Identification of new autoantibody specificities directed at proteins involved in the transforming growth factor beta pathway in patients with systemic sclerosis.

Abstract : ABSTRACT: INTRODUCTION: Antinuclear antibodies (ANA), usually detected by indirect immunofluorescence on HEp-2 cells, are identified in 90% of patients with systemic sclerosis (SSc). Thus, approximately 10% of SSc patients have no routinely detectable autoantibodies, and for 20% to 40% of those with detectable ANA, the ANA do not have identified specificity (non-identified ANA). In this work, we aimed to identify new target autoantigens in SSc patients. METHODS: Using a proteomic approach combining 2-D electrophoresis and immunoblotting with HEp-2 cell total and enriched nuclear protein extracts as sources of autoantigens, we systematically analysed autoantibodies in SSc patients. Sera from 45 SSc patients were tested in 15 pools from groups of 3 patients with the same phenotype. A sera pool from 12 healthy individuals was used as a control. Proteins of interest were identified by mass spectrometry and analysed using Pathway Studio software. RESULTS: We identified 974 and 832 protein spots in HEp-2 cell total and enriched nuclear protein extracts, respectively. Interestingly, alpha-enolase was recognised by immunoglobulin-G (IgG) from all pools of patients in both extracts. Fourteen and 4 proteins were recognised by IgG from at least 75% of the 15 pools in total and enriched nuclear protein extracts, respectively, whereas 15 protein spots were specifically recognised by IgG from at least 4 of the 10 pools from patients with non-identified ANA. The IgG intensity for a number of antigens was higher in sera from patients than in those from healthy controls; these antigens included triosephosphate isomerase, superoxide dismutase mitochondrial precursor, heterogeneous nuclear ribonucleoprotein L and lamin A/C. In addition, peroxiredoxin-2, cofilin-1 and calreticulin were specifically recognised by sera from phenotypic subsets of patients with non-identified ANA. Interestingly, several identified target antigens were involved in the transforming growth factor-beta pathway. CONCLUSIONS: We identified several new target antigens shared among patients with SSc or specific to a given phenotype. The specification of new autoantibodies could help in understanding the pathophysiology of SSc. Moreover, these autoantibodies could represent new diagnostic and/or prognostic markers for SSc.
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Arthritis Research and Therapy, BioMed Central, 2011, 13 (3), pp.R74. 〈10.1186/ar3336〉
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Guillaume Bussone, Hanadi Dib, Mathieu Tamby, Cedric Broussard, Christian Federici, et al.. Identification of new autoantibody specificities directed at proteins involved in the transforming growth factor beta pathway in patients with systemic sclerosis.. Arthritis Research and Therapy, BioMed Central, 2011, 13 (3), pp.R74. 〈10.1186/ar3336〉. 〈inserm-00606111〉

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