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

Abstract

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 = 0.001) and FM (P = 0.004) controls. Seronegative patients had higher levels than seropositive ones (P = 0.032). Anti-PTX3 antibodies correlated with CDAI (r = 0.255), PtGA (r = 0.257), VAS-GH (r = -0.235), VAS-pain (r = 0.233), and HAQ (r = 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 = 0.206, P = 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 = 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.

Keywords: CDAI; DMARDs; PTX3; RA; biological; pain; patient global assessment; pentraxin.

Figure 1.

Correlations between anti-PTX3 antibody titre and disease outcomes. Cases are reported as dots, regression line, and 95% confidence interval for r. FACIT-Fatigue: Functional Assessment of Chronic Illness Therapy-Fatigue; PtGA: Patient Global Assessment; PhGA: Physician Global Assessment; PtGH: patient global health

Figure 2.

Anti-PTX3 antibodies are higher in patients with near-controlled than profoundly controlled RA, with titres comparable to patients with objectively active RA. Brown-Forsythe ANOVA P = 0.0187; adjusted P = 0.0480

Figure 3.

Anti-PTX3 antibodies are more prevalent in seronegative RA patients. Bullets and squares depict individual values. The mean and S.D. are represented by horizontal lines. P-values refer to two-tailed unpaired t-test with Welch correction. SNRA: seronegative rheumatoid arthritis; SPRA: seropositive rheumatoid arthritis

Figure 4.

Anti-pentraxin-3 (anti-PTX3) antibody serum titres in unmatched patients with RA (SPRA, n = 42, SNRA, n = 41), FM (n = 21), and PsA (n = 21). Horizontal black lines represent the median for each group, symbols are individual data. P-values adjusted for multiple comparisons between groups are shown (Kruskal−Wallis test with Dunn’s multiple comparison tests, ANOVA P = 0.0003). ^aData retrieved from Bassi et al. [10]