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For: Pandya JM, Loell I, Hossain MS, Zong M, Alexanderson H, Raghavan S, Lundberg IE, Malmström V. Effects of conventional immunosuppressive treatment on CD244+ (CD28null) and FOXP3+ T cells in the inflamed muscle of patients with polymyositis and dermatomyositis. Arthritis Res Ther 2016;18:80. [PMID: 27039301 PMCID: PMC4818535 DOI: 10.1186/s13075-016-0974-5] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Accepted: 03/14/2016] [Indexed: 12/12/2022] Open

For:	Pandya JM, Loell I, Hossain MS, Zong M, Alexanderson H, Raghavan S, Lundberg IE, Malmström V. Effects of conventional immunosuppressive treatment on CD244+ (CD28null) and FOXP3+ T cells in the inflamed muscle of patients with polymyositis and dermatomyositis. Arthritis Res Ther 2016;18:80. [PMID: 27039301 PMCID: PMC4818535 DOI: 10.1186/s13075-016-0974-5] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Accepted: 03/14/2016] [Indexed: 12/12/2022] Open

Number

Cited by Other Article(s)

Chen Y, Liu H, Luo Z, Zhang J, Dong M, Yin G, Xie Q. ASM is a therapeutic target in dermatomyositis by regulating the differentiation of naive CD4 + T cells into Th17 and Treg subsets. Skelet Muscle 2024;14:16. [PMID: 39026344 PMCID: PMC11256435 DOI: 10.1186/s13395-024-00347-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 06/29/2024] [Indexed: 07/20/2024] Open

Li W, Deng C, Yang H, Tian X, Chen L, Liu Q, Gao C, Lu X, Wang G, Peng Q. Upregulation of the CD155-CD226 Axis Is Associated With Muscle Inflammation and Disease Severity in Idiopathic Inflammatory Myopathies. NEUROLOGY(R) NEUROIMMUNOLOGY & NEUROINFLAMMATION 2023;10:e200143. [PMID: 37491355 PMCID: PMC10368451 DOI: 10.1212/nxi.0000000000200143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 06/01/2023] [Indexed: 07/27/2023]

Abstract

BACKGROUND AND OBJECTIVES

The CD155-CD226/T-cell Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) pathway plays a critical role in regulating T-cell responses and is being targeted clinically. However, research on the role of this pathway in autoimmune diseases is limited. This study aimed to investigate the expression and tissue-specific roles of CD155-CD226/TIGIT pathway molecules in the inflamed muscles of patients with idiopathic inflammatory myopathies (IIMs).

METHODS

Immunohistochemistry, Western blot analysis, and polychromatic immunofluorescence staining were performed to examine the expression of CD155, CD226, and TIGIT in skeletal muscle biopsies from 30 patients with dermatomyositis (DM), 10 patients with amyopathic DM (ADM), 20 patients with immune-mediated necrotizing myopathy (IMNM), 5 patients with dysferlinopathy, and 4 healthy controls. Flow cytometry analysis was used to analyze the functions of T cells with different phenotypes.

RESULTS

Strong expression of CD155 was observed in patients with DM and IMNM, while its expression was largely negative in those with ADM and dysferlinopathy and healthy controls. The costimulatory receptor CD226 was highly expressed on muscle-infiltrating cells, while the coinhibitory receptor TIGIT was expressed at low levels. These infiltrating CD226+ cells were mainly activated effector T cells that localized adjacent to CD155-expressing myofibers, but were faintly detectable within the muscle fascicles lacking CD155. A strong positive correlation between CD155 and CD226 expression scores was also observed. Polychromatic immunofluorescence staining revealed that CD155+ muscle cells coexpressed major histocompatibility complex classes I and II, and tumor necrosis factor alpha expression was detected in CD226+ T cells at their close sites with the myofibers. Furthermore, the expression levels of CD155 and CD226 showed a positive correlation with creatine kinase, lactate dehydrogenase, and the muscle histopathology damage scores and an inverse correlation with the Manual Muscle Testing-8 scores. In addition, CD155 and CD226 expressions were significantly decreased in representative patients who achieved remission posttreatment.

DISCUSSION

These findings demonstrate that the CD155-CD226 axis is highly activated in inflamed muscle tissues of patients with IIM and is associated with muscle disease severity. Our data uncover the immunopathogenic role of the axis in the pathology of IIMs.

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Affiliation(s)

