Antiinflammatory autoimmune cellular responses to cardiac troponin I in idiopathic dilated cardiomyopathy

J Card Fail. 2011 May;17(5):359-65. doi: 10.1016/j.cardfail.2011.01.003. Epub 2011 Feb 26.

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.

Methods and 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.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Cardiomyopathy, Dilated / immunology*
  • Cardiomyopathy, Dilated / metabolism
  • Cardiomyopathy, Dilated / prevention & control
  • Case-Control Studies
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Humans
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Interferon-gamma / metabolism
  • Interferon-gamma / physiology*
  • Interleukin-10 / metabolism
  • Interleukin-10 / physiology*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Troponin I / pharmacology*
  • Troponin I / physiology

Substances

  • Inflammation Mediators
  • Troponin I
  • Interleukin-10
  • Interferon-gamma

Supplementary concepts

  • Idiopathic dilation cardiomyopathy