggests a role for the S228P mutation in preventing the IgG4 arm exchange. In addition, this unusual Fc conformation suggests possible structural diversity between IgG subclasses and shows that use of isolated antibody fragments could mask potentially important interactions, owing to molecular flexibility.

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

    Science.gov (United States)

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

    1995-07-01

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

  13. 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

    molecular weight 125I fraction was achieved with an excess of unlabelled rIL-1 alpha but not with rIL-1 beta. The serum factors binding to [125I]rIL-1 alpha were located in the molecular weight range 100,000-200,000, judged by fractionation on a Sephacryl S-400 column, and the factors were bound...

  14. 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

  15. 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)

  16. Protein array autoantibody profiles to determine diagnostic markers for neuropsychiatric systemic lupus erythematosus.

    Science.gov (United States)

    van der Meulen, Pomme M; Barendregt, Anouk M; Cuadrado, Eloy; Magro-Checa, César; Steup-Beekman, Gerda M; Schonenberg-Meinema, Dieneke; Van den Berg, J Merlijn; Li, Quan-Zhen; Baars, Paul A; Wouters, Diana; Voskuyl, Alexandre E; Ten Berge, Ineke R J M; Huizinga, Tom W J; Kuijpers, Taco W

    2017-08-01

    The aim was to investigate the association between autoantibodies (autoAbs) and neuropsychiatric (NP) involvement in patients with SLE and to evaluate whether any autoAb or a combination of these autoAbs could indicate the underlying pathogenic process. Using a multiplexed protein array for 94 antigens, we compared the serum autoAb profiles of 69 NPSLE patients, 203 SLE patients without NP involvement (non-NPSLE) and 51 healthy controls. Furthermore, we compared the profiles of NPSLE patients with clinical inflammatory (n = 38) and ischaemic (n = 31) NP involvement. In total, 75 IgG and 47 IgM autoAbs were associated with SLE patients in comparison with healthy controls. Comparing NPSLE with non-NPSLE and healthy control sera, 9 IgG (amyloid, cardiolipin, glycoprotein 2, glycoprotein 210, heparin, heparan sulphate, histone H2A, prothrombin protein and vimentin) and 12 IgM (amyloid, cardiolipin, centromere protein A, collagen II, histones H2A and H2B, heparan sulphate, heparin, mitochondrial 2, nuclear Mi-2, nucleoporin 62 and vimentin) autoAbs were present at significantly different levels in NPSLE. The combination of IgG autoAbs against heparan sulphate, histone H2B and vimentin could differentiate NPSLE from non-NPSLE (area under the curve 0.845, 99.97% CI: 0.756, 0.933; P < 0.0001). Compared with non-NPSLE, four IgG and seven IgM autoAbs were significantly associated with inflammatory NPSLE. In ischaemic NPSLE, three IgG and three IgM autoAbs were significantly different from non-NPSLE patients. In our cohort, the presence of high levels of anti-heparan sulphate and anti-histone H2B combined with low levels of anti-vimentin IgG autoAbs is highly suggestive of NPSLE. These results need to be validated in external cohorts.

  17. Whole-Proteome Peptide Microarrays for Profiling Autoantibody Repertoires within Multiple Sclerosis and Narcolepsy.

    Science.gov (United States)

    Zandian, Arash; Forsström, Björn; Häggmark-Månberg, Anna; Schwenk, Jochen M; Uhlén, Mathias; Nilsson, Peter; Ayoglu, Burcu

    2017-02-09

    The underlying molecular mechanisms of autoimmune diseases are poorly understood. To unravel the autoimmune processes across diseases, comprehensive and unbiased analyses of proteins targets recognized by the adaptive immune system are needed. Here we present an approach starting from high-density peptide arrays to characterize autoantibody repertoires and to identify new autoantigens. A set of ten plasma and serum samples from subjects with multiple sclerosis, narcolepsy, and without any disease diagnosis were profiled on a peptide array representing the whole proteome, hosting 2.2 million 12-mer peptides with a six amino acid lateral shift. On the basis of the IgG reactivities found on these whole-proteome peptide microarrays, a set of 23 samples was then studied on a targeted array with 174 000 12-mer peptides of single amino acid lateral shift. Finally, verification of IgG reactivities was conducted with a larger sample set (n = 448) using the bead-based peptide microarrays. The presented workflow employed three different peptide microarray formats to discover and resolve the epitopes of human autoantibodies and revealed two potentially new autoantigens: MAP3K7 in multiple sclerosis and NRXN1 in narcolepsy. The presented strategy provides insights into antibody repertoire reactivity at a peptide level and may accelerate the discovery and validation of autoantigens in human diseases.

  18. Human Blood Autoantibodies in the Detection of Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Ola H Negm

    Full Text Available Colorectal cancer (CRC is the second most common malignancy in the western world. Early detection and diagnosis of all cancer types is vital to improved prognosis by enabling early treatment when tumours should be both resectable and curable. Sera from 3 different cohorts; 42 sera (21 CRC and 21 matched controls from New York, USA, 200 sera from Pittsburgh, USA (100 CRC and 100 controls and 20 sera from Dundee, UK (10 CRC and 10 controls were tested against a panel of multiple tumour-associated antigens (TAAs using an optimised multiplex microarray system. TAA specific IgG responses were interpolated against the internal IgG standard curve for each sample. Individual TAA specific responses were examined in each cohort to determine cutoffs for a robust initial scoring method to establish sensitivity and specificity. Sensitivity and specificity of combinations of TAAs provided good discrimination between cancer-positive and normal serum. The overall sensitivity and specificity of the sample sets tested against a panel of 32 TAAs were 61.1% and 80.9% respectively for 6 antigens; p53, AFP, K RAS, Annexin, RAF1 and NY-CO16. Furthermore, the observed sensitivity in Pittsburgh sample set in different clinical stages of CRC; stage I (n = 19, stage II (n = 40, stage III (n = 34 and stage IV (n = 6 was similar (73.6%, 75.0%, 73.5% and 83.3%, respectively, with similar levels of sensitivity for right and left sided CRC. We identified an antigen panel of sufficient sensitivity and specificity for early detection of CRC, based upon serum profiling of autoantibody response using a robust multiplex antigen microarray technology. This opens the possibility of a blood test for screening and detection of early colorectal cancer. However this panel will require further validation studies before they can be proposed for clinical practice.

  19. 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.

  20. Modulation of c-Jun NH2-Terminal (JNK) by Cholinergic Autoantibodies from Patients with Sjögren’s Syndrome

    OpenAIRE

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

    2017-01-01

    Background: We wanted to determine (via an immunopharmacological approach) whether the c-Jun NH2 terminal kinase (JNK) cascade is phosphorylated in the submandibular gland by carbachol and cholinergic autoantibodies (IgG) present in the sera of patients with primary Sjögren’s syndrome (pSS) by interaction and activation of salivary gland muscarinic acetylcholine receptors (mAChRs). Methods: The JNK, PGE2 and NOS assays were measured in rat sub- mandibular gland with pSS IgG and carbachol alon...

  1. 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...

  2. Antineutrophil cytoplasmic autoantibody-associated small-vessel vasculitis

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    2007-01-01

    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 micro

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

    Science.gov (United States)

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

    2012-12-01

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

  4. [Interferon alpha antibodies show no cross reactions with typical autoantibodies].

    Science.gov (United States)

    Görg, S; Klouche, M; Wilhelm, D; Kirchner, H

    1993-04-01

    Patients treated with natural human interferon alpha develop anti-interferon antibodies (IFN-AB) only in very rare cases. By contrast, patients with autoimmune disorders are able to generate high-titered IFN-AB against endogenous interferon alpha. One explanation for the development of auto-IFN-AB could be cross-reactivity with typical autoimmune antigens. We investigated the cross-reactivity of 3 high-titered IgG IFN-AB of female autoimmune patients (aged 32, 36, 74 years; two severe cases of SLE, one case of autoimmune thyroiditis) as well as 25 low-titered natural IgM IFN-AB of healthy blood donors (aged 19-48 years). Typical autoimmune antigens including dsDNA, ENA, as well as natural interferon beta and recombinant interferon gamma are not able to inhibit binding of IFN-AB to interferon alpha in an ELISA test system. Preincubation of sera containing either dsDNA antibodies (dsDNA-AB) (24 patients), thyroid peroxidase (TPO-AB) (9 patients) or thyroglobulin (TG-AB) (12 patients) with interferon alpha resulted in no change in the respective autoantibody titer. These data suggest that there is no cross-reactivity between IFN-alpha-AB and dsDNA-AB, TPO-AB or TG-AB. Thus, an explanation for the occurrence of IFN-AB in autoimmune disorders cannot be found in a cross-reaction between interferon alpha with typical autoimmune antigens.

  5. Elevated Levels of Plasma IgA Autoantibodies against Oxidized LDL Found in Proliferative Diabetic Retinopathy but Not in Nonproliferative Retinopathy

    Science.gov (United States)

    Savolainen, Markku J.

    2016-01-01

    Aims. This study investigated the association of autoantibodies binding to oxidized low-density lipoproteins (oxLDL) in diabetic retinopathy (DR). Methods. Plasma from 229 types 1 and 2 patients with DR including diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) was analysed with ELISA-based assay to determine IgA, IgG, and IgM autoantibody levels binding to oxLDL. The controls were 106 diabetic patients without retinopathy (NoDR) and 139 nondiabetic controls (C). Results. PDR group had significantly higher IgA autoantibody levels than DME or NoDR: mean 94.9 (SD 54.7) for PDR, 75.5 (41.8) for DME (p = 0.001), and 76.1 (48.2) for NoDR (p = 0.008). There were no differences in IgG, IgM, or IgA that would be specific for DR or for DME. Type 2 diabetic patients had higher levels of IgA autoantibodies than type 1 diabetic patients (86.0 and 65.5, resp., p = 0.004) and the highest levels in IgA were found in type 2 diabetic patients with PDR (119.1, p > 0.001). Conclusions. IgA autoantibodies were increased in PDR, especially in type 2 diabetes. The high levels of IgA in PDR, and especially in type 2 PDR patients, reflect the inflammatory process and enlighten the role of oxLDL and its autoantibodies in PDR.

  6. Uncommon structural motifs dominate the antigen binding site in human autoantibodies reactive with basement membrane collagen.

    Science.gov (United States)

    Foster, Mary H; Buckley, Elizabeth S; Chen, Benny J; Hwang, Kwan-Ki; Clark, Amy G

    2016-08-01

    Autoantibodies mediate organ destruction in multiple autoimmune diseases, yet their origins in patients remain poorly understood. To probe the genetic origins and structure of disease-associated autoantibodies, we engrafted immunodeficient mice with human CD34+ hematopoietic stem cells and immunized with the non-collagenous-1 (NC1) domain of the alpha3 chain of type IV collagen. This antigen is expressed in lungs and kidneys and is targeted by autoantibodies in anti-glomerular basement membrane (GBM) nephritis and Goodpasture syndrome (GPS), prototypic human organ-specific autoimmune diseases. Using Epstein Barr virus transformation and cell fusion, six human anti-alpha3(IV)NC1 collagen monoclonal autoantibodies (mAb) were recovered, including subsets reactive with human kidney and with epitopes recognized by patients' IgG. Sequence analysis reveals a long to exceptionally long heavy chain complementarity determining region3 (HCDR3), the major site of antigen binding, in all six mAb. Mean HCDR3 length is 25.5 amino acids (range 20-36), generated from inherently long DH and JH genes and extended regions of non-templated N-nucleotides. Long HCDR3 are suited to forming noncontiguous antigen contacts and to binding recessed, immunologically silent epitopes hidden from conventional antibodies, as seen with self-antigen crossreactive broadly neutralizing anti-HIV Ig (bnAb). The anti-alpha3(IV)NC1 collagen mAb also show preferential use of unmutated variable region genes that are enriched among human chronic lymphocytic leukemia antibodies that share features with natural polyreactive Ig. Our findings suggest unexpected relationships between pathogenic anti-collagen Ig, bnAb, and autoreactive Ig associated with malignancy, all of which arise from B cells expressing unconventional structural elements that may require transient escape from tolerance for successful expansion. Published by Elsevier Ltd.

  7. Uncommon Structural Motifs Dominate the Antigen Binding Site in Human Autoantibodies Reactive with Basement Membrane Collagen

    Science.gov (United States)

    Foster, Mary H.; Buckley, Elizabeth S.; Chen, Benny J.; Hwang, Kwan-Ki; Clark, Amy G.

    2016-01-01

    Autoantibodies mediate organ destruction in multiple autoimmune diseases, yet their origins in patients remain poorly understood. To probe the genetic origins and structure of disease-associated autoantibodies, we engrafted immunodeficient mice with human CD34+ hematopoietic stem cells and immunized with the non-collagenous-1 (NC1) domain of the alpha3 chain of type IV collagen. This antigen is expressed in lungs and kidneys and is targeted by autoantibodies in anti-glomerular basement membrane (GBM) nephritis and Goodpasture syndrome (GPS), prototypic human organ-specific autoimmune diseases. Using Epstein Barr virus transformation and cell fusion, six human anti-alpha3(IV)NC1 collagen monoclonal autoantibodies (mAb) were recovered, including subsets reactive with human kidney and with epitopes recognized by patients’ IgG. Sequence analysis reveals a long to exceptionally long heavy chain complementarity determining region3 (HCDR3), the major site of antigen binding, in all six mAb. Mean HCDR3 length is 25.5 amino acids (range 20–36), generated from inherently long DH and JH genes and extended regions of non-templated N-nucleotides. Long HCDR3 are suited to forming noncontiguous antigen contacts and to binding recessed, immunologically silent epitopes hidden from conventional antibodies, as seen with self-antigen crossreactive broadly neutralizing anti-HIV Ig (bnAb). The anti-alpha3(IV)NC1 collagen mAb also show preferential use of unmutated variable region genes that are enriched among human chronic lymphocytic leukemia antibodies that share features with natural polyreactive Ig. Our findings suggest unexpected relationships between pathogenic anti-collagen Ig, bnAb, and autoreactive Ig associated with malignancy, all of which arise from B cells expressing unconventional structural elements that may require transient escape from tolerance for successful expansion. PMID:27450516

  8. Loss of heterozygosity and its correlation with expression profiles in subclasses of invasive breast cancers.

    Science.gov (United States)

    Wang, Zhigang C; Lin, Ming; Wei, Lee-Jen; Li, Cheng; Miron, Alexander; Lodeiro, Gabriella; Harris, Lyndsay; Ramaswamy, Sridhar; Tanenbaum, David M; Meyerson, Matthew; Iglehart, James D; Richardson, Andrea

    2004-01-01

    Gene expression array profiles identify subclasses of breast cancers with different clinical outcomes and different molecular features. The present study attempted to correlate genomic alterations (loss of heterozygosity; LOH) with subclasses of breast cancers having distinct gene expression signatures. Hierarchical clustering of expression array data from 89 invasive breast cancers identified four major expression subclasses. Thirty-four of these cases representative of the four subclasses were microdissected and allelotyped using genome-wide single nucleotide polymorphism detection arrays (Affymetrix, Inc.). LOH was determined by comparing tumor and normal single nucleotide polymorphism allelotypes. A newly developed statistical tool was used to determine the chromosomal regions of frequent LOH. We found that breast cancers were highly heterogeneous, with the proportion of LOH ranging widely from 0.3% to >60% of heterozygous markers. The most common sites of LOH were on 17p, 17q, 16q, 11q, and 14q, sites reported in previous LOH studies. Signature LOH events were discovered in certain expression subclasses. Unique regions of LOH on 5q and 4p marked a subclass of breast cancers with "basal-like" expression profiles, distinct from other subclasses. LOH on 1p and 16q occurred preferentially in a subclass of estrogen receptor-positive breast cancers. Finding unique LOH patterns in different groups of breast cancer, in part defined by expression signatures, adds confidence to newer schemes of molecular classification. Furthermore, exclusive association between biological subclasses and restricted LOH events provides rationale to search for targeted genes.

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

    Science.gov (United States)

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

    2013-06-15

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

  10. Group G streptococcal IgG binding molecules FOG and protein G have different impacts on opsonization by C1q.

    Science.gov (United States)

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

    2007-06-15

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

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

    Directory of Open Access Journals (Sweden)

    L Renee Ruhaak

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

  12. Levels of Folate Receptor Autoantibodies in Maternal and Cord Blood and Risk of Neural Tube Defects in a Chinese population

    Science.gov (United States)

    Yang, Na; Wang, Linlin; Finnell, Richard H.; Li, Zhiwen; Jin, Lei; Zhang, Le; Cabrera, Robert M.; Ye, Rongwei; Ren, Aiguo

    2016-01-01

    Background After years of periconceptional folic acid supplementation, the prevalence of neural tube defects (NTDs) remains stable following the remarkable reduction observed immediately after the fortification practice. There is accumulating evidence that folate receptor (FR) autoimmunity may play a role in the etiology of folate-sensitive NTDs. Methods From 2011 to 2013, 118 NTD cases and 242 healthy controls were recruited from a population-based birth defects surveillance system in Northern China. Enzyme-linked immunosorbent assay was used to measure FR autoantibodies in maternal and cord blood. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI). Results Plasma FR autoantibodies levels were significantly elevated in mothers of infants with NTDs compared with mothers of healthy controls. Using the lowest tertile as the referent group, 2.20-fold (95% CI, 0.71–6.80) and 5.53-fold increased odds (95% CI, 1.90–16.08) of NTDs were observed for the second and third tertile of immunoglobulin G (IgG), respectively, and the odds of NTDs for each successive tertile of IgM was 0.98 (95% CI, 0.35–2.75) and 3.49 (95% CI, 1.45–8.39), respectively. A dose–response relationship was found between FR autoantibodies levels and risk of NTDs (P < 0.001 for IgG, P = 0.002 for IgM). The same pattern was observed in both subtypes of spina bifida and anencephaly. No significant difference in levels of cord blood FR autoantibodies was observed. Conclusion Higher levels of FR autoimmunity in maternal plasma are associated with elevated risk of NTDs in a dose–response manner. PMID:27166990

  13. Coumestrol inhibits autoantibody production through modulating Th1 response in experimental autoimmune thyroiditis

    Science.gov (United States)

    Zhao, Xuemin; Jin, Qian; Fan, Chenling; Li, Jing; Shan, Zhongyan; Teng, Weiping

    2016-01-01

    Coumestrol is a common phytoestrogen found in plants and Chinese medicinal herbs. Its influences on experimental autoimmune thyroiditis (EAT) were investigated in this study. Female adult CBA/J mice were fed with drinking water containing 1% Tween80 only (Control group), 0.8 mg/l (L group) and 8 mg/l coumestrol (H group) from 6 to 15 weeks of age, respectively. Their serum coumestrol concentrations were determined by high performance liquid chromatography, which were undetectable, 43.70 ± 21.74 ng/ml and 135.07 ± 70.40 ng/ml, respectively. In addition, the mice (n = 14–16/group) were immunized twice with thyroglobulin (Tg) and Freund's adjuvant to induce EAT during the meantime. Although no overt changes in the extent of intrathyroidal mononuclear cell infiltration were shown in the two coumestrol-treated groups as compared with the controls, serum anti-Tg IgG2a, IgG3 and IgG1 titers, ratio of IgG2a to IgG1 and the percentage of T helper (Th)1 cells in the splenocytes were significantly reduced in the L group. Another consistent change was the significantly decreased expression of splenic IFN-γ mRNA after low dose of coumestrol exposure. Uterine weight was also markedly reduced in the mice of L group. These findings suggest that coumestrol treatment may have some beneficial actions against thyroid-specific autoantibody production in the development of autoimmune thyroiditis through suppression of Th1 response due to its anti-estrogenic activity. PMID:27384679

  14. Predictors of shingles reports at diagnosis of common variable immunodeficiency and selective immunoglobulin G subclass deficiency in 212 Alabama adults

    Directory of Open Access Journals (Sweden)

    James C. Barton

    2012-07-01

    Full Text Available We sought to determine predictors of shingles reports in adults with common variable immunodeficiency or immunoglobulin (Ig G subclass deficiency (CVID/IgGSD. We tabulated observations at diagnosis of CVID/IgGSD in 212 white adult index patients (165 women, 47 men who responded to a question about having had shingles. None had been vaccinated for herpes zoster. We analyzed age, sex, and shingles reports; blood levels of CD19+, CD4+, CD8+, and CD56+ mononuclear cells; serum levels of IgG subclasses, IgA, and IgM; and positivity for human leukocyte antigen (HLA-A and -B haplotypes. Cell counts and immunoglobulin levels were normalized with loge (ln transformation for analyses. Thirty-one patients (14.6% reported shingles; 11 reported recurrent or disseminated shingles. Patients with shingles reports had greater mean age at diagnosis of CVID/IgGSD [54±13 (standard deviation years vs. 47±12 years; P=0.0130] and a greater prevalence of HLA-A*01, B*08 positivity (35.5% vs. 17.7%; P=0.0227. In a 13-factor logistic regression model, there was a positive association of age with shingles reports [P=0.0151; odds ratio (1.05, 95% confidence interval 1.01, 1.08]. HLA-A*01, B*08 positivity was also positively associated with shingles reports [P=0.0480; odds ratio 2.61 (1.00, 6.81]. During a mean followup interval of 7.5 years after CVID/IgGSD diagnosis, the prevalence of recurrent shingles was almost five-fold greater in patients with previous shingles reports. In conclusion, in white adults at CVID/IgGSD diagnosis, age at diagnosis and positivity for HLA-A*01, B*08 have significant positive associations with reports of previous shingles.

  15. 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

  16. A case of subepidermal blistering disease with autoantibodies to multiple laminin subunits who developed later autoantibodies to alpha-5 chain of type IV collagen associated with membranous glomerulonephropathy.

    Science.gov (United States)

    Sueki, Hirohiko; Sato, Yoshinori; Ohtoshi, Shinpei; Nakada, Tokio; Yoshimura, Ashio; Tateishi, Chiharu; Borza, Dorin-Bogdan; Fader, William; Ghohestani, Reza F; Hirako, Yoshiaki; Koga, Hiroshi; Ishii, Norito; Tsuchisaka, Atsunari; Qian, Hua; Li, Xiaoguang; Hashimoto, Takashi

    2015-09-01

    We report a 68-year-old Japanese female patient with subepidermal blistering disease with autoantibodies to multiple laminins, who subsequently developed membranous glomerulonephropathy. At skin disease stage, immunofluorescence demonstrated IgG anti-basement membrane zone antibodies reactive with dermal side of NaCl-split skin. Immunoblotting of human dermal extract, purified laminin-332, hemidesmosome-rich fraction and laminin-521 trimer recombinant protein (RP) detected laminin γ-1 and α-3 and γ-2 subunits of laminin-332. Three years after skin lesions disappeared, nephrotic symptoms developed. Antibodies to α-3 chain of type IV collagen (COL4A3) were negative, thus excluding the diagnosis of Goodpasture syndrome. All anti-laminin antibodies disappeared. Additional IB and ELISA studies of RPs of various COL4 chains revealed reactivity with COL4A5, but not with COL4A6 or COL4A3. Although diagnosis of anti-laminin γ-1 (p200) pemphigoid or anti-laminin-332-type mucous membrane pemphigoid could not be made, this case was similar to previous cases with autoantibodies to COL4A5 and/or COL4A6.

  17. 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.

  18. Anti-C1q autoantibodies

    NARCIS (Netherlands)

    Kallenberg, Cees G. M.

