High-Dimensional Cytometry Dissects Immunological Fingerprints of Idiopathic Inflammatory Myopathies
Christopher Nelke,
Marc Pawlitzki,
Christina B. Schroeter,
Niklas Huntemann,
Saskia Räuber,
Vera Dobelmann,
Corinna Preusse,
Andreas Roos,
Yves Allenbach,
Olivier Benveniste,
Heinz Wiendl,
Ingrid E. Lundberg,
Werner Stenzel,
Sven G. Meuth,
Tobias Ruck
Affiliations
Christopher Nelke
Department of Neurology, Medical Faculty, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany
Marc Pawlitzki
Department of Neurology, Medical Faculty, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany
Christina B. Schroeter
Department of Neurology, Medical Faculty, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany
Niklas Huntemann
Department of Neurology, Medical Faculty, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany
Saskia Räuber
Department of Neurology, Medical Faculty, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany
Vera Dobelmann
Department of Neurology, Medical Faculty, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany
Corinna Preusse
Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
Andreas Roos
Department of Neuropediatrics, University of Duisburg-Essen, 45147 Essen, Germany
Yves Allenbach
Service de Médecine Interne et Immunologie Clinique, University Hospital Pitié Salpêtrière, 75013 Paris, France
Olivier Benveniste
Service de Médecine Interne et Immunologie Clinique, University Hospital Pitié Salpêtrière, 75013 Paris, France
Heinz Wiendl
Department of Neurology with Institute of Translational Neurology, University Hospital Münster, 48149 Münster, Germany
Ingrid E. Lundberg
Division of Rheumatology, Department of Medicine, Solna, Karolinska Institutet, and Karolinska University Hospital, 171 77 Stockholm, Sweden
Werner Stenzel
Department of Neuropathology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
Sven G. Meuth
Department of Neurology, Medical Faculty, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany
Tobias Ruck
Department of Neurology, Medical Faculty, Heinrich Heine University Dusseldorf, 40225 Dusseldorf, Germany
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.
