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Summary Patients with insulin-dependent diabetes mellitus (IDDM) possess antibodies to the cytoplasmic domains of two closely related
tyrosine phosphatase-like proteins, IA-2 and phogrin, previously detected as 40 kDa and 37 kDa tryptic fragments, respectively.
A higher proportion of IDDM patients possess antibodies to IA-2 than to phogrin, and autoimmunity to phogrin might arise through
cross-reactivity with the highly homologous IA-2. In this study, we have investigated the major regions of IA-2 recognized
by antibodies in IDDM patients and examined the ability of phogrin to block antibody binding to these regions as a measure
of cross-reactivity. Analysis of antibody binding to in vitro transcribed and translated polypeptides representing different
regions of the cytoplasmic domain of IA-2 identified five different patterns of reactivity with antibodies in IDDM. Protein
footprinting analysis, whereby polypeptide fragments generated on protease treatment of immune complexes are studied, indicated
considerable heterogeneity in antibody recognition of IA-2, even between sera with similar reactivity to deletion mutants.
Blocking studies with recombinant phogrin indicated that IA-2 antibodies recognize epitopes that are both unique to IA-2 and
shared with phogrin. The amino-terminal 150 amino acids of the cytoplasmic domain of IA-2 encompass epitopes that are not
represented on phogrin, whereas shared epitopes are localized within the carboxy-terminal 220 amino acids. The results demonstrate
considerable heterogeneity between IDDM patients in autoantibody recognition of IA-2 in IDDM, whereas antibody recognition
of phogrin is restricted in most patients to epitopes also present on IA-2. [Diabetologia (1997) 40: 1327–1333]
Received: 4 April 1997 and in revised form: 2 July 1997 相似文献
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脑脊液髓鞘碱性蛋白(MBP)自身抗体固相发光免疫分析法,是一项免疫检测新技术,目前国外尚未见到对脱髓病研究的报道。本文作者于1988.5~1989.3首先采用本法并证实其可靠性后,进入临床研究,对36例脱髓鞘病及20例其他CNS疾病者的对照组,用三项免疫指标行对比分析。CSFMBP自身抗体含量及其和同量IgG自身抗体的百分比值分别为69.23±11.95ng/ml及3.24±0.52ug/mg±gG和对照组相比,P值分别为<0.05及<0.001,有显著差异,对本病诊断有意义。 相似文献
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We have identified an autoantigen that is recognized by antibodies from an 18-year-old female with a history of recurrent infections who later in her clinical course developed Raynaud's phenomenon and telangiectasias. By indirect immunofluorescence (IIF), the index serum produced a unique cytoplasmic discrete speckled (CDS) staining pattern that partially colocalized with early endosome antigen 1 (EEA1) but not Golgi complex or other cytoplasmic organelles in HEp-2 cells. When HEp-2 cells were treated with 0.1 N HCl, the cytoplasmic speckled staining of the index serum was markedly decreased, suggesting that the reactive antigen was soluble. Western blot analysis showed a reactive approximately 97 kDa protein in a saline soluble protein preparation from HeLa cells. Mass spectrometric analysis of the excised 97 kDa band that was immunoprecipitated from HeLa cell extracts identified GRASP-1 as a possible target. The index serum and anti-GRASP-1 antibodies colocalized to structures in the cytoplasm of HEp-2 cells. Synthetic peptides representing the full-length GRASP-1 protein were used to identify reactive epitopes. Like many other cytoplasmic autoantigens, GRASP-1 has numerous coiled-coil domains throughout the protein with the exception of short segments at the amino and carboxyl terminus. 相似文献
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BALB/c mice immunized with multimeric DWEYSVWLSN develop IgG1 anti-DNA antibodies and glomerular immunoglobulin deposits, leading us to investigate the role of IL-4 in this model of antigen induced lupus. Splenocytes from DWEYSVWLSN immunized mice secreted IL-4 but not gamma-interferon. Following peptide immunization, IgG1 anti-peptide and anti-DNA antibodies were significantly higher in IL-4 wild type mice, while IgM and IgG3 anti-DNA levels were significantly higher in IL-4 knockout mice. Titers of IgG anti-laminin and anti-histone, but not anti-Sm/RNP and anti-cardiolipin antibodies, were significantly higher in the IL-4 wild type group. Glomerular immunoglobulin deposition was substantially decreased in IL-4 knockout mice. We conclude that while IL-4 does not materially affect the generation of some autoantibody responses associated with peptide induced autoimmunity, IL-4 deficiency inhibits kidney immunoglobulin deposition. The effect of IL-4 on humoral autoimmunity in lupus is complex, and is dependent on genetic background, the antigenic trigger and stage of disease. 相似文献
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Giulia Kramar Teresa Aguado Jacques Louis Giuseppe Del Giudice Paul-Henri Lambert 《European journal of immunology》1993,23(10):2551-2556
BALB/c mice injected at birth with semi-allogeneic F1 spleen cells become tolerant to alloantigens as shown by their CTL unresponsiveness to the corresponding alloantigen and the persistence of donor F1 cells into the BALB/c host. Moreover, these mice develop a transient systemic lupus erythematosis-like autoimmune syndrome characterized by splenomegaly, glomerulonephritis, thrombocytopenia and abnormal serological findings, such as several autoantibodies and IgG1 hypergammaglobulinemia. Recent studies done in our laboratory have shown that donor F1 B cells persisting in the host are responsible for the production of autoantibodies and must be activated in vivo by the host CD4+ T lymphocytes in a MHC class II-restricted fashion. In the present work, we have focused our attention on the ability of splenic CD4+ T cells recovered at different periods from BALB/c mice injected at birth with (CBA/Ca × BALB. Ighb) Fl spleen cells to interact with and activate F1 semi-allogeneic spleen cells in vitro. We show that (i) only CD4+ T cells from 2- and 3-week-old tolerant BALB/c mice preferentially produce IL-4 and IL-5 in response to a F1 semi-allogeneic in vitro stimulation, (ii) CD4+ T cells purified from 3-week-old tolerant BALB/c mice are able to induce in vitro IgG and IgM production by F1 B cells. Taken together, these results strongly suggest that host CD4+ T cells, belonging to the TH2 subset progressively lose their reactivity towards the F1 semi-allogeneic persistent B cells, reaching a state of unresponsiveness that correlates with the disappearance of serum autoantibodies and autoimmune pathology. 相似文献
9.
血清抗甲状腺球蛋白抗体和抗甲状腺过氧化物酶抗体检测在甲状腺疾病诊断及甲亢预后判断中的价值 总被引:1,自引:0,他引:1
采用放免法检测甲状豚疾病患者抗甲状腺球蛋白抗体(TGAb)和抗甲状腺过氧化物酶抗体(TPOAb)、并对部分Graves病患者停药后随诊一年的结果进行分析。结果显示:(1)自身免疫性甲状腺疾病患者TGAb和TPOAb活性及阳性率明显高于非AITD,尤以桥本甲状腺炎为然。(2)GD治疗前及停药时TGAb和TPOAb均阴性者与均阳性者停药一年内的复发率分别为0.583和0.231。(3)TGAb和TPOAb均阴性,而停药时甲状腺刺激抗体(TSAb)阳性者,停药时GD复发的机率最大(0.909),提示TGAb和TPOAb检测在AITD诊断,鉴别诊断以及GD预后判断中具有重要的临床意义。 相似文献
10.
Martin Juenemann Holger Nef Helge Möllmann Pratibha Singh Christian Troidl Patrick Schramm Manfred Kaps Tibo Gerriets Franz Blaes Marlene Tschernatsch 《Immunobiology》2019,224(2):220-222