    2008-01-01

    Autoantibodies to complement components are associated with various diseases. Anti-C1q antibodies are present in all patients with hypocomplementemic urticarial vasculitis, but also, with varying prevalence, in other conditions. In SLE, these antibodies are neither sensitive nor specific for this co

  19. 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.

  20. Autoantibody profiling in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Hsieh SC

    2013-08-01

    Full Text Available Song-Chou Hsieh,1 Chia-Li Yu1,2 1Department of Internal Medicine, 2Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei, Taiwan Abstract: Systemic lupus erythematosus (SLE is an archetype of systemic autoimmune disease characterized by the production of a broad spectrum of autoantibodies. More than 100 autoantibodies have been found in the sera of patients with SLE, including antibodies against nuclear, cytoplasmic, surface-membrane, and extracellular antigens. There has been considerable debate as to whether these antinuclear autoantibodies (ANAs are merely biomarkers for disease or are responsible for organ/tissue damage in SLE. In recent years, sufficient evidence has supported the hypothesis that many ANAs, such as anti-double-stranded DNA (anti-dsDNA, antiribosomal P, anti-Sm, antiribonucleoprotein (anti-RNP, and even anti-Sjögren's syndrome (SS-B/La antibodies not only act against specific nuclear antigens but also cross-react with different surface-expressed cognate molecules. The binding of autoantibodies to the cell surface leads to their penetration into the cell's interior to elicit cellular damage. There are at least four conceivable routes for ANAs to penetrate the cytoplasm: (1 nonspecific Fcγ receptor-mediated uptake, (2 cell-surface caveolae-mediated endocytosis, (3 electrostatic interactions between positively charged amino acids of the complementarity-determining regions of the antibody molecule and the negatively charged surface membrane, and (4 the binding of the autoantibody with its cross-reactive cell surface-expressed cognate molecule, and its subsequent endocytosis into the cytoplasm. In this review, we discuss in detail the immunopathogenic mechanisms of the commonly encountered ANAs, such as anti-dsDNA, antiribosomal P, and anti-SSB/La, that are associated with lupus pathogenesis. Additionally, the detrimental thromboembolism-inducing anticardiolipin antibodies in patients with SLE

  1. Multigene phylogeny of the red algal subclass Nemaliophycidae.

    Science.gov (United States)

    Lam, Daryl W; Verbruggen, Heroen; Saunders, Gary W; Vis, Morgan L

    2016-01-01

    The red algae (Rhodophyta) are a lineage of primary endosymbionts whose ancestors represent some of the first photosynthetic eukaryotes on the planet. They primarily inhabit marine ecosystems, with only ∼5% of species found in freshwater systems. The subclass Nemaliophycidae is very diverse in ecological and life history features and therefore a useful model to study these traits, but the phylogenetic relationships among the orders are, for the most part, poorly resolved. To elucidate the phylogeny of the Nemaliophycidae, we constructed a nine-gene dataset comprised of nuclear, plastid, and mitochondrial markers for 67 red algal specimens. The resulting maximum likelihood (ML) phylogeny confirmed the monophyly of all orders. The sister relationship of the Acrochaetiales and Palmariales received high support and the relationship of the Balliales with Balbianiales and Entwisleiales with Colaconematales was moderately supported. The Nemaliales, Entwisleiales, Colaconematales, Palmariales and Acrochaetiales formed a highly supported clade. Unfortunately, all other relationships among the orders had low bootstrap support. Although the ML analysis did not resolve many of the relationships, further analyses suggested that a resolution is possible. A Phycas analysis supported a dichotomously branching tree and Bayesian analysis showed a similar topology with all relationships highly supported. Simulations extrapolating the number of nucleotide characters beyond the current size of the dataset suggested that most nodes in the phylogeny would be resolved if more data become available. Phylogenomic approaches will be necessary to provide a well-supported phylogeny of this subclass with all relationships resolved such that the evolution of freshwater species from marine ancestors as well as reproductive traits can be explored. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. IgG4 Related Sclerosing Cholangitis

    Directory of Open Access Journals (Sweden)

    D. Joshi

    2014-01-01

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

  3. IgG4-associated vasculitis.

    Science.gov (United States)

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

    2013-08-01

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

  4. A systems immunology approach to the host-tumor interaction: large-scale patterns of natural autoantibodies distinguish healthy and tumor-bearing mice.

    Directory of Open Access Journals (Sweden)

    Yifat Merbl

    Full Text Available Traditionally, immunology has considered a meaningful antibody response to be marked by large amounts of high-affinity antibodies reactive with the specific inciting antigen; the detection of small amounts of low-affinity antibodies binding to seemingly unrelated antigens has been considered to be beneath the threshold of immunological meaning. A systems-biology approach to immunology, however, suggests that large-scale patterns in the antibody repertoire might also reflect the functional state of the immune system. To investigate such global patterns of antibodies, we have used an antigen-microarray device combined with informatic analysis. Here we asked whether antibody-repertoire patterns might reflect the state of an implanted tumor. We studied the serum antibodies of inbred C57BL/6 mice before and after implantation of syngeneic 3LL tumor cells of either metastatic or non-metastatic clones. We analyzed patterns of IgG and IgM autoantibodies binding to over 300 self-antigens arrayed on slides using support vector machines and genetic algorithm techniques. We now report that antibody patterns, but not single antibodies, were informative: 1 mice, even before tumor implantation, manifest both individual and common patterns of low-titer natural autoantibodies; 2 the patterns of these autoantibodies respond to the growth of the tumor cells, and can distinguish between metastatic and non-metastatic tumor clones; and 3 curative tumor resection induces dynamic changes in these low-titer autoantibody patterns. The informative patterns included autoantibodies binding to self-molecules not known to be tumor-associated antigens (including insulin, DNA, myosin, fibrinogen as well as to known tumor-associated antigens (including p53, cytokeratin, carbonic anhydrases, tyrosinase. Thus, low-titer autoantibodies that are not the direct products of tumor-specific immunization can still generate an immune biomarker of the body-tumor interaction. System

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

    Directory of Open Access Journals (Sweden)

    Saibah Siregar

    2012-01-01

    Full Text Available 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.

  6. Pathogenic Roles of Glutamic Acid Decarboxylase 65 Autoantibodies in Cerebellar Ataxias.

    Science.gov (United States)

    Mitoma, Hiroshi; Manto, Mario; Hampe, Christiane S

    2017-01-01

    Reports suggesting a pathogenic role of autoantibodies directed against glutamic acid decarboxylase 65 (GAD65Abs) in cerebellar ataxias (CAs) are reviewed, and debatable issues such as internalization of antibodies by neurons and roles of epitopes are discussed. GAD65 is one of two enzymes that catalyze the conversion of glutamate to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). A pathogenic role of GAD65Ab in CAs is suggested by in vivo and in vitro studies. (1) Intracerebellar administration of cerebrospinal fluid (CSF) immunoglobulins (IgGs) obtained from GAD65Ab-positive CA patients impairs cerebellar modulation of motor control in rats. (2) CSF IgGs act on terminals of GABAergic neurons and decrease the release of GABA in cerebellar slices from rats and mice. (3) Absorption of GAD65Ab by recombinant GAD65 diminishes the above effects, and monoclonal human GAD65Ab (b78) mimic the effects of CSF IgGs in vivo and in vitro. Studies using GAD65-KO mice confirm that the target molecule is GAD65. (4) Notably, the effects of GAD65Ab depend on the epitope specificity of the monoclonal GAD65Ab. Taken together, these results indicate that epitope-specific GAD65Ab-induced impairment of GABA release is involved in the pathogenesis of GAD65Ab-positive CA and support the early detection of GAD65Ab-associated CA to initiate immunotherapy before irreversible neuronal death in the cerebellum.

  7. Pathogenic Roles of Glutamic Acid Decarboxylase 65 Autoantibodies in Cerebellar Ataxias

    Directory of Open Access Journals (Sweden)

    Hiroshi Mitoma

    2017-01-01

    Full Text Available Reports suggesting a pathogenic role of autoantibodies directed against glutamic acid decarboxylase 65 (GAD65Abs in cerebellar ataxias (CAs are reviewed, and debatable issues such as internalization of antibodies by neurons and roles of epitopes are discussed. GAD65 is one of two enzymes that catalyze the conversion of glutamate to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA. A pathogenic role of GAD65Ab in CAs is suggested by in vivo and in vitro studies. (1 Intracerebellar administration of cerebrospinal fluid (CSF immunoglobulins (IgGs obtained from GAD65Ab-positive CA patients impairs cerebellar modulation of motor control in rats. (2 CSF IgGs act on terminals of GABAergic neurons and decrease the release of GABA in cerebellar slices from rats and mice. (3 Absorption of GAD65Ab by recombinant GAD65 diminishes the above effects, and monoclonal human GAD65Ab (b78 mimic the effects of CSF IgGs in vivo and in vitro. Studies using GAD65-KO mice confirm that the target molecule is GAD65. (4 Notably, the effects of GAD65Ab depend on the epitope specificity of the monoclonal GAD65Ab. Taken together, these results indicate that epitope-specific GAD65Ab-induced impairment of GABA release is involved in the pathogenesis of GAD65Ab-positive CA and support the early detection of GAD65Ab-associated CA to initiate immunotherapy before irreversible neuronal death in the cerebellum.

  8. Pathogenic Roles of Glutamic Acid Decarboxylase 65 Autoantibodies in Cerebellar Ataxias

    Science.gov (United States)

    Hampe, Christiane S.

    2017-01-01

    Reports suggesting a pathogenic role of autoantibodies directed against glutamic acid decarboxylase 65 (GAD65Abs) in cerebellar ataxias (CAs) are reviewed, and debatable issues such as internalization of antibodies by neurons and roles of epitopes are discussed. GAD65 is one of two enzymes that catalyze the conversion of glutamate to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). A pathogenic role of GAD65Ab in CAs is suggested by in vivo and in vitro studies. (1) Intracerebellar administration of cerebrospinal fluid (CSF) immunoglobulins (IgGs) obtained from GAD65Ab-positive CA patients impairs cerebellar modulation of motor control in rats. (2) CSF IgGs act on terminals of GABAergic neurons and decrease the release of GABA in cerebellar slices from rats and mice. (3) Absorption of GAD65Ab by recombinant GAD65 diminishes the above effects, and monoclonal human GAD65Ab (b78) mimic the effects of CSF IgGs in vivo and in vitro. Studies using GAD65-KO mice confirm that the target molecule is GAD65. (4) Notably, the effects of GAD65Ab depend on the epitope specificity of the monoclonal GAD65Ab. Taken together, these results indicate that epitope-specific GAD65Ab-induced impairment of GABA release is involved in the pathogenesis of GAD65Ab-positive CA and support the early detection of GAD65Ab-associated CA to initiate immunotherapy before irreversible neuronal death in the cerebellum. PMID:28386570

  9. 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.

  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.

    2016-12-01

    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.

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Naoshi Nishina

    2012-01-01

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

  13. Autoantibodies to the beta(1)-Adrenoceptor from Patients with Periodontitis as a Risk Factor for Cardiac Dysfunction

    OpenAIRE

    Segovia, Marcela; Reina, Silvia Lorena; Borda, Enri Santiago; Sterin, Leonor Josefina

    2017-01-01

    The presence of serum autoantibodies in periodontitis (P) patients against â(1)-adrenoceptor (â(1)-AR), using cardiac membranes or a synthetic â(1)-AR peptide corresponding to the second extracellular loop of human â(1)-AR as antigens, permit us to detect circulating antibody from 40 P patients but not in 20 normal individuals (control). Simultaneously, the P patients exhibited a decrease in HRV. Anti-â(1)-AR IgG titters correlated with the decrease in HRV of the same patients and the anti-â(...

  14. Alpha-fodrin autoantibodies are reliable diagnostic markers for juvenile and adult Sjogren's syndrome.

    Science.gov (United States)

    Lawind, Mohamed F; Alyasky, Ahmed; Elwan, Nahed M; Mourad, Heba; Al-Bendary, Amal

    2004-01-01

    Sjogren's syndrome (SS) is like other systemic autoimmune diseases, characterized by a large number of autoantigens and autoantibodies and infiltration of glandular tissue by predominantly CD4 T lymphocytes. The presence of certain autoantibodies is required for the diagnosis to be made, especially Anti-Ro/SSA and anti-La/SSB. The aim of this study is to investigate the prevalence of anti-alpha fodrin and its association with anti-Ro and anti-La in juvenile and adult SS. Thirteen cases with juvenile SS and 11 old SS patients were examined. Selection and classification of the patients was based on the revised European Community Criteria. The Juvenile SS group included 10 girls and 3 boys, their age ranged from 7 to 14 years. Adult SS group included 2 males and 9 female, their age ranged from 21 to 54 years. Blood samples were subjected to Erythrocyte sedimentation rate (ESR) mm/1 degree h, Complete blood count (CBC), Latex agglutination test for estimating rheumatoid factor (RF) and antinuclear antibodies (ANA), and assessment of Anti-alpha Fodrin IgG/IgA, anti-Ro and anti-La using ELISA. The two groups were matched for sex ratio. There was a significant difference of age (10.1 +/- 2.4 vs 35.1 +/- 9.3 yr) between both groups (P anti-Ro, anti-La and anti-alpha fodrin IgG/IgA autoantibodies concentration in the sera of SS patients in both groups (P > 0.05) although their levels were elevated. The percentage of detection of anti-Ro, anti- La and anti-alpha fodrin IgG and IgA antibodies in the sera of Juvenile SS was 61.5%, 53.8%, 53.8% and 61.5% respectively, while in adult SS was 63.6%, 45.5%, 45.5% and 81.8%, respectively. Anti alpha fodrin IgA and IgG were positively detected in SS patients who had negative anti-Ro and/or anti-La. The anti-alpha fodrin IgG and IgA antibodies did not significantly correlated with antibodies against Ro and La, ESR and ANA (r 0.05). The detection of anti-alpha fodrin antibodies may prove to be a useful sensitive marker for SS. Routine

  15. Effects of autoantibodies against β1-adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca2+ currents

    Institute of Scientific and Technical Information of China (English)

    Kun Liu; Yu-Hua Liao; Zhao-Hui Wang; Shu-Li Li; Ming Wang; Ling-Lan Zeng; Ming Tang

    2004-01-01

    AIM: To investigate the effects of autoantibodies against β1-adrenoceptor in hepatitis virus myocarditis on action potential and L-type Ca2+ currents.METHODS: Fifteen samples of autoantibodies against β1-adrenoceptor positive sera of patients with hepatitis virus myocarditis were obtained and IgGs were purified by octanoic acid extraction. Binding of autoantibodies against β1-adrenoceptor to guinea pig cardiac myocytes was examined by immunofiuorescence. Using the patch clamp technique,the effects on the action potential and ICa-L of guinea pig cardiac myocytes caused by autoantibodies against β1-adrenoceptor in the absence and presence of metoprolol were investigated.Cell toxicity was examined by observing cell morphology and permeability of cardiac myocytes to trypan blue.RESULTS: The specific binding of autoantibodies against β1-adrenoceptor to guinea pig cardiomyocytes was observed.Autoantibodies against β1-adrenoceptor diluted at 1:80prolonged APD20, APD50 and APD90 by 39.2%, 29.1% and 15.2% respectively, and only by 7.2%, 5.3% and 4.1%correspondingly in the presence of 1 μmol/L metoprolol.Autoantibodies against β1-adrenoceptor diluted at 1:80,1:100 and 1:120 significantly increased the ICa-L peak current amplitude at 0 mV by 55.87±4.39%, 46.33±5.01% and 29.29±4.97% in a concentration-dependent manner. In contrast, after blocking of β1-adrenoceptors (1 μmol/L metoprolol), autoantibodies against β1-adrenoceptor diluted at 1:80 induced a slight increase of ICa-L peak amplitude only by 6.81±1.61%. A large number of cardiac myocytes exposed to high concentrations of autoantibodies against β1-adrenoceptor (1:80 and 1:100) were turned into rounded cells highly permeable to trypan blue.CONCLUSION: Autoantibodies against β1-adrenoceptor may result in arrhythmias and/or impairment of myocardiums in HVM, which would be mediated by the enhancement of ICa-L.

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

    Directory of Open Access Journals (Sweden)

    Yasufumi Masaki

    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.

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

    Science.gov (United States)

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

    2007-10-01

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

  18. Paediatric Crohn disease patients with stricturing behaviour exhibit ileal granulocyte–macrophage colony-stimulating factor (GM-CSF) autoantibody production and reduced neutrophil bacterial killing and GM-CSF bioactivity

    Science.gov (United States)

    Jurickova, I; Collins, M H; Chalk, C; Seese, A; Bezold, R; Lake, K; Allmen, D; Frischer, J S; Falcone, R A; Trapnell, B C; Denson, L A

    2013-01-01

    Granulocyte–macrophage colony-stimulating factor (GM-CSF) autoantibodies are associated with stricturing behaviour in Crohn disease (CD). We hypothesized that CD ileal lamina propria mononuclear cells (LPMC) would produce GM-CSF autoantibodies and peripheral blood (PB) samples would contain GM-CSF neutralizing capacity (NC). Paediatric CD and control PBMC and ileal biopsies or LPMC were isolated and cultured and GM-CSF, immunoglobulin (Ig)G and GM-CSF autoantibodies production were measured by enzyme-linked immunosorbent assay (ELISA). Basal and GM-CSF-primed neutrophil bacterial killing and signal transducer and activator of transcription 5 (STAT5) tyrosine phosphorylation (pSTAT5) were measured by flow cytometry. GM-CSF autoantibodies were enriched within total IgG for LPMC isolated from CD ileal strictures and proximal margins compared to control ileum. Neutrophil bacterial killing was reduced in CD patients compared to controls. Within CD, neutrophil GM-CSF-dependent STAT5 activation and bacterial killing were reduced as GM-CSF autoantibodies increased. GM-CSF stimulation of pSTAT5 did not vary between controls and CD patients in washed PB granulocytes in which serum was removed. However, GM-CSF stimulation of pSTAT5 was reduced in whole PB samples from CD patients. These data were used to calculate the GM-CSF NC. CD patients with GM-CSF NC greater than 25% exhibited a fourfold higher rate of stricturing behaviour and surgery. The likelihood ratio (95% confidence interval) for stricturing behaviour for patients with elevation in both GM-CSF autoantibodies and GM-CSF NC was equal to 5 (2, 11). GM-CSF autoantibodies are produced by LPMC isolated from CD ileal resection specimens and are associated with reduced neutrophil bacterial killing. CD peripheral blood contains GM-CSF NC, which is associated with increased rates of stricturing behaviour. PMID:23600834

  19. Autoantibody-mediated cytotoxicity in paediatric opsoclonus-myoclonus syndrome is dependent on ERK-1/2 phophorylation.

    Science.gov (United States)

    Fühlhuber, Verena; Bick, Sandra; Tschernatsch, Marlene; Dharmalingam, Backialakshmi; Kaps, Manfred; Preissner, Klaus T; Blaes, Franz

    2015-12-15

    Paediatric opsoclonus-myoclonus syndrome (OMS) is in 50% of the cases associated with a neuroblastoma as a paraneoplastic syndrome and is associated with surface-binding antibodies against cerebellar granular neurons (CGN). To evaluate possible pathogenic effects of these autoantibodies on CGN we examined their influence on the MAPKinase enzymes ERK-1/2 and p38 using flow cytometry and phospho-specific antibodies. OMS IgG but not IgG from neuroblastoma without OMS or healthy controls induced phosphorylation of ERK-1/2 in cerebellar granular neurons (pERK-1/2 was associated with an increased cytotoxicity of CGN, which could be blocked by ERK-1/2 pathway inhibitor U0126. We here show that IgG-mediated anti-neuronal cytotoxicity in OMS is mediated by ERK-1/2 phosphorylation in CGN.

  20. A cross-sectional study of autoantibody profiles in the Waikato systemic sclerosis cohort, New Zealand.

    Science.gov (United States)

    Chang, Winston S J; Schollum, Joanna; White, Douglas H N; Solanki, Kamal K

    2015-11-01

    The autoantibody profiles in New Zealand systemic sclerosis patients have not previously been reported. The aim of this study was to evaluate the autoantibody profiles of patients in the Waikato Hospital Systemic Sclerosis Clinic cohort. The EUROLINE (IgG) Systemic Sclerosis panel test kit (which tests for Scl-70, CENP-A, CENP-B, RP11, RP155, Fib, NOR90, Th/To, PM100, PM75, Ku, PDGFR and Ro-52) was selected for the purpose of this study. All patients attending the Waikato Hospital Systemic Sclerosis clinic were invited to participate. These patients were categorised by systemic sclerosis subtypes [1]. Results were compared with previously published data, including the EUSTAR database. Sixty patients (56 female) were recruited, with a median age of 61 years (range 29-81 years). Forty-one had limited cutaneous systemic sclerosis (lcSSc). Of these lcSSc patients, 31 (75.6%) were positive for CENP-A and CENP-B (anti-centromere) antibodies, 12 (29.3%) for Ro-52 antibodies, 5 (12.2%) for RP11 and RP155, 4 (9.8%) for Scl-70 and 1 (2.4%) each for anti-Fib and Th/To antibodies. Fifteen patients had diffuse cutaneous systemic sclerosis (dcSSc), of which 7 patients (47.6%) were positive for RP11 and RP155, 4 (26.7%) for Scl-70. Three dcSSc patients did not have either of these two major antibodies, but of these 15 dcSSc patients, 4 patients (26.7%) were positive also for Ro-52, 2 (13.3%) for anti-Ku, and 1 (6.7%) each for anti-Fib and NOR90. Four patients had overlap syndrome (OLS), 1 had CENP-A and CENP-B antibodies, 1 had Ro-52 autoantibodies 1 had anti-Ku antibodies. Three patients had no autoantibodies. This is the first study to look at the autoantibody profile of SSc patients in New Zealand. A higher prevalence of antibodies against centromere and RNA polymerase III was demonstrated in our group compared with the EUSTAR database suggesting that antibody prevalence may vary geographically.

  1. Angiotensin receptor agonistic autoantibodies and hypertension: preeclampsia and beyond.

    Science.gov (United States)

    Xia, Yang; Kellems, Rodney E

    2013-06-21

    Hypertensive disorders are life-threatening diseases with high morbidity and mortality, affecting billions of individuals worldwide. A multitude of underlying conditions may contribute to hypertension, thus the need for a plethora of treatment options to identify the approach that best meets the needs of individual patients. A growing body of evidence indicates that (1) autoantibodies that bind to and activate the major angiotensin II type I (AT₁) receptor exist in the circulation of patients with hypertensive disorders, (2) these autoantibodies contribute to disease pathophysiology, (3) antibody titers correlate to the severity of the disease, and (4) efforts to block or remove these pathogenic autoantibodies have therapeutic potential. These autoantibodies, termed AT₁ agonistic autoantibodies have been extensively characterized in preeclampsia, a life-threatening hypertensive condition of pregnancy. As reviewed here, these autoantibodies cause symptoms of preeclampsia when injected into pregnant mice. Somewhat surprisingly, these auto antibodies also appear in 3 animal models of preeclampsia. However, the occurrence of AT₁ agonistic autoantibodies is not restricted to pregnancy. These autoantibodies are prevalent among kidney transplant recipients who develop severe transplant rejection and malignant hypertension during the first week after transplantation. AT₁ agonistic autoantibodies are also highly abundant among a group of patients with essential hypertension that are refractory to standard therapy. More recently these autoantibodies have been seen in patients with the autoimmune disease, systemic sclerosis. These 3 examples extend the clinical impact of AT₁ agonistic autoantibodies beyond pregnancy. Research reviewed here raises the intriguing possibility that preeclampsia and other hypertensive conditions are autoimmune diseases characterized by the presence of pathogenic autoantibodies that activate the major angiotensin receptor, AT₁. These

  2. 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

  3. Induction of lupus-related specific autoantibodies by non-specific inflammation caused by an intraperitoneal injection of n-hexadecane in BALB/c mice.

