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An immunodominant La/SSB autoantibody proteome derives from public clonotypes.
- Source :
-
Clinical and experimental immunology [Clin Exp Immunol] 2013 Nov; Vol. 174 (2), pp. 237-44. - Publication Year :
- 2013
-
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.<br /> (© 2013 British Society for Immunology.)
- Subjects :
- Adolescent
Adult
Autoantibodies isolation & purification
Autoantigens immunology
Child
Child, Preschool
Chromatography, Affinity
Clonal Selection, Antigen-Mediated
Clone Cells
Female
Humans
Immune Tolerance
Immunity, Humoral
Immunodominant Epitopes immunology
Male
Mass Spectrometry
Proteomics
Ribonucleoproteins immunology
Young Adult
SS-B Antigen
Autoantibodies immunology
Autoantigens metabolism
B-Lymphocytes immunology
Immunodominant Epitopes metabolism
Ribonucleoproteins metabolism
Sjogren's Syndrome immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2249
- Volume :
- 174
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical and experimental immunology
- Publication Type :
- Academic Journal
- Accession number :
- 23841690
- Full Text :
- https://doi.org/10.1111/cei.12171