Derya Cengiz (Düsseldorf / DE), Dr. rer. nat. Corinna Preuße (Berlin / DE), Dr. Stefanie Bock (Düsseldorf / DE), Dr. Kathrin Koch (Düsseldorf / DE), Prof. Dr. med Anne Schänzer (Gießen / DE), Univ.-Prof. Dr. med. Dr. rer. nat. Sven G. Meuth (Düsseldorf / DE), Prof. Dr. med Werner Stenzel (Berlin / DE), PD Dr. med. Tobias Ruck (Düsseldorf / DE)
Abstract-Text (inkl. Referenzen)
Background
Anti-synthetase syndrome (ASyS) is an autoimmune condition, characterized by the presence of 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. Therefore, animal models are essential to achieve a detailed insight of the underlying pathomechanisms.
Methods
ASyS was induced in NOD.Idd3/5 mice by injection of 200 µg Jo-1, PL-7 or PL-12 recombinant protein emulsified in CFA in combination with OX86. Muscle force was assessed by rotarod tests and the effects on the peripheral immune system were investigated by flow cytometry in spleen and lymph nodes. Skeletal muscle and lung samples were analyzed by histology and immunohistochemistry.
Results
Immunization of mice led to clinical symptoms including muscle weakness and demonstrated variations in the immune cell response between the ARS subtypes. Histological analysis of skeletal muscle tissues showed infiltration by immune cells in the epimysium, spreading into the adjacent perifascicular area with progressing disease. Furthermore, the lungs were also affected early on.
Conclusion
We present a mouse model, which recapitulates features of the human phenotype of ASyS, to study the molecular pathogenesis and provide new insights into the pathomechanisms.