HLA system in solid organ transplantation part 20

HLA matching and genetically-related donation

In transplantation medicine, HLA matching refers to the degree of similarity of the HLA alleles between a donor and a recipient and is preferentially applicable to genetically related  donation, ie family members. But for a better understanding of the risk of rejection conferred by different degrees of histocompatibility between related donors and recipients, a brief explanation  on the inheritance rules for the HLA genes is pertinent. The set of HLA genes, from both class I and class II loci, in a given chromosome have the peculiar characteristic of being inherited together in block to further generation, and this complete set of closely related HLA alleles   is referred to as a haplotype. Thus, any individual would receive, following Mendelian rules, one maternally-derived and one paternally-derived haplotype, each consisting of an entire set of allels of class I HLA (HLA-A, -B, -C) and class II HLA (HLA-DR, -DP, -DQ) genes. These HLA alleles are inherited as haplotypes  because the recombination rate within the HLA genes during meiosis is lower than expected to most genes, so the HLA genes are said to be linkage disequilibrium as the genetic equilibrium would be the mixing of parental alleles before segregating them to other generations, rather than being linked together. As a consequence, every child would share a haplotype with each parent, which has been used for paternity assignment. In addition, there is a 25% probability of two siblings sharings both parental haplotypes (HLA identical/HLA identical by descent); a 50% probability of sharing at least one parental haplotype (HLA haplotypeidentical); and 25% probability of inheriting totally different parental haplotypes (HLA disparate or non-identical). A useful clinical consequence of all  this  is that HLA matching  can be achieved more easily among family members than among unrelated individuals, or even among individuals from the same ethnic group or with similar population migratory history than among those from distant ethnical or geographical backgrounds, depending on the allele and haplotype frequencies in the population.