Background/Objectives:: The subset of ANA-positive patients with systemic sclerosis (SSc) who lack prototypic SSc-specific autoantibodies (centromere, topoisomerase, RNA polymerase III, “triple negative SSc”) is poorly characterized. We assessed clinical features and prevalence of additional autoantibodies in these patients.
Methods:: In this case series patients with ANA+ and triple negative SSc antibodies were identified from two independent SSc cohorts (n=280) and demographic and clinical data were obtained over two years. Sera were screened for ANA and autoantibodies were examined by immunoblots. Significance was assessed through Fisher’s exact test and Student’s T-test.
Results:: Forty ANA+ triple negative SSc patients (14% of the two SSc cohorts) were identified. Mean age was 53 ± 14.5 years, 53% had limited disease, average disease duration was 9 ± 9.7 years, and MRSS was 7.6 ± 6.8. 47.5% of the patients had digital ulcers, 60% had interstitial lung disease and 15% had pulmonary hypertension. The most common immunofluorescence patterns were speckled and mixed speckled/nucleolar. Of 29 autoantibodies tested, the most prevalent were Ro-52 (50%), Th/To (40%), MDA5 (35%), SAE1 (28%). Ro-52 was associated with ILD (RR 2.67, p<0.001) and elevated CK (RR 2.64, p<0.05), and PM-75 was associated with digital ulcers (RR 2.18, p<0.05).
Conclusions:: ANA+ triple negative SSc patients represent an understudied and heterogeneous population of patients with a high prevalence of Ro-52 antibodies, an enrichment for myositis specific antibodies, and increased risk of interstitial lung disease. These patients are seen relatively frequently and should be regularly assessed for evidence of myopathy and lung involvement.