    Science.gov (United States)

    Kuroda, Yoshiki; Ono, Nobutaka; Akaogi, Jun; Nacionales, Dina C; Yamasaki, Yoshioki; Barker, Tolga T; Reeves, Westley H; Satoh, Minoru

    2006-02-01

    A single intraperitoneal (i.p.) injection of pristane, incomplete Freund's adjuvant (IFA), or the adjuvant oil squalene, but not high molecular weight medicinal mineral oils, induces lupus-related autoantibodies to nRNP/Sm and -Su in non-autoimmune strains of mice. This ability appears to be associated with the low molecular weight and adjuvanticity of hydrocarbon. n-Hexadecane (C(16)H(34)), which is present in petroleum, has adjuvant activity and induces arthritis in rodents like other lupus-inducing oils. In addition to dietary exposure to n-hexadecane in mineral oils, exposure also occurs via inhalation of oil mist, jet fuel, or diesel exhaust or by absorption through the skin. Since n-hexadecane is a low molecular weight adjuvant hydrocarbon oil similar to other lupus-inducing hydrocarbons, the present study examined whether it can also induce lupus-related autoantibodies in mice. Female BALB/cJ mice received a single i.p. injection of 0.5 ml of n-hexadecane, pristane, or saline (control). Pathology and serology (immunoglobulin levels, autoantibodies by immunofluorescence, immunoprecipitation, and ELISA) were examined 3 months later. Unexpectedly, all n-hexadecane-treated mice, but none in the other groups, developed inflammatory ascites within 2.5 months. n-Hexadecane induced hypergammaglobulinemia (IgG1, IgG2a), antinuclear (titer>1:160, 67%) and -cytoplasmic antibodies (58%) and autoantibodies to nRNP/Sm (25%), Su (33%), ssDNA (83%), and chromatin (100%). Therefore, non-specific inflammation caused by n-hexadecane resulted in the production of a limited set of specific autoantibodies. These previously unrecognized immunological effects of n-hexadecane may have implications in monitoring human exposure to hydrocarbons and in the pathogenesis of autoimmune diseases.

  4. Strategies for building reference standards for autoantibodies

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha

    DEFF Research Database (Denmark)

    Svenson, M; Hansen, M B; Thomsen, A R;

    2000-01-01

    High-affinity IgG autoantibodies (aAb) to IL-1alpha are among the most frequently found aAb to cytokines in humans. To establish an animal model with aAb to IL-1alpha, we immunised mice with recombinant murine IL-1alpha. Unprimed and Bacille Calmette-Guérin (BCG)-primed BALB/cA mice were vaccinated...... in mice by vaccination with recombinant murine IL-1alpha conjugated to PPD. Studies of the effects of IL-1alpha aAb in such animals may help clarify the importance of naturally occurring IL-1alpha aAb in humans and permit the evaluation of future therapies with cytokine aAb in patients...... with immunoinflammatory diseases and cytokine-dependent tumours....

  7. [Stiff-person syndrome and related autoantibodies].

    Science.gov (United States)

    Tomioka, Ryo; Tanaka, Keiko

    2013-04-01

    Central nervous system hyperexcitability disorders, known as stiff-man/person syndrome (SPS), are thought to be related to the regulatory disturbance of inhibitory synaptic transmission of motor neurons in the brainstem and spinal cord. SPS is characterized by stiffness and spasms of the axis and limbs and is divided into two clinical subgroups: classic SPS, which affects the lumbar, trunk, and proximal limb muscles, and SPS-plus syndrome. The latter comprises (1) the stiff-limb subtype, in which symptom is limited to the lower limbs; (2) jerking stiff-man syndrome, characterized by chronically progressive stiffness and myoclonus; and (3) acute-onset and progressive encephalomyelitis with rigidity and myoclonus. Almost 80% of patients with classic SPS harbor autoantibodies against glutamic acid decarboxylase 65 (GAD65). In approximately 30-40% of patients, SPS accompanies type I diabetes, and anti-GAD65 antibodies are detected frequently in type I diabetes. However, the antibody-recognizing epitopes might be different between SPS and diabetes. Other autoantibodies against glycine receptor α1 (12% of patients with SPS) and GABA(A)-receptor associated protein (70% of patients with SPS) have been reported. In paraneoplastic SPS, anti-amphiphysin antibodies have been shown in patients with breast cancer or small cell lung cancer. One case of mediastinal tumor with anti-gephyrin antibodies has also been reported. However, the roles of these autoantibodies in the pathomechanisms of SPS have not yet been elucidated.

  8. Characterisation of osteoprotegerin autoantibodies in coeliac disease.

    Science.gov (United States)

    Real, Ana; Gilbert, Nick; Hauser, Barbara; Kennedy, Nick; Shand, Alan; Gillett, Helen; Gillett, Peter; Goddard, Clive; Cebolla, Ángel; Sousa, Carolina; Fraser, William D; Satsangi, Jack; Ralston, Stuart H; Riches, Philip L

    2015-08-01

    Autoantibodies neutralising the effect of the bone regulatory cytokine osteoprotegerin (OPG) have been described in a patient with severe osteoporosis and coeliac disease. This study aimed to determine the prevalence and epitope specificity of autoantibodies to OPG in patients with coeliac disease, and correlate their presence with bone mineral density. A direct enzyme-linked immunosorbent assay was developed and used to screen patients with coeliac disease for autoantibodies to OPG. Recombinant fragments of OPG were made to evaluate the epitope specificity and affinity of these antibodies. Phenotype information of the patients was obtained by case note review. Raised titres of antibodies to OPG were found in 7/71 (9.8 %) patients with coeliac disease, compared with 1/72 (1.4 %) non-coeliac osteoporosis clinic control patients (p coeliac patients on univariate (p coeliac disease and are independently associated with lower bone mineral density Z-scores of the hip. Further work is required to establish the clinical utility of testing for OPG antibodies.

  9. AE Aquarii represents a new subclass of Cataclysmic Variables

    CERN Document Server

    Ikhsanov, N R

    2012-01-01

    We analyze properties of the unique nova-like star AE Aquarii identified with a close binary system containing a red dwarf and a very fast rotating magnetized white dwarf. It cannot be assigned to any of the three commonly adopted sub-classes of Cataclysmic Variables: Polars, Intermediate Polars, and Accreting non-magnetized White Dwarfs. Our study has shown that the white dwarf in AE Aqr is in the ejector state and its dipole magnetic moment is $\\mu ~ 1.5 \\times 10^{34} G cm^3$. It switched into this state due to intensive mass exchange between the system components during a previous epoch. A high rate of disk accretion onto the white dwarf surface resulted in temporary screening of its magnetic field and spin-up of the white dwarf to its present spin period. Transition of the white dwarf to the ejector state had occurred at a final stage of the spin-up epoch as its magnetic field emerged from the accreted plasma due to diffusion. In the frame of this scenario AE Aqr represents a missing link in the chain of...

  10. Search for Type Ia supernova NUV-optical subclasses

    Science.gov (United States)

    Cinabro, David; Scolnic, Daniel; Kessler, Richard; Li, Ashley; Miller, Jake

    2017-04-01

    In response to a recently reported observation of evidence for two classes of Type Ia supernovae (SNe Ia) distinguished by their brightness in the rest-frame near-ultraviolet (NUV), we search for the phenomenon in publicly available light-curve data. We use the SNANA supernova analysis package to simulate SN Ia light curves in the Sloan Digital Sky Survey (SDSS) Supernova Search and the Supernova Legacy Survey (SNLS) with a model of two distinct ultraviolet classes of SNe Ia and a conventional model with a single broad distribution of SN-Ia ultraviolet brightnesses. We compare simulated distributions of rest-frame colours with these two models to those observed in 158 SNe Ia in the SDSS and SNLS data. The SNLS sample of 99 SNe Ia is in clearly better agreement with a model with one class of SN Ia light curves and shows no evidence for distinct NUV sub-classes. The SDSS sample of 59 SNe Ia with poorer colour resolution does not distinguish between the two models.

  11. Search For Type Ia Supernova NUV-Optical Subclasses

    CERN Document Server

    Cinabro, David; Kessler, Richard; Li, Ashley; Miller, Jake

    2016-01-01

    In response to a recently reported observation of evidence for two classes of Type Ia Supernovae (SNe Ia) distinguished by their brightness in the rest-frame near ultraviolet (NUV), we search for the phenomenon in publicly available light-curve data. We use the SNANA supernova analysis package to simulate SN Ia-light curves in the Sloan Digital Sky Survey Supernova Search (SDSS) and the Supernova Legacy Survey (SNLS) with a model of two distinct ultraviolet classes of SNe Ia and a conventional model with a single broad distribution of SN-Ia ultraviolet brightnesses. We compare simulated distributions of rest-frame colors with these two models to those observed in 158 SNe Ia in the SDSS and SNLS data. The SNLS sample of 99 SNe Ia is in clearly better agreement with a model with one class of SN Ia light curves and shows no evidence for distinct NUV sub-classes. The SDSS sample of 59 SNe Ia with poorer color resolution does not distinguish between the two models.

  12. [Autoantibodies to glutamate and GABA in opiate addiction].

    Science.gov (United States)

    Vetrile, L A; Fomina, V G; Nevidimova, T I; Vetlugina, T P; Batukhtina, E I; Savochkina, D N; Zakharova, I A; Davydova, T V

    2015-01-01

    Blood serum from 129 patients with opium addiction at different stages of the disease and 63 donors (control group) was examined for the presence of autoantibodies to the exciting and inhibitory amino acids glutamate and GABA. It was shown enhanced production of autoantibodies to glutamate and GABA. Dependence of the level and frequency of detec- tion of autoantibodies to glutamate and GABA on the stage of the disease was revealed.

  13. IgG Binding Characteristics of Rhesus Macaque FcγR.

    Science.gov (United States)

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

    2016-10-01

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

  14. Autoantibody profiles in autoimmune hepatitis and chronic hepatitis C identifies similarities in patients with severe disease

    Science.gov (United States)

    Amin, Kawa; Rasool, Aram H; Hattem, Ali; Al-Karboly, Taha AM; Taher, Taher E; Bystrom, Jonas

    2017-01-01

    AIM To determine how the auto-antibodies (Abs) profiles overlap in chronic hepatitis C infection (CHC) and autoimmune hepatitis (AIH) and correlate to liver disease. METHODS Levels of antinuclear Ab, smooth muscle antibody (SMA) and liver/kidney microsomal-1 (LKM-1) Ab and markers of liver damage were determined in the sera of 50 patients with CHC infection, 20 AIH patients and 20 healthy controls using enzyme linked immunosorbent assay and other immune assays. RESULTS We found that AIH patients had more severe liver disease as determined by elevation of total IgG, alkaline phosphatase, total serum bilirubin and serum transaminases and significantly higher prevalence of the three non-organ-specific autoantibodies (auto-Abs) than CHC patients. Antinuclear Ab, SMA and LKM-1 Ab were also present in 36% of CHC patients and related to disease severity. CHC cases positive for auto-Abs were directly comparable to AIH in respect of most markers of liver damage and total IgG. These cases had longer disease duration compared with auto-Ab negative cases, but there was no difference in gender, age or viral load. KLM-1+ Ab CHC cases showed best overlap with AIH. CONCLUSION Auto-Ab levels in CHC may be important markers of disease severity and positive cases have a disease similar to AIH. Auto-Abs might have a pathogenic role as indicated by elevated markers of liver damage. Future studies will unravel any novel associations between these two diseases, whether genetic or other. PMID:28293081

  15. Autoantibodies against Muscarinic Receptors in Breast Cancer: Their Role in Tumor Angiogenesis

    Science.gov (United States)

    Lombardi, María Gabriela; Negroni, María Pía; Pelegrina, Laura Tatiana; Castro, María Ester; Fiszman, Gabriel L.; Azar, María Eugenia; Morgado, Carlos Cresta; Sales, María Elena

    2013-01-01

    The presence of autoantibodies in cancer has become relevant in recent years. We demonstrated that autoantibodies purified from the sera of breast cancer patients activate muscarinic acetylcholine receptors in tumor cells. Immunoglobulin G (IgG) from breast cancer patients in T1N0Mx stage (tumor size≤2 cm, without lymph node metastasis) mimics the action of the muscarinic agonist carbachol stimulating MCF-7 cell proliferation, migration and invasion. Angiogenesis is a central step in tumor progression because it promotes tumor invasion and metastatic spread. Vascular endothelial growth factor-A (VEGF-A) is the main angiogenic mediator, and its levels have been correlated with poor prognosis in cancer. The aim of the present work was to investigate the effect of T1N0Mx-IgG on the expression of VEGF-A, and the in vivo neovascular response triggered by MCF-7 cells, via muscarinic receptor activation. We demonstrated that T1N0Mx-IgG (10−8 M) and carbachol (10−9 M) increased the constitutive expression of VEGF-A in tumor cells, effect that was reverted by the muscarinic antagonist atropine. We also observed that T1N0Mx-IgG and carbachol enhanced the neovascular response produced by MCF-7 cells in the skin of NUDE mice. The action of IgG or carbachol was reduced in the presence of atropine. In conclusion, T1N0Mx-IgG and carbachol may promote VEGF-A production and neovascularization induced by breast tumor cells via muscarinic receptors activation. These effects may be accelerating breast tumor progression. PMID:23460876

  16. Autoantibodies against muscarinic receptors in breast cancer: their role in tumor angiogenesis.

    Directory of Open Access Journals (Sweden)

    María Gabriela Lombardi

    Full Text Available The presence of autoantibodies in cancer has become relevant in recent years. We demonstrated that autoantibodies purified from the sera of breast cancer patients activate muscarinic acetylcholine receptors in tumor cells. Immunoglobulin G (IgG from breast cancer patients in T1N0Mx stage (tumor size≤2 cm, without lymph node metastasis mimics the action of the muscarinic agonist carbachol stimulating MCF-7 cell proliferation, migration and invasion. Angiogenesis is a central step in tumor progression because it promotes tumor invasion and metastatic spread. Vascular endothelial growth factor-A (VEGF-A is the main angiogenic mediator, and its levels have been correlated with poor prognosis in cancer. The aim of the present work was to investigate the effect of T1N0Mx-IgG on the expression of VEGF-A, and the in vivo neovascular response triggered by MCF-7 cells, via muscarinic receptor activation. We demonstrated that T1N0Mx-IgG (10(-8 M and carbachol (10(-9 M increased the constitutive expression of VEGF-A in tumor cells, effect that was reverted by the muscarinic antagonist atropine. We also observed that T1N0Mx-IgG and carbachol enhanced the neovascular response produced by MCF-7 cells in the skin of NUDE mice. The action of IgG or carbachol was reduced in the presence of atropine. In conclusion, T1N0Mx-IgG and carbachol may promote VEGF-A production and neovascularization induced by breast tumor cells via muscarinic receptors activation. These effects may be accelerating breast tumor progression.

  17. Autoantibodies against muscarinic receptors in breast cancer: their role in tumor angiogenesis.

    Science.gov (United States)

    Lombardi, María Gabriela; Negroni, María Pía; Pelegrina, Laura Tatiana; Castro, María Ester; Fiszman, Gabriel L; Azar, María Eugenia; Morgado, Carlos Cresta; Sales, María Elena

    2013-01-01

    The presence of autoantibodies in cancer has become relevant in recent years. We demonstrated that autoantibodies purified from the sera of breast cancer patients activate muscarinic acetylcholine receptors in tumor cells. Immunoglobulin G (IgG) from breast cancer patients in T1N0Mx stage (tumor size≤2 cm, without lymph node metastasis) mimics the action of the muscarinic agonist carbachol stimulating MCF-7 cell proliferation, migration and invasion. Angiogenesis is a central step in tumor progression because it promotes tumor invasion and metastatic spread. Vascular endothelial growth factor-A (VEGF-A) is the main angiogenic mediator, and its levels have been correlated with poor prognosis in cancer. The aim of the present work was to investigate the effect of T1N0Mx-IgG on the expression of VEGF-A, and the in vivo neovascular response triggered by MCF-7 cells, via muscarinic receptor activation. We demonstrated that T1N0Mx-IgG (10(-8) M) and carbachol (10(-9) M) increased the constitutive expression of VEGF-A in tumor cells, effect that was reverted by the muscarinic antagonist atropine. We also observed that T1N0Mx-IgG and carbachol enhanced the neovascular response produced by MCF-7 cells in the skin of NUDE mice. The action of IgG or carbachol was reduced in the presence of atropine. In conclusion, T1N0Mx-IgG and carbachol may promote VEGF-A production and neovascularization induced by breast tumor cells via muscarinic receptors activation. These effects may be accelerating breast tumor progression.

  18. Elevated serum titers of proinflammatory cytokines and CNS autoantibodies in patients with chronic spinal cord injury.

    Science.gov (United States)

    Hayes, K C; Hull, T C L; Delaney, G A; Potter, P J; Sequeira, K A J; Campbell, K; Popovich, P G

    2002-06-01

    This study characterized the proinflammatory cytokines, interleukin-2 (IL-2) and tumor necrosis factor alpha (TNFalpha), the antiinflammatory cytokines, IL-4 and IL-10, autoantibodies specific for GM1 ganglioside (anti-GM1), IgG and IgM, and myelin-associated glycoprotein (anti-MAG), in the sera of infection-free, chronic (>12 months), traumatically injured SCI patients (n = 24). Healthy able-bodied subjects (n = 26) served as controls. The proinflammatory cytokines and anti-GM1 antibodies were of particular interest as they have been implicated in an autoimmune "channelopathy" component to central and peripheral conduction deficits in various chronic neuroinflammatory diseases. Antibody and cytokine titers were established using enzyme-linked immunosorbent assays (ELISA). The mean anti-GM(1) (IgM) titer value for the SCI group was significantly higher (p proinflammatory cytokines relative to control values. These results provide preliminary support for the hypothesis that chronic immunological activation in the periphery occurs in a subpopulation of chronic SCI patients. It remains to be established whether elevated serum titers of proinflammatory cytokines and autoantibodies against GM1 are beneficial to the patients or whether they are surrogate markers of a channelopathy that compounds the neurological impairment associated with traumatic axonopathy or myelinopathy.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. An impedimetric immunosensor for the detection of autoantibodies directed against gliadins.

    Science.gov (United States)

    Balkenhohl, T; Lisdat, F

    2007-04-01

    An immunosensor has been developed for the detection of autoantibodies directed against wheat gliadin, a protein fraction of cereal gluten which is involved in celiac disease. The immunosensor is based on the immobilization of gliadins onto gold electrodes covered with a polyelectrolyte layer of poly(4-styrenesulfonic acid sodium salt). The immobilization was monitored by quartz crystal microbalance (QCM) analysis. The antigen-antibody interaction signal was amplified by an incubation step with peroxidase-labeled immunoglobulins and subsequent peroxidase-catalyzed oxidation of 3-amino-9-ethylcarbazole (AEC). Changes in the insulating properties of the electrode layer were measured by electrochemical impedance spectroscopy (EIS) in the presence of ferri/ferro-cyanide. Impedance spectra could be fitted to a Randles equivalent circuit with high accuracy. Exposing the sensor electrodes to various antigliadin antibody concentrations resulted in proportional changes in the charge transfer resistance. A calibration graph for the detection of antigliadin antibodies was established for antibody concentrations between 10(-8) and 10(-6) M. Finally, the sensor was used for the determination of antigliadin autoantibodies of the IgG and IgA type in several human sera.

  1. Autoantibody Standardization in the Netherlands The Past, the Present, and the Future

    NARCIS (Netherlands)

    Damoiseaux, Jan; Tervaert, Jan Willem Cohen; Derksen, Ronald; Hamann, Dorte; Hooijkaas, Herbert; Klasen, Ina; Kallenberg, Cees; Limburg, Pieter; Smeenk, Ruud; Shoenfeld, Y; Gershwin, ME

    2009-01-01

    Several initiatives have been undertaken, independent of the European Autoantibody Standardization Initiative (EASI), to standardize autoantibodies in the Netherlands. The Dutch EASI team has made an inventory of which initiatives on autoantibody standardization are already available and what future

  2. IgG4-related sclerosing disease

    Institute of Scientific and Technical Information of China (English)

    Terumi Kamisawa; Atsutake Okamoto

    2008-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-02-01

    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.

  4. Autoantibodies to Multiple Epitopes on the Non-Collagenous-1 Domain of Type VII Collagen Induce Blisters.

    Science.gov (United States)

    Vorobyev, Artem; Ujiie, Hideyuki; Recke, Andreas; Buijsrogge, Jacqueline J A; Jonkman, Marcel F; Pas, Hendri H; Iwata, Hiroaki; Hashimoto, Takashi; Kim, Soo-Chan; Hoon Kim, Jong; Groves, Richard; Samavedam, Unni; Gupta, Yask; Schmidt, Enno; Zillikens, Detlef; Shimizu, Hiroshi; Ludwig, Ralf J

    2015-06-01

    Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease of the skin and mucous membranes, characterized by autoantibodies against type VII collagen (COL7), a major component of anchoring fibrils. Different clinical EBA phenotypes are described, including mechanobullous and inflammatory variants. Most EBA patients' sera react with epitopes located within the non-collagenous 1 (NC1) domain of human COL7. However, it has remained unclear whether antibody binding to these different epitopes is pathogenically relevant. To address this issue, we generated recombinant proteins covering the entire NC1 domain. IgG reactivity with these proteins was analyzed in sera of 69 EBA patients. Most recognized clusters of epitopes throughout the NC1 domain. No correlation was detected between antibody specificity and clinical phenotype. To study the pathogenicity of antibodies specific to different NC1 subdomains, rabbit antibodies were generated. All these antibodies caused dermal-epidermal separation ex vivo. Antibodies against two of these subdomains were injected into mice carrying null mutations of mouse COL7 and the human COL7 transgene and induced subepidermal blisters. We here document that autoantibodies to COL7, independent of the targeted epitopes, induce blisters both ex vivo and in vivo. In addition, using COL7-humanized mice, we provide in vivo evidence of pathogenicity of autoantibodies binding to human COL7.

  5. 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.

