AB0652 INCREASED SERUM ANTI-PTX3 ANTIBODY LEVELS CHARACTERIZE SERONEGATIVE RHEUMATOID ARTHRITIS PATIENTS WITH GOOD OUTCOMES

• Published in: Annals of the rheumatic diseases Vol. 83; no. Suppl 1; p. 1612
• Main Authors: Salvato, M., Giollo, A., Frizzera, F., Botsios, C., Calligaro, A., Zen, M., Ghirardello, A., Doria, A.
• Format: Journal Article
• Language: English
• Published: Kidlington BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2024; Elsevier B.V; Elsevier Limited
• Subjects: Antibodies; Arteriosclerosis; Autoantibodies; Citrulline; Connective tissue diseases; Connective tissues; Disease; Enzyme-linked immunosorbent assay; Musculoskeletal diseases; Optical density; Patients; Pentraxins; Prognostic factors; Rheumatoid arthritis; Rheumatoid factor; Rheumatoid synovitis; Scientific Abstracts; Systemic lupus erythematosus; Vasculitis; Prognostic factors; Autoantibodies
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2024-eular.4016

Background:Pentraxin-3 (PTX) levels are elevated in the serum and synovium of rheumatoid arthritis (RA) patients, and high PTX3 levels have been linked to increased disease activity and radiographic damage. Anti-PTX3 circulating antibodies have been found in up to 40% of patients with rheumatic musculoskeletal diseases, and they have been linked to improved outcomes in patients with systemic lupus erythematosus and vasculitis. However, the role of anti-PTX3 antibodies in RA patients has yet to be determined.Objectives:The aim of this study was to determine the levels of anti-PTX3 antibodies in the serum of RA patients and to describe their associations with disease characteristics.Methods:We conducted a single-center, cross-sectional, prospective study on consecutive adult patients diagnosed with RA using the 2010 ACR/EULAR criteria. An expert rheumatologist confirmed the diagnosis. Anti-PTX3 antibodies were measured in serum using a standardised in-house enzyme-linked immunosorbent assay (ELISA) method that had previously been validated in a larger population of patients with connective tissue diseases, including RA. The anti-PTX3 antibody titre was expressed as optical density (OD) at 405 nm. A positivity cut-off was previously determined by receiving operating characteristic (ROC) curve analyses in which sensitivity was calculated in 130 patients with SLE and specificity in 130 healthy subjects at a value of 0.234 (sensitivity 46.2% and specificity 92.8%) [1]. Demographic, clinical, laboratory, and treatment data were collected. Independent examiners evaluated disease activity. At the 6-month follow-up, disease flares were defined as a CDAI increase of >4.5 [2].Results:The study included 83 patients, 85.5% of whom were females with long disease duration and low disease activity (Table 1). Anti-PTX3 antibodies were found in the blood of all 83 participants, with a median OD titre of 0.111±0.107. A titre above the pre-established cut-off for positivity was found in 7/83 (anti-PTX3+, 8.4%) (median OD titre: 0.341±0.105 in anti-PTX3+ vs. 0.106±0.08 in anti-PTX3-; p<0.001). Anti-PTX3+ and anti-PTX3- patients were similar in terms of age, disease duration, serum CRP and ESR, and erosive disease. All anti-PTX3+ patients tested negative for rheumatoid factor and anti-citrullinated peptide antibody (ACPA) (p=0.013), and none had extra-articular RA (p=0.096; Figure 1A). The absence of ACPA (p=0.008) and extra-articular disease (p=0.013) were significantly associated with anti-PTX3 antibody titres in multivariable linear regression, independent of DAS28. The anti-PTX3 titre was slightly but significantly higher in patients treated with tumor necrosis factor inhibitors (TNFi) (0.149±0.090) than in patients treated with non-TNFi biologics (0.103±0.047; p=0.015; ANOVA; Figure 1B). At six months, we had eight flares, four of which required treatment escalation (bDMARD switch). All flares occurred in anti-PTX3- participants, while none of the anti-PTX3+ RA patients experienced disease flares after 6 months of follow-up.Conclusion:Significant titers of anti-PTX3+ antibodies were detected exclusively in seronegative RA patients and were associated with the absence of extra-articular features and disease flares at 6 months and the use of TNFi. Although preliminary and requiring validation in larger cohorts, these data suggest that anti-PTX3 antibodies may characterise a subset of seronegative RA with a good response to therapy.REFERENCES:[1] Bassi N, Zampieri S, Ghirardello A, Tonon M, Zen M, Cozzi F, Doria A. Pentraxins, anti-pentraxin antibodies, and atherosclerosis. Clin Rev Allergy Immunol. 2009 Aug;37(1):36-43. doi: 10.1007/s12016-008-8098-6. PMID: 19016000.[2] Konzett V, Kerschbaumer A, Smolen JS, et alDefinition of rheumatoid arthritis flare based on SDAI and CDAIAnnals of the Rheumatic Diseases 2024;83:169-176.Acknowledgements:NIL.Disclosure of Interests:None declared.