33PNew insights into the mouse model for Jo-1, PL-7, and PL-12 associated anti-synthetase syndrome

Abstract

Anti-synthetase syndrome (ASyS) is an autoimmune condition, characterized by autoantibodies directed against an aminoacyl-tRNA synthetase (anti-ARS). Patients present clinical symptoms such as myositis, interstitial lung disease, Raynaud’s phenomenon, and arthritis. Anti-Jo-1, anti-PL-7 and anti-PL-12 are the most frequent anti-ARS. However, their role in ASyS pathogenesis remains incompletely understood and an animal model could be essential to gain new insights into the underlying pathophysiology. Therefore, aiming to characterize these pathophysiological features, we established and continued the studies on a mouse model for Jo-1, PL-7 and PL-12 associated ASyS. ASyS was induced in NOD.Idd3/5 mice by injection of Jo-1, PL-7 or PL-12 recombinant protein in Complete Freund’s Adjuvant (CFA) in combination with OX86. Controls received CFA and Phosphate Buffered Saline only. Muscle strength was assessed, and the reactivity of autoantibodies was evaluated in the sera of mice. Morphological characteristics of skeletal muscle and lung tissue and the tissue infiltrating immune cells were validated in detail using immunohistochemistry. Immunized mice displayed clinical symptoms including muscle weakness and specific reactivity of autoantibodies in the sera. Quantitative analyses of the muscle tissue revealed immune cells in the epimysium and the adjacent perifascicular area. Immunohistological analyses of lung specimens showed a pronounced peribronchial accumulation of lymphocyte aggregates, including B cells, T cells, and macrophages, within the lung tissue. Pending whole tissue RNA-seq and TCR/BCR sequencing will provide in-depth analysis of these immune cells. We present an update to the established mouse model, which recapitulates features of the human phenotype. The analysis of autoantibody reactivity and histological studies enhances our understanding of the molecular pathogenesis and immune cell involvement, providing new insights into the pathomechanisms of ASyS.