Impact of autoantibody status on stratifying the risk of organ involvement and mortality in SSc: experience from a multicentre French cohort of 1605 patients

Abstract

Introduction: Systemic sclerosis (SSc) is a rare autoimmune disease currently classified into two subgroups based on skin extension. The aim of this study was to determine in a large cohort whether the determination of autoantibody (AAb) profile among a full antinuclear AAbs panel including nine specificities had a higher impact than skin phenotype on stratifying the risk of organ involvement and mortality in SSc.

Methods: Data for patients with SSc followed in seven French university hospitals were retrospectively analysed in terms of skin phenotype, AAbs (anti-topoisomerase I (ATA), anticentromere (ACA), anti-RNA polymerase III (anti-RNAPIII), anti-U1RNP, anti-U3RNP, anti-Pm/Scl, anti-Ku, anti-Th/To, anti-NOR90), organ involvement and mortality. Multivariate analyses were performed to identify independent factors associated with organ involvement and mortality.

Results: We included 1605 patients with SSc (367 with diffuse cutaneous SSc). On multivariate analysis, ATAs were associated with interstitial lung disease and mortality (OR=3.27 (95% CI 2.42 to 4.42); HR=1.9 (95% CI 1.01 to 3.58)), anti-RNAPIII with scleroderma renal crisis and mortality (OR=7.05 (95% CI 2.98 to 16.72); HR=2.35 (95% CI 1.12 to 4.93)), anti-U1RNP with arthritis (OR=3.79 (95% CI 2.16 to 6.67)), anti-Pm/Scl and anti-Ku with myositis (OR=7.09 (95% CI 3.87 to 12.98) and 7.99 (95% CI 2.41 to 26.46)). The skin phenotype was not associated with survival or organ involvement on multivariate analysis without stepwise selection.

Conclusion: This study unravels, by contrast with skin phenotype, a strong association between AAbs specificities, organ involvement and outcome in SSc and suggests that patients' classification based on only skin extension is not sufficient for defining prognosis and phenotype.

Keywords: autoantibodies; classification; mortality; systemic sclerosis.

Figure 1. Schematic prevalence of nine SSc-related AAbs in the population: 365 patients had ATA, 789 ACA, 98 anti-RNAPIII, 65 anti-U1RNP, 41 anti-U3RNP, 55 anti-Pm/Scl, 12 anti-Ku, 9 anti-Th/To and 2 anti-NOR90. Thirty-two patients (1.9%) had several AAbs: 14 patients had ATA, 6 ACA, 16 anti-RNAPIII, 5 anti-U1RNP, 7 anti-U3RNP, 14 anti-Pm/Scl, 3 anti-Ku and 1 anti-NOR90. AAbs, autoantibodies; ATA, antitopoisomerase I antibody; ACA; anticentromere antibody; Anti-RNAPIII, anti RNA polymerase III antibody.

Figure 2. Survival curves of the SSc population by subgroups. Analyses were according to the skin phenotype (A) and the presence or absence of selected AAbs (B–F). AAb, autoantibody; ACA, anticentromere antibody; ATA, antitopoisomerase I antibody; Anti-RNAPIII, anti RNA polymerase III antibody; dcSSc, diffuse cutaneous systemic sclerosis; lcSSc, limited cutaneous systemic sclerosis.