Wenli Li From the Department of Rheumatology (W.L., H.Y., X.T., Q.L., C.G., X.L., G.W., Q.P.), Key Myositis Laboratories, China-Japan Friendship Hospital; Department of Rheumatology and Clinical Immunology (C.D.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; and Department of Blood Transfusion (L.C.), China-Japan Friendship Hospital, Beijing.
Chuiwen Deng From the Department of Rheumatology (W.L., H.Y., X.T., Q.L., C.G., X.L., G.W., Q.P.), Key Myositis Laboratories, China-Japan Friendship Hospital; Department of Rheumatology and Clinical Immunology (C.D.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; and Department of Blood Transfusion (L.C.), China-Japan Friendship Hospital, Beijing
Hanbo Yang From the Department of Rheumatology (W.L., H.Y., X.T., Q.L., C.G., X.L., G.W., Q.P.), Key Myositis Laboratories, China-Japan Friendship Hospital; Department of Rheumatology and Clinical Immunology (C.D.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; and Department of Blood Transfusion (L.C.), China-Japan Friendship Hospital, Beijing
Xiaolan Tian From the Department of Rheumatology (W.L., H.Y., X.T., Q.L., C.G., X.L., G.W., Q.P.), Key Myositis Laboratories, China-Japan Friendship Hospital; Department of Rheumatology and Clinical Immunology (C.D.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; and Department of Blood Transfusion (L.C.), China-Japan Friendship Hospital, Beijing
Lida Chen From the Department of Rheumatology (W.L., H.Y., X.T., Q.L., C.G., X.L., G.W., Q.P.), Key Myositis Laboratories, China-Japan Friendship Hospital; Department of Rheumatology and Clinical Immunology (C.D.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; and Department of Blood Transfusion (L.C.), China-Japan Friendship Hospital, Beijing
Qingyan Liu From the Department of Rheumatology (W.L., H.Y., X.T., Q.L., C.G., X.L., G.W., Q.P.), Key Myositis Laboratories, China-Japan Friendship Hospital; Department of Rheumatology and Clinical Immunology (C.D.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; and Department of Blood Transfusion (L.C.), China-Japan Friendship Hospital, Beijing
Chang Gao From the Department of Rheumatology (W.L., H.Y., X.T., Q.L., C.G., X.L., G.W., Q.P.), Key Myositis Laboratories, China-Japan Friendship Hospital; Department of Rheumatology and Clinical Immunology (C.D.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; and Department of Blood Transfusion (L.C.), China-Japan Friendship Hospital, Beijing
Xin Lu From the Department of Rheumatology (W.L., H.Y., X.T., Q.L., C.G., X.L., G.W., Q.P.), Key Myositis Laboratories, China-Japan Friendship Hospital; Department of Rheumatology and Clinical Immunology (C.D.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; and Department of Blood Transfusion (L.C.), China-Japan Friendship Hospital, Beijing
Guochun Wang From the Department of Rheumatology (W.L., H.Y., X.T., Q.L., C.G., X.L., G.W., Q.P.), Key Myositis Laboratories, China-Japan Friendship Hospital; Department of Rheumatology and Clinical Immunology (C.D.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; and Department of Blood Transfusion (L.C.), China-Japan Friendship Hospital, Beijing
Qinglin Peng From the Department of Rheumatology (W.L., H.Y., X.T., Q.L., C.G., X.L., G.W., Q.P.), Key Myositis Laboratories, China-Japan Friendship Hospital; Department of Rheumatology and Clinical Immunology (C.D.), Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; and Department of Blood Transfusion (L.C.), China-Japan Friendship Hospital, Beijing.

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Patil A, Lu J, Kassir M, Babaei M, Goldust M. Adult and juvenile dermatomyositis treatment. J Cosmet Dermatol 2023;22:395-401. [PMID: 36065712 DOI: 10.1111/jocd.15363] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 08/17/2022] [Accepted: 09/02/2022] [Indexed: 11/29/2022]

Goyal NA, Coulis G, Duarte J, Farahat PK, Mannaa AH, Cauchii J, Irani T, Araujo N, Wang L, Wencel M, Li V, Zhang L, Greenberg SA, Mozaffar T, Villalta SA. Immunophenotyping of Inclusion Body Myositis Blood T and NK Cells. Neurology 2022;98:e1374-e1383. [PMID: 35131904 PMCID: PMC8967422 DOI: 10.1212/wnl.0000000000200013] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 01/03/2022] [Indexed: 11/15/2022] Open

Affiliation(s)

Namita A Goyal Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA
Gérald Coulis Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA
Jorge Duarte Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA
Philip K Farahat Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA
Ali H Mannaa Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA
Jonathan Cauchii Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA
Tyler Irani Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA
Nadia Araujo Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA
Leo Wang Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA
Marie Wencel Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA
Vivian Li Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA
Lishi Zhang Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA
Steven A Greenberg Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA
Tahseen Mozaffar Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA
S Armando Villalta Department of Neurology (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M., S.A.V.), MDA ALS and Neuromuscular Center (N.A.G., J.C., T.I., N.A., M.W., V.L., T.M.), Department of Pathology and Laboratory Medicine (T.M.), Department of Physiology and Biophysics (G.C., J.D., P.K.F., A.H.M., S.A.V.), Institute for Immunology (G.C., J.D., P.K.F., A.H.M., T.M., S.A.V.), and Biostatistics, Epidemiology, and Research Design (BERD) Unit, Institute for Clinical Translational Sciences (L.Z.), University of California, Irvine; Department of Neurology (J.C.), University of New Mexico, Albuquerque; Department of Neurology (L.W.), University of Washington Medical Center, Seattle; Department of Neurology, Division of Neuromuscular Disease (S.A.G.), Brigham and Women's Hospital and Harvard Medical School; and Computational Health Informatics Program (S.A.G.), Boston Children's Hospital and Harvard Medical School, MA.

