Anti-Anxa1: New Diagnostic Marker For Sjögren’S Syndrome

Sjögren’s syndrome (SS), a chronic autoimmune disorder, lacks validated biomarkers for patients seronegative for anti-SSA and anti-SSB autoantibodies. This study aimed to assess the diagnostic potential of anti-ANXA1 autoantibodies in SS and to explore the role of p63 (an essential transcription factor for salivary gland epithelial progenitor cell maintenance) in regulating ANXA1 expression and its contribution to the disease pathogenesis. Anti-ANXA1 levels were measured by ELISA in serum from anti-SSA/SSB positive, anti-SSA/SSB negative SS patients, and controls. Expression of Anxa1 in p63 transgenic mice was analyzed via immunohistochemistry and Western blot. The p63 regulatory sites within the ANXA1 gene were identified by chromatin immunoprecipitation followed by reporter assays. Anti-ANXA1 positivity (≥3.26 ng/ml) occurred in 20.8% of anti-SSA/SSB negative and 50% of anti-SSA/SSB positive patients, with higher levels in anti-SSA/SSB negative patients comorbid with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) (p=0.140, Fisher’s Exact Test). Overexpression of p63 in mice upregulated Anxa1 expression in salivary glands. Moreover, we identified the p63 regulatory sites within the ANXA1, highly conserved sequences across human and mouse. Anti-ANXA1 autoantibodies may aid in diagnosing anti-SSA/SSB negative SS patients with SLE or RA comorbidity. However, larger cohorts are needed to validate these findings due to limited sample size. Our data also suggest that dysregulation of salivary gland epithelial cells can precede SS pathogenesis via p63-dependent hyperproduction of ANXA1 autoantigens.