Autoantibodies targeting TRIM72 compromise membrane repair and contribute to inflammatory myopathy
| Autor: | Brian J. Paleo, Kevin E. McElhanon, Noah Weisleder, Wael N. Jarjour, Nicholas A. Young, Chester V. Oddis, Rohit Aggarwal, Travis Gurney, Eric X Beck, Kyle Jablonski, Thomas A. Kwiatkowski, J. Hampton, Ana Capati, Miguel A. Lopez Perez |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adoptive cell transfer
Muscle Fibers Skeletal Inflammation medicine.disease_cause Autoimmune Diseases Autoimmunity Inflammatory myopathy Pathogenesis Mice Sarcolemma Animals Medicine Humans Barrier function Autoantibodies Mice Knockout Myositis business.industry Autoantibody Membrane Proteins Skeletal muscle General Medicine Plastic Surgery Procedures medicine.disease medicine.anatomical_structure Immunology Disease Progression Rabbits medicine.symptom business Research Article |
| Zdroj: | J Clin Invest |
| Popis: | Idiopathic inflammatory myopathies (IIM) involve chronic inflammation of skeletal muscle and subsequent muscle degeneration due to an uncontrolled autoimmune response; however, the mechanisms leading to pathogenesis are not well understood. A compromised sarcolemmal repair process could promote an aberrant exposure of intramuscular antigens with the subsequent initiation of an inflammatory response that contributes to IIM. Using an adoptive transfer mouse model of IIM, we show that sarcolemmal repair is significantly compromised in distal skeletal muscle in the absence of inflammation. We identified autoantibodies against TRIM72 (also known as MG53), a muscle-enriched membrane repair protein, in IIM patient sera and in our mouse model of IIM by ELISA. We found that patient sera with elevated levels of TRIM72 autoantibodies suppress sarcolemmal resealing in healthy skeletal muscle, and depletion of TRIM72 antibodies from these same serum samples rescues sarcolemmal repair capacity. Autoantibodies targeting TRIM72 lead to skeletal muscle fibers with compromised membrane barrier function, providing a continuous source of autoantigens to promote autoimmunity and further amplifying humoral responses. These findings reveal a potential pathogenic mechanism that acts as a feedback loop contributing to the progression of IIM. |
| Databáze: | OpenAIRE |
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