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Kobayashi S, Nagafuchi Y, Okubo M, Sugimori Y, Hatano H, Yamada S, Nakano M, Yoshida R, Takeshima Y, Ota M, Tsuchida Y, Iwasaki Y, Setoguchi K, Kubo K, Okamura T, Yamamoto K, Shoda H, Fujio K. Dysregulation of the gene signature of effector regulatory T cells in the early phase of systemic sclerosis. Rheumatology (Oxford) 2022;61:4163-4174. [PMID: 35040949 DOI: 10.1093/rheumatology/keac031] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 01/11/2022] [Indexed: 11/14/2022] Open

Affiliation(s)

Satomi Kobayashi Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo.,Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Japan. 35-2 Sakaechou, Itabashi-ku, 173-0015, Japan, Tokyo, Tokyo
Yasuo Nagafuchi Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo.,Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
Mai Okubo Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo
Yusuke Sugimori Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo
Hiroaki Hatano Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo
Saeko Yamada Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo
Masahiro Nakano Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo
Ryochi Yoshida Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo
Yusuke Takeshima Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo
Mineto Ota Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo.,Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
Yumi Tsuchida Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo
Yukiko Iwasaki Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo
Keigo Setoguchi Department of Rheumatology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Japan. 3-18-22 Honkomagome, Bunkyo-ku, 113-8677, Japan, Tokyo, Tokyo
Kanae Kubo Department of Medicine and Rheumatology, Tokyo Metropolitan Geriatric Hospital, Japan. 35-2 Sakaechou, Itabashi-ku, 173-0015, Japan, Tokyo, Tokyo
Tomohisa Okamura Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo.,Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
Kazuhiko Yamamoto Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo.,Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Japan. 1-7-22 Suehiro-cho, Tsurumi-ku, Kanagawa, 230-0045, Japan, Yokohama, Yokohama
Hirofumi Shoda Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo
Keishi Fujio Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Japan. 7-3-1 Hongo, Bunkyo-ku, 113-8655, Japan, Tokyo, Tokyo

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Shi J, Tang M, Zhou S, Xu D, Zhao J, Wu C, Wang Q, Tian X, Li M, Zeng X. Programmed Cell Death Pathways in the Pathogenesis of Idiopathic Inflammatory Myopathies. Front Immunol 2021;12:783616. [PMID: 34899749 PMCID: PMC8651702 DOI: 10.3389/fimmu.2021.783616] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 11/08/2021] [Indexed: 12/11/2022] Open

Affiliation(s)

Jia Shi Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
Mingwei Tang Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
Shuang Zhou Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
Dong Xu Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
Jiuliang Zhao Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
Chanyuan Wu Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
Qian Wang Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
Xinping Tian Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
Mengtao Li Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China
Xiaofeng Zeng Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Key Laboratory of Rheumatology & Clinical Immunology, Ministry of Education, Beijing, China.,National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, Beijing, China

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Boyer O, Butler-Browne G, Chinoy H, Cossu G, Galli F, Lilleker JB, Magli A, Mouly V, Perlingeiro RCR, Previtali SC, Sampaolesi M, Smeets H, Schoewel-Wolf V, Spuler S, Torrente Y, Van Tienen F. Myogenic Cell Transplantation in Genetic and Acquired Diseases of Skeletal Muscle. Front Genet 2021;12:702547. [PMID: 34408774 PMCID: PMC8365145 DOI: 10.3389/fgene.2021.702547] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 06/16/2021] [Indexed: 01/04/2023] Open

Abstract

This article will review myogenic cell transplantation for congenital and acquired diseases of skeletal muscle. There are already a number of excellent reviews on this topic, but they are mostly focused on a specific disease, muscular dystrophies and in particular Duchenne Muscular Dystrophy. There are also recent reviews on cell transplantation for inflammatory myopathies, volumetric muscle loss (VML) (this usually with biomaterials), sarcopenia and sphincter incontinence, mainly urinary but also fecal. We believe it would be useful at this stage, to compare the same strategy as adopted in all these different diseases, in order to outline similarities and differences in cell source, pre-clinical models, administration route, and outcome measures. This in turn may help to understand which common or disease-specific problems have so far limited clinical success of cell transplantation in this area, especially when compared to other fields, such as epithelial cell transplantation. We also hope that this may be useful to people outside the field to get a comprehensive view in a single review. As for any cell transplantation procedure, the choice between autologous and heterologous cells is dictated by a number of criteria, such as cell availability, possibility of in vitro expansion to reach the number required, need for genetic correction for many but not necessarily all muscular dystrophies, and immune reaction, mainly to a heterologous, even if HLA-matched cells and, to a minor extent, to the therapeutic gene product, a possible antigen for the patient. Finally, induced pluripotent stem cell derivatives, that have entered clinical experimentation for other diseases, may in the future offer a bank of immune-privileged cells, available for all patients and after a genetic correction for muscular dystrophies and other myopathies.

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Affiliation(s)

