Phenotypic characterization of infiltrates in dilated cardiomyopathy - diagnostic significance of T-lymphocytes and macrophages in inflammatory cardiomyopathy.
BACKGROUND
Dilated cardiomyopathy (DCM) is linked to inflammatory cardiomyopathy (InfCM). To gain a profound insight into the underlying mechanisms, we phenotypically characterized pan leukocytes (CD18), naive T-lymphocytes (CD3, CD2, CD4, CD8), activated lymphocytes (LFA-1, LFA-3, VLA-4, ICAM-1, CD69, CD45R0), macrophages (Mac-1, 27E10), B-lymphocytes (CD19) and NK-cells (CD57) in DCM and control hearts.


METHODS
Biopsies from DCM patients (n=164, LVEF<40%) and specimens from non-cardiac death causes (controls; n=17) were immunostained. Biopsies exceeding >2.0 CD3+ lymphocytes per high power field/hpf and/or >1.5 CD3+ lymphocytes/hpf with numerous foci and HLA class I/DR abundance were evaluated positive for InfCM.


RESULTS
InfCM+ biopsies (n=102; 63%) demonstrated significantly increased infiltrates with respect to all studied phenotypes except for CD19 and CD57 when compared with both DCM biopsies negative for InfCM (n=62) and the controls, whereas the latter two groups did not differ (Tukey-Kramer analysis). Virtually all phenotypes correlated with one another in multivariate analysis (except for B-lymphocytes and NK cells). Whereas HLA class I/DR abundance was present in 14% of the controls and 26% of the DCM biopsies not yielding InfCM, InfCM+ biopsies demonstrated significantly (<0.001) higher frequencies of HLA abundance (76%).


CONCLUSIONS
The inflammatory process in InfCM comprises T-lymphocytes and macrophages, whereas B-lymphocytes and NK-cells are not significantly increased. InfCM is associated with HLA induction. CD69+, CD45R0+ and adhesion molecule bearing infiltrates indicate the activated state of lymphocytes, and 27E10 of macrophages in InfCM, respectively. Our data are in accordance with the hypothesis of a 'chronic active inflammatory process' involved in DCM.
Department of Cardiology and Pneumonology, University Hospital Benjamin Franklin, Free University of Berlin, Germany. noutsias@zedat.fu-berlin.de
Michel
M
Noutsias
Matthias
M
Pauschinger
Heinz
H
Schultheiss
Uwe
U
K hl
D000328:Adult; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D015415:Biomarkers; D001706:Biopsy; D002311:Cardiomyopathy, Dilated / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D015415:Biomarkers; D006680:HLA Antigens