Clinical relevance of specific and non-specific autoantibodies in systemic sclerosis without overlap features

OBJECTIVES: The diagnosis of systemic sclerosis (SSc) relies on specific autoantibodies, but the clinical value of non-specific and other immune-mediated inflammatory disease (IMID)-associated antibodies in patients without overlap features is unclear. This study determines the frequency and clinical relevance of a broad autoantibody panel in this well-defined SSc cohort. METHODS: This is a cross-sectional study including 263 consecutive SSc patients without overlap syndromes. A panel was tested for anti-Scl70, anti-centromere, anti-RNApol-III, anti-PM-Scl, anti-dsDNA, anti-Sm, anti-Ro52, anti-La, anti-Jo1, anti-cardiolipin, anti-β2GPI, rheumatoid factor (RF), and anti-CCP by ELISA, and anti-fibrillarin, anti-Ku, anti-Th/To, and anti-RNP by line blot immunoassay. Clinical involvement, assessed at the last follow-up using standardized definitions with data from a structured electronic chart database, was correlated with antibody frequencies. RESULTS: The cohort (n = 263) had a mean age of 42.4 years, disease duration of 8.8 years, and included limited (53.6%), diffuse (35%), and sine scleroderma (11.4%) subtypes. SSc-specific autoantibodies were present in 88.2%, primarily anti-Scl70 (31.5%), anti-centromere (27%), and anti-RNApol-III (8%); these were largely mutually exclusive. Non-specific antibodies were also frequent, including anti-Ro52 (36.1%) and RF (18.5%). Key IMID-associated antibodies, such as anti-dsDNA, anti-Sm, and anti-Jo1, were confirmed negative by specific methods. The only significant clinical association was between anti-RNP and interstitial lung disease (P = 0.007). CONCLUSION: Non-specific and IMID-associated autoantibodies are frequent in SSc patients without overlap but show limited clinical correlation. These findings question the routine utility of broad, untargeted antibody testing in this specific population.