Assessment of the inflammatory process by endomyocardial biopsy in patients with dilated cardiomyopathy based on pathological and immunohistochemical methods.
BACKGROUND
Myocarditis may lead to dilated cardiomyopathy (DCM) in immunogenetically predisposed individuals. The diagnosis of myocardial inflammation is currently based on histopathological and immunohistochemical methods. Previous studies indicate that inflammatory cardiomyopathy occurs in approximately 50% of patients with DCM.


OBJECTIVE
The goal of the study was to assess the inflammatory process in patients with DCM by endomyocardial biopsy using histopathological and immunohistochemical methods.


METHODS
Endomyocardial biopsy specimens was examined using routine histopathological methods and immunochemical staining for T lymphocytes (CD3(+), n=84), major histocompatibility complex I (HLA ABC, n=48) and II (HLA DPQR, n=84) antigens and the adhesion molecules ICAM-1 (n=51) and VCAM-1 (n=48) in 84 patients (69 male, 15 female; mean age 35.0+/-10.5 years) with angiographically-confirmed DCM. Familial disease occurrence was noted in 14 (16.7%) patients. Cardiac samples obtained from 18 patients who died of non-cardiovascular causes were used as a control group.


RESULTS
Myocarditis was diagnosed, according to the Dallas criteria, in 8 (9.5%) patients. The frequency of inflammatory cardiomyopathy, defined as the presence of >2 CD3(+) T lymphocytes per high-power field (hpf) in myocardial biopsy, was 14.3%. When broader criteria were applied (presence of >2.0 CD3(+) lymphocytes/hpf and/or 1.5 CD3(+) lymphocytes/hpf in multiple foci and increased expression of class I/II HLA), inflammatory cardiomyopathy was diagnosed in 32.1% of patients. Inflammatory activation of the endothelium, indicated by increased expression of at least three adhesion molecules (class I and II HLA, ICAM-1, VCAM-1), was present in 22 (45.8%) patients. The expression of HLA DPQR, HLA ABC and ICAM-1 was observed on the endothelium of capillaries and larger vessels, interstitial cells, and the surface of activated lymphocytes; immunohistochemical reactions were diffuse. In patients with markedly elevated expression of the aforementioned adhesion molecules, the expression was also present on cardiomyocyte cell membranes. VCAM-1 was restricted to the endothelium of individual small veins. The control group did not demonstrate any signs of myocarditis, inflammatory cardiomyopathy or inflammatory endothelial activation.


CONCLUSIONS
The application of immunohistochemical methods to myocardial biopsy in order to identify the inflammatory cell phenotype and the presence of adhesion molecules permits the diagnosis of inflammatory cardiomyopathy in 14% or 32% of patients, depending on the criteria used, while conventional pathology allows for this diagnosis in 9% of patients. The observed frequency of inflammatory cardiomyopathy, defined as the presence of >2 CD3(+) T lymphocytes/hpf in the myocardium, was lower (14%) than in previous studies, while the frequency of inflammatory endothelial activation was similar (45%).
Prochorec-Sobieszek
Monika
M
Zakład Anatomii Patologicznej, Instytut Reumatologii, ul. Spartańska 1, 02-637 Warszawa. monika.prochorec@interia.pl
Bilińska
Zofia T
ZT
Grzybowski
Jacek
J
Mazurkiewicz
Lukasz
L
Skwarek
Mirosław
M
Walczak
Ewa
E
Michalak
Ewa
E
Cedro
Krzysztof
K
Chmielak
Zbigniew
Z
Debski
Artur
A
Demkow
Marcin
M
Witkowski
Adam
A
Wagner
Teresa
T
Ruzyłło
Witold
W
D000328:Adult; D015703:Antigens, CD / Q000032:analysis*; D001706:Biopsy; D002102:Cadaver; D002311:Cardiomyopathy, Dilated / Q000276:immunology* / Q000473:pathology*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000032:analysis; D005260:Female; D006684:HLA-DR Antigens / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology*; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1