  6. Agonistic Anti-PDGF Receptor Autoantibodies from Patients with Systemic Sclerosis Impact Human Pulmonary Artery Smooth Muscle Cells Function In Vitro

    Science.gov (United States)

    Svegliati, Silvia; Amico, Donatella; Spadoni, Tatiana; Fischetti, Colomba; Finke, Doreen; Moroncini, Gianluca; Paolini, Chiara; Tonnini, Cecilia; Grieco, Antonella; Rovinelli, Marina; Gabrielli, Armando

    2017-01-01

    One of the earliest events in the pathogenesis of systemic sclerosis (SSc) is microvasculature damage with intimal hyperplasia and accumulation of cells expressing PDGF receptor. Stimulatory autoantibodies targeting PDGF receptor have been detected in SSc patients and demonstrated to induce fibrosis in vivo and convert in vitro normal fibroblasts into SSc-like cells. Since there is no evidence of the role of anti-PDGF receptor autoantibodies in the pathogenesis of SSc vascular lesions, we investigated the biologic effect of agonistic anti-PDGF receptor autoantibodies from SSc patients on human pulmonary artery smooth muscle cells and the signaling pathways involved. The synthetic (proliferation, migration, and type I collagen gene α1 chain expression) and contractile (smooth muscle-myosin heavy chain and smooth muscle-calponin expression) profiles of human pulmonary artery smooth muscle cells were assessed in vitro after incubation with SSc anti-PDGF receptors stimulatory autoantibodies. The role of reactive oxygen species, NOX isoforms, and mammalian target of rapamycin (mTOR) was investigated. Human pulmonary artery smooth muscle cells acquired a synthetic phenotype characterized by higher growth rate, migratory activity, gene expression of type I collagen α1 chain, and less expression of markers characteristic of the contractile phenotype such as smooth muscle-myosin heavy chain and smooth muscle-calponin when stimulated with PDGF and autoantibodies against PDGF receptor, but not with normal IgG. This phenotypic profile is mediated by increased generation of reactive oxygen species and expression of NOX4 and mTORC1. Our data indicate that agonistic anti-PDGF receptor autoantibodies may contribute to the pathogenesis of SSc intimal hyperplasia. PMID:28228756

  7. Discovery of a new subclass of alpha-conotoxins in the venom of Conus australis

    Digital Repository Service at National Institute of Oceanography (India)

    Lebbe, E.K.M.; Peigneur, S.; Maiti, M.; Mille, B.G.; Prabhadevi; Ravichandran, S.; Lescrinier, E.; Waelkens, E.; DeSouza, L.; Herdewijn, P.; Tytgat, J.

    -conotoxins, acts on nicotinic acetylcholine receptors (nAChRs) which dysfunctions play important roles in pathologies such as epilepsy, myasthenic syndromes, schizophrenia, Parkinson's disease and Alzheimer's disease. Here we define a new subclass of the alpha...

  8. On Certain New Subclass of Meromorphic Close-to-Convex Functions

    Directory of Open Access Journals (Sweden)

    Jing-Ping Yi

    2013-01-01

    Full Text Available We introduce a certain new subclass of meromorphic close-to-convex functions. Such results as inclusion relationship, coefficient inequalities, distortion, and growth theorems for this class of functions are derived.

  9. 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. PMID:26617921

  10. 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...

  11. 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.

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

    Science.gov (United States)

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

    2003-07-01

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

  13. Platelet Apoptosis in Adult Immune Thrombocytopenia: Insights into the Mechanism of Damage Triggered by Auto-Antibodies

    Science.gov (United States)

    Goette, Nora P.; Glembotsky, Ana C.; Lev, Paola R.; Grodzielski, Matías; Contrufo, Geraldine; Pierdominici, Marta S.; Espasandin, Yesica R.; Riveros, Dardo; García, Alejandro J.; Molinas, Felisa C.; Heller, Paula G.

    2016-01-01

    Mechanisms leading to decreased platelet count in immune thrombocytopenia (ITP) are heterogeneous. This study describes increased platelet apoptosis involving loss of mitochondrial membrane potential (ΔΨm), caspase 3 activation (aCasp3) and phosphatidylserine (PS) externalization in a cohort of adult ITP patients. Apoptosis was not related to platelet activation, as PAC-1 binding, P-selectin exposure and GPIb-IX internalization were not increased. Besides, ITP platelets were more sensitive to apoptotic stimulus in terms of aCasp3. Incubation of normal platelets with ITP plasma induced loss of ΔΨm, while PS exposure and aCasp3 remained unaltered. The increase in PS exposure observed in ITP platelets could be reproduced in normal platelets incubated with ITP plasma by adding normal CD3+ lymphocytes to the system as effector cells. Addition of leupeptin -a cathepsin B inhibitor- to this system protected platelets from apoptosis. Increased PS exposure was also observed when normal platelets and CD3+ lymphocytes were incubated with purified IgG from ITP patients and was absent when ITP plasma was depleted of auto-antibodies, pointing to the latter as responsible for platelet damage. Apoptosis was present in platelets from all patients carrying anti-GPIIb-IIIa and anti-GPIb auto-antibodies but was absent in the patient with anti-GPIa-IIa auto-antibodies. Platelet damage inversely correlated with platelet count and decreased during treatment with a thrombopoietin receptor agonist. These results point to a key role for auto-antibodies in platelet apoptosis and suggest that antibody-dependent cell cytotoxicity is the mechanism underlying this phenomenon. PMID:27494140

  14. 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)....

  15. 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)....

  16. 21 CFR 866.5660 - Multiple autoantibodies immunological test system.

    Science.gov (United States)

    2010-04-01

    .... Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Multiple autoantibodies immunological test system. 866.5660 Section 866.5660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

  17. Musculoskeletal manifestations and autoantibodies in children and adolescents with leprosy

    OpenAIRE

    Luciana Neder; Daniel A. Rondon; Silvana S. Cury; Clovis A. da Silva

    2014-01-01

    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 perfor...

  18. Regulatory and pathogenetic mechanisms of autoantibodies in SLE

    NARCIS (Netherlands)

    Radic, M.; Herrmann, M.; Vlag, J. van der; Rekvig, O.P.

    2011-01-01

    In the 53 years since the discovery of anti-DNA autoantibodies in lupus [1, 2, 3] , recalcitrant questions have been pondered and possible answers have been debated. The discovery of anti-DNA autoantibodies presented many puzzles: How is immunological tolerance to native B-form DNA broken? What elic

  19. How Relevant Are GFAP Autoantibodies in Autism and Tourette Syndrome?

    Science.gov (United States)

    Kirkman, Nikki J.; Libbey, Jane E.; Sweeten, Thayne L.; Coon, Hilary H.; Miller, Judith N.; Stevenson, Edward K.; Lainhart, Janet E.; McMahon, William M.; Fujinami, Robert S.

    2008-01-01

    Controversy exists over the role of autoantibodies to central nervous system antigens in autism and Tourette Syndrome. We investigated plasma autoantibody titers to glial fibrillary acidic protein (GFAP) in children with classic onset (33) and regressive onset (26) autism, controls (25, healthy age- and gender-matched) and individuals with…

  20. Infliximab-induced autoantibodies: a multicenter study.

    Science.gov (United States)

    Vaz, João Luiz Pereira; Fernandes, Vander; Nogueira, Felipe; Arnóbio, Adriano; Levy, Roger A

    2016-02-01

    The purpose of this study was to assess autoantibody incidence in patients treated with infliximab for various diseases, and the development of autoimmune diseases using a multicenter, longitudinal, open-label, phase IV observational study. All patients received anti-tumor necrosis factor (anti-TNF) according to local treatment guidelines. The autoantibodies assessed before and after infliximab treatment were ANA, anti-Sm, anti-dsDNA, anticardiolipin IgM/IgG, anti-Scl70, anti-centromere B, anti-chromatin, anti-ribosomal P, anti-Sm-RNP, anti-RNP A, anti-RNP 68 kD, anti-La/SSB, anti-Ro/SSA 52 kD and 60 kD, and anti-Jo1. ANA was determined by indirect immunofluorescence on HEp-2 cells (INOVA); the remaining was assessed using BioPlexTM 2200. The Fisher exact test, Wilcoxon test, and the McNemar were used when appropriate.Two hundred eighty-six patients were included (139 with rheumatoid arthritis, 77 with ankylosing spondylitis, 29 with inflammatory bowel disease, 27 with psoriatic arthritis, and 14 with psoriasis), 167 females and 119 males, with mean age of 46.3 years. Subjects received at least five infusions of infliximab (6-month treatment). A significant difference was observed in antinuclear antibody (ANA) detection between samplings (p = 0.001). Among patients that had ANA before treatment (n = 92), six became ANA-negative, 48 had increased titers, 29 maintained, and nine decreased titers after treatment; a total of 186 patients had a positive ANA after treatment. Fine speckled nuclear pattern was most commonly observed (both before and after infliximab treatment). The number of patients with anti-dsDNA had a statistically significant increase (p = 0.003). No significant differences were noted for anticardiolipin and the remaining autoantibodies tested. Among the 286 patients included in the study, only one (0.35 %) showed clinical signs of drug-induced lupus, presenting elevated ANA and anti-dsDNA titers that normalized once treatment was

  1. Autoantibody recognition mechanisms of MUC1

    Science.gov (United States)

    Phillips, J. C.

    2017-03-01

    The most cost-effective blood-based, noninvasive molecular early cancer biomarkers are based on p53 epitopes and MUC1 tandem repeats. Here we use dimensionally compressed bioinformatic fractal scaling analysis to compare the two distinct and comparable probes, which examine different sections of the autoantibody population, achieving combined sensitivities of order 50%. We explain the experimental observation that glycosylation does not enhance, and can depress, the sensitivity of MUC1 tandem repeat biomarkers. We propose a possible supplementary MUC1 epitope in the SEA region outside the tandem repeats.

  2. Cytokine vaccination: neutralising IL-1alpha autoantibodies induced by immunisation with homologous IL-1alpha

    DEFF Research Database (Denmark)

    Svenson, M; Hansen, M B; Thomsen, Allan Randrup;

    2000-01-01

    High-affinity IgG autoantibodies (aAb) to IL-1alpha are among the most frequently found aAb to cytokines in humans. To establish an animal model with aAb to IL-1alpha, we immunised mice with recombinant murine IL-1alpha. Unprimed and Bacille Calmette-Guérin (BCG)-primed BALB/cA mice were vaccinated...... in mice by vaccination with recombinant murine IL-1alpha conjugated to PPD. Studies of the effects of IL-1alpha aAb in such animals may help clarify the importance of naturally occurring IL-1alpha aAb in humans and permit the evaluation of future therapies with cytokine aAb in patients...... with IL-1alpha coupled to purified protein derivative of tuberculin (PPD). Both unprimed and primed animals developed IgG aAb to IL-1alpha. These aAb persisted at high levels more than 100 days after vaccination and did not cross-react with murine IL-1beta. The induced anti-IL-1alpha aAb inhibited binding...

  3. Binding of circulating autoantibodies in breast cancer to native and peroxynitrite-modified RNA

    Institute of Scientific and Technical Information of China (English)

    Sheereen TARANNUM; Zarina ARIF; Khursheed ALAM

    2013-01-01

    Peroxynitrite (ONOO-) is a powerful oxidant and nitrosative agent and has in vivo existence.The half life of ONOO-at physiological pH is less than 1 s.It can react with nucleic acids,proteins,lipoproteins,saccharides,cardiolipin,etc.,and can modify their native structures.Action of ONOO-,synthesized in the authors' laboratory by a rapid quenched flow process,on structural changes of commercially available RNA was studied by ultraviolet (UV),fluorescence,and agarose gel electrophoresis.Compared to native RNA,the ONOO--modified RNA showed hyperchromicity at 260 nm.Furthermore,the ethidium bromide (EtBr) assisted emission intensities of ONOO--modified RNA samples were found to be lower than the emission intensity of native RNA-EtBr complex.Agarose gel electrophoresis of ONOO--modified RNA showed a gradual decrease in band intensities compared to native RNA,an observation clearly due to the poor intercalation of EtBr with ONOO--modified RNA.Native and ONOO--modified RNA samples were used as an antigen to detect autoantibodies in sera of patients with clinically defined breast cancer.Both direct binding and inhibition enzyme-linked immunosorbent assay (ELISA) confirmed the prevalence of native and 0.8 mmol/L ONOO--modified RNA specific autoantibodies in breast cancer patients.Moreover,the progressive retardation in the mobility of immune complexes formed with native or 0.8 mmol/L ONOO--modified RNA and affinity purified immunoglobulin G (IgG) from sera of breast cancer patients supports the findings of the direct binding and inhibition ELISAs.The peroxynitrite treatment to RNA at a higher concentration appears to have damaged or destroyed the typical epitopes on RNA and thus there was a sharp decrease in autoantibodies binding to 1.4 mmol/L ONOO--modified RNA.It may be interpreted that cellular nitrosative stress can modify and confer immunogenicity on RNA molecules.Higher concentrations of nitrogen reactive species can be detrimental to RNA.However,the emergence of

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

    Science.gov (United States)

    Dechavanne, Célia; Guillonneau, François; Chiappetta, Giovanni; Sago, Laïla; Lévy, Prisca; Salnot, Virginie; Guitard, Evelyne; Ehrenmann, François; Broussard, Cédric; Chafey, Philippe; Le Port, Agnès; Vinh, Joëlle; Mayeux, Patrick; Dugoujon, Jean-Michel; Lefranc, Marie-Paule; Migot-Nabias, Florence

    2012-01-01

    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.

  5. 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.

  6. Critical Role of the Neonatal Fc Receptor (FcRn) in the Pathogenic Action of Antimitochondrial Autoantibodies Synergizing with Anti-desmoglein Autoantibodies in Pemphigus Vulgaris.

    Science.gov (United States)

    Chen, Yumay; Chernyavsky, Alex; Webber, Robert J; Grando, Sergei A; Wang, Ping H

    2015-09-25

    Pemphigus vulgaris (PV) is a life-long, potentially fatal IgG autoantibody-mediated blistering disease targeting mucocutaneous keratinocytes (KCs). PV patients develop pathogenic anti-desmoglein (Dsg) 3 ± 1 and antimitochondrial antibodies (AMA), but it remained unknown whether and how AMA enter KCs and why other cell types are not affected in PV. Therefore, we sought to elucidate mechanisms of cell entry, trafficking, and pathogenic action of AMA in PV. We found that PVIgGs associated with neonatal Fc receptor (FcRn) on the cell membrane, and the PVIgG-FcRn complexes entered KCs and reached mitochondria where they dissociated. The liberated AMA altered mitochondrial membrane potential, respiration, and ATP production and induced cytochrome c release, although the lack or inactivation of FcRn abolished the ability of PVIgG to reach and damage mitochondria and to cause detachment of KCs. The assays of mitochondrial functions and keratinocyte adhesion demonstrated that although the pathobiological effects of AMA on KCs are reversible, they become irreversible, leading to epidermal blistering (acantholysis), when AMA synergize with anti-Dsg antibodies. Thus, it appears that AMA enter a keratinocyte in a complex with FcRn, become liberated from the endosome in the cytosol, and are trafficked to the mitochondria, wherein they trigger pro-apoptotic events leading to shrinkage of basal KCs uniquely expressing FcRn in epidermis. During recovery, KCs extend their cytoplasmic aprons toward neighboring cells, but anti-Dsg antibodies prevent assembly of nascent desmosomes due to steric hindrance, thus rendering acantholysis irreversible. In conclusion, FcRn is a common acceptor protein for internalization of AMA and, perhaps, for PV autoantibodies to other intracellular antigens, and PV is a novel disease paradigm for investigating and elucidating the role of FcRn in this autoimmune disease and possibly other autoimmune diseases.

  7. Age-dependent increase of blood-brain barrier permeability and neuron-binding autoantibodies in S100B knockout mice.

    Science.gov (United States)

    Wu, Hao; Brown, Eric V; Acharya, Nimish K; Appelt, Denah M; Marks, Alexander; Nagele, Robert G; Venkataraman, Venkat

    2016-04-15

    S100B is a calcium-sensor protein that impacts multiple signal transduction pathways. It is widely considered to be an important biomarker for several neuronal diseases as well as blood-brain barrier (BBB) breakdown. In this report, we demonstrate a BBB deficiency in mice that lack S100B through detection of leaked Immunoglobulin G (IgG) in the brain parenchyma. IgG leaks and IgG-binding to selected neurons were observed in S100B knockout (S100BKO) mice at 6 months of age but not at 3 months. By 9 months, IgG leaks persisted and the density of IgG-bound neurons increased significantly. These results reveal a chronic increase in BBB permeability upon aging in S100BKO mice for the first time. Moreover, coincident with the increase in IgG-bound neurons, autoantibodies targeting brain proteins were detected in the serum via western blots. These events were concurrent with compromise of neurons, increase of activated microglia and lack of astrocytic activation as evidenced by decreased expression of microtubule-associated protein type 2 (MAP2), elevated number of CD68 positive cells and unaltered expression of glial fibrillary acidic protein (GFAP) respectively. Results suggest a key role for S100B in maintaining BBB functional integrity and, further, propose the S100BKO mouse as a valuable model system to explore the link between chronic functional compromise of the BBB, generation of brain-reactive autoantibodies and neuronal dysfunctions.

  8. 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.

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

    Science.gov (United States)

    Pisani, Francesco; Settanni, Paolo; Rosito, Stefania; Mola, Maria Grazia; Iorio, Raffaele; Tortorella, Carla; Ruggieri, Maddalena; Trojano, Maria; Svelto, Maria; Frigeri, Antonio; Nicchia, Grazia Paola

    2015-01-01

    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.

  10. 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

    PURPOSE: To establish and validate a rapid, cost-effective and accurate screening assay for the simultaneous testing of human naturally occurring anti-cytokine autoantibodies (c-aAb) targeting interleukin-1α (IL-1α), interleukin-6 (IL-6), interleukin-10 (IL-10), granulocyte-macrophage colony...... 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...

  11. Cancer-associated autoantibodies to MUC1 and MUC4--a blinded case–control study of colorectal cancer in UK collaborative trial of ovarian cancer screening

    DEFF Research Database (Denmark)

    Pedersen, Johannes W; Gentry-Maharaj, Aleksandra; Nøstdal, Alexander;

    2014-01-01

    of colorectal cancer diagnosis and healthy controls. Subsequently, the selected biomarkers were evaluated in a blinded nested case–control study using stored serum samples from among the 50,640 women randomized to the multimodal arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), where...... women gave annual blood samples for several years. Cases were 97 postmenopausal women who developed colorectal cancer after recruitment and were age-matched to 97 women without any history of cancer. MUC1-STn and MUC1-Core3 IgG autoantibodies identified cases with 8.2 and 13.4% sensitivity, respectively......, at 95% specificity. IgA to MUC4 glycoforms were unable to discriminate between cases and controls in the UKCTOCS sera. Additional analysis was undertaken by combining the data of MUC1-STn and MUC1-Core3 with previously generated data on autoantibodies to p53 peptides, which increased the sensitivity...

  12. Heterogeneity of Brunsting-Perry type pemphigoid: a case showing blister formation at the lamina lucida, immune deposition beneath the lamina densa and autoantibodies against the 290-kD polypeptide along the lamina densa.

    Science.gov (United States)

    Minato, Haruka; Ishii, Norito; Fukuda, Shunpei; Wakasa, Tomoko; Wakasa, Ken'ichi; Sogame, Ryosuke; Hashimoto, Takashi; Horiguchi, Yuji

    2011-09-01

    An otherwise healthy 31-year-old man presented with multiple, vesicular, subepidermal blistering on the head, face, chest and oral cavity, leaving shallow scar formation, typical of Brunsting-Perry type pemphigoid. Direct immunofluorescence showed linear deposition of immunoglobulin (Ig)G and C3 along the basement membrane zone (BMZ), and indirect showed anti-BMZ autoantibodies (IgG, >40×) reacting with the dermal side under the salt-split study. Immunofluorescence staining for type IV collagen and laminins, as well as routine electron microscopy, demonstrated that the cleavage level of the blister was intra-lamina lucida. The immunoperoxidase method applied to lesional skin demonstrated IgG deposits along the lamina densa. The post-embedding immunogold method demonstrated that the autoantibodies against BMZ reacted with the lamina densa and the dermis just beneath it. Immunoblot studies demonstrated that the autoantibodies reacted with the 290-kD polypeptide (suggesting type VII collagen) when dermal extract was used as the substrate. The patient was treated with combination therapy consisting of 30 mg prednisolone, 900 mg nicotinamide and 750 mg tetracycline, and the number of newly forming blisters decreased. We concluded that Brunsting-Perry type pemphigoid, a rare autoimmune blistering disease, includes cases showing characteristics of epidermolysis bullosa acquisita as well as bullous pemphigoid. This case showed discrepancy between the blistering level (intra-lamina lucida) and location of antigen (lamina densa and sub-lamina densa areas). © 2011 Japanese Dermatological Association.

  13. 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

  14. Autoantibody recognition mechanisms of p53 epitopes

    Science.gov (United States)

    Phillips, J. C.

    2016-06-01

    There is an urgent need for economical blood based, noninvasive molecular biomarkers to assist in the detection and diagnosis of cancers in a cost-effective manner at an early stage, when curative interventions are still possible. Serum autoantibodies are attractive biomarkers for early cancer detection, but their development has been hindered by the punctuated genetic nature of the ten million known cancer mutations. A landmark study of 50,000 patients (Pedersen et al., 2013) showed that a few p53 15-mer epitopes are much more sensitive colon cancer biomarkers than p53, which in turn is a more sensitive cancer biomarker than any other protein. The function of p53 as a nearly universal "tumor suppressor" is well established, because of its strong immunogenicity in terms of not only antibody recruitment, but also stimulation of autoantibodies. Here we examine dimensionally compressed bioinformatic fractal scaling analysis for identifying the few sensitive epitopes from the p53 amino acid sequence, and show how it could be used for early cancer detection (ECD). We trim 15-mers to 7-mers, and identify specific 7-mers from other species that could be more sensitive to aggressive human cancers, such as liver cancer. Our results could provide a roadmap for ECD.

  15. The intrinsic pathogenic role of autoantibodies to aquaporin 4 mediating spinal cord disease in a rat passive-transfer model.

    Science.gov (United States)

    Geis, Christian; Ritter, Christian; Ruschil, Christoph; Weishaupt, Andreas; Grünewald, Benedikt; Stoll, Guido; Holmoy, Trygve; Misu, Tatsuro; Fujihara, Kazuo; Hemmer, Bernhard; Stadelmann, Christine; Bennett, Jeffrey L; Sommer, Claudia; Toyka, Klaus V

    2015-03-01

    Neuromyelitis optica (NMO) is causally linked to autoantibodies (ABs) against aquaporin 4 (AQP4). Here, we focused on the pathogenic effects exclusively mediated by human ABs to AQP4 in vivo. We performed cell-free intrathecal (i.th.) passive transfer experiments in Lewis rats using purified patient NMO immunoglobulin G (IgG) and various recombinant human anti-AQP4 IgG-ABs via implanted i.th. catheters. Repetitive application of patient NMO IgG fractions and of recombinant human anti-AQP4 ABs induced signs of spinal cord disease. Magnetic resonance imaging (MRI) revealed longitudinal spinal cord lesions at the site of application of anti-AQP4 IgG. Somatosensory evoked potential amplitudes were reduced in symptomatic animals corroborating the observed functional impairment. Spinal cord histology showed specific IgG deposition in the grey and white matter in the affected areas. We did not find inflammatory cell infiltration nor activation of complement in spinal cord areas of immunoglobulin deposition. Moreover, destructive lesions showing axon or myelin damage and loss of astrocytes and oligodendrocytes were all absent. Immunoreactivity to AQP4 and to the excitatory amino acid transporter 2 (EAAT2) was markedly reduced whereas immunoreactivity to the astrocytic marker glial fibrillary acid protein (GFAP) was preserved. The expression of the NMDA-receptor NR1 subunit was downregulated in areas of IgG deposition possibly induced by sustained glutamatergic overexcitation. Disease signs and histopathology were reversible within weeks after stopping injections. We conclude that in vivo application of ABs directed at AQP 4 can induce a reversible spinal cord disease in recipient rats by inducing distinct histopathological abnormalities. These findings may be the experimental correlate of "penumbra-like" lesions recently reported in NMO patients adjacent to effector-mediated tissue damage.

