LAUSR

Background: The paracaspase Malt1 is a cysteine protease, which forms a complex leading to the activation of the in proinflammatory transcription factor NF-κB in lymphocytes with CARMA1 and Bcl10. Previously, we showed that the myeloid equivalent of CARMA1, Card9 is important in neutrophils in Fcγ receptor-mediated cytokine release together with Bcl10 and Malt1. In line with these findings, we observed a significant decrease in the severity of autoantibody-triggered arthritis in the absence of Card9 and Bcl10. Objectives: Our aim was to directly investigate whether the genetic deficiency of Malt1, the third component of the complex altered the process of the K/BxN serum transfer arthritis (that resembles to the effector phase of rheumatoid arthritis). Methods: We used wild type and Malt1–/– mice for our experiments. Autoantibody-mediated arthritis was induced by a single intraperitoneal injection of K/BxN serum. Clinical signs of joint inflammation were scored on a scale based on the cardinal inflammatory clues for two weeks. Ankle thickness was measured by a spring-loaded caliper. Results: Similar to the deficiency of the other two components of the complex, Malt1–/– mice showed a partial, but significant decrease in the macroscopic joint inflammation compared to arthritic serum-treated wild type animals during the entire experimental process. In line with this phenomenon, Malt1–/– animals had reduced autoantibody-triggered ankle thickening. Conclusion: Our results show that Malt1 seems to be an important molecule in the development and progression of experimental autoantibody-induced arthritis in mice, highlighting the role of the molecule as a potential therapeutic target in the future. Disclosure of Interests: None declared