Abstract

Objective: To identify target antigens of anti-fibroblasts antibodies (AFAs) 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 (IPAH) patients, tested in pooled sera for groups of 3, were compared to a sera pool from 14 healthy controls (HCs). Serum IgG reactivity was analyzed by use of a 2-D electrophoresis and immunoblotting technique with normal human fibroblasts antigens. In the second part, serum IgG reactivity for 2 groups - 158 SSc, 67 IPAH and 100 HCs; and 35 SSc and 50 HCs - was tested against α-enolase from Saccharomyces cerevisiae (Sc) and human recombinant (rHu) α-enolase, respectively, on ELISA.

Results: In the first part, we identified α-enolase as a main target antigen of AFAs from SSc patients. In the second part, 37/158 (23%) SSc patients, 6/67 (9%) IPAH patients and 4/100 (4%) HCs (p<0.0001) had anti-Sc α-enolase antibodies; 12/35 (34%) SSc patients and 3/50 (6%) HCs had anti-rHu α-enolase antibodies (p=0.001). In SSc, the presence of anti-Sc α-enolase antibodies was associated with interstitial lung disease (ILD), decreased total lung capacity (73.2 vs. 89.7%, p=0.0001) and diffusion capacity for carbon monoxide (47.4 vs. 62.3%, p=0.0009)], and anti-topoisomerase 1 antibodies (46 vs. 21%, p=0.005) but not anti-centromere Abs (11 vs. 34%, p=0.006). Results were similar with rHu α-enolase testing.

Conclusion: In SSc, AFAs recognize α-enolase and are associated with ILD and anti-topoisomerase antibodies.