  16. 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.

  17. A human systemic lupus erythematosus-related anti-cardiolipin/single-stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 V[sub H] gene

    Energy Technology Data Exchange (ETDEWEB)

    Van Es, J.H.; Aanstoot, H.; Gmelig-Meyling, F.H.J.; Derksen, R.H.W.M.; Logtenberg, T. (Univ. Hospital Utrecht (Netherlands))

    1992-09-15

    The authors report the Ig H and L chain V region sequences from the cDNAs encoding a monoclonal human IgG anti-cardiolipin/ssDNA autoantibody (R149) derived from a patient with active SLE. Comparison with the germ-line V-gene repertoire of this patient revealed that R149 likely arose as a consequence of an Ag-driven selection process. The Ag-binding portions of the V regions were characterized by a high number of arginine residues, a property that has been associated with anti-dsDNA autoantibodies from lupus-prone mice and patients with SLE. The V[sub H] gene encoding autoantibody R149 was a somatically mutated variant of the 51P1 gene segment, which is frequently associated with the restricted fetal B cell repertoire, malignant CD5 B cells, and natural antibodies. These data suggest that in SLE patients a common antigenic stimulus may evoke anti-DNA and anti-cardiolipin autoantibodies and provide further evidence that a small set of developmentally restricted V[sub H] genes can give rise to disease-associated autoantibodies through Ag-selected somatic mutations. 42 refs., 5 figs.

  18. IgA1 dominant subclass of latent IgA mesangial deposition in donated kidney.

    Science.gov (United States)

    Oka, Kazumasa; Nishimura, Kenji; Kishikawa, Hidefumi; Ichikawa, Yasuji

    2016-01-01

    In the pathogenesis of immunoglobulin A nephropathy (IgAN), the IgA1 subclass is more important than the IgA2 subclass. In healthy men, the prevalence of mesangial IgA deposition has been previously investigated. However, it remains unknown whether the presence of urinary abnormalities depends on the subclass of IgA deposition. We researched the subclasses of IgA (IgA1 and IgA2) by the direct immunofluorescence (IF) staining method using specimens in which we identified the deposition of IgA through zero-hour renal transplant biopsies from donors without urinary abnormalities. The samples of the zero-hour biopsies were collected from 46 cases of living renal transplant patients at Nishinomiya Hospital, Hyogo Prefecture, from January 2011 to December 2013. In seven of the 46 cases (15%), IgA deposition and C3 in mesangium were confirmed. All seven cases showed IgA1 predominant mesangial deposition on IF. The results of the histological evaluations for all seven cases were Oxford Classification M0.S0.E0.T0. This study showed similar patterns of latent mesangial IgA deposition according to IgA subclass and frequency of C3 deposition as IgAN. Latent mesangial IgA deposition may require some, as yet undefined factors, to become clinically apparent as IgAN.

  19. The role of autoantibodies in the pathophysiology of rheumatoid arthritis.

    Science.gov (United States)

    Derksen, V F A M; Huizinga, T W J; van der Woude, D

    2017-06-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation. The presence of autoantibodies in the sera of RA patients has provided many clues to the underlying disease pathophysiology. Based on the presence of several autoantibodies like rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), anti-carbamylated protein antibodies (anti-CarP), and more recently anti-acetylated protein antibodies RA can be subdivided into seropositive and seronegative disease. The formation of these autoantibodies is associated with both genetic and environmental risk factors for RA, like specific human leukocyte antigen (HLA) alleles and smoking. Autoantibodies can be detected many years before disease onset in a subset of patients, suggesting a sequence of events in which the first autoantibodies develop in predisposed hosts, before an inflammatory response ensues leading to clinically apparent arthritis. Research on the characteristics and effector functions of these autoantibodies might provide more insight in pathophysiological processes underlying arthritis in RA. Recent data suggests that ACPA might play a role in perpetuating inflammation once it has developed. Furthermore, pathophysiological mechanisms have been discovered supporting a direct link between the presence of ACPA and both bone erosions and pain in RA patients. In conclusion, investigating the possible pathogenic potential of autoantibodies might lead to improved understanding of the underlying pathophysiological processes in rheumatoid arthritis.

  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. Comparison of Immunoglobulin G Subclass Profiles Induced by Measles Virus in Vaccinated and Naturally Infected Individuals

    Science.gov (United States)

    Isa, María Beatríz; Martínez, Laura; Giordano, Miguel; Passeggi, Carlos; de Wolff, María Cristina; Nates, Silvia

    2002-01-01

    A total of 258 human sera positive for measles antibodies were divided into four different groups: group 1 contained 54 sera from children after natural measles infection (immunoglobulin M [IgM] positive, early infection phase), group 2 contained 28 sera from children after measles vaccination (IgM positive, early infection phase), group 3 contained 100 sera from healthy adults (natural long-lasting immunity), and group 4 contained 76 sera from healthy children (postvaccinal long-lasting immunity). In the early phase of infection, the percent distributions of measles virus-specific IgG isotypes were similar between natural and postvaccinal immune responses. IgG1 and IgG4 were the dominant isotypes, with mean levels of detection of 100% (natural infection) and 100% (postvaccinal) for IgG1 and 96% (natural infection) and 92% (postvaccinal) for IgG4. In comparison, the IgG4 geometric mean titer (GMT) in the early phase of natural infection was significantly higher than the IgG4 GMT detected in the postvaccinal immune response (80 versus 13; 95% confidence interval). In the memory phase, IgG2 and IgG3 responses decreased significantly in both natural infection and postvaccinal groups, while IgG1 levels were maintained. In contrast, the IgG4 postvaccinal immune response decreased strongly in the memory phase, whereas IgG4 natural long-lasting immunity remained unchanged (9 versus 86%; P < 0.05). The results obtained suggest that IgG4 isotype could be used in the early phase of infection as a quantitative marker and in long-lasting immunity as a qualitative marker to differentiate between natural and postvaccinal immune responses. PMID:11986279

  2. Heat sensitivity of porcine IgG.

    Science.gov (United States)

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

    1975-09-01

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

  3. 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.

  4. 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.

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

    Science.gov (United States)

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

    2015-02-01

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

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

    Institute of Scientific and Technical Information of China (English)

    王文生

    2015-01-01

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

  7. Dermatomyositis and polymyositis: Clinical presentation, autoantibodies, and pathogenesis.

    Science.gov (United States)

    Mammen, Andrew L

    2010-01-01

    Dermatomyositis (DM) and polymyositis (PM) are autoimmune myopathies characterized clinically by proximal muscle weakness, muscle inflammation, extramuscular manifestations, and frequently, the presence of autoantibodies. Although there is some overlap, DM and PM are separate diseases with different pathophysiological mechanisms. Furthermore, unique clinical phenotypes are associated with each of the myositis-specific autoantibodies (MSAs) associated with these disorders. This review will focus on the clinical features, pathology, and immunogenetics of PM and DM with an emphasis on the importance of autoantibodies in defining unique phenotypes and, perhaps, as clues to help elucidate the mechanisms of disease.

  8. IgG4-Related Nasal Pseudotumor

    Directory of Open Access Journals (Sweden)

    L. K. Døsen

    2015-01-01

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

  9. Chronic smoke exposure induces rheumatoid factor and anti-heat shock protein 70 autoantibodies in susceptible mice and humans with lung disease.

    Science.gov (United States)

    Newkirk, Marianna M; Mitchell, Simeon; Procino, Michael; Li, Zhenhong; Cosio, Manuel; Mazur, Witold; Kinnula, Vuokko L; Hudson, Marie; Baron, Murray; Fritzler, Marvin J; El-Gabalawy, Hani S

    2012-04-01

    The impact of cigarette smoke (CS), a risk factor for rheumatoid arthritis (RA), on sauto-antibody production was studied in humans and mice with and without chronic lung disease (LD). Rheumatoid factor (RF), anti-cyclic citrullinated peptides (CCPs), and anti-HSP70 autoantibodies were measured in several mouse strains and in cohorts of smokers and nonsmokers with and without autoimmune disease. Chronic smoking-induced RFs in AKR/J mice, which are most susceptible to LD. RFs were identified in human smokers, preferentially in those with LD. Anti-HSP70 auto-antibodies were identified in CS-exposed AKR/J mice but not in ambient air exposed AKR/J controls. Whereas inflammation could induce anti-HSP70 IgM, smoke exposure promoted the switch to anti-HSP70 IgG autoantibodies. Elevated anti-CCP autoantibodies were not detected in CS-exposed mice or smokers. AKR/J splenocytes stimulated in vitro by immune complexes (ICs) of HSP70/anti-HSP70 antibodies produced RFs. The CD91 scavenger pathway was required as anti-CD91 blocked the HSP70-IC-induced RF response. Blocking Toll-like receptors did not influence the HSP70-IC-induced RFs. These studies identify both anti-HSP70 and RFs as serological markers of smoke-related LD in humans and mice. Identification of these autoantibodies could suggest a common environmental insult, namely CS, in a number of different disease settings. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Directory of Open Access Journals (Sweden)

    Leili Aghebati Maleki

    2013-08-01

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

  11. 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.

  12. Coefficient Estimates for Certain Subclasses of Bi-Univalent Ma-Minda Mocanu-Convex Functions

    Institute of Scientific and Technical Information of China (English)

    C.Selvaraj; O.S.Babu; G.Murugusundaramoorthy

    2014-01-01

    In this paper, we introduce and investigate a new subclass of the function classΣof bi-univalent functions of the Mocanu-convex type defined in the open unit disk, satisfy Ma and Minda subordination conditions. Furthermore, we find estimates on the Taylor-Maclaurin coefficients |a2| and |a3| for functions in the new subclass introduced here. Further Application of Hohlov operator to this class is obtained. Sev-eral (known or new) consequences of the results are also pointed out.

  13. Basis-free expressions for derivatives of a subclass of nonsymmetric isotropic tensor functions

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The present paper generalizes the method for solving the derivatives of symmetric isotropic tensor-valued functions proposed by Dui and Chen (2004) to a subclass of nonsymmetric tensor functions satisfying the commutative condition.This subclass of tensor functions is more general than those investigated by the existing methods.In the case of three distinct eigenvalues, the commutativity makes it possible to introduce two scalar functions, which will be used to construct the general nonsymmetric tensor functions and their derivatives.In the cases of repeated eigenvalues, the results are acquired by taking limits.

  14. IgG from patients with systemic sclerosis bind to DNA antitopoisomerase 1 in normal human fibroblasts extracts

    Directory of Open Access Journals (Sweden)

    Mathieu C Tamby

    2008-09-01

    Full Text Available Mathieu C Tamby1, Amélie Servettaz1, Nicolas Tamas1, Joseph Reinbolt2, Frédéric Caux3, Olivier Meyer4, Yannick Allanore5, André Kahan5, Loïc Guillevin6, Luc Mouthon1,61Paris-Descartes University, Faculty of Medicine, UPRES-EA 4058, Paris, France; 2UPR 9002, Centre National de la Recherche Scientifique, Strasbourg, France; 3UPRES EA 2436, Paris-Nord University, Bobigny, France; 4Rheumatology Department, Bichat Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP, Paris, France; 5Rheumatology A Department, Cochin Hospital, AP-HP; 6Paris-Descartes University, Faculty of Medicine, Department of Internal Medicine and French Reference Center for Necrotizing Vasculitides and Systemic Sclerosis, Cochin Hospital, AP-HP, Paris, FranceAbstract: By using a semi-quantitative immunoblotting technique, we have analyzed serum immunoglobulin G (IgG reactivities of patients with limited cutaneous systemic sclerosis and anticentromere antibodies, patients with diffuse systemic sclerosis and antitopoisomerase 1 antibodies, patients with diffuse systemic sclerosis without antitopoisomerase 1 or anticentromere antibodies and age- and gender-matched healthy controls with normal human skin fibroblasts and HEp-2 cells antigens. Serum IgG reactivities of patients with diffuse systemic sclerosis and antitopoisomerase 1 antibodies differed significantly from those of healthy controls or systemic sclerosis patients in other groups for reactivity with fibroblast proteins. IgG from patients with antitopoisomerase 1 antibodies bound to a 90 kDa fibroblast band and to a 100 kDa protein band in a HEp-2 cell protein extract. These two bands were further identified as DNA topoisomerase 1. Our results indicate that IgG from patients with diffuse systemic sclerosis bind DNA topoisomerase 1 in normal human fibroblasts extracts.Keywords: systemic sclerosis, autoantibodies, IgG, fibroblast, DNA topoisomerase 1

  15. IgG4-associated cholangitis.

    Science.gov (United States)

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

    2014-12-01

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

  16. IgG4-Related Perineural Disease

    Directory of Open Access Journals (Sweden)

    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.

  17. IgG4 Related Lung Disease

    Directory of Open Access Journals (Sweden)

    Mihir Patel

    2016-01-01

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

  18. Autoantibodies against small nucleolar ribonucleoprotein complexes and their clinical associations.

    NARCIS (Netherlands)

    Eenennaam, H. van; Vogelzangs, J.H.P.; Bisschops, L.L.A.; Boome, L.C. te; Seelig, H.P.; Renz, M.; Brouwer, R.; Pluk, W.L.L.P.; Hoogen, F.H.J. van den; Rooij, D.J.R.A.M. de; Pruijn, G.J.M.; Venrooij, W.J.W. van

    2002-01-01

    Sera from patients suffering from systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) have been shown to contain reactivities to nuclear components. Autoantibodies specifically targeting nucleolar antigens are found most frequently in patients

  19. Anti-neutrophil cytoplasm autoantibodies (ANCA) in autoimmune liver diseases

    NARCIS (Netherlands)

    Roozendaal, C.; Kallenberg, Cees

    1999-01-01

    Anti-neutrophil cytoplasm antibodies (ANCA) are autoantibodies directed against cytoplasmic constituents of neutrophil granulocytes and monocytes. ANCA have been detected in serum from patients with inflammatory bowel diseases (mainly ulcerative colitis) and autoimmune mediated liver diseases (mainl

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-07

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

  2. Pancreatic autoantibodies after pancreas-kidney transplantation - do they matter?

    Science.gov (United States)

    Martins, La Salete; Henriques, Antonio C; Fonseca, Isabel M; Rodrigues, Anabela S; Oliverira, José C; Dores, Jorge M; Dias, Leonidio S; Cabrita, Antonio M; Silva, José D; Noronha, Irene L

    2014-04-01

    Type 1 diabetes recurrence has been documented in simultaneous pancreas-kidney transplants (SPKT), but this diagnosis may be underestimated. Antibody monitoring is the most simple, noninvasive, screening test for pancreas autoimmune activity. However, the impact of the positive autoimmune markers on pancreas graft function remains controversial. In our cohort of 105 SPKT, we studied the cases with positive pancreatic autoantibodies. They were immunosuppressed with antithymocyte globulin, tacrolimus, mycophenolate, and steroids. The persistence or reappearance of these autoantibodies after SPKT and factors associated with their evolution and with graft outcome were analyzed. Pancreatic autoantibodies were prospectively monitored. Serum samples were collected before transplantation and at least once per year thereafter. At the end of the follow-up (maximum 138 months), 43.8% of patients were positive (from pre-transplant or after recurrence) for at least one autoantibody - the positive group. Antiglutamic acid decarboxylase was the most prevalent (31.4%), followed by anti-insulin (8.6%) and anti-islet cell autoantibodies (3.8%). Bivariate analysis showed that the positive group had higher fasting glucose, higher glycated hemoglobin (HbA1c), lower C-peptide levels, and a higher number of HLA-matches. Analyzing the sample divided into four groups according to pre-/post-transplant autoantibodies profile, the negative/positive group tended to present the higher HbA1c values. Multivariate analysis confirmed the significant association between pancreas autoimmunity and HbA1c and C-peptide levels. Positivity for these autoantibodies pre-transplantation did not influence pancreas survival. The unfavorable glycemic profile observed in the autoantibody-positive SPKT is a matter of concern, which deserves further attention.

  3. 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...... autoantibodies had a response to treatment with immunosuppressive agents. CONCLUSIONS: In six patients with chylomicronemia, GPIHBP1 autoantibodies blocked the ability of GPIHBP1 to bind and transport lipoprotein lipase, thereby interfering with lipoprotein lipase-mediated processing of triglyceride...

  4. 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.

  5. Congenital heart block: identification of autoantibody binding site on the extracellular loop (domain I, S5-S6) of alpha(1D) L-type Ca channel.

    Science.gov (United States)

    Karnabi, Eddy; Qu, Yongxia; Wadgaonkar, Raj; Mancarella, Salvatore; Yue, Yuankun; Chahine, Mohamed; Clancy, Robert M; Buyon, Jill P; Boutjdir, Mohamed

    2010-03-01

    Congenital heart block (CHB) is an autoimmune disease associated with autoantibodies against intracellular ribonucleoproteins SSB/La and SSA/Ro. The hallmark of CHB is complete atrioventricular block. We have recently established that anti-SSA/Ro -SSB/La autoantibodies inhibit alpha(1D) L-type Ca current, I(Ca-L), and cross-react with the alpha(1D) Ca channel protein. This study aims at identifying the possible binding sites on alpha(1D) protein for autoantibodies from sera of mothers with CHB children. GST fusion proteins of the extracellular regions between the transmembrane segments (S5-S6) of each of the four alpha(1D) Ca channel protein domains I-IV were prepared and tested for reactivity with sera from mothers with CHB children and controls using ELISA. Sera containing anti-Ro/La autoantibodies from 118 mothers with CHB children and from 15 mothers with anti-Ro/La autoantibodies but have healthy children, and from 28 healthy mothers without anti-Ro/La autoantibodies and healthy children were evaluated. Seventeen of 118 (14.4%) sera from mothers with CHB children reacted with the extracellular loop of domain I S5-S6 region (E1). In contrast, only 2 of 28 (7%) of sera from healthy mothers (-anti-Ro/La) and healthy children reacted with E1 loop and none (0 of 15) of sera from healthy mothers (+anti-Ro/La) and healthy children reacted with the E1 loop. Preincubation of E1 loop with the positive sera decreased the O.D reading establishing the specificity of the response. Electrophysiological characterization of the ELISA positive sera and purified IgG showed inhibition (44.1% and 49.8%, respectively) of the alpha(1D) I(Ca-L) expressed in tsA201 cells. The inhibition was abolished when the sera were pre-incubated with E1 fusion protein. The results identified the extracellular loop of domain I S5-S6 of L-type Ca channel alpha(1D) subunit as a target for autoantibodies from a subset of mothers with CHB children. This novel finding provides insights into the

  6. A systematic approach to obtain validated partial least square models for predicting lipoprotein subclasses from serum NMR spectra.

    Science.gov (United States)

    Mihaleva, Velitchka V; van Schalkwijk, Daniël B; de Graaf, Albert A; van Duynhoven, John; van Dorsten, Ferdinand A; Vervoort, Jacques; Smilde, Age; Westerhuis, Johan A; Jacobs, Doris M

    2014-01-07

    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 HPLC-derived lipoprotein subclasses. The PLS models were validated using an independent test set. In addition to total VLDL, LDL, and HDL lipoproteins, statistically significant PLS models were obtained for 13 subclasses, including 5 VLDLs (particle size 64-31.3 nm), 4 LDLs (particle size 28.6-20.7 nm) and 4 HDLs (particle size 13.5-9.8 nm). The best models were obtained for triglycerides in VLDL (0.82 < Q(2) <0.92) and HDL (0.69 < Q(2) <0.79) subclasses and for cholesterol in HDL subclasses (0.68 < Q(2) <0.96). Larger variations in the model performance were observed for triglycerides in LDL subclasses and cholesterol in VLDL and LDL subclasses. The potential of the NMR-PLS model was assessed by comparing the LPD of 52 subjects before and after a 4-week treatment with dietary supplements that were hypothesized to change blood lipids. The supplements induced significant (p < 0.001) changes on multiple subclasses, all of which clearly exceeded the prediction errors.

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

    Energy Technology Data Exchange (ETDEWEB)

    Saurat, J.H.; Schifferli, J.; Steiger, G.; Dayer, J.M.; Didierjean, L. (Department of Dermatology, University Hospital, Geneva (Switzerland))

    1991-08-01

    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.

  8. Population variation in anti-S. aureus IgG isotypes influences surface protein A mediated immune subversion.

    Science.gov (United States)

    Whitehouse, Julia; Flaxman, Amy; Rollier, Christine; O'Shea, Matthew K; Fallowfield, Joanne; Lindsay, Michael; Gunner, Frances; Knox, Kyle; Wyllie, David H; Yamaguchi, Yuko

    2016-04-04

    Staphylococcus aureus is a pathogen which causes life-threatening infection, the incidence of which rises during adult life. This, together with the emergence of drug-resistant strains and the expansion of more susceptible elderly populations, represents the rationale for the ongoing development of S. aureus vaccines targeting adult populations. Humoral responses to S. aureus naturally develop early in life, influence susceptibility to infection, and potentially influence the effect of vaccination. Despite this, the nature of pre-existing anti-S. aureus antibodies in healthy adult populations is not fully characterised. Immunoglobulin levels against S. aureus surface antigens were measured by a filter membrane enzyme-linked immunosorbent assay using fixed ΔSpA S. aureus as an antigen in serum samples obtained from three clinical cohorts comprising 133 healthy adult volunteers from 19 to 65 years of age. Functional capacity of antibody was also assessed, using antibody-mediated attachment of FITC-stained S. aureus to differentiated HL-60 cells. Wide variation in the concentrations of immunoglobulins recognising S. aureus surface antigens was observed among individuals in all three cohorts. There was a decline of anti-S. aureus IgG1 with age, and a similar trend was observed in IgM, but not in IgA or other IgG sub-classes. Antibody mediated bacterial attachment to cells was associated with IgG1 and IgG3 concentrations in serum. The presence of SpA on the bacterial cell surface reduced antibody-mediated binding of bacteria to phagocytes in serum with low, but not high, levels of naturally occurring anti-S. aureus IgG3 antibodies. Naturally acquired immunoglobulin responses to S. aureus are heterogeneous in populations and their concentrations alter during adulthood. Elevated IgG1 or IgG3 titres against S. aureus enhance S. aureus recognition by phagocytosis and may be correlates of natural protection and/or vaccine efficacy in adult populations. Copyright © 2016 The

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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 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.

