Anti-pentraxin 3 antibodies and residual disease activity in rheumatoid arthritis

Objectives: This study quantified anti-PTX3 antibodies in the serum of seropositive and seronegative RA patients, examining their associations with disease activity and patient-reported outcome measures (PROMs). Methods: In this cross-sectional study, RA patients diagnosed per ACR/EULAR 2010 criteria were recruited. Seronegative RA was defined as ACPA <7 kU/L. Data on demographics, clinical characteristics, medications, and PROMs were collected. Serum anti-PTX3 antibodies were measured using an in-house ELISA method. Comparative analyses were conducted with historical controls having PsA and FM. Results: The cohort included 83 RA patients (42 seropositive, 41 seronegative). Seropositive patients had lower anti-PTX3 antibody levels than PsA (P ¼ 0.001) and FM (P ¼ 0.004) controls. Seronegative patients had higher levels than seropositive ones (P ¼ 0.032). Anti-PTX3 antibodies correlated with CDAI (r ¼ 0.255), PtGA (r ¼ 0.257), VAS-GH (r ¼ −0.235), VAS-pain (r ¼ 0.233), and HAQ (r ¼ 0.311), but not with joint counts, inflammatory markers, or physician’s global assessment. The PtGA association remained significant when adjusted for BMI, SJC28, ESR, and prednisone dosage (β ¼ 0.206, P ¼ 0.042). Patients with near-controlled RA (SJC28 ≤ 2, PtGA > 2) had higher anti-PTX3 levels than those with controlled disease (SJC28 ≤ 2, PtGA ≤ 2; P ¼ 0.048). Tocilizumab or abatacept-treated patients had lower levels compared with those on TNFi or JAKi. Conclusion: Elevated anti-PTX3 antibodies in RA indicate residual active disease despite controlled inflammation. They may serve as a biomarker for true active disease, especially in seronegative RA patients who might be undertreated.