POS1039 ANTI-CITRULLINATED PROTEIN ANTIBODY (ACPA) REACTIVITY TOWARDS NEUTROPHIL-DERIVED ANTIGENS: THE IMPACT OF CLONAL DIVERSITY AND INTER-INDIVIDUAL VARIATION

Background Why the adaptive immune system turns against citrullinated antigens in rheumatoid arthritis (RA) and whether anti-citrullinated protein antibodies (ACPAs) contribute to pathogenesis are questions that have triggered intense research but still not fully answered. Neutrophils may be crucial this context, as sources of also targets ACPAs. Objectives To better understand how ACPAs neutrophils RA pathogenesis, we studied reactivity a broad spectrum patient-derived ACPA clones activated or resting neutrophils, compared neutrophil binding using CCP2 captured polyclonal from different patients. Methods Human were isolated peripheral blood healthy volunteers, individuals at risk for [1] patients with established RA. The cells Ca 2+ ionophore, phorbol 12-myristate 13-acetate (PMA), nigericin, zymosan IL-8. monoclonal preparations was flow cytometry confocal microscopy. Neutrophil extracellular trap formation (NETosis) analyzed IncuCyteZOOM TM . role arginine deiminase (PAD)2 PAD4 obtained PAD-deficient mice inhibitors. Osteoclast cultures human monocytes presence M-CSF RANK-L. Results targeted NET-like structures all tested conditions did bind surface intact influence NETosis. We observed prominent clonal diversity capacity neutrophil-derived antigens. PAD2 dispensable majority required binding. When patients, high patient-to-patient variability targeting Similar inter-individual another cellular effect ACPAs: stimulation osteoclast differentiation. Conclusion can important under lead activation, NETosis extrusion intracellular material. A substantial among both suggest RA-related symptoms variability. Reference Hensvold A, Kisten Y, Circiumaru Hansson M, Sun Fei G, Vivar N, af Klint E, Rezaei H, Klareskog L, Antovic Catrina A. Development Ultrasound Detectable Arthritis Among Positive Subjects Musculoskeletal Symptoms: Risk Prospective Study [abstract]. Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/development-of-ultrasound-detectable-arthritis-among-acpa-positive-subjects-with-musculoskeletal-symptoms-the-risk-ra-prospective-study/ Acknowledgements None. Disclosure Interests Alexandra Cîrciumaru: None declared, Marcelo Gomes Afonso: Heidi Wähämaa: Akilan Krishnamurthy: Monika Hansson: Linda Mathsson-Alm Employee of: Thermo Fisher Scientific, Lena Israelsson: Ragnhild Stålesen: Charlotte de Vries: Miriam Shelef: Vivianne Malmström: Lars Klareskog: Anca Catrina: Caroline Grönwall: Aase Hensvold: Bence Réthi: declared.