High-Dimensional Cytometry Dissects Immunological Fingerprints of Idiopathic Inflammatory Myopathies

• Published in: Cells (Basel, Switzerland) Vol. 11; no. 20; p. 3330
• Main Authors: Nelke, Christopher, Pawlitzki, Marc, Schroeter, Christina B, Huntemann, Niklas, Räuber, Saskia, Dobelmann, Vera, Preusse, Corinna, Roos, Andreas, Allenbach, Yves, Benveniste, Olivier, Wiendl, Heinz, Lundberg, Ingrid E, Stenzel, Werner, Meuth, Sven G, Ruck, Tobias
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.10.2022; MDPI
• Subjects: Algorithms; Antibodies; Autoimmunity; Care and treatment; CD18 antigen; CD38 antigen; CD4 antigen; CD8 antigen; Cell differentiation; Clustering; Cytokines; cytometry; Cytotoxicity; Dermatomyositis; Disease; Dosage and administration; Flow cytometry; Health aspects; Helper cells; immune signature; Immunoglobulin G; Immunoglobulin G4; Immunology; Immunosuppressive agents; Immunotherapy; Inflammation; inflammatory idiopathic myopathy; Lymphocytes T; Medical examination; Medicin och hälsovetenskap; Muscle weakness; Muscles; Musculoskeletal system; Myositis; Patients; Phenotypes; Skeletal muscle; Statistical analysis; Topography; Germany; United States > US
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11203330

Chronic inflammation of skeletal muscle is the common feature of idiopathic inflammatory myopathies (IIM). Given the rarity of the disease and potential difficulty of routinely obtaining target tissue, i.e., standardized skeletal muscle, our understanding of immune signatures of the IIM spectrum remains incomplete. Further insight into the immune topography of IIM is needed to determine specific treatment targets according to clinical and immunological phenotypes. Thus, we used high-dimensional flow cytometry to investigate the immune phenotypes of anti-synthetase syndrome (ASyS), dermatomyositis (DM) and inclusion-body myositis (IBM) patients as representative entities of the IIM spectrum and compared them to healthy controls. We studied the CD8, CD4 and B cell compartments in the blood aiming to provide a contemporary overview of the immune topography of the IIM spectrum. ASyS was characterized by altered CD4 composition and expanded T follicular helper cells supporting B cell-mediated autoimmunity. For DM, unsupervised clustering identified expansion of distinct B cell subtypes highly expressing immunoglobulin G4 (IgG4) and CD38. Lastly, terminally differentiated, cytotoxic CD8 T cells distinguish IBM from other IIM. Interestingly, these terminally differentiated CD8 T cells highly expressed the integrin CD18 mediating cellular adhesion and infiltration. The distinct immune cell topography of IIM might provide the framework for targeted treatment approaches potentially improving therapeutic outcomes.