Antifibroblast antibodies from systemic sclerosis patients bind to α-enolase and are associated with interstitial lung disease

Abstract

Objective:To identify target antigens of antifibroblast antibodies (AFA) in systemic sclerosis (SSc) patients.Patients and Methods:In the first part, sera from 24 SSc patients (12 with pulmonary arterial hypertension (PAH) and 12 without) and 36 idiopathic PAH patients, tested in pooled sera for groups of three, were compared with a sera pool from 14 healthy controls (HC). Serum IgG reactivity was analysed by the use of a two-dimensional electrophoresis and immunoblotting technique with normal human fibroblasts antigens. In the second part, serum IgG reactivity for two groups: 158 SSc, 67 idiopathic PAH and 100 HC; and 35 SSc and 50 HC was tested against α-enolase from Saccharomyces cerevisiae and recombinant human (rHu) α-enolase, respectively, on ELISA.Results:In the first part, α-enolase was identified as a main target antigen of AFA from SSc patients. In the second part, 37/158 (23%) SSc patients, 6/67 (9%) idiopathic PAH patients and 4/100 (4%) HC (p<0.001) had anti-S cerevisiae α-enolase antibodies; 12/35 (34%) SSc patients and 3/50 (6%) HC had anti-rHu α-enolase antibodies (p = 0.001). In SSc, the presence of anti-S cerevisiae α-enolase antibodies was associated with interstitial lung disease (ILD), decreased total lung capacity (73.2% vs 89.7%; p<0.001) and diffusion capacity for carbon monoxide (47.4% vs 62.3%; p<0.001), and antitopoisomerase 1 antibodies (46% vs 21%; p = 0.005) but not anticentromere antibodies (11% vs 34%; p = 0.006). Results were similar with rHu α-enolase testing.Conclusion:In SSc, AFA recognise α-enolase and are associated with ILD and antitopoisomerase antibodies.