Cargando…

High-Dimensional Cytometry Dissects Immunological Fingerprints of Idiopathic Inflammatory Myopathies

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 rem...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9601098/
https://www.ncbi.nlm.nih.gov/pubmed/36291195
http://dx.doi.org/10.3390/cells11203330
_version_ 1784816973009387520
author 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
author_facet 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
author_sort Nelke, Christopher
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9601098
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-96010982022-10-27 High-Dimensional Cytometry Dissects Immunological Fingerprints of Idiopathic Inflammatory Myopathies 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 Cells Article 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. MDPI 2022-10-21 /pmc/articles/PMC9601098/ /pubmed/36291195 http://dx.doi.org/10.3390/cells11203330 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
High-Dimensional Cytometry Dissects Immunological Fingerprints of Idiopathic Inflammatory Myopathies
title High-Dimensional Cytometry Dissects Immunological Fingerprints of Idiopathic Inflammatory Myopathies
title_full High-Dimensional Cytometry Dissects Immunological Fingerprints of Idiopathic Inflammatory Myopathies
title_fullStr High-Dimensional Cytometry Dissects Immunological Fingerprints of Idiopathic Inflammatory Myopathies
title_full_unstemmed High-Dimensional Cytometry Dissects Immunological Fingerprints of Idiopathic Inflammatory Myopathies
title_short High-Dimensional Cytometry Dissects Immunological Fingerprints of Idiopathic Inflammatory Myopathies
title_sort high-dimensional cytometry dissects immunological fingerprints of idiopathic inflammatory myopathies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9601098/
https://www.ncbi.nlm.nih.gov/pubmed/36291195
http://dx.doi.org/10.3390/cells11203330
work_keys_str_mv AT nelkechristopher highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies
AT pawlitzkimarc highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies
AT schroeterchristinab highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies
AT huntemannniklas highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies
AT raubersaskia highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies
AT dobelmannvera highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies
AT preussecorinna highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies
AT roosandreas highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies
AT allenbachyves highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies
AT benvenisteolivier highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies
AT wiendlheinz highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies
AT lundbergingride highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies
AT stenzelwerner highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies
AT meuthsveng highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies
AT rucktobias highdimensionalcytometrydissectsimmunologicalfingerprintsofidiopathicinflammatorymyopathies