Detection and Clinical Associations of Autoantibodies to Heterogeneous Nuclear Ribonucleoprotein (hnRNP) A2/B1 in Patients with Systemic Sclerosis

Autoantibodies targeting heterogeneous nuclear ribonucleoproteins (hnRNPs) have been seldom described in autoimmune diseases but remain poorly characterized in systemic sclerosis (SSc). This study aims to investigate the prevalence and clinical significance of anti-hnRNP autoantibodies in SSc. Serum samples from 25 well-characterized SSc patients were analyzed using protein immunoprecipitation (IP) to detect autoantibodies against hnRNP components A1, A2/B1, C1/C2, H, L, and U. Clinical data including organ involvement and autoantibody profiles were also collected over a 10-year follow-up period. Anti-hnRNP A2/B1 autoantibodies were identified in 40% of SSc patients and significantly associated with gastrointestinal involvement (80% vs. 27%; <i>p</i> = 0.015; OR 17, 95% CI 2.2-381). Additional components such as anti-hnRNP L antibodies exhibited variable protein-IP band patterns, with a trend toward an association between a "double" band pattern and cancer history (<i>p</i> = 0.066). Anti-hnRNP U antibodies were detected in a single patient presenting with severe digital ulcers. No patient tested positive for antibodies against other components, including A1, C1/C2, and H. In this preliminary hypothesis-generating study, anti-hnRNP autoantibodies were frequent in SSc patients with distinct prevalence and clinical associations depending on the target component. Anti-hnRNP A2/B1 correlate with gastrointestinal involvement but, contrary to previous reports, show no association with arthritis. Further exploration on anti-hnRNP L and the rarer anti-hnRNP U autoantibodies is warranted.