POS0386 EVOLUTION OF ANTI-MODIFIED PROTEIN ANTIBODY RESPONSES CAN BE DRIVEN BY CONSECUTIVE EXPOSURE TO DIFFERENT POST-TRANSLATIONAL MODIFICATIONS

Background: Besides anti-citrullinated protein antibodies (ACPA), rheumatoid arthritis patients (RA) often display autoantibody reactivities against other post-translationally modified (PTM) proteins, more specifically carbamylated and acetylated proteins. Immunizing mice with one PTM results in an anti-modified antibody (AMPA) response recognizing multiple PTMs. Furthermore, human AMPA, isolated based on their reactivity to PTM, cross-react PTMs at the monoclonal polyclonal level. However, it is unclear whether AMPA profile “fixed” time, or consecutive exposure different can shape evolving AMPA-response. Objectives: To investigate evolution of controlled as well AMPA-positive humans. Methods: Mice were immunized (or carbamylated) (ovalbumin) twice cross-immunized then a vice versa) serum was analyzed for responses ELISA using backbone (fibrinogen) bearing same modifications. Longitudinally collected samples individuals risk RA early tested Results: either solely ovalbumin (AcOVA CaOVA) developed both antigens. Irrespective used first immunization, booster immunization resulted increased titers second/booster (Figure 1A), suggesting that defined PTM-antigen leads generation anti-PTM memory B cells able cross-recognize immunizing CaOVA boosting AcOVA skewed overall AMPA-response towards relatively higher “booster” 1B). Human data also illustrated dynamic changes profiles (not shown). Conclusion: The relationship between within dynamic. initial antigen induces cross-reactive be boosted by pattern subsequent These might explain temporal point possibility responsible initiation may differ from predominantly recognized later time. Disclosure Interests: None declared