Elevated ITGAV Expression in Seropositive Rheumatoid Arthritis: Diagnostic Potential and Immunopathological Insights

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Despite advances in treatment, reliable biomarkers for early diagnosis remain elusive. This study investigates the expression of integrin alpha V (ITGAV) as a potential diagnostic biomarker in RA.

Peripheral blood samples were collected from patients with RA, osteoarthritis (OA), and healthy controls (HC). ITGAV expression was quantified by ELISA, and its correlation with clinical parameters-including serological markers, musculoskeletal ultrasound scores, and disease activity indices-was assessed. Transcriptomic datasets and single-cell RNA sequencing were analyzed to explore ITGAV expression in immune cell subsets. ROC curve analyses were conducted to evaluate its diagnostic performance.

ITGAV levels were significantly elevated in the peripheral blood of RA patients, particularly in those seropositive for both rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. ITGAV expression correlated positively with RF and CCP titres but showed no significant association with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), tender joint count (TJC) or swollen joint count (SJC). Single-cell transcriptomic analyses revealed ITGAV enrichment in pro-inflammatory macrophages and T cells. Moreover, ITGAV levels were positively associated with ultrasound-assessed synovial thickness. ROC analyses demonstrated high diagnostic accuracy, with AUCs exceeding 0.96 after multivariate adjustment.

ITGAV is significantly upregulated in seropositive RA and exhibits potential as a non-invasive biomarker for disease diagnosis and stratification. Its preferential expression in inflammatory immune cell subsets and association with subclinical synovial inflammation highlight its promise as both a diagnostic and mechanistic target in RA. Future longitudinal and functional studies are warranted to validate its role in personalized disease management.