title: Th1 response and systemic treg deficiency in inclusion body myositis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Immunlogy-Immunopathology-Immunotherpapy (I3), Sorbonne Universités, Pierre and Marie Curie University Paris 06, Paris, France; Immunlogy-Immunopathology-Immunotherpapy (I3), Centre National de la Recherche Scientifique UMR 7211, Paris, France; Immunlogy-Immunopathology-Immunotherpapy (I3), UMRS_959, Institut National de la Santé et de la Recherche Médicale, Paris, France; Inflammation-Immunopathology-Biotherapy (i2B), Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris, France; Internal Medicine Department 1, Centre de référence Maladie Neuromusculaire, Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Allenbach
authors.affiliation: Immunlogy-Immunopathology-Immunotherpapy (I3), Sorbonne Universités, Pierre and Marie Curie University Paris 06, Paris, France; Immunlogy-Immunopathology-Immunotherpapy (I3), Centre National de la Recherche Scientifique UMR 7211, Paris, France; Immunlogy-Immunopathology-Immunotherpapy (I3), UMRS_959, Institut National de la Santé et de la Recherche Médicale, Paris, France; Inflammation-Immunopathology-Biotherapy (i2B), Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Wahiba
authors.initials: W
authors.lastname: Chaara
authors.affiliation: Immunlogy-Immunopathology-Immunotherpapy (I3), Sorbonne Universités, Pierre and Marie Curie University Paris 06, Paris, France; Immunlogy-Immunopathology-Immunotherpapy (I3), Centre National de la Recherche Scientifique UMR 7211, Paris, France; Immunlogy-Immunopathology-Immunotherpapy (I3), UMRS_959, Institut National de la Santé et de la Recherche Médicale, Paris, France; Inflammation-Immunopathology-Biotherapy (i2B), Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Michelle
authors.initials: M
authors.lastname: Rosenzwajg
authors.affiliation: Immunlogy-Immunopathology-Immunotherpapy (I3), Sorbonne Universités, Pierre and Marie Curie University Paris 06, Paris, France; Immunlogy-Immunopathology-Immunotherpapy (I3), Centre National de la Recherche Scientifique UMR 7211, Paris, France; Immunlogy-Immunopathology-Immunotherpapy (I3), UMRS_959, Institut National de la Santé et de la Recherche Médicale, Paris, France; Inflammation-Immunopathology-Biotherapy (i2B), Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Six
authors.affiliation: Immunlogy-Immunopathology-Immunotherpapy (I3), Sorbonne Universités, Pierre and Marie Curie University Paris 06, Paris, France; Immunlogy-Immunopathology-Immunotherpapy (I3), Centre National de la Recherche Scientifique UMR 7211, Paris, France; Immunlogy-Immunopathology-Immunotherpapy (I3), UMRS_959, Institut National de la Santé et de la Recherche Médicale, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Prevel
authors.affiliation: U974, Sorbonne Universités, Pierre and Marie Curie University, Paris 06, Paris, France; U974, Institut National de la Santé et de la Recherche Médicale, Paris, France; Genethon, Evry, France.
authors.forename: Federico
authors.initials: F
authors.lastname: Mingozzi
authors.affiliation: Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Wanschitz
authors.affiliation: Department of immunochemistry, Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Pierre and Marie Curie University Paris 06, Paris, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Musset
authors.affiliation: Department of immunochemistry, Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Pierre and Marie Curie University Paris 06, Paris, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Charuel
authors.affiliation: Department of neurology, Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Pierre and Marie Curie University, Paris 06, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Eymard
authors.affiliation: Immunlogy-Immunopathology-Immunotherpapy (I3), Sorbonne Universités, Pierre and Marie Curie University Paris 06, Paris, France; Immunlogy-Immunopathology-Immunotherpapy (I3), Centre National de la Recherche Scientifique UMR 7211, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Salomon
authors.affiliation: Department of neuropathology, Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Pierre and Marie Curie University Paris 06, Paris, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Duyckaerts
authors.affiliation: Department of neuropathology, Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Pierre and Marie Curie University Paris 06, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Maisonobe
authors.affiliation: Department of neuropathology, Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Pierre and Marie Curie University Paris 06, Paris, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Dubourg
authors.affiliation: Inflammation-Immunopathology-Biotherapy (i2B), Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris, France; Internal Medicine Department 1, Centre de référence Maladie Neuromusculaire, Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière Paris, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Herson
authors.affiliation: Immunlogy-Immunopathology-Immunotherpapy (I3), Sorbonne Universités, Pierre and Marie Curie University Paris 06, Paris, France; Immunlogy-Immunopathology-Immunotherpapy (I3), Centre National de la Recherche Scientifique UMR 7211, Paris, France; Immunlogy-Immunopathology-Immunotherpapy (I3), UMRS_959, Institut National de la Santé et de la Recherche Médicale, Paris, France; Inflammation-Immunopathology-Biotherapy (i2B), Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.affiliation: Inflammation-Immunopathology-Biotherapy (i2B), Hôpital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris, France; Internal Medicine Department 1, Centre de référence Maladie Neuromusculaire, Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière Paris, France; U974, Sorbonne Universités, Pierre and Marie Curie University, Paris 06, Paris, France; U974, Institut National de la Santé et de la Recherche Médicale, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Benveniste
mesh_terms: D000368:Aged; D018106:CD28 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D019070:Cell Lineage / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology; D018925:Chemokines / Q000097:blood; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D018655:Lymphocyte Count; D008297:Male; D018979:Myositis, Inclusion Body / Q000097:blood / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D018106:CD28 Antigens; D018925:Chemokines; D007371:Interferon-gamma