Galectin-1 levels do not predict outcomes in undifferentiated arthritis: a two-year prospective observational study

Introduction: Undifferentiated arthritis (UA) represents an early and heterogeneous phase of inflammatory joint disease that may evolve into defined rheumatic conditions. This phase is characterized by immune dysregulation with loss of tolerance and early autoantibody production. Despite extensive research, reliable biomarkers for early diagnosis and prognosis remain lacking. Galectin-1 (Gal-1), an immunomodulatory lectin with anti-inflammatory properties, has been reported to be elevated in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study aimed to evaluate the diagnostic and prognostic value of serum Gal-1 levels in UA patients over a two-year follow-up. Methods: This study analyzed patients from the observational PEARL study, that were classified as UA at baseline visit. After four standardized visits (0, 6, 12 and 24 months), in which biological samples, clinical, laboratory, and treatment data were systematically collected, a definitive diagnosis was established. Serum Gal-1 levels were measured by ELISA at all visits and analyzed in relation to clinical characteristics, final diagnosis, disease activity, and treatment intensity. Multivariate regression models were adjusted for relevant confounders. Results: A total of 139 patients were included. After two years, 44.6% (n=62/139) progressed to a chronic inflammatory rheumatic disease, mostly RA (67%; n=42/62), while 40.2% (n=56/139) remained as persistent UA. Baseline Gal-1 levels were not associated with seropositivity, functional disability or treatment intensity. A non-significant trend toward lower Gal-1 levels was observed in patients evolving to spondyloarthritis (SpA) whereas no major differences were observed among other diagnostic groups. Over the two-year follow-up, Gal-1 levels remained largely stable across all diseases and did not correlate with disease activity despite significant clinical improvement. Conclusion: Overall, Gal-1 showed stable serum levels irrespective of disease activity or outcome, with limited predictive or monitoring value in UA. Lower concentrations observed in SpA suggest disease-specific modulation.