Abstract：
:The La/SSB autoantigen is a major target of long-term humoral autoimmunity in primary Sjögren's Syndrome (SS) and systemic lupus erythematosus. A majority of patients with linked anti-Ro60/Ro52/La responses target an NH2-terminal epitope designated LaA that is expressed on Ro/La ribonucleoprotein complexes and the surface membrane of apoptotic cells. In this study, we used high-resolution Orbitrap mass spectrometry to determine the clonality, isotype and V-region sequences of LaA-specific autoantibodies in seven patients with primary SS. Anti-LaA immunoglobulin (Ig)Gs purified from polyclonal sera by epitope-specific affinity chromatography were analysed by combined database and de-novo mass spectrometric sequencing. Autoantibody responses comprised two heavily mutated IgG1 kappa-restricted monoclonal species that were shared (public) across unrelated patients; one clonotype was specified by an IGHV3-30 heavy chain paired with IGKV3-15 light chain and the second by an IGHV3-43/IGKV3-20 pairing. Shared amino acid replacement mutations were also seen within heavy and light chain complementarity-determining regions, consistent with a common breach of B cell tolerance followed by antigen-driven clonal selection. The discovery of public clonotypic autoantibodies directed against an immunodominant epitope on La, taken together with recent findings for the linked Ro52 and Ro60 autoantigens, supports a model of systemic autoimmunity in which humoral responses against protein-RNA complexes are mediated by public sets of autoreactive B cell clonotypes.
journal_name
Clin Exp Immunoljournal_title
Clinical and experimental immunologyauthors
Thurgood LA,Arentz G,Lindop R,Jackson MW,Whyte AF,Colella AD,Chataway TK,Gordon TPdoi
10.1111/cei.12171subject
Has Abstractpub_date
2013-11-01 00:00:00pages
237-44issue
2eissn
0009-9104issn
1365-2249journal_volume
174pub_type
杂志文章abstract：:The specificities of a panel of erythrocyte-reactive MoAbs derived from NZB mice with autoimmune haemolytic anaemia (AIHA) were determined by immunoprecipitation and immunoblotting. Of the eight antibodies, two (IgG1 MoAb 105-2H and IgG2a MoAb 34-3C) immunoprecipitated a 105-kD component identified as the erythrocyte ...
journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：10.1046/j.1365-2249.1996.d01-772.x
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abstract：:Thyroid peroxidase purified from porcine thyroid (pTPO) was found to induce an experimental murine thyroiditis with genetic restriction which was very different from that induced by mouse thyroglobulin (mTg). C57BL/6 and C57BL/10 (both H-2b) were good responders for thyroiditis, whereas A/J (H-2a), BALB/c (H-2d), DBA/...
journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：10.1111/j.1365-2249.1990.tb06434.x
更新日期：1990-04-01 00:00:00
abstract：:Mononuclear cells from twenty-one patients with depressed cellular reactivity were assessed for the ability to produce leucocyte inhibitory factor (LIF) and to transform after PHA stimulation, in the presence or absence of levamisole. Cells from nineteen patients failed to produce significant lymphokines when stimulat...
journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1976-11-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1987-03-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
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pub_type： 杂志文章
doi：10.1111/j.1365-2249.2005.02731.x
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：10.1046/j.1365-2249.2003.02145.x
更新日期：2003-05-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1988-08-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1989-02-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1980-07-01 00:00:00
abstract：:The BB rat is a well-known animal model for the study of autoimmune thyroid disease. Antithyroglobulin antibodies can be detected in the circulation from the age of 6 weeks onwards, and accumulations of lymphoid cells occurs in the thyroid of up to 60% of animals at the age of 20 weeks and over. The rat, however, stay...
journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1989-05-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1985-07-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1985-08-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1984-10-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1985-02-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1987-04-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1977-05-01 00:00:00
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pub_type： 临床试验,杂志文章,多中心研究
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更新日期：2002-11-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
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更新日期：1991-09-01 00:00:00
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journal_title：Clinical and experimental immunology
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doi：
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1978-08-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1983-10-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：10.1111/j.1365-2249.1991.tb05799.x
更新日期：1991-11-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：10.1046/j.1365-2249.1998.00647.x
更新日期：1998-08-01 00:00:00
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pub_type： 杂志文章
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更新日期：2002-02-01 00:00:00
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pub_type： 杂志文章
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更新日期：2005-04-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：10.1111/j.1365-2249.1993.tb03375.x
更新日期：1993-01-01 00:00:00
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journal_title：Clinical and experimental immunology
pub_type： 杂志文章
doi：
更新日期：1983-01-01 00:00:00
