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

摘要

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-gamma) 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-gamma 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.