Genetic susceptibility to rheumatic heart disease and streptococcal pharyngitis: association with HLA-DR alleles

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Abstract
Acute rheumatic fever (ARF) is a systemic inflammatory disease that develops as a consequence of an exaggerated immune response to group A beta-haemolytic streptococci, which causes pharyngitis. Major manifestations of ARF include carditis, arthritis and chorea. Several investigators have attempted to establish a relation between ARF and human leucocyte antigens (HLA). Heterogeneity in various studies has been found, although associations with certain antigens were reported. The aim of this study was to analyse whether HLA-DR alleles play a role in the resistance or susceptibility to streptococci-related disorders including rheumatic heart disease (RHD) as a sequela of ARF and recurrent streptococcal pharyngitis in Turkish patients. The study included 102 patients with RHD, 71 persons with recurrent streptococcal pharyngitis and 130 healthy controls. HLA-DR alleles were typed by using polymerase chain reaction (PCR)-sequence-specific primers. Positive association with HLA-DRB1*07 allele was found for RHD when compared with healthy controls [29.4% vs 13.1%; P < 0.01, P-corrected: P < 0.01, odds ratio (OR) 2.78, 95% confidence interval (CI) 1.43-5.26] and also for recurrent streptococcal pharyngitis (26.8% vs 13.1%; P < 0.05, P-corrected: P < 0.05, OR 2.44, 95% CI 1.17-3.56). The frequency of HLA-DRB1*11 allele was decreased in patients with RHD (23.5% vs 42.3%; P < 0.01, P-corrected: P < 0.01, OR 0.42, 95% CI 0.24-0.75). Data suggest that HLA-DRB1*07 allele may be a genetic factor in increasing the susceptibility to develop RHD and recurrent streptococcal pharyngitis. HLA-DRB1*11 allele seems to be a protective factor against RHD.