PREFERENTIAL RECOGNITION OF HUMAN MYOCARDIAL ANTIGENS BY T-LYMPHOCYTES FROM RHEUMATIC HEART-DISEASE PATIENTS

Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) are auto immune sequelae of upper respiratory infections with group A streptoco cci (GAS). To gain a better understanding of the pathogenesis of these diseases, we examined the in vitro proliferative responses of periphe ral blood mononuclear cells (PBMC) from RHD patients to human myocardi al proteins in a T-cell Western assay. A number of myocardial proteins fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophor esis were recognized by PBMC from both patients and controls. However, PBMC from a significant percentage of RHD patients (40%) responded to a discrete band of myocardial proteins migrating with an apparent mol ecular mass of 50 to 54 kDa while none of the control subject PBMC res ponded to this protein band (P less than or equal to 0.0001). To furth er investigate the link between infections with GAS and autoimmune car ditis, we studied the proliferative responses of PBMC from patients an d controls to myocardial proteins before and after in vitro stimulatio n of the cells with opsonized GAS isolated from ARF patients. Priming of PBMC with rheumatogenic GAS caused the percentage of RHD patients r esponding to the 50- to 54-kDa myocardial proteins to increase from 43 to 90% (P less than or equal to 0.0284). By contrast, PBMC from contr ol subjects failed to recognize the 50- to 54-kDa myocardial proteins even after stimulation with the opsonized streptococci (P less than or equal to 0.0001). The assay sensitivity was increased from 40 to 90% after priming of a patient's cells with opsonized GAS, but the positiv e predictive value was 100% in both unprimed and primed cultures. Anti bodies generated to partially purified 50- to 54-MDa myocardial protei ns did not cross-react with either streptococcal homogenates, purified M protein, myosin, laminin, or vimentin, suggesting a lack of cross-r eactivity at the humoral level. This study suggests that the 50- to 54 -kDa myocardial proteins contain a putative antigen that is preferenti ally recognized by T cells from RHD patients and demonstrates that exp osure to streptococcal antigens enhances the ability of patients to re cognize these proteins.