Myocardial inflammatory infiltrate in human chronic chagasic cardiomyopathy: Immunohistochemical findings.

Chagas' disease is the most common form of chronic myocarditis in the world. It is characterized by a progressive chronic myocarditis that leads to cardiomegaly, arrhythmias, cardiac failure, and thromboembolic phenomena. This communication reports studies on the immunohistochemistry of chronic infiltrates in 30 endomyocardial biopsies and in contracting and specialized myocardium of autopsies of four patients suffering from Chagas' cardiomyopathy. Expression of the following antigens was studied: common leucocyte antigen (CLA-CD45R), L-26(CD20), CD68, kappa and lambda light chains and T-UCLH-1 (CD45RO), and MB-1. Streptavidin-peroxidase and streptavidin-alkaline phosphatase with biotinylated anti-mouse IgG were used as detection systems. Double immunostaining for the simultaneous demonstration of T lymphocytes (CD45R0) and macrophages was performed using both immunoenzymatic techniques consecutively. Expression of CD31 was detected for the demonstration of endothelial cells. In endomyocardial biopsies, tissue forms of trypanosomes were not found. The percentage of fibrous tissue was 24.1% ± 12.8% (range 8.2%-49%). Eosinophils were scarce (1/high-power field), but associated with necrotic areas of the myocardium. Mast cells were scarce or absent. They were always situated in fibrotic areas. The most remarkable 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 infiltration was particularly associated with necrotic and degenerative myocardial lesions. Thirty percent of the infiltrate was composed of macrophages (positive CD68 cells). The remaining infiltrate was composed of mononuclear cells resembling macrophages and CLA-negative mononuclear cells. Contacts between CD68-positive cells and T lymphocytes were frequently found. CD31 antibodies clearly pointed out normal endothelial cells, in either normal or damaged vessels. No isolated cells positive for these antibodies were found within the mononuclear infiltrate. In autopsied hearts, myocardial lesions consisted of a chronic inflammatory process with fibrotic scars and extensive mononuclear infiltrates. No amastigote nests were found. A statistically significant difference (p < 0.05) was obtained when the percentage of fibrosis was compared 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 were scarce or absent in specialized and in contracting myocardium. Almost all the lymphocytic population was T lymphocytes. Such infiltrates were more prominent in the working myocardium (39%) and in the specialized cells of the left branch of the His bundle than in the atrioventricular node and in the right Hisian branch (34.4%). The 31% of mononuclear cells were CD68 positive, thus corresponding to macrophages. Contacts among T lymphocytes and macrophages were frequently observed. Although much that is concerned with Chagas' cardiomyopathy is controversial, these may be the major ingredients for its pathogenesis: the parasite 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.