Abstract 16011: Potential Protective Effects of Myeloid and Plasmacytoid Dendritic Cells in Dilated Cardiomyopathy
BACKGROUND: Dilated cardiomyopathy (DCM) is frequently the result of myocardial viral infection leading to chronic heart failure. The immunomodulating role of dendritic cells (DC) in heart muscle disease is unclear. We investigated the presence of DCs, macrophages, HLA-DR expression and activated T-cells in the DCM myocardia and their potential prognostic value.
METHODS: Left ventricular endomyocardial biopsies (EMB) of 52 DCM patients were immunohistochemically analyzed for the presence of myeloic DCs (mDCs, fascin+), plasmacytoid DCs (pDCs, CD304+), macrophages (CD68+), HLA-DR expression and activated T-Cells (CD69+). Post-mortem myocardial specimens of age-matched suicide or accident victims (n = 18) were used as controls. Myocardial fibrosis was histologically quantified and the presence of viral genome of parvovirus B19, enterovirus and adenovirus by polymerase chain reaction. Echocardiographic data were measured at first diagnosis and at 3-6 months follow-up.
RESULTS: Compared to controls, in DCM patients significantly lower mDCs (2,5fold, p<0.001), pDCs (1,4fold, p<0.05), HLA-DR (1,8fold, p<0.001) and activated T-cells (2.5fold, p<0.001) were observed, whereas macrophages did not differ significantly. Virus positive EMBs had significantly less mDCs (1,6fold, p<0,01) and pDCs (1.4fold, p<0.05). mDCs correlated with HLA-DR (r=0.58, p<0.001), pDCs (r=0.48, p<0.001), activated T-cells (r=0.412, p<0.01), ΔEF (r=0.41, p=0.02) and intracoronary septum thickness (ICS, r=0.37, p=0.03) at follow-up, and inversely with fibrosis (r=-0.28, p<0.05) and myocardial viruses (r=-0.43, p<0.01). HLA-DR expression correlated with pDCs (r=0.43, p<0.01), ICS (r=0.5, p<0.01) and EF (r=0.47, p<0.01) at follow-up and inversely with fibrosis (r=-0.33; p<0.02). Activated T-cells inversely correlated with fibrosis (r=-0.38, p<0.01). No correlation was found for macrophages.
CONCLUSIONS: We show significantly decreased presence of DCs and DC activity in the myocardia affected by DCM, predominantly in those with pronounced LV deterioration in terms of fibrosis and function. This might be due to a defective recruitment, leading to an incomplete clearance of myocardial viruses.
- © 2011 by American Heart Association, Inc.