Olivier Boyer Department of Immunology & Biotherapy, Rouen University Hospital, Normandy University, Inserm U1234, Rouen, France
Gillian Butler-Browne Sorbonne Université, Inserm, Institut de Myologie, Centre de Recherche en Myologie, Paris, France
Hector Chinoy Manchester Centre for Clinical Neurosciences, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, The University of Manchester, Manchester, United Kingdom
Giulio Cossu Division of Cell Matrix Biology & Regenerative Medicine, The University of Manchester, Manchester, United Kingdom Muscle Research Unit, Experimental and Clinical Research Center, a Cooperation Between the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association and the Charité, Universitätsmedizin Berlin, Berlin, Germany InSpe and Division of Neuroscience, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Milan, Italy
Francesco Galli National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, The University of Manchester, Manchester, United Kingdom
James B. Lilleker Manchester Centre for Clinical Neurosciences, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, Salford, United Kingdom National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, The University of Manchester, Manchester, United Kingdom
Alessandro Magli Department of Medicine, Lillehei Heart Institute, Stem Cell Institute, University of Minnesota, Minneapolis, MN, United States
Vincent Mouly Sorbonne Université, Inserm, Institut de Myologie, Centre de Recherche en Myologie, Paris, France
Rita C. R. Perlingeiro Department of Medicine, Lillehei Heart Institute, Stem Cell Institute, University of Minnesota, Minneapolis, MN, United States
Stefano C. Previtali InSpe and Division of Neuroscience, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Milan, Italy
Maurilio Sampaolesi Translational Cardiomyology Laboratory, Department of Development and Regeneration, KU Leuven, Leuven, Belgium Human Anatomy Unit, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy
Hubert Smeets Department of Toxicogenomics, Maastricht University Medical Centre, Maastricht, Netherlands School for Mental Health and Neurosciences (MHeNS), Maastricht University, Maastricht, Netherlands School for Developmental Biology and Oncology (GROW), Maastricht University, Maastricht, Netherlands
Verena Schoewel-Wolf Muscle Research Unit, Experimental and Clinical Research Center, a Cooperation Between the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association and the Charité, Universitätsmedizin Berlin, Berlin, Germany
Simone Spuler Muscle Research Unit, Experimental and Clinical Research Center, a Cooperation Between the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association and the Charité, Universitätsmedizin Berlin, Berlin, Germany
Yvan Torrente Unit of Neurology, Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Centro Dino Ferrari, Università degli Studi di Milano, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
Florence Van Tienen Department of Toxicogenomics, Maastricht University Medical Centre, Maastricht, Netherlands School for Mental Health and Neurosciences (MHeNS), Maastricht University, Maastricht, Netherlands

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Zhang SX, Wang J, Sun HH, Zhang JQ, Liu GY, Luo J, He PF, Li XF. Circulating regulatory T cells were absolutely decreased in dermatomyositis/polymyositis patients and restored by low-dose IL-2. Ann Rheum Dis 2021;80:e130. [PMID: 31611221 DOI: 10.1136/annrheumdis-2019-216246] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Accepted: 09/04/2019] [Indexed: 12/16/2022]

Ye Q, Chen Z. MicroRNA-409-3p regulates macrophage migration in polymyositis through targeting CXCR4. Autoimmunity 2021;54:353-361. [PMID: 34142881 DOI: 10.1080/08916934.2021.1937610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]

Miao M, Li Y, Huang B, Chen J, Jin Y, Shao M, Zhang X, Sun X, He J, Li Z. Treatment of Active Idiopathic Inflammatory Myopathies by Low-Dose Interleukin-2: A Prospective Cohort Pilot Study. Rheumatol Ther 2021;8:835-847. [PMID: 33852146 PMCID: PMC8217480 DOI: 10.1007/s40744-021-00301-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 03/17/2021] [Indexed: 11/01/2022] Open

Affiliation(s)

Miao Miao Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China
Yuhui Li Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China
Bo Huang Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China
Jiali Chen Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China
Yuebo Jin Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China
Miao Shao Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China
Xia Zhang Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China
Xiaolin Sun Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China. Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.
Jing He Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China. Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China.
Zhanguo Li Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, 100044, China. Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China. Peking-Tsinghua Center for Life Sciences, Beijing, China.

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Pathogenesis of inclusion body myositis. Curr Opin Rheumatol 2021;32:542-547. [PMID: 32941249 DOI: 10.1097/bor.0000000000000752] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]

Zhao L, Wang Q, Zhou B, Zhang L, Zhu H. The Role of Immune Cells in the Pathogenesis of Idiopathic Inflammatory Myopathies. Aging Dis 2021;12:247-260. [PMID: 33532139 PMCID: PMC7801271 DOI: 10.14336/ad.2020.0410] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 04/10/2020] [Indexed: 12/15/2022] Open

The Generation and Regulation of Tissue-Resident Tregs and Their Role in Autoimmune Diseases. J Immunol Res 2020. [DOI: 10.1155/2020/8815280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open

Wang J, Zhang SX, Hao YF, Qiu MT, Luo J, Li YY, Gao C, Li XF. The numbers of peripheral regulatory T cells are reduced in patients with psoriatic arthritis and are restored by low-dose interleukin-2. Ther Adv Chronic Dis 2020;11:2040622320916014. [PMID: 32523664 PMCID: PMC7236566 DOI: 10.1177/2040622320916014] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 02/18/2020] [Indexed: 12/11/2022] Open

Greenberg SA. Inclusion body myositis: clinical features and pathogenesis. Nat Rev Rheumatol 2020;15:257-272. [PMID: 30837708 DOI: 10.1038/s41584-019-0186-x] [Citation(s) in RCA: 166] [Impact Index Per Article: 33.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]

Jensen KY, Jacobsen M, Schrøder HD, Aagaard P, Nielsen JL, Jørgensen AN, Boyle E, Bech RD, Rosmark S, Diederichsen LP, Frandsen U. The immune system in sporadic inclusion body myositis patients is not compromised by blood-flow restricted exercise training. Arthritis Res Ther 2019;21:293. [PMID: 31852482 PMCID: PMC6921522 DOI: 10.1186/s13075-019-2036-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Accepted: 10/21/2019] [Indexed: 01/17/2023] Open

Abstract

BACKGROUND

Sporadic inclusion body myositis (sIBM) is clinically characterised by progressive proximal and distal muscle weakness and impaired physical function while skeletal muscle tissue displays abnormal cellular infiltration of T cells, macrophages, and dendritic cells. Only limited knowledge exists about the effects of low-load blood flow restriction exercise in sIBM patients, and its effect on the immunological responses at the myocellular level remains unknown. The present study is the first to investigate the longitudinal effects of low-load blood flow restriction exercise on innate and adaptive immune markers in skeletal muscle from sIBM patients.