  11. The Inclusion Problem for Some Subclasses of Context-Free Languages

    NARCIS (Netherlands)

    Asveld, Peter R.J.; Nijholt, Anton

    2000-01-01

    By a reduction to Post's Correspondence Problem we provide a direct proof of the known fact that the inclusion problem for unambiguous context-free grammars is undecidable. The argument or some straightforward modification also applies to some other subclasses of context-free languages such as line

  12. Associations between intensive diabetes therapy and NMR-determined lipoprotein subclass profiles in type 1 diabetes.

    Science.gov (United States)

    Zhang, Ying; Jenkins, Alicia J; Basu, Arpita; Stoner, Julie A; Lopes-Virella, Maria F; Klein, Richard L; Lyons, Timothy J

    2016-02-01

    Our objective is to define differences in circulating lipoprotein subclasses between intensive versus conventional management of type 1 diabetes during the randomization phase of the Diabetes Control and Complications Trial (DCCT). NMR-determined lipoprotein subclass profiles (NMR-LSPs), which estimate molar subclass concentrations and mean particle diameters, were determined in 1,294 DCCT subjects after a median of 5 years (interquartile range: 4-6 years) of randomization to intensive or conventional diabetes management. In cross-sectional analyses, we compared standard lipids and NMR-LSPs between treatment groups. Standard total, LDL, and HDL cholesterol levels were similar between randomization groups, while triglyceride levels were lower in the intensively treated group. NMR-LSPs showed that intensive therapy was associated with larger LDL diameter (20.7 vs. 20.6 nm, P = 0.01) and lower levels of small LDL (median: 465 vs. 552 nmol/l, P = 0.007), total IDL/LDL (mean: 1,000 vs. 1,053 nmol/l, P = 0.01), and small HDL (mean: 17.3 vs. 18.6 μmol/l, P diabetes therapy was associated with potentially favorable changes in LDL and HDL subclasses in sera. Further research will determine whether these changes contribute to the beneficial effects of intensive diabetes management on vascular complications.

  13. A Remarkable Angular Distribution of the Intermediate Subclass of $\\gamma$-Ray Bursts

    CERN Document Server

    Mészáros, A; Horváth, I L; Balázs, L; Vavrek, R; Meszaros, Attila; Bagoly, Zsolt; Horvath, Istvan; Balazs, Lajos G.

    2000-01-01

    In the article a test is developed, which allows to test the null-hypothesis of the intrinsic randomness in the angular distribution of gamma-ray bursts collected at the Current BATSE Catalog. The method is a modified version of the well-known counts-in-cells test, and fully eliminates the non-uniform sky-exposure function of BATSE instrument. Applying this method to the case of all gamma-ray bursts no intrinsic non-randomness was found. The test also did not find intrinsic non-randomnesses for the short and long gamma-ray bursts, respectively. On the other hand, using the method to the new intermediate subclass of gamma-ray bursts, the null-hypothesis of the intrinsic randomness for 181 intermediate gamma-ray bursts is rejected on the 96.4% confidence level. Taking 92 dimmer bursts from this subclass itself, we obtain the surprising result: This "dim" subclass of the intermediate subclass has an intrinsic non-randomness on the 99.3% confidence level. On the other hand, the 89 "bright" GRBs show no intrinsic ...

  14. Mixture subclass discriminant analysis link to restricted Gaussian model and other generalizations.

    Science.gov (United States)

    Gkalelis, Nikolaos; Mezaris, Vasileios; Kompatsiaris, Ioannis; Stathaki, Tania

    2013-01-01

    In this paper, a theoretical link between mixture subclass discriminant analysis (MSDA) and a restricted Gaussian model is first presented. Then, two further discriminant analysis (DA) methods, i.e., fractional step MSDA (FSMSDA) and kernel MSDA (KMSDA) are proposed. Linking MSDA to an appropriate Gaussian model allows the derivation of a new DA method under the expectation maximization (EM) framework (EM-MSDA), which simultaneously derives the discriminant subspace and the maximum likelihood estimates. The two other proposed methods generalize MSDA in order to solve problems inherited from conventional DA. FSMSDA solves the subclass separation problem, that is, the situation in which the dimensionality of the discriminant subspace is strictly smaller than the rank of the inter-between-subclass scatter matrix. This is done by an appropriate weighting scheme and the utilization of an iterative algorithm for preserving useful discriminant directions. On the other hand, KMSDA uses the kernel trick to separate data with nonlinearly separable subclass structure. Extensive experimentation shows that the proposed methods outperform conventional MSDA and other linear discriminant analysis variants.

  15. On a certain subclass of meromorphic univalent functions with fixed second positive coefficients

    Directory of Open Access Journals (Sweden)

    Firas Ghanim

    2010-03-01

    Full Text Available In the present paper, we consider the subclass of meromorphic univalent functions Sp*[k,α,β,c] with fixed second positive coefficient. The object of the present paper is to show coefficient estimates, onvex liner combinations, some distortion theorems, and redii of star likeness and convexity for f(z in the class Sp*[k,α,β,c].

  16. IgM AUTOANTIBODIES TO DNA IN BLOOD SERUM OF THE PATIENTS WITH HEMORRHAGIC FEVER WITH RENAL SYNDROME

    Directory of Open Access Journals (Sweden)

    D. G. Ishmukhametova

    2010-01-01

    Full Text Available Levels of IgM autoantibodies (AAbs to native (double-stranded and denaturated (single-stranded DNA were studied in blood serum of sixty patients with hemorrhagic fever with renal syndrome (HFRS and twenty-five healthy persons, using an ELISA technique. The median levels of IgM AAbs to double-stranded DNA in blood serum of healthy persons and HFRS patients corresponded to 0.41 and 0.53 arbitrary units, respectively. Thus, the difference between the samples from HFRS and healthy persons proved to be non-significant. The median level of IgM AAbs to single-stranded DNA in blood sera of HFRS patients (0.71 arbitrary units did significantly exceed serum values of healthy persons (0.57 arbitrary units. A probable involvement of IgM AAbs into regulation of IgG AAbs' production during virus-induced activation of autoimmune events in HFRS patients is discussed.

  17. 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.

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    Harry S Courtney

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

  20. Anti-aquaporin-4 autoantibodies in systemic lupus erythematosus persist for years and induce astrocytic cytotoxicity but not CNS disease.

    Science.gov (United States)

    Alexopoulos, Harry; Kampylafka, Eleni I; Fouka, Penelope; Tatouli, Ioanna; Akrivou, Sofia; Politis, Panagiotis K; Moutsopoulos, Haralampos M; Tzioufas, Athanasios G; Dalakas, Marinos C

    2015-12-15

    Anti-aquaporin-4 autoantibodies are specific for the neuromyelitis optica spectrum disorders (NMOSD) and they have also been described in patients with systemic lupus erythematosus (SLE) with neurological signs consistent with NMOSD. Our objective was to test for the presence and pathogenicity of anti-AQP4 antibodies in SLE patients without neurological disease. Sera from 89 non-CNS-SLE patients were screened for anti-AQP4 autoantibodies. Two of the 89 patients were positive. Archived samples dating back 11 years were also positive. A brain and spinal cord MRI did not reveal any NMOSD-compatible lesions. An in vitro cytotoxicity assay showed that either sera or purified IgG from these patients induced a complement-mediated damage in cultured astrocytes comparable to antibodies obtained from typical NMO patients. We conclude that AQP4-antibodies can be present in SLE patients and persist for many years, without concurrent clinical or radiological NMOSD signs. It is unclear why the anti-AQP4 antibodies did not induce CNS disease.

  1. IgG4-related Disease of the Genitourinary Tract

    Directory of Open Access Journals (Sweden)

    Mukul K. Divatia

    2014-02-01

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

  2. Antineutrophil cytoplasmic autoantibodies in ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Vodjgani M

    2000-10-01

    Full Text Available Antineutrophil cytoplasmic autoanibodies (ANCA were detecte in patients with certain autoimmune vascular disease such as Wegner’s granulomatosis, polyarthrits nodosa and systemic luuc erythematous. Indirect immunofluorescence (IIF technique was employed to detec these autoantibodies.ANCA have been recently detected in some forms of inflammatory bowel disease (IBD, ulcerative colitis (U.C. Crohn’s disease (C.D and primary sclerosing cholangitis (PSC. By IIF method, two general patterns of ANCA were seen: a cytoplasmic (C-ANCA and perinuclear form (P-ANCA. In this study we evaluated the presece of ANCA in 52 U.C. patients and 69 matched normal control group by IIF technique, and it’s relationship with disease activity. Site of colon involvement and, lesion extent. The results showed that all control group were ANCA negative, but 58% of patients had ANCA, and most cases (70% had C- ANCA. The obtained results also revealed that there was no relationship between ANCA and disease activity

  3. Biological variation of thyroid autoantibodies and thyroglobulin

    DEFF Research Database (Denmark)

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

    2007-01-01

    is unknown, we investigated this in fertile women during one complete regular menstrual cycle. METHODS: A total of 24 healthy women (23-46 years) were investigated twice a week between 07:30 and 11:00 h. Antibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb), and thyrotropin receptor (TRAb) were.......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. Clinical features of autoimmune autonomic ganglionopathy and the detection of subunit-specific autoantibodies to the ganglionic acetylcholine receptor in Japanese patients.

    Directory of Open Access Journals (Sweden)

    Shunya Nakane

    Full Text Available Autoimmune autonomic ganglionopathy (AAG is a rare acquired channelopathy that is characterized by pandysautonomia, in which autoantibodies to ganglionic nicotinic acetylcholine receptors (gAChR may play a central role. Radioimmunoprecipitation (RIP assays have been used for the sensitive detection of autoantibodies to gAChR in the serum of patients with AAG. Here, we developed luciferase immunoprecipitation systems (LIPS to diagnose AAG based on IgGs to both the α3 and β4 gAChR subunits in patient serum. We reviewed the serological and clinical data of 50 Japanese patients who were diagnosed with AAG. With the LIPS testing, we detected anti-α3 and -β4 gAChR antibodies in 48% (24/50 of the patients. A gradual mode of onset was more common in the seropositive group than in the seronegative group. Patients with AAG frequently have orthostatic hypotension and upper and lower gastrointestinal tract symptoms, with or without anti-gAChR. The occurrence of autonomic symptoms was not significantly different between the seropositive and seronegative group, with the exception of achalasia in three patients from the seropositive group. In addition, we found a significant overrepresentation of autoimmune diseases in the seropositive group and endocrinological abnormalities as an occasional complication of AAG. Our results demonstrated that the LIPS assay was a useful novel tool for detecting autoantibodies against gAChR in patients with AAG.

  5. Role of early glycation Amadori products of lysine-rich proteins in the production of autoantibodies in diabetes type 2 patients.

    Science.gov (United States)

    Ansari, Nadeem Ahmad; Moinuddin; Mir, Abdul Rouf; Habib, Safia; Alam, Khursheed; Ali, Asif; Khan, Rizwan Hasan

    2014-11-01

    In diabetes, protein glycation mostly occurs at intrachain lysine residues resulting in the formation of early stage Amadori products which are finally converted to advance glycation end products (AGEs). Several studies have reported autoantibodies against AGEs in diabetes but not much data are found in respect of Amadori products. In this study, poly-L-lysine (PLL) was glycated with 50 mM glucose and the resultant Amadori products were estimated by fructosamine or nitroblue tetrazolium assay. We report high content of Amadori products in PLL upon glycation. Glycated PLL showed marked hyperchromicity in the UV spectrum, ellipticity changes in CD spectroscopy, and variations in ε-methylene protons shift in NMR. It was better recognized by autoantibodies in type 2 diabetics compared to the native PLL. Induced antibodies against glycated PLL were successfully used to probe early glycation in the IgG isolated from diabetes type 2 patients. Role of Amadori products of glycated proteins in the induction of autoantibodies in type 2 diabetes as well as in associated secondary complications has been discussed.

  6. Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice.

    Science.gov (United States)

    Krishnan, Meera R; Wang, Congmiao; Marion, Tony N

    2012-07-01

    The strongest serological correlate for lupus nephritis is antibody to double-stranded DNA, although the mechanism by which anti-DNA antibodies initiate lupus nephritis is unresolved. Most recent reports indicate that anti-DNA must bind chromatin in the glomerular basement membrane or mesangial matrix to form glomerular deposits. Here we determined whether direct binding of anti-DNA antibody to glomerular basement membrane is critical to initiate glomerular binding of anti-DNA in experimental lupus nephritis. Mice were co-injected with IgG monoclonal antibodies or hybridomas with similar specificity for DNA and chromatin but different IgG subclass and different relative affinity for basement membrane. Only anti-DNA antibodies that bound basement membrane bound to glomeruli, activated complement, and induced proteinuria whether injected alone or co-injected with a non-basement-membrane-binding anti-DNA antibody. Basement membrane-binding anti-DNA antibodies co-localized with heparan sulfate proteoglycan in glomerular basement membrane and mesangial matrix but not with chromatin. Thus, direct binding of anti-DNA antibody to antigens in the glomerular basement membrane or mesangial matrix may be critical to initiate glomerular inflammation. This may accelerate and exacerbate glomerular immune complex formation in human and murine lupus nephritis.

  7. Use of a novel elution regimen reveals the dominance of polyreactive antinuclear autoantibodies in lupus kidneys.

    Science.gov (United States)

    Xie, Chun; Liang, Zhiyan; Chang, Sooghee; Mohan, Chandra

    2003-08-01

    The autoantibody specificities that dominate the deposits in lupus kidneys remain unclear. Reasoning that previously utilized elution buffers such as acidic glycine and ammonium thiocyanate may not have been maximally effective in eluting all Ig deposits from the kidneys, this study was conducted to experiment with a stronger dissociating agent, urea-glycine. Seven antinuclear antibody-positive, nephritic female (SWR x NZB)F(1) (SNF1) lupus mice were selected for the elution study. Deposited Ig was eluted from their kidneys using 3 different elution buffers: 0.15M glycine-HCl buffer, 1.3M ammonia thiocyanate/0.15M glycine-HCl buffer, and 5M urea/0.15M glycine-HCl buffer. All eluates were tested for specificity against a variety of nuclear and glomerular antigens. Compared with conventional elution buffers, the urea-based regimen eluted severalfold more IgG and IgM antinuclear antibodies from the kidneys of nephritic SNF1 lupus mice. IgG anti-double-stranded DNA (anti-dsDNA) antibodies were not only the most prevalent species in these renal deposits, they were also heavily enriched in the kidneys, relative to the corresponding serum levels. A substantial fraction of the anti-single-stranded DNA and antihistone/DNA (but not antihistone) reactivity in these eluates was due to cross-reactive anti-dsDNA antibodies. No reactivity with SSA, SSB, Sm, RNP, Jo-1, Scl-70, or ribosomal P antigens could be demonstrated in these eluates. Importantly, the urea-glycine eluates differed from the conventional eluates in having significantly greater reactivity to glomerular substrate and laminin. This novel urea-based elution provides further support for the dominance of antibodies in lupus kidneys, with strong polyreactivity to DNA and glomerular substrate.

  8. High prevalence of anti-apolipoprotein/A-1 autoantibodies in maintenance hemodialysis and association with dialysis vintage.

    Science.gov (United States)

    Pruijm, Menno; Schmidtko, Jan; Aho, Anthony; Pagano, Sabrina; Roux-Lombard, Pascale; Teta, Daniel; Burnier, Michel; Vuilleumier, Nicolas

    2012-12-01

    Autoantibodies to apolipoprotein/A-1 (anti-ApoA-1 IgG) have pro-atherogenic properties in patients at high cardiovascular risk, but its prevalence in patients with end-stage kidney disease is unknown. The aims of this single-center, cross-sectional study were to assess the prevalence of anti-ApoA-1 antibodies in patients on maintenance hemodialysis (MHD), and to examine its correlation with inflammatory biomarkers related to atherosclerotic plaque vulnerability and dialysis vintage. To this purpose, anti-ApoA-1 IgG levels and the concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), metalloproteinase-9 (MMP-9), tumor necrosis factor-α, and C-reactive protein (CRP) were assessed in the sera of 66 MHD patients (mean age: 68 ± 14 years, 36% women, 32% diabetics). Anti-ApoA-1 IgG positivity (defined as a blood value ≥ 97.5(th) percentile of the normal distribution as assessed in healthy blood donors) was 20%. Circulating levels of anti-ApoA-1 IgG correlated positively with dialysis vintage, but not with cardiovascular risk factors or previous cardiovascular events; no significant correlations were found between the anti-ApoA1 IgG levels and circulating levels of IL-6, IL-8, MCP-1, MMP-9, CRP, or low-density lipoprotein-cholesterol. In multivariable linear regression, adjusted for age and sex, only dialysis vintage remained positively and independently associated with anti-ApoA-1 titers (β = 0.05, 95% CI: 0.006; 0.28, P = 0.049). In conclusion, the prevalence of anti-ApoA-1 IgG is raised in the MHD-population, and positively associated with dialysis vintage, a major determinant of cardiovascular outcome. Whether antiApoA-1 antibodies play a role in the pathophysiology of accelerated atherosclerosis in the MHD-population merits further study.

  9. IgG4-related pleuritis with chylothorax.

    Science.gov (United States)

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

    2014-01-01

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

  10. Changes in LDL and HDL subclasses in normal pregnancy and associations with birth weight, birth length and head circumference.

    Science.gov (United States)

    Zeljkovic, Aleksandra; Vekic, Jelena; Spasic, Slavica; Jelic-Ivanovic, Zorana; Spasojevic-Kalimanovska, Vesna; Gojkovic, Tamara; Ardalic, Daniela; Mandic-Markovic, Vesna; Cerovic, Nikola; Mikovic, Zeljko

    2013-04-01

    Pregnancy is associated with alterations in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, but the exact pattern of these variations remains controversial. This study investigates longitudinal changes of plasma LDL and HDL particles distributions during the course of normal pregnancy, as well as associations of maternal LDL and HDL subclasses distributions before delivery with parameters of newborn size. Blood samples were collected from 41 healthy pregnant women throughout entire pregnancy, before delivery and 7 weeks postpartum. LDL and HDL subclasses were determined by gradient gel electrophoresis, while other biochemical parameters were measured by standard laboratory methods. During gestation LDL size significantly decreased (P LDL I (P LDL II (P HDL size and proportions of HDL 2a particles significantly decreased (P HDL 3b and 3c subclasses (P LDL subclasses distribution during gestation was transient, while postpartum HDL subclasses distribution remained shifted toward smaller particles. Higher proportion of LDL IVB in maternal plasma before delivery was an independent predictor of smaller birth weights and lengths, while higher proportions of LDL IVB and HDL 2a subclasses were independent determinants of newborns' smaller head circumferences. Routine gestational and prenatal care in otherwise normal pregnancy could be complemented with evaluation of LDL and HDL particles distribution in order to ensure an adequate size of the newborn.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Charkiewicz, Karol; Zbucka-Kretowska, Monika; Goscik, Joanna; Wolczynski, Slawomir; Lemancewicz, Adam; Laudanski, Piotr

    2016-01-01

    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.

  13. Regulatory and pathogenetic mechanisms of autoantibodies in SLE.

    Science.gov (United States)

    Radic, Marko; Herrmann, Martin; van der Vlag, Johan; Rekvig, Ole Petter

    2011-08-01

    In the 53 years since the discovery of anti-DNA autoantibodies in lupus [1, 2, 3] , recalcitrant questions have been pondered and possible answers have been debated. The discovery of anti-DNA autoantibodies presented many puzzles: How is immunological tolerance to native B-form DNA broken? What elicits characteristic systemic lupus erythematosus (SLE) autoantibodies? Which of the diverse anti-nuclear reactivities are pathogenic? What is the role of autoantibodies in the clinical presentation of disease? How do genetic predisposition and environmental triggers contribute to SLE? These questions were brought into focus by Professor David Stollar in an introductory presentation to an intense, three-day meeting set among the rugged and inspiring scenery of the Norwegian arctic coastline (the Scientific Program is included as supplemental File 1). Other participants presented and discussed topics directed to understanding the origin and clinico-pathological impact of autoantibodies to chromatin and phospholipid antigens. In the following, several aspects of the workshop are discussed.

  14. The prevalence of hypothyroidism after treatment for laryngeal and hypopharyngeal carcinomas : are autoantibodies of influence?

    NARCIS (Netherlands)

    Lo Galbo, Annalisa M.; De Bree, Remco; Kuik, Dirk J.; Lips, Paul Th. A. M.; Von Blomberg, B. Mary E.; Langendijk, Johannes A.; Leemans, C. Rene

    2007-01-01

    Conclusions. The incidence rate of hypothyroidism after treatment for laryngeal and hypopharyngeal cancer is high, especially after combination treatment. An association between hypothyroidism and autoantibodies was found. Objectives. The incidences of hypothyroidism and autoantibodies were assessed

  15. NEUTROPHIL CYTOPLASMIC AUTOANTIBODIES AFTER LIVER-TRANSPLANTATION IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS

    NARCIS (Netherlands)

    Haagsma, E.B.; MULDER, A.H.L.; Gouw, A.S.H.; MEERMAN, L.; Slooff, M.JH; Kallenberg, Cees; Horst, G.

    1993-01-01

    The immunopathogenic importance of neutrophil cytoplasmic autoantibodies in ulcerative colitis and primary sclerosing cholangitis is unknown. These autoantibodies were investigated before and after liver transplantation in 9 patients with primary sclerosing cholangitis. Sera from 10 patients transpl

  16. Shift in epitope dominance of IgM and IgG responses to Plasmodium falciparum MSP1 block 4

    Directory of Open Access Journals (Sweden)

    Leke Rose GF

    2010-01-01

    Full Text Available Abstract Background Plasmodium falciparum merozoite surface protein-1 (MSP1 has been extensively studied as a blood-stage malaria vaccine candidate, with most work focused on the conserved 19 kDa and semi-conserved 42 kDa C-terminal regions (blocks 16-17 and the hypervariable N-terminal repeat region (block 2. However, recent genotyping studies suggest that additional regions of MSP1 may be under selective pressure, including a locus of intragenic recombination designated as block 4 within the 3' region of the gene. Methods The current study examined the antibody response to the two parental and two recombinant forms of block 4 and to blocks 16-17 (3D7 in study populations from Colombia, Papua New Guinea and Cameroon that differ in malaria transmission intensity and ethnic composition. Results IgM and IgG antibodies were detected against parental and recombinant MSP1 block 4 peptides in all three populations. Overall, 32-44% of the individuals produced IgM to one or more of the peptides, with most individuals having IgM antibodies reactive with both parental and recombinant forms. In contrast, IgG seropositivity to block 4 varied among populations (range 15-65%, with the majority of antibodies showing specificity for one or a pair of block 4 peptides. The IgG response to block 4 was significantly lower than that to blocks 16-17, indicating block 4 is subdominant. Antibodies to block 4 and blocks 16-17 displayed distinct IgG subclass biases, with block 4 responses biased toward IgG3 and blocks 16-17 toward IgG1. These patterns of responsiveness were consistently observed in the three study populations. Conclusions Production of antibodies specific for each parental and recombinant MSP1 block 4 allele in different populations exposed to P. falciparum is consistent with balancing selection of the MSP1 block 4 region by the immune response of individuals in areas of both low and high malaria transmission. MSP1 block 4 determinants may be important

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

    Directory of Open Access Journals (Sweden)

    Yuying Su

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

  18. CUTANEOUS LUPUS ERYTHEMATOSUS WITH AUTOANTIBODIES COLOCALIZING WITH GLIAL FIBRILLARY ACIDIC PROTEIN

    Directory of Open Access Journals (Sweden)

    Abreu-Velez Ana Maria

    2011-01-01

    Full Text Available Background: Discoid lupus erythematosus (DLE is a chronic, inflammatory skin disorder, presenting with scarring lesions predominating on sun exposed areas of the face and scalp. Case Report: A 43-year-old African American female was evaluated for possible DLE. Methods: Skin biopsies for hematoxylin and eosin (H&E examination, as well as for direct immunofluorescence (DIF analysis were performed. Results: H&E staining demonstrated classic features of cutaneous lupus erythematosus, with the pertinent presence of perineural lymphohistiocitic infiltrates, especially those associated with skin appendices. DIF revealed strong deposits of immunoglobulins IgG, IgM, fibrinogen and Complement/C3, present in a shaggy, linear pattern at or near the basement membrane zone (BMZ of selected eccrine and sebaceous glands, and around some blood vessels. The BMZ positivity in these structures consistently colocalized with positive staining in multiple, punctate areas for glial fibrillary acidic protein (GFAP, including within cytoid bodies. Conclusions:. The observed colocalization of the patient’s autoantibodies in cutaneous lupus with GFAP may have pathophysiologic relevance. Specifically, our data could be consistent with previously described DLE patients with or without overt central nervous system manifestations, or could represent an epiphenomenon. Additional, larger studies are needed to satisfactorily address this possibility.

