J. Milei et al., MYOCARDIAL INFLAMMATORY INFILTRATE IN HUMAN CHRONIC CHAGASIC CARDIOMYOPATHY - IMMUNOHISTOCHEMICAL FINDINGS, Cardiovascular pathology, 5(4), 1996, pp. 209-219
Chagas' disease is the most common form of chronic myocarditis in the
world. It is characterized by a progressive chronic myocarditis that l
eads to cardiomegaly, arrhythmias, cardiac failure, and thromboembolic
phenomena. This communication reports studies on the immunohistochemi
stry of chronic infiltrates in 30 endomyocardial biopsies and in contr
acting and specialized myocardium of autopsies of four patients suffer
ing from Chagas' cardiomyopathy. Expression of the following antigens
was studied: common leucocyte antigen (CLA-CD45R), L-26(CD20), CD68, k
appa and lambda light chains and T-UCLH-1 (CD45RO), and MB-1. Streptav
idin-peroxidase and streptavidin-alkaline phosphatase with biotinylate
d anti-mouse IgG were used as detection systems. Double immunostaining
for the simultaneous demonstration of T lymphocytes (CD45RO) and macr
ophages was performed using both immunoenzymatic techniques consecutiv
ely. Expression of CD31 was detected for the demonstration of endothel
ial cells. In endomyocardial biopsies, tissue forms of trypanosomes we
re not found. The percentage of fibrous tissue was 24.1% +/- 12.8% (ra
nge 8.2%-49%). Eosinophils were scarce (1/high-power field), but assoc
iated with necrotic areas of the myocardium. Mast cells were scarce or
absent. They were always situated in fibrotic areas. The most remarka
ble finding was the presence of infiltrates consisting of macrophages
and CLA-positive mononuclear cells. Twenty-six and one-half percent of
them were T lymphocytes, and 10.5% were B lymphocytes. Lymphocytic in
filtration was particularly associated with necrotic and degenerative
myocardial lesions. Thirty percent of the infiltrate was composed of m
acrophages (positive CD68 cells). The remaining infiltrate was compose
d of mononuclear cells resembling macrophages and CLA-negative mononuc
lear cells. Contacts between CD68-positive cells and T lymphocytes wer
e frequently found. CD31 antibodies clearly pointed out normal endothe
lial cells, in either normal or damaged vessels. No isolated cells pos
itive for these antibodies were found within the mononuclear infiltrat
e. In autopsied hearts, myocardial lesions consisted of a chronic infl
ammatory process with fibrotic scars and extensive mononuclear infiltr
ates. No amastigote nests were found. A statistically significant diff
erence (p < 0.05) was obtained when the percentage of fibrosis was com
pared in the specialized and contracting myocardiums (51.6% +/- 18% vs
. 43.4% +/- 8%). Eosinophils were scarce in infiltrates, reaching 5%,
and they were associated with necrotic myocardium. Mast cells also wer
e scarce or absent in specialized and in contracting myocardium. Almos
t all the lymphocytic population was T lymphocytes. Such infiltrates w
ere more prominent in the working myocardium (39%) and in the speciali
zed cells of the left branch of the His bundle than in the atrioventri
cular node and in the right Hisian branch (34.4%). The 31% of mononucl
ear cells were CD68 positive, thus corresponding to macrophages. Conta
cts among T lymphocytes and macrophages were frequently observed. Alth
ough much that is concerned with Chagas' cardiomyopathy is controversi
al, these may be the major ingredients for its pathogenesis: the paras
ite or a part of it, lymphocytes and macrophages, and fibrosis. Then a
multifactorial or ''combined theory'' may be suggested to explain the
sequence of events that lead to the chronic stage of the disease.