The muscle tissue transcriptome of idiopathic inflammatory myopathy reflects the muscle damage process by monocytes and presence of skin lesions.

Autor: Izuka S; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Umezawa N; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Komai T; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Sugimori Y; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Kimura N; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Mizoguchi F; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Fujieda Y; Department of Rheumatology, Endocrinology and Nephrology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Sapporo, Japan., Ninagawa K; Department of Rheumatology, Endocrinology and Nephrology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Sapporo, Japan., Iwasaki T; Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Suzuki K; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan., Takeuchi T; Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan., Ohmura K; Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Mimori T; Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.; Takeda Clinic for Rheumatic Diseases, Kyoto, Japan., Atsumi T; Department of Rheumatology, Endocrinology and Nephrology, Graduate School of Medicine and Faculty of Medicine, Hokkaido University, Sapporo, Japan., Kawakami E; Center for Integrative Medical Sciences, the Institute of Physical and Chemical Research (RIKEN), 1-7-22 Suehirocho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan., Suzuki A; Center for Integrative Medical Sciences, the Institute of Physical and Chemical Research (RIKEN), 1-7-22 Suehirocho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan., Kochi Y; Center for Integrative Medical Sciences, the Institute of Physical and Chemical Research (RIKEN), 1-7-22 Suehirocho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan., Yamamoto K; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Center for Integrative Medical Sciences, the Institute of Physical and Chemical Research (RIKEN), 1-7-22 Suehirocho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan., Yasuda S; Department of Rheumatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Okamura T; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Ota M; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.; Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Fujio K; Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Jazyk: angličtina
Zdroj: Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2024 Aug 20. Date of Electronic Publication: 2024 Aug 20.
DOI: 10.1002/art.42972
Abstrakt: Objective: To investigate transcriptomic and immunophenotypic features of muscle specimens from patients with idiopathic inflammatory myopathy (IIM).
Methods: Bulk RNA-sequencing was performed on muscle biopsy samples from 16 patients with dermatomyositis (DM) and 9 patients with polymyositis (PM). Seven tested positive for anti-aminoacyl t-RNA synthetase antibodies in the DM patients (ARS-DM). We conducted weighted gene coexpression network analysis (WGCNA), differentially expressed gene (DEG) analysis, and gene set variation analysis (GSVA) to assess contributions of specific pathways. Cell proportions in muscle specimens were estimated using a deconvolution approach.
Results: WGCNA revealed significant positive correlations between serum creatine kinase (CK) levels and gene modules involved in cellular respiration, phagocytosis, and oxidative phosphorylation (OXPHOS). Significant positive correlations were also observed between CK levels and proportions of CD16-positive and -negative monocytes and myeloid dendritic cells. Notably, DM patients demonstrated enrichment of complement and interferon-α and -γ pathway genes compared to those with PM. Furthermore, ARS-DM demonstrated a higher proportion of Th1 cells and DEGs related to OXPHOS. Additionally, serum Krebs von den Lungen-6 levels correlated with gene modules associated with extracellular matrix and transforming growth factor-β signaling pathway.
Conclusion: Our study highlights a significant involvement of monocytes in muscle damage and delineates pathological differences among IIM subtypes. DM was characterized by complement, interferon-α and -γ signaling, whilst ARS-DM was associated with OXPHOS. Distinctive gene expression variations in muscle specimens suggest that different pathologic mechanisms underlie muscle damage in each IIM phenotype.
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Databáze: MEDLINE
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