METHODS

Twenty-two biopsy-validated sIBM patients were randomised into either 12 weeks of low-load blood flow restriction exercise (BFRE) or no exercise (CON). Five patients from the control group completed 12 weeks of BFRE immediately following participation in the 12-week control period leading to an intervention group of 16 patients. Muscle biopsies were obtained from either the m. tibialis anterior or the m. vastus lateralis for evaluation of CD3-, CD8-, CD68-, CD206-, CD244- and FOXP3-positive cells by three-colour immunofluorescence microscopy and Visiopharm-based image analysis quantification. A linear mixed model was used for the statistical analysis.

RESULTS

Myocellular infiltration of CD3^-/CD8⁺ expressing natural killer cells increased following BFRE (P < 0.05) with no changes in CON. No changes were observed for CD3⁺/CD8^- or CD3⁺/CD8⁺ T cells in BFRE or CON. CD3⁺/CD244⁺ T cells decreased in CON, while no changes were observed in BFRE. Pronounced infiltration of M1 pro-inflammatory (CD68⁺/CD206^-) and M2 anti-inflammatory (CD68⁺/CD206⁺) macrophages were observed at baseline; however, no longitudinal changes in macrophage content were observed for both groups.

CONCLUSIONS

Low-load blood flow restriction exercise elicited an upregulation in CD3^-/CD8⁺ expressing natural killer cell content, which suggests that 12 weeks of BFRE training evokes an amplified immune response in sIBM muscle. However, the observation of no changes in macrophage or T cell infiltration in the BFRE-trained patients indicates that patients with sIBM may engage in this type of exercise with no risk of intensified inflammatory activity.

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Affiliation(s)

Kasper Yde Jensen Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster (SMRC), University of Southern Denmark, Odense, Denmark.,Department of Pathology, Odense University Hospital, Odense, Denmark.,Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Mikkel Jacobsen Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster (SMRC), University of Southern Denmark, Odense, Denmark.,Department of Rheumatology, Odense University Hospital, Odense, Denmark.,Department of Pathology, Odense University Hospital, Odense, Denmark
Henrik Daa Schrøder Department of Pathology, Odense University Hospital, Odense, Denmark.,Department of Clinical Research, University of Southern Denmark, Odense, Denmark
Per Aagaard Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster (SMRC), University of Southern Denmark, Odense, Denmark
Jakob Lindberg Nielsen Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster (SMRC), University of Southern Denmark, Odense, Denmark
Anders Nørkær Jørgensen Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster (SMRC), University of Southern Denmark, Odense, Denmark.,Department of Clinical Research, University of Southern Denmark, Odense, Denmark
Eleanor Boyle Department of Sport Science and Clinical Biomechanics, Research Unit of Clinical Biomechanics, University of Southern Denmark, Odense, Denmark
Rune Dueholm Bech Department of Orthopaedics and Traumatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Sofie Rosmark Department of Rheumatology, Odense University Hospital, Odense, Denmark
Louise Pyndt Diederichsen Department of Rheumatology, Odense University Hospital, Odense, Denmark. .,Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Ulrik Frandsen Department of Sports Science and Clinical Biomechanics, SDU Muscle Research Cluster (SMRC), University of Southern Denmark, Odense, Denmark

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Yang SH, Chang C, Lian ZX. Polymyositis and dermatomyositis - challenges in diagnosis and management. J Transl Autoimmun 2019;2:100018. [PMID: 32743506 PMCID: PMC7388349 DOI: 10.1016/j.jtauto.2019.100018] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2019] [Accepted: 10/04/2019] [Indexed: 02/06/2023] Open

Anoveros-Barrera A, Bhullar AS, Stretch C, Dunichand-Hoedl AR, Martins KJB, Rieger A, Bigam D, McMullen T, Bathe OF, Putman CT, Field CJ, Baracos VE, Mazurak VC. Immunohistochemical phenotyping of T cells, granulocytes, and phagocytes in the muscle of cancer patients: association with radiologically defined muscle mass and gene expression. Skelet Muscle 2019;9:24. [PMID: 31521204 PMCID: PMC6744687 DOI: 10.1186/s13395-019-0209-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Accepted: 08/16/2019] [Indexed: 02/06/2023] Open

Abstract

BACKGROUND

Inflammation is a recognized contributor to muscle wasting. Research in injury and myopathy suggests that interactions between the skeletal muscle and immune cells confer a pro-inflammatory environment that influences muscle loss through several mechanisms; however, this has not been explored in the cancer setting. This study investigated the local immune environment of the muscle by identifying the phenotype of immune cell populations in the muscle and their relationship to muscle mass in cancer patients.

