HLA class II associations with rheumatic heart disease are more evident and consistent among clinically homogeneous patients

Background-Discrepancies in reported HLA class II associations with rheumat ic heart disease (RHD) may have been due to inaccuracies of serological typ ing reagents and/or lack of defined clinical classification of patients ana lyzed. The molecular association between HLA and RHD was investigated in pa tients with defined clinical outcome. Methods and Results-Class II allele/haplotype distribution was determined i n 2 groups of RHD patients (n=88) and a control group (n=59), Patients were divided into the mitral valve disease (MVD) category (ie, those with mitra l regurgitation with or without mitral stenosis) and the multivalvular lesi ons (MVL) category, with impairment of aortic and/or tricuspid valves in ad dition to mitral valve damage, The MVD category (n=65) accounted for 74% of patients and included significantly fewer recurrent RF episodes compared w ith MVL patients (P=0.002), Conclusions-Significant increases in DRB1*0701 and DQA1*0201 alleles and DR B1*0701-DQA1*0201 haplotypes were found in patients. Removal of the MVL pat ients from analysis increased the strength of PILE associations among the M VD sample. The frequency of DQA1*0103 allele was decreased and the DQB1*060 3 allele was absent from the patient group, suggesting that these alleles m ay confer protective effects against RHD. DQ alleles in linkage disequilibr ium with DR alleles appear to influence risk/protection effect: whereas the DRB1*13-DQA1*0501-3-DQB1*0301 haplotype showed a trend toward risk, the DR B1*13-DQA1*0103-DQB1*0603 haplotype was absent in the RHD sample. Our data indicate that certain class II alleles/haplotypes are associated with risk or protection from RHD and that these associations appear to be stronger an d more consistent when analyzed in patients with relatively more homogeneou s clinical manifestations.