Phylogenetic landscape of peptide-binding domains of classical <i>HLA</i> alleles reported in the Indian population: Plausible implications for stem cell transplantation

Objectives Hematopoietic stem cell transplantation (HSCT) is preferred for several malignant and non-malignant hematopoietic conditions. However, high diversity in the histocompatibility genes, i.e., human leukocyte antigen (HLA) , poses a challenge due to the unavailability of HLA-identical donors for most cases. This has increased haplo-identical HSCT in the last few years, which can lead to enhanced allorecognition and propensity for graft-versus-host disease (GvHD). The population-specific molecular diversity of peptide-binding domains (PBD) of HLA alleles defines allo-sensitivity. Therefore, we attempted to analyze reported Indian HLA diversity for their phylogenetic relatedness in PBD, towards plausible implications for population-specific donor selection for haplo-identical HSCT here. Material and Methods For this observational study, published literature, allelefrequencies.net, and immuno polymorphism database (IPD) - international ImMunoGeneTics information system (IMGT)/HLA databases were referred to cumulatively estimate the degree of reported HLA diversity in the Indian population for the PBD region, with reference to global diversity. CLUSTAL omega and interactive tree of life (iTOL) were used for estimating phylogenetic relatedness. Results Comprehensive analysis of reported HLA data for Indian population revealed a heterogenous distribution pattern representing the majority of globally present allelic groups (one field). At two fields, 114 HLA-A, 185 HLA-B and 68 HLA-C alleles for HLA class I are reported for Indian population. The dendrograms highlighted phylogenetic relatedness between small clusters usually having same allele group (one field level), though few exceptions were also observed. Conclusion The observed heterogeneity in distribution of class I and class II and their phylogenetic relatedness could be attributed to diverse microflora and environmental conditions. Our analyses could plausibly facilitate formulating algorithms guiding optimal selection of permissible histocompatible donor for transplantation.