Association of HLA class II alleles in children and young adults with acute rheumatic fever and rheumatic heart disease from Limpopo province, South Africa

Introduction: Acute rheumatic fever (ARF) leading to rheumatic heart disease (RHD) is an immunological complication of Group A Streptococcus (GAS). The conditions continue to affect children and young adults mostly in poverty-stricken populations. Reports have shown an association between human leukocyte antigens (HLA) alleles and the risk of developing ARF/RHD. The current study aimed to describe the epidemiology and genomic HLA Class II profiles of patients with ARF and/or RHD in Limpopo Province, South Africa. Methodology: A retrospective assessment of the Limpopo province RHD patient registry was conducted to determine the RHD prevalence rate. Additionally, blood samples for HLA typing were collected from patients aged from 3 to 20 years, having ARF (50), RHD (50) and control group (50) at two regional and provincial hospitals of Limpopo province. Next generation sequencing of the HLA Class I and Class II types 11 loci platform was performed. Results: The recorded RHD prevalence rate was 21,7%. The median age of the patients was 10 years. There was a distribution of 52% males to 48% females. HLA Class II DRB1*06 (72% and 98%) and DRB1*11 (96% and 100%) were the most common alleles in ARF and RHD patients respectively compared to the control group while HLA-DRB1*01,*03,*08,*10, and*17 (<0.001) were common among the control group, as compared to the cases. Discussion: Patients with ARF/RHD in Limpopo province were found to be harboring HLA-DRB1*06 and*11 alleles compared to the controls; therefore, these may be contributing towards the disease predisposition. The control group were found harboring DRB1*01,*03,*08,*10,*17 alleles compared to the cases; therefore, they are hypothesized as the protective alleles in the studied cohort. Conclusions: The results of this baseline study for HLA types in the selected group of patients may support the hypothesis that certain HLA class II alleles are associated with risk of RHD.