An immunodominant La/SSB autoantibody proteome derives from public clonotypes.

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.

Clinical and laboratory characteristics of 19 patients with Churg-Strauss syndrome from a single South Australian centre.

BACKGROUND: Churg-Strauss syndrome (CSS) is a rare, idiopathic systemic vasculitis. There is emerging evidence of an association between the presence or absence of antineutrophil cytoplasmic antibodies (ANCA) and clinical phenotype. Thromboembolism is an increasingly recognised complication of the disease. AIMS: Given the paucity of Australian data, the aim of this study was to examine the clinical and laboratory features of CSS in a single Australian centre. METHODS: We performed a retrospective review of all patients who fulfilled the American College of Rheumatology classification criteria for CSS managed at the Department of Immunology, Royal Adelaide Hospital between 2002 and 2008. RESULTS: Nineteen patients were included. All patients had asthma and most had upper airway involvement. Peripheral nerve, musculoskeletal, gastrointestinal and cutaneous involvement was common. Renal and cardiac involvement was uncommon in this series. Histological confirmation was obtained in 15 patients (78.9%). Ten patients (52.6%) were ANCA+, and these were more likely to have musculoskeletal involvement, such as arthralgia or myalgia (odds ratio 57, P = 0.005). Thrombosis was a feature at diagnosis in six patients (31.6%); two of these recurred with relapse. Sixteen patients (84.2%) were followed up; five died, and mean survival was 8.9 years. CONCLUSIONS: This is the first Australian study to focus on CSS. Our results demonstrate similar presentation and prognosis of CSS to previous descriptions; however, we noted that musculoskeletal involvement was more common in ANCA+ patients. In our series, thrombosis was a significant complication and we suggest that thromboprophylaxis may be warranted.