Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr 1;64(4):1672-1678.
doi: 10.1093/rheumatology/keae529.

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

Mariangela Salvato  1 , Francesca Frizzera  1 , Anna Ghirardello  1 , Antonia Calligaro  1 , Costantino Botsios  1 , Margherita Zen  1 , Andrea Doria  1 , Alessandro Giollo  1
Affiliations

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

Mariangela Salvato et al. Rheumatology (Oxford). .

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.

PubMed Disclaimer

Figures

Figure 1.
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.
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.
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.
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]
See this image and copyright information in PMC

References

    1. Li K, Mo W, Wu L. et al. Novel autoantibodies identified in ACPA-negative rheumatoid arthritis. Ann Rheum Dis 2021;80:739–47. - PubMed
    1. Inforzato A, Jaillon S, Moalli F. et al. The long pentraxin PTX3 at the crossroads between innate immunity and tissue remodelling. Tissue Antigens 2011;77:271–82. - PubMed
    1. Jaillon S, Peri G, Delneste Y. et al. The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps. J Exp Med 2007;204:793–804. - PMC - PubMed
    1. Jaillon S, Jeannin P, Hamon Y. et al. Endogenous PTX3 translocates at the membrane of late apoptotic human neutrophils and is involved in their engulfment by macrophages. Cell Death Differ 2009;16:465–74. - PubMed
    1. Boutet M-A, Nerviani A, Lliso-Ribera G. et al. Circulating and synovial pentraxin-3 (PTX3) expression levels correlate with rheumatoid arthritis severity and tissue infiltration independently of conventional treatments response. Front Immunol 2021;12:686795. - PMC - PubMed