  19. Estudo de imunoglobulinas, complementos e auto-anticorpos em 58 trabalhadores expostos à sílica Immunoglobulins, complements and autoantibodies in 58 workers exposed to silica

    Directory of Open Access Journals (Sweden)

    Hermano Albuquerque de Castro

    2004-06-01

    Full Text Available INTRODUÇÃO: A silicose é a doença pulmonar ocupacional de maior prevalência em nosso meio. O agente patogênico da silicose é a poeira de sílica-livre ou dióxido de silício (SiO2 na forma cristalina. O processo inflamatório envolvendo o sistema imunológico na silicose ainda não está bem esclarecido. OBJETIVO: Estudar o perfil de IgG, IgM, IgA, C3, C4 e alguns auto-anticorpos no soro de trabalhadores expostos à sílica, com ou sem silicose, através de avaliação laboratorial imunológica, abrangendo tanto a imunidade inespecífica quanto a específica. MÉTODO: Foi examinada uma amostra de 58 pacientes ambulatoriais, do sexo masculino, constituída por trabalhadores expostos à sílica. Foram realizadas avaliações imunológica, radiológica e funcional pulmonar. Foram dosadas as imunoglobulinas IgG, IgA e IgM, os componentes C3 e C4 do sistema complemento e determinados auto-anticorpos. RESULTADOS: Vinte trabalhadores apresentaram radiograma normal e 38 apresentaram-no alterado, compatível com silicose. As médias dos valores de IgG no grupo com silicose foi maior que no grupo com radiograma normal (p 0.05. O percentual de positividade dos auto-anticorpos foi maior no grupo silicótico em relação ao grupo com radiograma normal. CONCLUSÃO: O aumento de IgG nos doentes com silicose constitui um achado importante pois pode indicar a continuidade da reação granulomatosa, mesmo com o trabalhador afastado da exposição. Entretanto, ainda são necessários estudos que possibilitem a compreensão do processo imunogênico na silicose.BACKGROUND: The primary work-related lung disease in Brazil is silicosis. Its pathogenic agent is the dust of crystalline free silica (SiO2; silicon dioxide. The inflammatory process of silicosis is not yet well understood. OBJECTIVE: To analyze, through immunologic laboratory evaluation, including nonspecific and specific immunity, the profile of IgG, IgM, IgA, C3, C4 and autoantibodies in the serum

  20. Absence of autoantibodies connected to autoimmune polyendocrine syndrome type I and II and Addison's disease in girls and women with Turner syndrome

    Directory of Open Access Journals (Sweden)

    Kämpe Olle

    2007-12-01

    Full Text Available Abstract Background A disturbance in the immune system has been described in Turner syndrome (45,X, with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45,X, thyroiditis being the most common. Other autoimmune diseases seen are inflammatory bowel disease, insulin dependent diabetes mellitus, Addison's disease, rheumatoid arthritis, myasthenia gravis, vitiligo, alopecia, pernicious anaemia and hypoparathyroidism, but the association to Turner syndrome is not definite. Besides the typical features of Turner syndrome (short stature, failure to enter puberty spontaneously and infertility due to ovarian insufficiency ear problems are common. Otitis media and a progressive sensorineural hearing disorder are commonly seen. In the normal population there are known inner ear disorders related to autoimmune diseases. The aim of this study was to investigate patients with Turner syndrome regarding autoantibodies connected to the autoimmune disorders; autoimmune polyendocrine syndrome type I and II and Addison's disease, to screen for overlapping profile of autoantibodies. Blood samples from 110 Turner patients (7–65 years were investigated using in vitro transcription, translation and immunoprecipitation techniques regarding autoantibodies connected to autoimmune polyendocrine syndrome type I and II and Addison's disease (21-hydroxylase, 17α-hydroxylase, side-chain cleavage enzyme, aromatic L-amino acid decarboxylase, tyrosine hydroxylase and tryptophan hydroxylase. Results The autoantibodies investigated were not overrepresented among the Turner patients. Conclusion The autoimmune disorders associated with Turner syndrome do not seem to be of the same origin as Addison's disease, the type I or II autoimmune polyendocrine syndrome.

  1. Absence of autoantibodies connected to autoimmune polyendocrine syndrome type I and II and Addison's disease in girls and women with Turner syndrome

    Science.gov (United States)

    Stenberg, Annika E; Sylvén, Lisskulla; Hedstrand, Håkan; Kämpe, Olle; Hultcrantz, Malou

    2007-01-01

    Background A disturbance in the immune system has been described in Turner syndrome (45,X), with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45,X), thyroiditis being the most common. Other autoimmune diseases seen are inflammatory bowel disease, insulin dependent diabetes mellitus, Addison's disease, rheumatoid arthritis, myasthenia gravis, vitiligo, alopecia, pernicious anaemia and hypoparathyroidism, but the association to Turner syndrome is not definite. Besides the typical features of Turner syndrome (short stature, failure to enter puberty spontaneously and infertility due to ovarian insufficiency) ear problems are common. Otitis media and a progressive sensorineural hearing disorder are commonly seen. In the normal population there are known inner ear disorders related to autoimmune diseases. The aim of this study was to investigate patients with Turner syndrome regarding autoantibodies connected to the autoimmune disorders; autoimmune polyendocrine syndrome type I and II and Addison's disease, to screen for overlapping profile of autoantibodies. Blood samples from 110 Turner patients (7–65 years) were investigated using in vitro transcription, translation and immunoprecipitation techniques regarding autoantibodies connected to autoimmune polyendocrine syndrome type I and II and Addison's disease (21-hydroxylase, 17α-hydroxylase, side-chain cleavage enzyme, aromatic L-amino acid decarboxylase, tyrosine hydroxylase and tryptophan hydroxylase). Results The autoantibodies investigated were not overrepresented among the Turner patients. Conclusion The autoimmune disorders associated with Turner syndrome do not seem to be of the same origin as Addison's disease, the type I or II autoimmune polyendocrine syndrome. PMID:18088406

  2. 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...

  3. Autoantibodies in chronic hepatitis C: A clinical perspective

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Non-organ-specific autoantibodies and thyroid autoantibodieshave been frequently found in chroniccarriers of hepatitis C virus (HCV). With respect toendomysial antibodies and tissue transglutaminase,it is controversial whether the prevalence of glutenrelatedseromarkers is higher in patients with HCV. Insuch cases, in addition to acknowledging any currentlyexisting autoimmune disease, recognizing the risk ofthe patient developing an autoimmune disease duringinterferon (IFN)-based treatment must be a principleconcern. From a clinical point-of-view, the presence ofautoantibodies arouses suspicion that an autoimmunedisease may be present or may be precipitated by IFNbasedHCV treatment. In this paper, we review theprevalence of autoantibodies in individuals with hepatitisC, the clinical significance of these autoantibodies, andthe approach recommended for such situations.

  4. Autoantibodies against tumor-associated antigens fordetection of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the mostcommon tumors worldwide. The survival rate after theonset of symptoms is generally less than one year forthe late presentation of HCC, and reliable tools for earlydiagnosis are lacking. Therefore, novel biomarkers forthe early detection of HCC are urgently required. Recentstudies show that the abnormal release of proteins bytumor cells can elicit humoral immune responses toself-antigens called tumor-associated antigens (TAAs).The corresponding autoantibodies can be detectedbefore the clinical diagnosis of cancer. Therefore, thereis growing interest in using serum autoantibodies ascancer biomarkers. In this review, we focus on theadvances in research on autoantibodies against TAAs asserum biomarker for detection of HCC, the mechanismof the production of TAAs, and the association ofautoantibodies with patients' clinical characteristics.

  5. Autoimmune Hemolytic Anemia and Red Blood Cell Autoantibodies.

    Science.gov (United States)

    Quist, Erin; Koepsell, Scott

    2015-11-01

    Autoimmune hemolytic anemia is a rare disorder caused by autoreactive red blood cell (RBC) antibodies that destroy RBCs. Although autoimmune hemolytic anemia is rare, RBC autoantibodies are encountered frequently and can complicate transfusion workups, impede RBC alloantibody identification, delay distribution of compatible units, have variable clinical significance that ranges from benign to life-threatening, and may signal an underlying disease or disorder. In this review, we discuss the common presenting features of RBC autoantibodies, laboratory findings, ancillary studies that help the pathologist investigate the clinical significance of autoantibodies, and how to provide appropriate patient care and consultation for clinical colleagues. Pathologists must be mindful of, and knowledgeable about, this entity because it not only allows for direct clinical management but also can afford an opportunity to preemptively treat an otherwise silent malignancy or disorder.

  6. Human subtelomeric WASH genes encode a new subclass of the WASP family.

    Directory of Open Access Journals (Sweden)

    Elena V Linardopoulou

    2007-12-01

    Full Text Available Subtelomeres are duplication-rich, structurally variable regions of the human genome situated just proximal of telomeres. We report here that the most terminally located human subtelomeric genes encode a previously unrecognized third subclass of the Wiskott-Aldrich Syndrome Protein family, whose known members reorganize the actin cytoskeleton in response to extracellular stimuli. This new subclass, which we call WASH, is evolutionarily conserved in species as diverged as Entamoeba. We demonstrate that WASH is essential in Drosophila. WASH is widely expressed in human tissues, and human WASH protein colocalizes with actin in filopodia and lamellipodia. The VCA domain of human WASH promotes actin polymerization by the Arp2/3 complex in vitro. WASH duplicated to multiple chromosomal ends during primate evolution, with highest copy number reached in humans, whose WASH repertoires vary. Thus, human subtelomeres are not genetic junkyards, and WASH's location in these dynamic regions could have advantageous as well as pathologic consequences.

  7. The effects of exercise on the lipoprotein subclass profile: A meta-analysis of 10 interventions.

    Science.gov (United States)

    Sarzynski, Mark A; Burton, Jeffrey; Rankinen, Tuomo; Blair, Steven N; Church, Timothy S; Després, Jean-Pierre; Hagberg, James M; Landers-Ramos, Rian; Leon, Arthur S; Mikus, Catherine R; Rao, D C; Seip, Richard L; Skinner, James S; Slentz, Cris A; Thompson, Paul D; Wilund, Kenneth R; Kraus, William E; Bouchard, Claude

    2015-12-01

    The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. Nuclear magnetic resonance spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P, respectively) before and after an exercise intervention in 1555 adults from six studies, encompassing 10 distinct exercise programs: APOE (N = 106), DREW (N = 385), GERS (N = 79), HERITAGE (N = 715), STRRIDE I (N = 168) and II (N = 102). Random-effects meta-analyses were performed to evaluate the overall estimate of mean change across the unadjusted and adjusted mean change values from each exercise group. Meta-analysis of unadjusted data showed that regular exercise induced significant decreases in the concentration of large VLDL-P, small LDL-P, and medium HDL-P and mean VLDL-P size, with significant increases in the concentration of large LDL-P and large HDL-P and mean LDL-P size. These changes remained significant in meta-analysis with adjustment for age, sex, race, baseline body mass index, and baseline trait value. Despite differences in exercise programs and study populations, regular exercise produced putatively beneficial changes in the lipoprotein subclass profile across 10 exercise interventions. Further research is needed to examine how exercise-induced changes in lipoprotein subclasses may be associated with (concomitant changes in) cardiovascular disease risk. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Establishment of age-dependent reference values for IgA subclasses.

    Science.gov (United States)

    Schauer, Uwe; Stemberg, Frank; Rieger, Christian H L; Borte, Michael; Schubert, Simone; Riedel, Frank; Herz, Udo; Renz, Harald; Wick, Manfred; Herzog, Wilhelm

    2003-02-01

    Recently, subclass-specific antisera have been introduced for application in a nephelometric assay. The aim of this study was to establish age-dependent reference values for serum concentrations of the two IgA subclasses in children and adults. Serum levels of IgA1 and IgA2 were measured by automated immunonephelometry in samples from 235 clinically healthy children between 6 months and 18 years of age and 36 healthy adults. Both IgA1 and IgA2 were detectable in all samples, and both IgA1 and IgA2 increased with increasing age. In adults, the mean value for IgA1 is 1.46 g/l for IgA2 0.21 g/l and for total IgA 1.94 g/l. Individual IgA2 values correlate significantly (p < 0.0001) with IgA1 values (r(2) = 0.5433). In addition, there was a highly significant (p < 0.0001) correlation (r(2) = 0.9530) between the measured total IgA and the sum of the two IgA subclasses indicating that immunonephelometry using highly specific polyclonal antisera might be superior to other methods. These results and the availability of age-dependent reference values make it worthwhile to reassess the role of IgA subclasses in immunodeficiency and autoimmune diseases where conventional methods have led to conflicting results. Copyright 2002 Elsevier Science B.V.

  9. SOME CONVOLUTION AND INCLUSION PROPERTIES FOR SUBCLASSES OF MEROMORPHIC p-VALENT FUNCTIONS INVOLVING INTEGRAL OPERATOR

    Institute of Scientific and Technical Information of China (English)

    R. M. EL-ASHWAH

    2013-01-01

    Making use of the linear operator Lmp (λ,ℓ)f (z)= 1zp + ∞X k=1 ?ℓℓ+λk ?m akzk-p, where ℓ > 0,λ > 0, p ∈ N, m ∈ N0 = N∪{0}, z ∈ U* and f(z) ∈ Σp, we introduce two subclasses of meromorphic p-valent analytic functions and investigate convolution and inclusion properties for these classes.

  10. Subclasses of Starlike Functions Associated with Fractional q-Calculus Operators

    Directory of Open Access Journals (Sweden)

    G. Murugusundaramoorthy

    2013-01-01

    Full Text Available Making use of fractional q-calculus operators, we introduce a new subclass ℳq(λ,γ,k of starlike functions and determine the coefficient estimate, extreme points, closure theorem, and distortion bounds for functions in ℳq(λ,γ,k. Furthermore we discuss neighborhood results, subordination theorem, partial sums, and integral means inequalities for functions in ℳq(λ,γ,k.

  11. Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment.

    Science.gov (United States)

    Lal, Preeti; Su, Zheng; Holweg, Cecile T J; Silverman, Gregg J; Schwartzman, Sergio; Kelman, Ariella; Read, Simon; Spaniolo, Greg; Monroe, John G; Behrens, Timothy W; Townsend, Michael J

    2011-12-01

    Rituximab significantly improves the signs and symptoms of rheumatoid arthritis (RA) and slows the progression of joint damage. The aim of this study was to identify clinical characteristics and biomarkers that identify patients with RA in whom the clinical benefit of rituximab may be enhanced. The study group comprised 1,008 RA patients from 2 independent randomized placebo-controlled phase III clinical trials (REFLEX [Randomized Evaluation of Long-Term Efficacy of Rituximab in Rheumatoid Arthritis] and SERENE [Study Evaluating Rituximab's Efficacy in Methotrexate Inadequate Responders]). A novel threshold selection method was used to identify baseline candidate biomarkers present in at least 20% of patients that enriched for placebo-corrected American College of Rheumatology 50% improvement (ACR50 response; a high clinical efficacy bar) at week 24 after the first course of rituximab. The presence of IgM rheumatoid factor (IgM-RF), IgG-RF, IgA-RF, and IgG anti-cyclic citrullinated peptide (anti-CCP) antibodies together with an elevated C-reactive protein (CRP) level were associated with enhanced placebo-corrected ACR50 response rates in the REFLEX patients with RA who had an inadequate response to anti-tumor necrosis factor therapies. These findings were independently replicated using samples from patients in SERENE who had an inadequate response to disease-modifying antirheumatic drug treatment. The combination of an elevated baseline CRP level together with an elevated level of any RF isotype and/or IgG anti-CCP antibodies was further associated with an enhanced benefit to rituximab. The presence of any RF isotype and/or IgG anti-CCP autoantibodies together with an elevated CRP level identifies a subgroup of patients with RA in whom the benefit of rituximab treatment may be enhanced. Although the clinical benefit of rituximab was greater in the biomarker-positive population compared with the biomarker-negative population, the clinical benefit of rituximab

  12. Phase transitions in human IgG solutions.

    Science.gov (United States)

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

    2013-09-28

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

  13. [Investigation of the presence of autoantibodies in patients with toxocariasis].

    Science.gov (United States)

    Kaya, Selçuk; Demirci, Mustafa; Sesli Cetin, Emel; Cicioğlu Aridoğan, Buket; Sahin, Mehmet; Taş, Tekin; Korkmaz, Metin

    2009-10-01

    Immunopathologic reactions may occur during toxocariasis due to tissue invasion and destruction by the secretions of larvae containing various enzymes with broad spectrum. The aim of this study was to search for autoantibodies such as anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (ASMA), anti-neutrophil cytoplasmic (ANCA), anti-myeloperoxidase (MPO) and liver-kidney microsomal type 1 (LKM-1) antibodies in patients with toxocariasis, in order to investigate the role of toxocariasis as a trigger factor for autoimmune reactions. Forty patients (22 were male; mean age: 35.6 +/- 10.7 years) diagnosed as toxocariasis by clinical findings (abdominal pain, allergic symptoms and/or eosinophilia, without detection of any other causative agents, and without liver dysfunction, diabetes mellitus, cardiac or renal failure, and autoimmune disease) and in-house ELISA positivity and 32 healthy controls (16 were male; mean age: 40.7 +/- 11.2 years) were included to the study. ANA (screen), dsDNA, SS-A, SS-B, Scl-70, LKM-1, MPO and M2 autoantibodies have been investigated by ELISA (Euroimmun, Germany), while ANCA, AMA and ASMA antibodies by indirect immunofluorescence (IMMCO, NY) methods. Autoantibody positivity was detected in 18 (45%) patients of whom 11 yielded a single type, and 7 yielded > or = 2 types of autoantibodies. This rate was 12.5% for control group (two subjects were positive for ANA-Screen, one for anti-M2 and one for anti-LKM-1). The difference between the total positivity rates in patient and control groups was found statistically significant (chi2 = 5.72, p = 0.004). The most frequent autoantibody type among patients were ASMA (n = 6), followed by anti-dsDNA (n = 5), anti-M2 (n = 5), anti-SS-B (n = 4), anti-LKM-1 (n = 3), anti-SS-A (n = 2), ANCA (n = 2) and anti-MPO (n = 1). Positivity rate for ASMA was found statistically significant in patients' group compared to controls (chi2 = 12.24, p = 0.03), while there was no significant difference

  14. Thyroid Autoantibodies in Pregnancy: Their Role, Regulation and Clinical Relevance

    Directory of Open Access Journals (Sweden)

    Francis S. Balucan

    2013-01-01

    Full Text Available Autoantibodies to thyroglobulin and thyroid peroxidase are common in the euthyroid population and are considered secondary responses and indicative of thyroid inflammation. By contrast, autoantibodies to the TSH receptor are unique to patients with Graves' disease and to some patients with Hashimoto's thyroiditis. Both types of thyroid antibodies are useful clinical markers of autoimmune thyroid disease and are profoundly influenced by the immune suppression of pregnancy and the resulting loss of such suppression in the postpartum period. Here, we review these three types of thyroid antibodies and their antigens and how they relate to pregnancy itself, obstetric and neonatal outcomes, and the postpartum.

  15. Detection of herbicide subclasses by an optical multibiosensor based on an array of photosystem II mutants.

    Science.gov (United States)

    Giardi, Maria Teresa; Guzzella, Licia; Euzet, Pierre; Rouillon, Regis; Esposito, Dania

    2005-07-15

    Massive use of herbicides in agriculture over the last few decades has become a serious environmental problem. The residual concentration of these compounds frequently exceeds the maximum admissible concentration in drinking water for human consumption and is a real environmental risk for the aquatic ecosystem. Herbicides inhibiting photosynthesis via targeting photosystem II function still represent the basic means of weed control. A multibiosensor was constructed for detecting herbicides using as biosensing elements photosynthetic preparations coupled to an optical fluorescence transduction system (Giardi et al. EU patent EP1134585, 01830148.1-2204); this paper is about its application in the detection of herbicide subclasses in river water. Photosynthetic material was immobilized on a silicio septum inside a series of flow cells, close to diodes so as to activate photosystem II (PSII) fluorescence. The principle of the detection was based on the factthat herbicides selectively modify PSII fluorescence activity. The multibiosensor has the original feature of being able to distinguish the subclasses of the photosynthetic herbicides by using specific immobilized biomediators isolated from mutated organisms. This setup resulted in a reusable, portable multibiosensor for the detection of herbicide subclasses with a half-life of 54 h for spinach thylakoids and limit of detection of 3 x 10(-9) M for herbicides present in river water.

  16. 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.

  17. Ultraviolet cross-linking of helical oligonucleotides to two monoclonal MRL-1pr/1pr anti-DNA autoantibodies. Variations in H and L chain binding to DNA

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Y.J.; Stollar, B.D. (Tufts Univ., Boston, MA (USA))

    1990-11-15

    Experiments were performed to determine whether both H and L chains of different anti-native DNA autoantibodies are uniformly involved in binding to DNA. Two purified monoclonal mouse (MRL-1pr/1pr) IgG autoantibodies, H241 and 2C10, were tested. They both bound synthetic helical oligonucleotides of 10 to 20 base pairs in a gel electrophoresis retardation assay but differed in their preferences for given base sequences. Exposure of antibody-radiolabeled oligonucleotide mixtures to UV light (254 nm) for 10 min led to specific covalent cross-linking of oligonucleotide to both the H and the L chains of H241 but only to the H chain of 2C10. Single labeling events were detected without higher aggregation. The oligonucleotides were not cross-linked to unrelated IgG, even after 2 h of irradiation. Cross-linked (radioactively labeled) H and L chains of H241 and 2C10 were isolated from denaturing electrophoresis gels and digested with lysyl endopeptidase and/or staphylococcal V8 protease. H241 and 2C10 H chains each yielded a major labeled peptide fragment, but the peptides from the two antibodies were different. These experiments measured only some of the antibody-DNA interactions, probably with bases in the major groove of the DNA. They indicated that two MRL-1pr/1pr IgG anti-native DNA antibodies differ in their H and L chain contacts with DNA and provide an approach to identifying affinity-labeled binding sites in the antibodies.

  18. 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.

  19. IgE and IgG4 Epitope Mapping of Food Allergens with a Peptide Microarray Immunoassay.

    Science.gov (United States)

    Martínez-Botas, Javier; de la Hoz, Belén

    2016-01-01

    Peptide microarrays are a powerful tool to identify linear epitopes of food allergens in a high-throughput manner. The main advantages of the microarray-based immunoassay are the possibility to assay thousands of targets simultaneously, the requirement of a low volume of serum, the more robust statistical analysis, and the possibility to test simultaneously several immunoglobulin subclasses. Among them, the last one has a special interest in the field of food allergy, because the development of tolerance to food allergens has been associated with a decrease in IgE and an increase in IgG4 levels against linear epitopes. However, the main limitation to the clinical use of microarray is the automated analysis of the data. Recent studies mapping the linear epitopes of food allergens with peptide microarray immunoassays have identified peptide biomarkers that can be used for early diagnosis of food allergies and to predict their severity or the self-development of tolerance. Using this approach, we have worked on epitope mapping of the two most important food allergens in the Spanish population, cow's milk and chicken eggs. The final aim of these studies is to define subsets of peptides that could be used as biomarkers to improve the diagnosis and prognosis of food allergies. This chapter describes the protocol to produce microarrays using a library of overlapping peptides corresponding to the primary sequences of food allergens and data acquisition and analysis of IgE- and IgG4-binding epitopes.

