Human leukocyte antigens class I and class II alleles associated with vertical human immunodeficiency virus transmission - an exploratory study from Mumbai, India

Abstract

Background Human leukocyte antigens (HLA) an important host genetic factor is responsible for influencing human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) transmission and disease progression. Contributions of HLA I and II alleles have not been reported in the Indian population with respect to vertical HIV transmission. Aim In the current study we determined the frequencies of HLA class I and class II alleles in a cohort of children exposed to HIV through their mothers. Method In this exploratory study children perinatally exposed to HIV-1 who fit the study criteria and had completed 18 month follow-up were typed for HLA class I and class II alleles using polymerase chain reaction combined with sequence-specific oligonucleotides probes (PCR-SSOP) and sequence-specific primer (SSP) method. HLA typing was done in 30 positive and 60 HIV negative children along with confounding factors such as treatment regimens, viral load and CD4 count of the mother, feeding option, etc. SPSS software was used for statistical analysis and online docking tools for in-silico analysis. Results HLA-B*40 (p = 0.018) was significantly higher in negative children and was associated with protection, whereas HLA-A*01 (p = 0.05), HLA-B*37 (p = 0.032) and HLA-DRB1*09 (p = 0.017) were associated with transmission. Known protective allele HLA-B*27 was only present in negative children. Many specific haplotypes were exclusively present in the negative children or the positive ones. In-silico analysis was performed to predict the ability of HLA-B*40 to bind to antigenic peptides obtained from HIV-1 sequences in our study group. Limitations Small sample size is a concerning limitation of the study. Nonetheless this is a comprehensive study on HLA alleles in HIV exposed Indian children Conclusion Our study highlights the contribution of HLA class I and II alleles in the Indian children and further adds to understanding the immunogenetic mechanisms. These can be developed as markers for prediction of infection transmission. The observations also contribute to the database of genetic makeup of our population and can help in designing vaccine strategies.