Th1 Response and Systemic Treg Deficiency in Inclusion Body Myositis

• Published in: PloS one Vol. 9; no. 3; p. e88788
• Main Authors: Allenbach, Yves, Chaara, Wahiba, Rosenzwajg, Michelle, Six, Adrien, Prevel, Nicolas, Mingozzi, Federico, Wanschitz, Julia, Musset, Lucile, Charuel, Jean-Luc, Eymard, Bruno, Salomon, Benoit, Duyckaerts, Charles, Maisonobe, Thierry, Dubourg, Odile, Herson, Serge, Klatzmann, David, Benveniste, Olivier
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04.03.2014; Public Library of Science (PLoS)
• Subjects: Aged; Biology; Case-Control Studies; CD28 Antigens - metabolism; Cell Lineage - immunology; Cell Polarity - immunology; Chemokines - blood; Comparative analysis; Cytokines; Cytotoxicity; Disease; Female; Guillain-Barre syndrome; Human health and pathology; Humans; Immune response; Immune system; Immunologic Memory; Immunological tolerance; Inflammation; Inflammatory diseases; Interferon-gamma - biosynthesis; Internal medicine; Life Sciences; Ligands; Lymphocyte Count; Lymphocytes; Lymphocytes T; Male; Medicine; Musculoskeletal diseases; Myositis; Myositis, Inclusion Body - blood; Myositis, Inclusion Body - immunology; Myositis, Inclusion Body - pathology; Neuropathology; Phenotype; Principal components analysis; T cell receptors; T cells; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology; Th1 Cells - immunology; Th1 Cells - pathology; Transcription factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0088788

Sporadic inclusion body myositis (sIBM), the most frequent myositis in elderly patients, is characterized by the presence muscle inflammation and degeneration. We aimed at characterizing immune responses and regulatory T cells, considered key players in the maintenance of peripheral immune tolerance, in sIBM. Serum and muscle tissue levels of 25 cytokines and phenotype of circulating immune cells were measured in 22 sIBM patients and compared with 22 healthy subjects. Cytokine data were analysed by unsupervised hierarchical clustering and principal components analysis. Compared to healthy controls, sIBM patients had increased levels of Th-1 cytokines and chemokines such as IL-12 (261±138 pg/mL vs. 88±19 pg/mL; p<0.0001), CXCL-9 (186±12 pg/mL vs. 13±7 pg/mL; p<0.0001), and CXCL-10 (187±62 pg/mL vs. 13±6 pg/mL; p<0.0001). This was associated with an increased frequency of CD8+CD28- T cells (45.6±18.5% vs. 13.5±9.9%; p<0.0001), which were more prone to produce IFN-γ (45.6±18.5% vs. 13.5±9.9%; p<0.0001). sIBM patients also had a decreased frequency of circulating regulatory T cells (CD4+CD25+CD127lowFOXP3+, 6.9±1.7%; vs. 5.2±1.1%, p = 0.01), which displayed normal suppressor function and were also present in affected muscle. sIBM patients present systemic immune activation with Th1 polarization involving the IFN-γ pathway and CD8+CD28- T cells associated with peripheral regulatory T cell deficiency.