title: Antiinflammatory autoimmune cellular responses to cardiac troponin I in idiopathic dilated cardiomyopathy.
abstract: BACKGROUND
  Autoimmune mechanisms, particularly through generation of autoantibodies, may contribute to the pathophysiology of idiopathic dilated cardiomyopathy (iDCM). The precise role of cellular autoimmune responses to cardiac-specific antigens has not been well described in humans. The purpose of this study was to characterize the cellular autoimmune response to cardiac troponin I (cTnI), specifically, the release of cytokines by peripheral blood mononuclear cells (PBMCs), in subjects with iDCM and healthy control subjects.
  
  
  RESULTS
  We performed enzyme-linked immunospot assays on PBMCs isolated from subjects with iDCM and healthy control subjects to examine the ex vivo interferon-gamma (IFN-γ) and interleukin-10 (IL-10) production in response to cTnI exposure. Thirty-five consecutive subjects with iDCM (mean age 53 ± 11 years, 60% male, left ventricular ejection fraction 23 ± 7%) and 26 control subjects (mean age 46 ± 13 years, 46% male) were prospectively enrolled. IFN-γ production in response to cTnI did not differ between the groups (number of secreting cells 26 ± 49 vs 38 ± 53, respectively; P = .1). In contrast, subjects with iDCM showed significantly higher IL-10 responses to cTnI compared with control subjects (number of secreting cells 386 ± 428 vs 152 ± 162, respectively; P < .05). Among iDCM subjects, heightened IL-10 response to cTnI was associated with reduced systemic inflammation and lower prevalence of advanced diastolic dysfunction compared with those with normal IL-10 response to cTnI.
  
  
  CONCLUSIONS
  Our preliminary findings suggest that a heightened cellular autoimmune IL-10 response to cTnI is detectable in a subset of patients with iDCM, which may be associated with reduced systemic levels of high-sensitivity C-reactive protein and lower prevalence of advanced diastolic dysfunction.
authors.affiliation: Heart and Vascular Institute, Cleveland, Ohio 44195, USA.
authors.forename: Carmel M
authors.initials: CM
authors.lastname: Halley
authors.forename: Jason M
authors.initials: JM
authors.lastname: Lappé
authors.forename: Anne C
authors.initials: AC
authors.lastname: Cotleur
authors.forename: Kevin
authors.initials: K
authors.lastname: Shrestha
authors.forename: Allen G
authors.initials: AG
authors.lastname: Borowski
authors.forename: Clara
authors.initials: C
authors.lastname: Pelfrey
authors.forename: Richard
authors.initials: R
authors.lastname: Ransohoff
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism / Q000502:physiology*; D016753:Interleukin-10 / Q000378:metabolism / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D019210:Troponin I / Q000494:pharmacology* / Q000502:physiology
chemical_list: D018836:Inflammation Mediators; D019210:Troponin I; D016753:Interleukin-10; D007371:Interferon-gamma