Anti-fibroblast and anti-endothelial cell autoantibodies in pulmonary arterial hypertension (PAH) in patients with connective tissue diseases (CTD).

Abstract

Pulmonary arterial hypertension (PAH) is a rare disease that may be associated with CTD. Anti-fibroblast (AFA) and AECA have been identified in idiopathic and SSc-associated PAH. The aim was to identify autoantibodies discriminating for PAH associated with SLE, MCTD and primary SS, and their target antigens. Sera were collected in the French multicentre auto-HTAP study from 86 patients with CTD excluding SSc, including 32 with PAH (PAH+) and 54 without (PAH-). AFA and AECA were identified using one- (1D) and two-dimensional (2D) immunoblots and proteomics. ELISA tests using human recombinant proteins were used to confirm PAH-associated IgG reactivities. PAH+ patients had similar IgG AFA and AECA reactivities in 56.2% and 40.6% of the cases in 1D immunoblots, respectively. In 2D immunoblots, serum IgG pools from SLE patients (n = 14), MCTD (n = 10), SS (n = 9) and 14 healthy controls (n = 1) recognized, respectively, 273 ± 79, 205 ± 77, 109 ± 11 and 109 protein spots in fibroblasts and 189 ± 48, 146 ± 30, 88 ± 33 and 190 protein spots in endothelial cell extracts. Serum IgG from PAH+ patients recognized 39 fibroblast and 34 endothelial cell protein spots that were not recognized by IgG from PAH- patients, including Annexin A5 (ANXA5). Anti-ANXA5 IgG reactivity was significantly higher in PAH+ compared with PAH- patients with MCTD (73% vs 0%, P < 0.001) and SLE (33% vs 0%, P = 0.009). Anti-ANXA5 IgG autoantibody reactivity might represent a predictive biomarker for PAH associated with MCTD and SLE.