ANTI-NEUTROPHIL EXTRACELLULAR TRAP ANTIBODIES IN AUTOIMMUNE RHEUMATIC DISEASES: A SUITABLE BIOMARKER OF THROMBOSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS

Background: The release of intracellular material during neutrophil extracellular trap (NET) formation – NETosis – could have a role in breaking immunological tolerance to self-components. When NETs are formed in an uncontrolled manner or are not cleared properly, the immune system might recognize NETs and trigger an autoimmune reaction against NET components, giving rise to anti-NET antibodies. Indeed, several proteins identified in NETs are known to be the target of autoantibodies (citrullinated proteins, MPO, PR3, histones, LL37, C1q) [1]. To date, limited information is available regarding the prevalence and the clinical significance of anti-NET antibodies in Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) and Systemic Sclerosis (SSc) patients. Objectives: This study aimed to elucidate the prevalence and the potential role as biomarker of anti-NET antibodies in SLE, RA and SSc patients. Methods: Serum samples from SLE, RA, SSc and healthy donors (HD) were evaluated for anti-NET IgG, using an ELISA home-made coated with phorbol myristate acetate (PMA)-induced NET. Based on a positivity threshold set at the 99th percentile for HD sera we calculated the positive samples. Results: We enrolled 349 patients with autoimmune rheumatic diseases (ARD), mean age of 53 years (SD 14.6) and a female predominant ratio (6:1), founding a prevalence of anti-NET of about 40% (Figure 1). Of the 136 SLE patients 50 (36.8%) were anti-NET positive, revealing an association between anti-NET and Antiphospholipid Syndrome (APS) (OR 3.37 [95% CI 1.22-9.36], p=0.02) and with an history of arterial thrombosis regardless of coexisting Secondary APS (SAPS) (OR 5.52 [95% CI 1.07-28.52], p=0.032). In RA patients 52 out 131 (39.7%) tested positive for anti-NET and we found a significant difference in the anti-NET OD between seronegative (33/131) and seropositive patients (median 0.079 OD [IQR 0.04] vs median 0.084 OD [IQR 0.05] respectively; p = 0.04). Almost all RA patients (88.6%) with a positive anti-NET test were ACPA-positive. Indeed, our results revealed a significant association between testing positive for anti-NET and the presence of ACPA (p=0.049). In addition, the anti-NET OD was significantly greater in RA patients than in those with SLE (p=0.016). Of the 82 SSc patients enrolled 33 (40%) were anti-NET positive, and we found an inverse association between anti-NET and gastroesophageal reflux disease (GERD) (p=0.01). Conclusion: These results reveal the presence of anti-NET in ARD patients. In SLE patients, they are associated with APS and arterial thrombosis, a major cause of mortality in SLE patients. In RA patients, their association with ACPA further highlighted the possible role of NETosis in RA pathogenesis. REFERENCES: [1] Knight JS, Carmona-Rivera C, Kaplan MJ. Proteins derived from neutrophil extracellular traps may serve as self-antigens and mediate organ damage in autoimmune diseases. Front Immunol. 2012;14:380. Acknowledgements: NIL. Disclosure of Interests: None declared. DOI: 10.1136/annrheumdis-2024-eular.2789 Keywords: Autoantibodies, Biomarkers Citation: , volume 83, supplement 1, year 2024, page 294Session: Basic Poster Tours: Pathophysiological concepts in Lupus and lupus nephritis (Poster Tours)

Autoantibodies, Biomarkers