Anti-NOR-90 autoantibodies and clinical associations in systemic sclerosis: an international retrospective cohort study

Abstract

Autoantibodies against NOR-90 are rare and have been associated with systemic sclerosis (SSc). This study seeks to identify the characteristics of SSc participants with anti-NOR-90 autoantibodies. An international (Canada, Australia, USA, Mexico) cohort of 2143 SSc participants was included. Sera were tested using a line immunoassay (Euroimmun, Lübeck, Germany). Clinical associations with anti-NOR-90 autoantibodies were investigated. Single-specificity anti-NOR-90-positive was defined as anti-NOR-90-positivity without other SSc-related autoantibodies, except for anti-Ro52/TRIM21. 115 (5%) participants were anti-NOR-90-positive, of whom the majority overlapped with other autoantibodies. Anti-NOR-90 positivity overall was associated with a higher frequency of calcinosis (35% vs. 24%, OR 1.70, 95% CI: 1.13, 2.52), digital ulcers (62% vs. 49%, OR 1.70, 95% CI: 1.12, 2.61) and arthritis (37% vs. 29%, OR 1.61, 95% CI: 1.06, 2.40). Single-specificity anti-NOR-90-positive participants ( n  = 21) a significantly lower mean % predicted forced vital capacity (FVC, 82.0% vs. 91.3%) and diffusing capacity (DLCO, 58.9% vs. 69.0%), and a trend toward higher prevalence of interstitial lung disease (61% vs. 40%, OR 2.36, 95% CI: 0.92, 6.45) and lower median mRSS (4.0 vs. 7.0). Anti-NOR-90 autoantibodies were not associated with increased cancer (10% vs. 8%) or mortality (adjusted HR 1.28, 95% CI: 0.92, 1.79, log rank p  = 0.3). Results from sensitivity analyses excluding anti-Ro52/TRIM21 from single-specificity definition were consistent in direction and magnitude. In this large multicentre cohort, anti-NOR-90 autoantibodies commonly overlapped with other SSc-autoantibodies. Single-specificity anti-NOR-90 positivity was associated with more frequent interstitial lung disease and a tendency for lower mRSS.