  20. Eosinophil localization to the basement membrane zone is autoantibody- and complement-dependent in a human cryosection model of bullous pemphigoid.

    Science.gov (United States)

    Messingham, Kelly N; Wang, Jeffrey W; Holahan, Heather M; Srikantha, Rupasree; Aust, Samantha C; Fairley, Janet A

    2016-01-01

    Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by antibodies (IgG and IgE) targeting cell-substrate adhesion proteins. A variety of BP models suggest that autoantibody-dependent neutrophil degranulation is essential for blister formation. However, lesional biopsies reveal a predominance of eosinophils and few neutrophils. Our goal was to evaluate the role of antibodies and complement in eosinophil localization, degranulation and split formation at the dermo-epidermal junction (DEJ) utilizing a human skin cryosection model of BP paired with a human eosinophilic cell line, 15HL-60. Expression of receptors for IgG (FcγRII), IgE (FcεRI) and complement (CR1 and CR3) was confirmed on 15HL-60 cells using flow cytometry. 15HL-60 expression of granule protein [eosinophil derived neurotoxin (EDN) and eosinophil peroxidase (EPO)] mRNA and their degranulation in vitro was confirmed using RT-PCR and ELISA, respectively. For cryosection experiments, BP or control sera or IgG and IgE antibodies purified from BP sera were utilized in combination with 15HL-60 cells ± fresh complement. Both BP serum and fresh complement were required for localization of 15-HL60 cells to the DEJ. Interestingly, eosinophil localization to the DEJ was dependent on IgG, but not IgE, and complement. However, no subepidermal split was observed. Additionally, the 15HL-60 cells did not degranulate under any experimental conditions and direct application of cell lysate to cryosections did not result in a split. Our observation that eosinophil localization to the DEJ is dependent on IgG mediated complement fixation provides additional insight into the sequence of events during the development of BP lesions.

  1. Guanine polynucleotides are self-antigens for human natural autoantibodies and are significantly reduced in the human genome.

    Science.gov (United States)

    Fattal, Ittai; Shental, Noam; Ben-Dor, Shifra; Molad, Yair; Gabrielli, Armando; Pokroy-Shapira, Elisheva; Oren, Shirly; Livneh, Avi; Langevitz, Pnina; Zandman-Goddard, Gisele; Sarig, Ofer; Margalit, Raanan; Gafter, Uzi; Domany, Eytan; Cohen, Irun R

    2015-11-01

    In the course of investigating anti-DNA autoantibodies, we examined IgM and IgG antibodies to poly-G and other oligonucleotides in the sera of healthy persons and those diagnosed with systemic lupus erythematosus (SLE), scleroderma (SSc), or pemphigus vulgaris (PV); we used an antigen microarray and informatic analysis. We now report that all of the 135 humans studied, irrespective of health or autoimmune disease, manifested relatively high amounts of IgG antibodies binding to the 20-mer G oligonucleotide (G20); no participants entirely lacked this reactivity. IgG antibodies to homo-nucleotides A20, C20 or T20 were present only in the sera of SLE patients who were positive for antibodies to dsDNA. The prevalence of anti-G20 antibodies led us to survey human, mouse and Drosophila melanogaster (fruit fly) genomes for runs of T20 and G20 or more: runs of T20 appear > 170,000 times compared with only 93 runs of G20 or more in the human genome; of these runs, 40 were close to brain-associated genes. Mouse and fruit fly genomes showed significantly lower T20/G20 ratios than did human genomes. Moreover, sera from both healthy and SLE mice contained relatively little or no anti-G20 antibodies; so natural anti-G20 antibodies appear to be characteristic of humans. These unexpected observations invite investigation of the immune functions of anti-G20 antibodies in human health and disease and of runs of G20 in the human genome.

  2. Functional autoantibodies against SSX-2 and NY-ESO-1 in multiple myeloma patients after allogeneic stem cell transplantation.

    Science.gov (United States)

    Luetkens, Tim; Kobold, Sebastian; Cao, Yanran; Ristic, Marina; Schilling, Georgia; Tams, Sinje; Bartels, Britta Marlen; Templin, Julia; Bartels, Katrin; Hildebrandt, York; Yousef, Sara; Marx, Andreas; Haag, Friedrich; Bokemeyer, Carsten; Kröger, Nicolaus; Atanackovic, Djordje

    2014-11-01

    Multiple myeloma (MM) is the malignancy with the most frequent expression of the highly immunogenic cancer-testis antigens (CTA), and we have performed the first analysis of longitudinal expression, immunological properties, and fine specificity of CTA-specific antibody responses in MM. Frequency and characteristics of antibody responses against cancer-testis antigens MAGE-A3, NY-ESO-1, PRAME, and SSX-2 were analyzed using peripheral blood (N = 1094) and bone marrow (N = 200) plasma samples from 194 MM patients. We found that antibody responses against CTA were surprisingly rare, only 2.6 and 3.1 % of patients evidenced NY-ESO-1- and SSX-2-specific antibodies, respectively. NY-ESO-1-specific responses were observed during disease progression, while anti-SSX-2 antibodies appeared after allogeneic stem cell transplantation and persisted during clinical remission. We found that NY-ESO-1- and SSX-2-specific antibodies were both capable of activating complement and increasing CTA uptake by antigen-presenting cells. SSX-2-specific antibodies were restricted to IgG3, NY-ESO-1 responses to IgG1 and IgG3. Remarkably, NY-ESO-1-positive sera recognized various non-contiguous regions, while SSX-2-specific responses were directed against a single 6mer epitope, SSX-2(85-90). We conclude that primary autoantibodies against intracellular MM-specific tumor antigens SSX-2 and NY-ESO-1 are rare but functional. While their contribution to disease control still remains unclear, our data demonstrate their theoretic ability to affect cellular anti-tumor immunity by formation and uptake of mono- and polyvalent immune complexes.

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

    Science.gov (United States)

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

    2017-01-01

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

  4. 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...

  5. The significance of autoantibodies against beta(2)-glycoprotein I

    NARCIS (Netherlands)

    de Groot, Philip G.; Urbanus, Rolf T.

    2012-01-01

    The antiphospholipid syndrome (APS) is defined by the persistent presence of antiphospholipid antibodies in patients with a history of thrombosis and/or pregnancy morbidity, including fetal loss. APS is an autoimmune disease with a confusing name because the pathologic auto-antibodies are shown to b

  6. MHC associations with clinical and autoantibody manifestations in European SLE.

    Science.gov (United States)

    Morris, D L; Fernando, M M A; Taylor, K E; Chung, S A; Nititham, J; Alarcón-Riquelme, M E; Barcellos, L F; Behrens, T W; Cotsapas, C; Gaffney, P M; Graham, R R; Pons-Estel, B A; Gregersen, P K; Harley, J B; Hauser, S L; Hom, G; Langefeld, C D; Noble, J A; Rioux, J D; Seldin, M F; Vyse, T J; Criswell, L A

    2014-04-01

    Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the highest number and most statistically significant associations. HLA-DRB1*03:01 was significantly associated with both sub-phenotypes. We found evidence of associations independent of MHC class II variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro and anti-La subsets are independently associated with HLA-DRB1*0301, and that the HLA-DRB1*03:01 association with SLE is largely but not completely driven by the association of this allele with these sub-phenotypes. Our results provide strong evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the association with anti-Ro and anti-La antibody-positive SLE is much stronger than SLE without these autoantibodies.

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

    Directory of Open Access Journals (Sweden)

    C. Poggialini

    2014-02-01

    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.

  8. 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

  9. IgG4 Inflammatory Pseudotumor of the Kidney

    Directory of Open Access Journals (Sweden)

    Ahmed N. Alkhasawneh

    2012-01-01

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

  10. Structural Basis for Fc[gamma]RIIa Recognition of Human IgG and Formation of Inflammatory Signaling Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Ramsland, Paul A.; Farrugia, William; Bradford, Tessa M.; Sardjono, Caroline Tan; Esparon, Sandra; Trist, Halina M.; Powell, Maree S.; Tan, Peck Szee; Cendron, Angela C.; Wines, Bruce D.; Scott, Andrew M.; Hogarth, P. Mark (Burnet); (Monash); (LICR); (Melbourne)

    2011-09-20

    The interaction of Abs with their specific FcRs is of primary importance in host immune effector systems involved in infection and inflammation, and are the target for immune evasion by pathogens. Fc{gamma}RIIa is a unique and the most widespread activating FcR in humans that through avid binding of immune complexes potently triggers inflammation. Polymorphisms of Fc{gamma}RIIa (high responder/low responder [HR/LR]) are linked to susceptibility to infections, autoimmune diseases, and the efficacy of therapeutic Abs. In this article, we define the three-dimensional structure of the complex between the HR (arginine, R134) allele of Fc{gamma}RIIa (Fc{gamma}RIIa-HR) and the Fc region of a humanized IgG1 Ab, hu3S193. The structure suggests how the HR/LR polymorphism may influence Fc{gamma}RIIa interactions with different IgG subclasses and glycoforms. In addition, mutagenesis defined the basis of the epitopes detected by FcR blocking mAbs specific for Fc{gamma}RIIa (IV.3), Fc{gamma}RIIb (X63-21), and a pan Fc{gamma}RII Ab (8.7). The epitopes detected by these Abs are distinct, but all overlap with residues defined by crystallography to contact IgG. Finally, crystal structures of LR (histidine, H134) allele of Fc{gamma}RIIa and Fc{gamma}RIIa-HR reveal two distinct receptor dimers that may represent quaternary states on the cell surface. A model is presented whereby a dimer of Fc{gamma}RIIa-HR binds Ag-Ab complexes in an arrangement that possibly occurs on the cell membrane as part of a larger signaling assembly.

  11. 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.

  12. Afferent facilitation of corticomotor responses is increased by IgGs of patients with NMDA-receptor antibodies.

    Science.gov (United States)

    Manto, Mario; Dalmau, Josep; Didelot, Adrien; Rogemond, Véronique; Honnorat, Jérôme

    2011-01-01

    A severe subacute encephalitis associated with auto-antibodies to the NMDA receptor (NMDA-R) has been reported in humans. These antibodies are directed to NR1/NR2 heteromers of the NMDA receptor. We studied the effects of patients' cerebrospinal fluid (CSF) injected in rFr2 (the prefrontal area) on the afferent facilitation in a conditioning paradigm for corticomotor responses. The afferent facilitation was assessed in forelimbs and hindlimbs of rats, before and after application of trains of high-frequency stimulation (HFS) which are known to modulate the excitability of M1. Before HFS, patients' CSF did not modify afferent facilitation. After HFS, the amplitudes of corticomotor responses before conditioning were significantly larger in forelimbs and hindlimbs. There was an increase of the afferent facilitation in forelimbs. The same effect was observed after injection of purified IgGs from patients' sera. Our results highlight that IgGs of patients with NMDA-R antibodies induce a state of corticomotor hyperexcitability following application of HFS over the prefrontal area.

  13. 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.

  14. Specificity of islet cell autoantibodies and coexistence with other organ specific autoantibodies in type 1 diabetes mellitus.

    Science.gov (United States)

    Tsirogianni, Alexandra; Pipi, Elena; Soufleros, Konstantinos

    2009-07-01

    Type 1 diabetes mellitus (T1DM) has been shown to be a disease characterized by immune-mediated destruction of the insulin-producing islet beta-cells (beta-cells) in the pancreas. Intensive studies, in both patients and animal models are trying to elucidate the specific antigenic targets that are responsible for islet cell autoimmunity. So far, the most important molecules that have been recognized are the native insulin, the 65-kDa form of glutamic acid decarboxylase (GAD(65)) and the insulinoma-antigen 2 (IA-2). Identification of those specific autoantibodies that are involved in the primary immunological events of the autoimmune disease process will allow the development of novel diagnostic procedures for early detection and initiation of potential therapy prior to irreversible loss of beta-cells. Within the framework of polyglandular disorders, T1DM may coexist with other organ specific autoimmune diseases such as autoimmune thyroid disease (ATD), autoimmune gastritis (AG), celiac disease (CD) and Addison's disease (AD), which are associated with the production of organ-specific autoantibodies. So, as a subset of patients with those autoantibodies will develop clinical disease, screening T1DM patients could prognosticate morbidity relative to unrecognised clinical entities. The close follow-up of patients with organ-specific autoantibodies could lead to seasonable identification of those requiring therapy.

  15. Autoantibody profile in rheumatoid arthritis during long-term infliximab treatment

    Science.gov (United States)

    Bobbio-Pallavicini, Francesca; Alpini, Claudia; Caporali, Roberto; Avalle, Stefano; Bugatti, Serena; Montecucco, Carlomaurizio

    2004-01-01

    The aim of the present study was to investigate the effect of long-term infliximab treatment on various autoantibodies in patients with rheumatoid arthritis. Serum samples from 30 consecutive patients, who were prospectively followed during infliximab and methotrexate therapy for refractory rheumatoid arthritis, were tested at baseline and after 30, 54 and 78 weeks. At these points, median values of the Disease Activity Score were 6.38 (interquartile range 5.30–6.75), 3.69 (2.67–4.62), 2.9 (2.39–4.65) and 3.71 (2.62–5.06), respectively. Various autoantibodies were assessed by standard indirect immunofluorescence and/or ELISA. Initially, 50% of patients were positive for antinuclear antibodies, and this figure increased to 80% after 78 weeks (P = 0.029). A less marked, similar increase was found for IgG and IgM anticardiolipin antibody titre, whereas the frequency of anti-double-stranded DNA antibodies (by ELISA) exhibited a transient rise (up to 16.7%) at 54 weeks and dropped to 0% at 78 weeks. Antibodies to proteinase-3 and myeloperoxidase were not detected. The proportion of patients who were positive for rheumatoid factor (RF) was similar at baseline and at 78 weeks (87% and 80%, respectively). However, the median RF titre exhibited a progressive reduction from 128 IU/ml (interquartile range 47–290 IU/ml) to 53 IU/ml (18–106 IU/ml). Anti-cyclic citrullinated peptide (CCP) antibodies were found in 83% of patients before therapy; anti-CCP antibody titre significantly decreased at 30 weeks but returned to baseline thereafter. In conclusion, the presence of anti-double-stranded DNA antibodies is a transient phenomenon, despite a stable increase in antinuclear and anticardiolipin antibodies. Also, the evolution of RF titres and that of anti-CCP antibody titres differed during long-term infliximab therapy. PMID:15142273

  16. Characterization of Polyclonal Antibody Induced by Autoantibody TPO (Thyroidperoxidase) From Autoimmune Thyroid Disease (AITD) Serum with ELISA and Western Blotting

    OpenAIRE

    Maulidya Aulia Fiqriyana; Aulanni'am Aulanni'am; Anna Roosdiana

    2013-01-01

    Autoantibody TPO is a potential marker for early detection of autoimmune thyroid disease (AITD). Autoantibody TPO has a specifity and a sensitivity ranging from 82% to100% in comparison to other AITD serology markers. Concentration of autoantibody TPO in sera had a positive correlation with activities of chronic AITD. This research have been conducted to investigate the characteristic of polyclonal antibody TPO induced by autoantibody TPO from serum of AITD patients. The autoantibody TPO was ...

  17. 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 PLA2R was a useful predictor for achieving CR, but there was a high heterogeneity; (2) there was significant correlation between the baseline and decrease in 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.

  18. IgG4-related disease and the kidney.

    Science.gov (United States)

    Cortazar, Frank B; Stone, John H

    2015-10-01

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

  19. Flavonoids, flavonoid subclasses and breast cancer risk: a meta-analysis of epidemiologic studies.

    Directory of Open Access Journals (Sweden)

    Chang Hui

    Full Text Available BACKGROUND: Studies have suggested the chemopreventive effects of flavonoids on carcinogenesis. Yet numbers of epidemiologic studies assessing dietary flavonoids and breast cancer risk have yielded inconsistent results. The association between flavonoids, flavonoid subclasses (flavonols, flavan-3-ols, etc. and the risk of breast cancer lacks systematic analysis. OBJECTIVE: We aimed to examine the association between flavonoids, each flavonoid subclass (except isoflavones and the risk of breast cancer by conducting a meta-analysis. DESIGN: We searched for all relevant studies with a prospective cohort or case-control study design published before July 1(st, 2012, using Cochrane library, MEDLINE, EMBASE and PUBMED. Summary relative risks (RR were calculated using fixed- or random-effects models. All analyses were performed using STATA version 10.0. RESULTS: Twelve studies were included, involving 9 513 cases and 181 906 controls, six of which were prospective cohort studies, and six were case-control studies. We calculated the summary RRs of breast cancer risk for the highest vs lowest categories of each flavonoid subclass respectively. The risk of breast cancer significantly decreased in women with high intake of flavonols (RR=0.88, 95% CI 0.80-0.98 and flavones (RR=0.83, 95% CI: 0.76-0.91 compared with that in those with low intake of flavonols and flavones. However, no significant association of flavan-3-ols (RR=0.93, 95% CI: 0.84-1.02, flavanones (summary RR=0.95, 95% CI: 0.88-1.03, anthocyanins (summary RR=0.97, 95% CI: 0.87-1.08 or total flavonoids (summary RR=0.98, 95% CI: 0.86-1.12 intake with breast cancer risk was observed. Furthermore, summary RRs of 3 case-control studies stratified by menopausal status suggested flavonols, flavones or flavan-3-ols intake is associated with a significant reduced risk of breast cancer in post-menopausal while not in pre-menopausal women. CONCLUSIONS: The present study suggests the intake of flavonols

  20. IgG glycosylation changes and MBL2 polymorphisms

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  1. 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.

  2. Clinical study on IgG4-related autoimmune pancreatitis

    Institute of Scientific and Technical Information of China (English)

    吴庆军

    2013-01-01

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

  3. Heterogeneity of IgG glycosylation in adult periodontal disease.

    Science.gov (United States)

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

    2005-10-01

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

  4. Reducing sample complexity of polyclonal human autoantibodies by chromatofocusing.

    Science.gov (United States)

    Hagemann, Sascha; Faude, Alexander; Rabenstein, Monika; Balzer-Geldsetzer, Monika; Nölker, Carmen; Bacher, Michael; Dodel, Richard

    2010-08-15

    Chromatofocusing was performed in order to separate a polyclonal antigen-specific mixture of human immunoglobulins (IgGs) that would then allow for further analyses of as few different IgGs as possible. Because polyclonal IgGs only differ by amino acid sequence and possible post-translational modifications but not by molecular weight, we chose chromatofocusing for protein separation by different isoelectric points. We isolated antigen-specific IgGs from commercially available intravenous immunoglobulins (IVIG) using a combination of affinity- and size exclusion-chromatography and in order to reduce the complexity of the starting material IVIG was then replaced by single-donor plasmapheresis material. Using two-dimensional gel electrophoresis (2-DE), we observed a clear decrease in the number of different light and heavy chains in the chromatofocusing peak as compared to the starting material. In parallel, we monitored slight problems with the selected peak in isoelectric focusing as the first dimension of 2-DE, displayed in by the less proper focusing of the spots. When we tested whether IgGs were binding to their specific antigen after chromatofocusing, we were able to show that they were still in native conformation. In conclusion, we showed that chromatofocusing can be used as a first step in the analysis of mixtures of very similar proteins, e.g. polyclonal IgG preparations, in order to minimize the amount of different proteins in separated fractions in a reproducible way. Copyright 2010 Elsevier B.V. All rights reserved.

  5. 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.

  6. Two major autoantibody clusters in systemic lupus erythematosus.

    Directory of Open Access Journals (Sweden)

    Kathryn H Ching

    Full Text Available Systemic lupus erythematosus is a chronic autoimmune disease of complex clinical presentation and etiology and is likely influenced by numerous genetic and environmental factors. While a large number of susceptibility genes have been identified, the production of antibodies against a distinct subset of nuclear proteins remains a primary distinguishing characteristic in disease diagnosis. However, the utility of autoantibody biomarkers for disease sub-classification and grouping remains elusive, in part, because of the difficulty in large scale profiling using a uniform, quantitative platform. In the present study serological profiles of several known SLE antigens, including Sm-D3, RNP-A, RNP-70k, Ro52, Ro60, and La, as well as other cytokine and neuronal antigens were obtained using the luciferase immunoprecipitation systems (LIPS approach. The resulting autoantibody profiles revealed that 88% of a pilot cohort and 98% of a second independent cohort segregated into one of two distinct clusters defined by autoantibodies against Sm/anti-RNP or Ro/La autoantigens, proteins often involved in RNA binding activities. The Sm/RNP cluster was associated with a higher prevalence of serositis in comparison to the Ro/La cluster (P = 0.0022. However, from the available clinical information, no other clinical characteristics were associated with either cluster. In contrast, evaluation of autoantibodies on an individual basis revealed an association between anti-Sm (P = 0.006, RNP-A (P = 0.018 and RNP-70k (P = 0.010 autoantibodies and mucocutaneous symptoms and between anti-RNP-70k and musculoskeletal manifestations (P = 0.059. Serologically active, but clinically quiescent disease also had a higher prevalence of anti-IFN-α autoantibodies. Based on our findings that most SLE patients belong to either a Sm/RNP or Ro/La autoantigen cluster, these results suggest the possibility that alterations in RNA-RNA-binding protein interactions may

  7. The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients.

    Science.gov (United States)

    Liu, Jin; Bian, Lingling; Ji, Li; Chen, Yang; Chen, Heng; Gu, Yong; Ma, Bingqin; Gu, Wei; Xu, Xinyu; Shi, Yun; Wang, Jian; Zhu, Dalong; Sun, Zilin; Ma, Jianhua; Jin, Hui; Shi, Xing; Miao, Heng; Xin, Bing; Zhu, Yan; Zhang, Zhenwen; Bu, Ruifang; Xu, Lan; Shi, Guangde; Tang, Wei; Li, Wei; Zhou, Dongmei; Liang, Jun; Cheng, Xingbo; Shi, Bimin; Dong, Jixiang; Hu, Ji; Fang, Chen; Zhong, Shao; Yu, Weinan; Lu, Weiping; Wu, Chenguang; Qian, Li; Yu, Jiancheng; Gao, Jialin; Fei, Xiaoqiang; Zhang, Qingqing; Wang, Xueqin; Cui, Shiwei; Cheng, Jinluo; Xu, Ning; Wang, Guofeng; Han, Guoqing; Xu, Chunrong; Xie, Yun; An, Minmin; Zhang, Wei; Wang, Zhixiao; Cai, Yun; Fu, Qi; Fu, Yu; Zheng, Shuai; Yang, Fan; Hu, Qingfang; Dai, Hao; Jin, Yu; Zhang, Zheng; Xu, Kuanfeng; Li, Yifan; Shen, Jie; Zhou, Hongwen; He, Wei; Zheng, Xuqin; Han, Xiao; Yu, Liping; She, Jinxiong; Zhang, Mei; Yang, Tao

    2016-09-01

    Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests i