Rheumatic heart disease: 15 years of clinical and immunological follow-up

Abstract

Rheumatic fever (RF) is a sequel of group A streptococcal throat infection and occurs in untreated susceptible children. Rheumatic heart disease (RHD), the major sequel of RF, occurs in 30%-45% of RF patients. RF is still considered endemic in some regions of Brazil and is responsible for approximately 90% of early childhood valvular surgery in the country. In this study, we present a 15-year clinical follow-up of 25 children who underwent surgical valvular repair. Histopathological and immunological features of heart tissue lesions of RHD patients were also evaluated. The patients presented severe forms of RHD with congestive symptoms at a very young age. Many of them had surgery at the acute phase of RF. Histological analysis showed the presence of dense valvular inflammatory infiltrates and Aschoff nodules in the myocardium of 21% of acute RHD patients. Infiltrating T-cells were mainly CD4+ in heart tissue biopsies of patients with rheumatic activity. In addition, CD4+ and CD8+ infiltrating T-cell clones recognized streptococcal M peptides and cardiac tissue proteins. These findings may open the possibilities of new ways of immunotherapy. In addition, we demonstrated that the surgical procedure during acute phase of the disease improved the quality of life of young RHD patients.

Figure 1

Kaplan-Meier survival curve: follow-up of 25 rheumatic valve disease patients. (A) Event-free survival (death and reoperation); (B) probability of survival.

Figure 2

The presence of heart tissue T lymphocytes is related with rheumatic activity. The number of infiltrating T and B lymphocytes and their relation with rheumatic activity in both valve and myocardium tissues are presented. Black bars, mean tissue with rheumatic activity and white bars, without rheumatic activity. *P = 0.03; **P = 0.03. HPF, high power microscopic field.

Figure 3

Heart infiltrating T-cells. Heart tissue biopsies were cut in small fragments and kept in culture until establishment of T-cell lines. The picture represents lymphoblasts cultivated for 15 days in Dulbecco’s modified Eagle medium supplemented with IL-2. Photograph from Immunology Laboratory, Heart Institute; original magnification ×200.