METHODS

Intraoperative muscle biopsies were collected from cancer patients (n = 30, 91% gastrointestinal malignancies). Muscle mass was assessed histologically (muscle fiber cross-sectional area, CSA; μm²) and radiologically (lumbar skeletal muscle index, SMI; cm²/m² by computed tomography, CT). T cells (CD4 and CD8) and granulocytes/phagocytes (CD11b, CD14, and CD15) were assessed by immunohistochemistry. Microarray analysis was conducted in the muscle of a second cancer patient cohort.

RESULTS

T cells (CD3+), granulocytes/phagocytes (CD11b+), and CD3-CD4+ cells were identified. Muscle fiber CSA (μm²) was positively correlated (Spearman's r = > 0.45; p = < 0.05) with the total number of T cells, CD4, and CD8 T cells and granulocytes/phagocytes. In addition, patients with the smallest SMI exhibited fewer CD8 T cells within their muscle. Consistent with this, further exploration with gene correlation analyses suggests that the presence of CD8 T cells is negatively associated (Pearson's r = ≥ 0.5; p = <0.0001) with key genes within muscle catabolic pathways for signaling (ACVR2B), ubiquitin proteasome (FOXO4, TRIM63, FBXO32, MUL1, UBC, UBB, UBE2L3), and apoptosis/autophagy (CASP8, BECN1, ATG13, SIVA1).

CONCLUSION

The skeletal muscle immune environment of cancer patients is comprised of immune cell populations from the adaptive and innate immunity. Correlations of T cells, granulocyte/phagocytes, and CD3-CD4+ cells with muscle mass measurements indicate a positive relationship between immune cell numbers and muscle mass status in cancer patients. Further exploration with gene correlation analyses suggests that the presence of CD8 T cells is negatively correlated with components of muscle catabolism.

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Affiliation(s)

Ana Anoveros-Barrera Department of Agricultural, Food & Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, 4-002 Li Ka Shing Centre, Edmonton, Alberta, T6G 2P5, Canada
Amritpal S Bhullar Department of Agricultural, Food & Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, 4-002 Li Ka Shing Centre, Edmonton, Alberta, T6G 2P5, Canada
Cynthia Stretch Department of Oncology, University of Calgary, Calgary, Alberta, Canada
Abha R Dunichand-Hoedl Department of Agricultural, Food & Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, 4-002 Li Ka Shing Centre, Edmonton, Alberta, T6G 2P5, Canada
Karen J B Martins Department of Agricultural, Food & Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, 4-002 Li Ka Shing Centre, Edmonton, Alberta, T6G 2P5, Canada
Aja Rieger Flow Cytometry Facility, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
David Bigam Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
Todd McMullen Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
Oliver F Bathe Department of Oncology and Department of Surgery, University of Calgary, Calgary, Alberta, Canada
Charles T Putman Faculty of Kinesiology, Sport, and Recreation, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
Catherine J Field Department of Agricultural, Food & Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, 4-002 Li Ka Shing Centre, Edmonton, Alberta, T6G 2P5, Canada
Vickie E Baracos Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
Vera C Mazurak Department of Agricultural, Food & Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, 4-002 Li Ka Shing Centre, Edmonton, Alberta, T6G 2P5, Canada.

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Helmers SB, Bruton M, Loell I, Ulfgren AK, Gracie AJ, McInnes IB, Lundberg IE. Expression of interleukin-18 in muscle tissue of patients with polymyositis or dermatomyositis and effects of conventional immunosuppressive treatment. Rheumatology (Oxford) 2019;57:2149-2157. [PMID: 30102381 DOI: 10.1093/rheumatology/key222] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2017] [Indexed: 01/25/2023] Open

Abstract

Objectives

To investigate the expression of IL-18 in symptomatic and asymptomatic muscle tissues of patients with PM and DM and the effects of conventional immunosuppressive treatment on such expression.

Methods

Two cohorts of patients were included in this study. The first cohort consisted of 10 new-onset myositis patients. IL-18 expression was compared between symptomatic and asymptomatic muscle biopsies that were taken prior to treatment. The second cohort consisted of another 10 patients with repeated muscle biopsies before and after 8 months with conventional immunosuppressive treatment. Using immunohistochemistry, IL-18 expression in muscle tissues was compared before and after treatment. Biopsies from seven healthy individuals were included as controls.

Results

IL-18 expression was predominantly localized to inflammatory cells and capillaries in patients and mostly to capillaries in healthy controls. Total IL-18 expression in muscle tissues from the new-onset patients, at both symptomatic and asymptomatic sites, was significantly higher compared with healthy controls (P = 0.007 and P = 0.002) with no statistical difference in appearances between symptomatic and asymptomatic sites. The number of IL-18 positive capillaries was not different among symptomatic, asymptomatic and healthy muscles. Total IL-18 expression appeared lower in biopsies from patients receiving and improving with immunosuppressive treatment, particularly the number of IL-18 positive inflammatory cells but not the number of IL-18 positive capillaries, which was consistent with significantly decreased expression of CD68+ macrophages (P = 0.04).

Conclusion

IL-18 is highly expressed in muscle tissue in the context of inflammatory myopathies and based on its plausible effector functions could provide a novel therapeutic target in future.

