Xin 2, cofilin 1 and calreticulin were specifically recognised by Rosiglitazone sera from phenotypic subsets of patients with unidentified ANAs. Interestingly, several identified target antigens were involved in the transforming growth factor b 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.* Correspondence: luc.mouthon@cch.aphp.fr 1 Institut Cochin, Universit?Paris Descartes, CNRS UMR 8104, 8 rue M hain, F-75014 Paris, France Full list of author information is available at the end of the article?2011 Bussone et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Bussone et al. Arthritis Research Therapy 2011, 13:R74 http://arthritis-research.com/content/13/3/RPage 2 ofIntroduction Systemic sclerosis (SSc) is a connective tissue disorder characterised by excessive collagen deposition in the dermis and internal organs, vascular hyperreactivity and obliteration phenomena [1]. A large number of autoantibodies have been identified in the sera of SSc patients. Antinuclear antibodies (ANAs), usually detected by indirect immunofluorescence on HEp-2 cells, are identified in 90 of patients [2]. Some of them are diseasespecific and mutually exclusive: anticentromere antibodies (ACAs), associated with limited cutaneous SSc (lcSSc) and possibly pulmonary arterial hypertension (PAH); anti-topoisomerase I antibodies (ATAs), associated with diffuse cutaneous SSc (dcSSc) and interstitial lung disease (ILD); and anti-RNA polymerase III antibodies, associated with dcSSc and scleroderma renal crisis (SRC) [3]. In addition, other autoantibodies have been found in the sera of SSc patients and include antifibrillarin, antifibrillin 1, anti-Th/To, anti-PM/Scl [3], antifibroblast [4-6] and anti-endothelial cell antibodies [7-9]. Overall, the only specific autoantibodies routinely tested for in SSc patients are ACAs, ATAs and, more recently, anti-RNA polymerase III antibodies. Thus, approximately 10 of SSc patients have no routinely detectable autoantibodies, and for 20 to 40 of those with detectable ANAs, the nuclear target antigens of these ANAs have not been identified [2]. Therefore, further work is warranted to better determine the disease subset and prognosis for these patients. The specification of new autoantibodies could help in understanding thepathophysiology of SSc and reveal new diagnostic and/or prognostic markers. Using a proteomic approach combining two-dimensional electrophoresis (2-DE) and immunoblotting, we recently identified target antigens of antifibroblast antibodies in patients with PAH [10]. In this work, using a similar proteomic approach with total and enriched nuclear protein extracts of HEp-2 cells as sources of autoantigens, we systematically analysed autoantibodies in SSc patients and identified a number of new target antigens for these autoantibodies.Materials and methodsImmunoglobulin sourcesSera were obtained from 45 patients who PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/7500280 fulfilled the LeRoy and Medsger criteria and/or the American Rheumatism Association crite.