Lack of T cell response to cardiac myosin and a reduced response to PPD in patients with idiopathic dilated cardiomyopathy.
Idiopathic dilated cardiomyopathy (IDCM) is the main cause of cardiac transplantation in young adults in the 20-40 years age group in the Western world. Recent evidence supports a possible role for autoimmune pathogenesis in IDCM and it has been suggested that T cells could mediate the disease. Cardiac myosin is one of the putative autoantigens recognized by antibodies from patients with IDCM, but T cell responses to cardiac myosin have not previously been assessed. Proliferation to cardiac myosin by peripheral blood mononuclear cells (PBMC) from patients, their relatives and controls was assessed in a lymphoproliferation assay specifically designed to measure low frequency T cell precursor responses. The study group consisted of 23 patients with IDCM and 29 relatives. The control groups consisted of 10 patients with heart failure secondary to ischaemic heart disease (IHD) and 22 healthy laboratory controls. A response to myosin was observed in 16.7% of the subjects studied. However, these responses were all of low precursor frequency and no dose response for antigen-specific proliferation could be observed. More importantly, there was no correlation between myosin-specific T cell responses and IDCM, as only one IDCM patient and four IDCM relatives (three out of the four with left ventricular enlargement (LVE)) were among the 14 subjects whose PBMC exhibited a proliferative response. However, proliferation of PBMC to purified protein derivative of Mycobacterium bovis (PPD) was significantly suppressed in IDCM patients when compared with the laboratory control group (P<0.05). PPD response data suggested that the PPD suppression correlated with disease progression. The results of our present study indicate an absence, or lack, of cardiac myosin-specific peripheral blood T cells in IDCM patients, along with the possibility of underlying impaired cell mediated immunity, reflected in the suppressed responses to PPD. Future studies looking at T cell immune mechanisms in IDCM should concentrate on the analysis of T cells from the heart itself, or look at other potential cardiac antigens from normal and diseased heart tissue.
Bromelow
K V
KV
Department of Cardiological Sciences, St. George's Hospital Medical School, London, UK.
Souberbielle
B
B
Alavi
A
A
Goldman
J H
JH
Libera
L D
LD
Dalgleish
A G
AG
McKenna
W J
WJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001324:Autoantigens / Q000276:immunology; D002311:Cardiomyopathy, Dilated / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology*; D009218:Myosins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014373:Tuberculin / Q000276:immunology*
D001324:Autoantigens; D014373:Tuberculin; D009218:Myosins