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Zhang J, Wen XY, Gao RP. Hepatitis B virus-related liver cirrhosis complicated with dermatomyositis: A case report. World J Clin Cases 2019;7:1206-1212. [PMID: 31183354 PMCID: PMC6547324 DOI: 10.12998/wjcc.v7.i10.1206] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 03/25/2019] [Accepted: 04/09/2019] [Indexed: 02/05/2023] Open

Hoeppli RE, Pesenacker AM. Targeting Tregs in Juvenile Idiopathic Arthritis and Juvenile Dermatomyositis-Insights From Other Diseases. Front Immunol 2019;10:46. [PMID: 30740105 PMCID: PMC6355674 DOI: 10.3389/fimmu.2019.00046] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Accepted: 01/09/2019] [Indexed: 12/22/2022] Open

Habiel DM, Espindola MS, Kitson C, Azzara AV, Coelho AL, Stripp B, Hogaboam CM. Characterization of CD28^null T cells in idiopathic pulmonary fibrosis. Mucosal Immunol 2019;12:212-222. [PMID: 30315241 PMCID: PMC6301115 DOI: 10.1038/s41385-018-0082-8] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 07/02/2018] [Accepted: 08/08/2018] [Indexed: 02/04/2023]

Tang Q, Ramsköld D, Krystufkova O, Mann HF, Wick C, Dastmalchi M, Lakshmikanth T, Chen Y, Mikes J, Alexanderson H, Achour A, Brodin P, Vencovsky J, Lundberg IE, Malmström V. Effect of CTLA4-Ig (abatacept) treatment on T cells and B cells in peripheral blood of patients with polymyositis and dermatomyositis. Scand J Immunol 2018;89:e12732. [PMID: 30451307 DOI: 10.1111/sji.12732] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 11/07/2018] [Accepted: 11/08/2018] [Indexed: 11/29/2022]

Affiliation(s)

Quan Tang Division of Rheumatology, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
Daniel Ramsköld Division of Rheumatology, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
Olga Krystufkova Institute of Rheumatology Prague, Prague, Czech Republic
Herman F Mann Institute of Rheumatology Prague, Prague, Czech Republic
Cecilia Wick Division of Rheumatology, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
Maryam Dastmalchi Division of Rheumatology, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
Tadepally Lakshmikanth Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
Yang Chen Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
Jaromir Mikes Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
Helene Alexanderson Division of Rheumatology, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden.,Functional Area Occupational Therapy and Physical Therapy, Karolinska University Hospital, and Division of Physiotherapy, Department of NVS, Karolinska Institutet, Stockholm, Sweden
Adnane Achour Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
Petter Brodin Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.,Department of Neonatology, Karolinska University Hospital, Stockholm, Sweden
Jiri Vencovsky Institute of Rheumatology Prague, Prague, Czech Republic
Ingrid E Lundberg Division of Rheumatology, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
Vivianne Malmström Division of Rheumatology, Department of Medicine, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden

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Novel insights of disability assessment in adult myositis. Curr Opin Rheumatol 2018;29:591-597. [PMID: 28796006 DOI: 10.1097/bor.0000000000000433] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]

Tjärnlund A, Tang Q, Wick C, Dastmalchi M, Mann H, Tomasová Studýnková J, Chura R, Gullick NJ, Salerno R, Rönnelid J, Alexanderson H, Lindroos E, Aggarwal R, Gordon P, Vencovsky J, Lundberg IE. Abatacept in the treatment of adult dermatomyositis and polymyositis: a randomised, phase IIb treatment delayed-start trial. Ann Rheum Dis 2018;77:55-62. [PMID: 28993346 DOI: 10.1136/annrheumdis-2017-211751] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2017] [Revised: 07/14/2017] [Accepted: 08/05/2017] [Indexed: 11/04/2022]

Affiliation(s)

Anna Tjärnlund Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden
Quan Tang Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden
Cecilia Wick Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden
Maryam Dastmalchi Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden
Herman Mann Department of Rheumatology, Institute of Rheumatology, Prague, Czech Republic
Jana Tomasová Studýnková Department of Rheumatology, Institute of Rheumatology, Prague, Czech Republic
Radka Chura Department of Rheumatology, King's College Hospital NHS Foundation Trust, London, UK
Nicola J Gullick Department of Rheumatology, King's College Hospital NHS Foundation Trust, London, UK
Rosaria Salerno Department of Rheumatology, King's College Hospital NHS Foundation Trust, London, UK
Johan Rönnelid Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
Helene Alexanderson Division of Physiotherapy, Department of Neurobiology, Karolinska Institutet and Physical Therapy Clinic, Karolinska University Hospital, Stockholm, Sweden
Eva Lindroos Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden
Rohit Aggarwal Division of Rheumatology and Clinical Rheumatology, University of Pittsburgh School of Medicine, Pittsburgh, USA
Patrick Gordon Department of Rheumatology, King's College Hospital NHS Foundation Trust, London, UK
Jiri Vencovsky Department of Rheumatology, Institute of Rheumatology, Prague, Czech Republic
Ingrid E Lundberg Rheumatology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden

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Shimojima Y, Matsuda M, Ishii W, Kishida D, Sekijima Y. T-cell receptor-mediated characteristic signaling pathway of peripheral blood T cells in dermatomyositis and polymyositis. Autoimmunity 2017;50:481-490. [PMID: 29172719 DOI: 10.1080/08916934.2017.1405942] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]

