Complement in autoimmune inflammatory myopathies, the role of myositis-associated antibodies, COVID-19 associations, and muscle amyloid deposits.
The inflammatory myopathies (IM) have now evolved into distinct subsets requiring clarification about their immunopathogenesis to guide applications of targeted therapies
Immunohistopathologic criteria of IM with a focus on complement, anti-complement therapeutics, and other biologic immunotherapies. The COVID19-triggered muscle autoimmunity along with the correct interpretation of muscle amyloid deposits is discussed.
The IM, unjustifiably referred as idiopathic, comprise Dermatomyositis (DM), Necrotizing Autoimmune Myositis (NAM), Anti-synthetase syndrome-overlap myositis (Anti-SS-OM), and Inclusion-Body-Myositis (IBM). In DM, complement activation with MAC-mediated endomysial microvascular destruction and perifascicular atrophy is the fundamental process, while innate immunity activation factors, INF1 and MxA, sense and secondarily enhance inflammation. Complement participates in muscle fiber necrosis from any cause and may facilitate muscle-fiber necrosis in NAM but seems unlikely that myositis-associated antibodies participate in complement-fixing. Accordingly, anti-complement therapeutics should be prioritized for DM. SARS-CoV-2 can potentially trigger muscle autoimmunity, but systematic studies are needed as the reported autopsy findings are not clinically relevant. In IBM, tiny amyloid deposits within muscle fibers are enhanced by inflammatory mediators contributing to myodegeneration; in contrast, spotty amyloid deposits in the endomysial connective tissue do not represent ‘amyloid myopathy’ but only have diagnostic value for amyloidosis due to any cause.
Dalakas, Marinos, "Complement in autoimmune inflammatory myopathies, the role of myositis-associated antibodies, COVID-19 associations, and muscle amyloid deposits." (2022). Department of Neurology Faculty Papers. Paper 297.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
This is the final published version of the article from the journal Expert Review of Clinical Immunology, 2022 Apr;18(4):413-423.
The article can also be accessed on the journal's website: https://doi.org/10.1080/1744666X.2022.2054803
Copyright. The Authors.