POS0608 TARGETING THE JAK/STAT PATHWAY IN MYOSITIS INHIBITS B CELL PROLIFERATION, DIFFERENTIATION AND ANTIBODY PRODUCTION
نویسندگان
چکیده
Background Idiopathic inflammatory myopathies (IIM) or myositis are characterized as inflammatory, autoimmune disorders with a wide spectrum of symptoms and affected tissues. The presence circulating autoantibodies B-lineage cells in tissues, point towards an essential role B the pathogenesis IIM. This sparked interest cell depleting anti-CD20 antibody rituximab new treatment opportunity However, despite its beneficial effects, results long-term depletion does not target CD20-negative, long-lived plasma cells, which may maintain response. Hence, further research aimed at more specific reversible therapies targeting is warranted. Janus kinase (JAK)-signal transducer activator transcription (STAT) signalling pathway for several aspects biology, making it attractive novel patients Objectives To study whether JAK-STAT using tofacitinib, small molecule inhibitor JAK1/JAK3, impairs functions isolated from Methods lineage phenotyping was performed by flow cytometry, PBMCs obtained 3 IIM phenotypes (dermatomyositis, overlap-myositis, anti-synthetase syndrome) healthy donors (HD). Functional assays were culturing stimuli IL-21/anti-CD40 IL-2/CpG to activate JAK/STAT T cell-independent cell-dependent manner, respectively. After 6-day culture, effects tofacitinib on proliferation, differentiation, production assessed cytometry ELISA. Results Peripheral blood composition showed reduced fractions memory increase transitional naive comparison HD reference values. Targeting significantly induced plasmablast differentiation HD. this effect observed lesser extent upon stimulation IL-2/CpG. Interestingly, exerted irrespective phenotype. Conclusion Our data demonstrate that peripheral compartment altered. Furthermore, vitro inhibition functional responses, including production, clinical Consequently, represent modality myositis. REFERENCES: NIL. Acknowledgements: Disclosure Interests None Declared.
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ژورنال
عنوان ژورنال: Annals of the Rheumatic Diseases
سال: 2023
ISSN: ['1468-2060', '0003-4967']
DOI: https://doi.org/10.1136/annrheumdis-2023-eular.3037