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 rheumatic heart disease (RHD) may have been due to inaccuracies of serological typing reagents and/or lack of defined clinical classification of patients analyzed. The molecular association between HLA and RHD was investigated in patients with defined clinical outcome.

METHODS AND RESULTS

Class II allele/haplotype distribution was determined in 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 mitral regurgitation with or without mitral stenosis) and the multivalvular lesions (MVL) category, with impairment of aortic and/or tricuspid valves in addition to mitral valve damage. The MVD category (n=65) accounted for 74% of patients and included significantly fewer recurrent RF episodes compared with MVL patients (P=0.002).

CONCLUSIONS

Significant increases in DRB10701 and DQA10201 alleles and DRB10701-DQA10201 haplotypes were found in patients. Removal of the MVL patients from analysis increased the strength of HLA associations among the MVD sample. The frequency of DQA10103 allele was decreased and the DQB10603 allele was absent from the patient group, suggesting that these alleles may confer protective effects against RHD. DQ alleles in linkage disequilibrium with DR alleles appear to influence risk/protection effect: whereas the DRB113-DQA10501-3-DQB10301 haplotype showed a trend toward risk, the DRB113-DQA10103-DQB10603 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 and more consistent when analyzed in patients with relatively more homogeneous clinical manifestations.