Clinical Significance of Antinuclear Antibodies in Patients with Rheumatoid Arthritis: From SETOUCHI-RA Registry

Background/Objectives: Rheumatoid arthritis (RA) is a representative systemic autoimmune rheumatic disease (SARD) characterized by synovial inflammation. While antinuclear antibodies (ANAs) positivity in patients with RA varies widely, the relationship between ANA patterns and clinical features remains unclear. This study aimed to evaluate the clinical significance of ANA in patients with RA. Methods: This single-center RA registry study included 814 Japanese patients after excluding those with coexisting SARDs. ANA titers and staining patterns were assessed by indirect immunofluorescence assays on HEp-2 cells. Clinical and laboratory features were analyzed, and logistic regression was used to identify risk factors for pulmonary involvement. Hierarchical clustering and statistical analyses were performed to explore associations between ANA patterns and clinical features. Results: ANA positivity was observed in 41.5% of patients, with the speckled and homogeneous patterns being the most common. ANA-positive patients exhibited significantly higher rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) positivity rates and titers, along with elevated disease activity markers, including Evaluator's Global Assessment and Swollen Joint Count. Nucleolar pattern positivity was independently associated with pulmonary complications, predominantly interstitial lung disease, and higher rates of JAK inhibitor use. Discrete-speckled pattern-positive patients exhibited high ANA titers but lower RF and ACPA levels, reflecting a distinct subset of RA. Conclusions: ANA staining patterns and titers are clinically relevant in RA, with nucleolar and discrete-speckled patterns indicating distinct clinical and pathophysiological profiles. ANA should be interpreted alongside other serological markers and clinical parameters rather than as a standalone tool. Further studies are needed to refine its clinical applicability and integration into RA management.