ALPHA-ENOLASE: A TARGET OF ANTI-FIBROBLAST ANTIBODIES IN SYSTEMIC SCLEROSIS

Background: Fibroblast dysfunction has been identified in SSc patients, and anti-fibroblasts antibodies (AFA) exhibiting a pathogenic role have been detected in the serum. We used a proteomic approach combining two-dimensional electrophoresis and immunoblotting in order to identify the target antigens of AFA in SSc patients.Methods: Sera from 24 SSc patients (12 with pulmonary arterial hypertension (PAH) and 12 without) were collected. SSc patients fulfilled the Leroy and Medsger and/or the American Rheumatism Association criteria. We tested pools of sera from 3 patients based on clinical and autoantibody profiles. Sera from 14 healthy blood donors were also pooled and used as control. Serum IgG reactivities were analyzed using a 2-dimensional immunoblotting technique with normal human dermal fibroblasts antigens. Then, serum IgG reactivities from 200 SSc patients and 100 healthy controls were tested by ELISA against Saccharomyces cerevisiae (Sc) alpha-enolase, and serum IgG reactivities from 50 SSc patients and 50 healthy controls were tested against human recombinant (rHu) alpha-enolase.Results: Serum IgG from healthy blood donors recognized 43 protein spots, and those from SSc patients with or without PAH recognized 81 et 44 protein spots respectively. Seven protein spots that were recognized more intensely by SSc patients than healthy blood donors were selected, among which alpha-enolase. By ELISA, 47/200 (24%) SSc patients and 4/100 (4%) healthy blood donors had anti-Sc alpha-enolase antibodies (p<0.0001); 13/50 (26%) SSc patients and 3/50 (6%) healthy blood donors had anti-rHu alpha-enolase antibodies (p=0.01). In SSc patients, the presence of both anti-Sc or anti-rHu alpha-enolase antibodies was significantly associated with diffuse SSc, interstitial lung disease (ILD) and anti-topoisomerase 1 antibodies.Conclusion: AFA in SSc patients recognize alpha-enolase. These antibodies are associated with diffuse cutaneous SSc, ILD and anti-topoisomerase antibodies. The pathogenic role of these antibodies remains to be determined.Citation: Ann Rheum Dis, volume 67, supplement II, year 2008, page 147Session: Humoral aspects – Autoantibodies