Abstract

The characteristics of T cell expression in peripheral blood have been previously described in dermatomyositis (DM) and polymyositis (PM); however, their intracellular signaling profiles remain unknown. The purpose of this study was to investigate the T-cell receptor (TCR)-mediated intracellular signaling in peripheral blood T cells in DM and PM. Peripheral blood T cells from 86 patients with DM (n = 57) and PM (n = 29) were used for experimental investigations. T-cell subtypes and TCR-induced phosphorylated zeta-chain-associated protein kinase 70 (pZAP70) were analyzed by flow cytometry. Signal transducer and activator of transcription (STAT) and some inhibitory factors in T cells with TCR stimulation were also investigated by quantitative real-time polymerase chain reaction. T cell counts were significantly lower in DM than in PM. In addition, STAT, forkhead box transcription factor (FoxP3), and pZAP70 expression in CD4⁺ T cells was suppressed in DM, whereas STAT and pZAP70 expression in CD8⁺ T cells was induced in PM. Especially in DM, a positive correlation between CD4⁺ T cell counts and STAT expression was detected. In addition, low CD4⁺ T cell counts as well as reduced STAT expression were prominent in patients with interstitial lung disease. STAT and pZAP70 expression significantly improved after clinical remission in both DM and PM, although expression of FoxP3 remained suppressed. Besides, upregulation of suppressor of cytokine signaling-3 (SOCS3) and downregulation of interleukin 6 signal transducer (IL6ST) in CD4⁺ T cells were observed in both DM and PM; however, no significant improvements were detected after clinical remission. The results of the present study suggested that TCR-mediated signaling may be a key pathway to determine the different characteristics of peripheral blood T cells between DM and PM. In addition, upregulation of SOCS3 and downregulation of IL6ST and FoxP3 in CD4⁺ T cells may cause an imbalance in intracellular signaling, especially in DM, suggesting that further studies are required to identify how the impaired signaling contributes to the development of the disease.

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John S, Antonia SJ, Rose TA, Seifert RP, Centeno BA, Wagner AS, Creelan BC. Progressive hypoventilation due to mixed CD8⁺ and CD4⁺ lymphocytic polymyositis following tremelimumab - durvalumab treatment. J Immunother Cancer 2017;5:54. [PMID: 28716137 PMCID: PMC5514517 DOI: 10.1186/s40425-017-0258-x] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 06/14/2017] [Indexed: 12/11/2022] Open

Pandya JM, Venalis P, Al-Khalili L, Shahadat Hossain M, Stache V, Lundberg IE, Malmström V, Fasth AER. CD4+ and CD8+ CD28(null) T Cells Are Cytotoxic to Autologous Muscle Cells in Patients With Polymyositis. Arthritis Rheumatol 2017;68:2016-26. [PMID: 26895511 DOI: 10.1002/art.39650] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2015] [Accepted: 02/16/2016] [Indexed: 12/12/2022]

Mandel DE, Malemud CJ, Askari AD. Idiopathic Inflammatory Myopathies: A Review of the Classification and Impact of Pathogenesis. Int J Mol Sci 2017;18:ijms18051084. [PMID: 28524083 PMCID: PMC5454993 DOI: 10.3390/ijms18051084] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 05/02/2017] [Accepted: 05/09/2017] [Indexed: 12/13/2022] Open

Loell I, Raouf J, Chen YW, Shi R, Nennesmo I, Alexanderson H, Dastmalchi M, Nagaraju K, Korotkova M, Lundberg IE. Effects on muscle tissue remodeling and lipid metabolism in muscle tissue from adult patients with polymyositis or dermatomyositis treated with immunosuppressive agents. Arthritis Res Ther 2016;18:136. [PMID: 27287443 PMCID: PMC4902919 DOI: 10.1186/s13075-016-1033-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Accepted: 05/25/2016] [Indexed: 12/24/2022] Open

Abstract

Background

Polymyositis (PM) and dermatomyositis (DM) are autoimmune muscle diseases, conventionally treated with high doses of glucocorticoids in combination with immunosuppressive drugs. Treatment is often dissatisfying, with persisting muscle impairment. We aimed to investigate molecular mechanisms that might contribute to the persisting muscle impairment despite immunosuppressive treatment in adult patients with PM or DM using gene expression profiling of repeated muscle biopsies.

Methods

Paired skeletal muscle biopsies from six newly diagnosed adult patients with DM or PM taken before and after conventional immunosuppressive treatment were examined by gene expression microarray analysis. Selected genes that displayed changes in expression were analyzed by Western blot. Muscle biopsy sections were evaluated for inflammation, T lymphocytes (CD3), macrophages (CD68), major histocompatibility complex (MHC) class I expression and fiber type composition.

Results

After treatment, genes related to immune response and inflammation, including inflammasome pathways and interferon, were downregulated. This was confirmed at the protein level for AIM-2 and caspase-1 in the inflammasome pathway. Changes in genes involved in muscle tissue remodeling suggested a negative effect on muscle regeneration and growth. Gene markers for fast type II fibers were upregulated and fiber composition was switched towards type II fibers in response to treatment. The expression of genes involved in lipid metabolism was altered, suggesting a potential lipotoxic effect on muscles of the immunosuppressive treatment.

Conclusion

The anti-inflammatory effect of immunosuppressive treatment was combined with negative effects on genes involved in muscle tissue remodeling and lipid metabolism, suggesting a negative effect on recovery of muscle performance which may contribute to persisting muscle impairment in adult patients with DM and PM.

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