Clinical phenotype in scleroderma patients based on autoantibodies

We aimed to characterize the clinical phenotype of patients with SSc based on autoantibodies (topoisomerase antibody (Scl-70), ACA and ANA).

We included patients with SSc who fulfilled the 2013 ACR/EULAR criteria, with disease duration ≤15 years. Six groups of patients were defined: ACA-lcSSC, Scl-70-lcSSc, ANA-lcSSc, Scl-70-dcSSc, ANA-dcSSc and ACA-dcSSc patients. We compared the different groups of patients. In the ANA subgroup, we included patients negative for SSc-specific antibodies (Scl-70 and ACA). We assessed the following: risk of interstitial lung disease (ILD), myositis, scleroderma renal crisis, cardiac involvement, gastrointestinal involvement, pulmonary hypertension, treatment, cancer and all-cause mortality.

One hundred and thirteen SSc patients were included: 72 (64%) females, 82 (73%) lcSSc and 31 (27%) dcSSc. Among patients with lcSSc, 43 (52%) were ACA⁺, 16 (19%) Scl-70⁺ and 23 (28%) ANA⁺, and among patients with dcSSc, 13 (42%) patients were Scl-70⁺, 11 (35%) ANA⁺ and 7 (23%) ACA⁺. Scl-70-lcSSc patients had a significantly shorter time from RP to SSc diagnosis (P = 0.04), higher CRP (P = 0.04), renal scleroderma crisis (P = 0.02), ILD (P = 0.03) and diastolic dysfunction (P = 0.04) than ANA-lcSSc patients. Scl-70-dcSSc patients had a higher rate of myositis (P = 0.04), renal crisis (P = 0.03), CRP elevation (P = 0.002), ILD (P = 0.04), pericardial effusion (P = 0.03) and cancer (P = 0.04) than ANA-dcSSc patients. The risk of ILD was higher in Scl-70 patients during the first 10 years than in ACA⁺ and ANA⁺ patients (P = 0.03 and P = 0.02, respectively). The risk of major organ involvement was higher in Scl-70⁺ patients, followed by ANA⁺ and ACA⁺ patients, throughout 15 years of follow-up. All-cause mortality was higher in dcSSc patients than in lcSSc patients, but no differences were found regarding antibody positivity.

We have characterized the clinical phenotype of patients based on autoantibodies: Scl-70 patients show the greatest risk of major organ involvement, followed by ANA⁺ patients and ACA⁺ patients. The risk of ILD in Scl-70⁺ patients suggests that these patients should be monitored closely, irrespective of skin involvement. These results might provide new ways to help with the early diagnosis and management and in assessment of the prognosis of the disease.