Anti-Th/To antibodies in systemic sclerosis: analysis of long-term follow-up of pulmonary involvement, organ damage accrual and mortality in an Italian cohort with a case-control study.

Objectives: In systemic sclerosis (SSc) American patients, anti-Th/To antibodies were reported to be associated with interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). Few data in European patients are available, so we aimed at describing the clinical associations of anti-Th/To antibodies, focusing on ILD outcome, organ damage and mortality in an Italian single-centre cohort.

Methods: Case-control study: anti-Th/To+ SSc patients vs. anti-topoisomerase (anti-topo)1+, anticentromere (ACA)+ and quadruple-negative (anti-topo 1-, ACA-, anti-RNAP3-, anti-Th/To-) SSc patients (1:3; matched for sex and age at SSc onset). Organ damage was assessed with the SCTC-Damage Index.

Results: Thirteen anti-Th/To+ patients were evaluated: 100% had limited cutaneous involvement; 46% digital ulcers; none had PAH, synovitis, joint contractures. As compared to anti-topo 1+ and quadruple-negative patients, anti-Th/To+ patients developed less frequently ILD (40% vs. 85% and 84%), that required less immunosuppression (8% vs. 41% and 44%), and rarely had functional worsening (15.4% at 5 years), without development of long-term complications (no need for O2, pulmonary hypertension, death). In anti-Th/To+ patients, the Damage Index was lower than in anti-topo 1+ and quadruple-negative patients at various timepoints, and remained low during the long-term follow-up (median: 16 years). The 5- and 10-year survival of anti-Th/To+ patients was 92% and 72%, respectively, and did not differ from those of the SSc matched patients; none of the anti-Th/To+ patients died due to SSc, while mortality was mainly related to cancer.

Conclusions: In this study, anti-Th/To+ patients showed a mild SSc phenotype, characterised by low organ damage, favourable ILD outcome and good survival.