Skeletal muscle fibers produce B-cell stimulatory factors in chronic myositis

IntroductionWe aimed to identify B-cell-mediated immunomechanisms in inclusion body myositis (IBM) and polymyositis (PM) as part of the complex pathophysiology.Materials and methodsHuman primary myotube cultures were derived from orthopedic surgery. Diagnostic biopsy specimens from patients with IBM...

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Main Authors: Per-Ole Carstens, Luisa M. Müllar, Arne Wrede, Sabrina Zechel, Martin M. Wachowski, Almuth Brandis, Sabine Krause, Stephan Zierz, Jens Schmidt
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-09-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1177721/full
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author Per-Ole Carstens
Luisa M. Müllar
Arne Wrede
Arne Wrede
Sabrina Zechel
Martin M. Wachowski
Almuth Brandis
Almuth Brandis
Sabine Krause
Stephan Zierz
Jens Schmidt
Jens Schmidt
Jens Schmidt
author_facet Per-Ole Carstens
Luisa M. Müllar
Arne Wrede
Arne Wrede
Sabrina Zechel
Martin M. Wachowski
Almuth Brandis
Almuth Brandis
Sabine Krause
Stephan Zierz
Jens Schmidt
Jens Schmidt
Jens Schmidt
author_sort Per-Ole Carstens
collection DOAJ
description IntroductionWe aimed to identify B-cell-mediated immunomechanisms in inclusion body myositis (IBM) and polymyositis (PM) as part of the complex pathophysiology.Materials and methodsHuman primary myotube cultures were derived from orthopedic surgery. Diagnostic biopsy specimens from patients with IBM (n=9) and PM (n=9) were analyzed for markers of B cell activation (BAFF and APRIL) and for chemokines that control the recruitment of B cells (CXCL-12 and CXCL-13). Results were compared to biopsy specimens without myopathic changes (n=9) and hereditary muscular dystrophy (n=9).ResultsThe mRNA expression of BAFF, APRIL, and CXCL-13 was significantly higher in IBM and PM compared to controls. Patients with IBM displayed the highest number of double positive muscle fibers for BAFF and CXCL-12 (48%) compared to PM (25%), muscular dystrophy (3%), and non-myopathic controls (0%). In vitro, exposure of human myotubes to pro-inflammatory cytokines led to a significant upregulation of BAFF and CXCL-12, but APRIL and CXCL-13 remained unchanged.ConclusionThe results substantiate the hypothesis of an involvement of B cell-associated mechanisms in the pathophysiology of IBM and PM. Muscle fibers themselves seem to contribute to the recruitment of B cells and sustain inflammation.
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spelling doaj.art-23060bdf8e2743068f853639ee4aa7c12023-09-05T09:27:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.11777211177721Skeletal muscle fibers produce B-cell stimulatory factors in chronic myositisPer-Ole Carstens0Luisa M. Müllar1Arne Wrede2Arne Wrede3Sabrina Zechel4Martin M. Wachowski5Almuth Brandis6Almuth Brandis7Sabine Krause8Stephan Zierz9Jens Schmidt10Jens Schmidt11Jens Schmidt12Department of Neurology, University Medical Center Göttingen, Göttingen, GermanyDepartment of Neurology, University Medical Center Göttingen, Göttingen, GermanyInstitute of Neuropathology, University Medical Center Göttingen, Göttingen, GermanyInstitute of Neuropathology, Saarland University Medical Center and Medical Faculty of Saarland University, Homburg, GermanyInstitute of Neuropathology, University Medical Center Göttingen, Göttingen, GermanyDepartment of Trauma Surgery, Orthopaedics and Plastic Surgery, University Medical Center Göttingen, Göttingen, GermanyDepartment of Pathology, Klinikum Region Hannover, Hannover, GermanyInstitute of Pathology and Neuropathology, Medical University Hannover, Hannover, GermanyFriedrich-Baur-Institute, Department of Neurology, Ludwig-Maximilians-University of München, München, GermanyDepartment of Neurology, University Hospital Halle/Saale, Halle, GermanyDepartment of Neurology, University Medical Center Göttingen, Göttingen, GermanyDepartment of Neurology and Pain Treatment, Neuromuscular Center, Center for Translational Medicine, Immanuel Klinik Rüdersdorf, University Hospital of the Brandenburg Medical School Theodor Fontane, Rüdersdorf bei Berlin, Germany0Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, Rüdersdorf bei, Berlin, GermanyIntroductionWe aimed to identify B-cell-mediated immunomechanisms in inclusion body myositis (IBM) and polymyositis (PM) as part of the complex pathophysiology.Materials and methodsHuman primary myotube cultures were derived from orthopedic surgery. Diagnostic biopsy specimens from patients with IBM (n=9) and PM (n=9) were analyzed for markers of B cell activation (BAFF and APRIL) and for chemokines that control the recruitment of B cells (CXCL-12 and CXCL-13). Results were compared to biopsy specimens without myopathic changes (n=9) and hereditary muscular dystrophy (n=9).ResultsThe mRNA expression of BAFF, APRIL, and CXCL-13 was significantly higher in IBM and PM compared to controls. Patients with IBM displayed the highest number of double positive muscle fibers for BAFF and CXCL-12 (48%) compared to PM (25%), muscular dystrophy (3%), and non-myopathic controls (0%). In vitro, exposure of human myotubes to pro-inflammatory cytokines led to a significant upregulation of BAFF and CXCL-12, but APRIL and CXCL-13 remained unchanged.ConclusionThe results substantiate the hypothesis of an involvement of B cell-associated mechanisms in the pathophysiology of IBM and PM. Muscle fibers themselves seem to contribute to the recruitment of B cells and sustain inflammation.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1177721/fullautoimmune diseasesneuromuscular diseaseinflammatory muscle diseasemyositisB cells
spellingShingle Per-Ole Carstens
Luisa M. Müllar
Arne Wrede
Arne Wrede
Sabrina Zechel
Martin M. Wachowski
Almuth Brandis
Almuth Brandis
Sabine Krause
Stephan Zierz
Jens Schmidt
Jens Schmidt
Jens Schmidt
Skeletal muscle fibers produce B-cell stimulatory factors in chronic myositis
Frontiers in Immunology
autoimmune diseases
neuromuscular disease
inflammatory muscle disease
myositis
B cells
title Skeletal muscle fibers produce B-cell stimulatory factors in chronic myositis
title_full Skeletal muscle fibers produce B-cell stimulatory factors in chronic myositis
title_fullStr Skeletal muscle fibers produce B-cell stimulatory factors in chronic myositis
title_full_unstemmed Skeletal muscle fibers produce B-cell stimulatory factors in chronic myositis
title_short Skeletal muscle fibers produce B-cell stimulatory factors in chronic myositis
title_sort skeletal muscle fibers produce b cell stimulatory factors in chronic myositis
topic autoimmune diseases
neuromuscular disease
inflammatory muscle disease
myositis
B cells
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1177721/full
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