How do I interpret and utilize HLA typing report data?

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The human leukocyte antigen (HLA) system plays a vital role in adaptive immunity and transplantation outcomes. HLA typing aims to characterize an individual’s HLA allele variants across several genes that encode HLA proteins. The results are reported in an HLA typing report that details the allele groups, haplotypes, and ambiguities for Class I (HLA-A, HLA-B, HLA-C) and Class II (HLA-DRB1, HLA-DQB1, HLA-DPB1) genes. However, making sense of the complex nomenclature and terminology in these reports can be challenging. 

Decoding HLA Nomenclature

HLA allele names consist of up to four sets of digits separated by colons. The first field indicates the HLA locus, the second defines the allele group, and the third and fourth (if present) denote synonymous mutations that do not alter the protein sequence. For example, HLA-A01:01:01:01 tells us this is an HLA-A allele from the HLA-A01 group with three synonymous mutations. Understanding the basics of this standardized nomenclature is key to comprehending your HLA typing report.

Assessing Resolution

HLA typing resolution describes the degree of detail to which HLA alleles are characterized. Low-resolution typing identifies the main allele groups (2-digits, e.g. HLA-A01). Intermediate resolution further defines common subgroups (4-digits, e.g. HLA-A01:01). High-resolution characterization assesses specific protein sequence variants (6-8 digits, e.g. HLA-A*01:01:01:01). High-resolution is optimal for applications like donor matching. Resolution can vary across loci in a given report.

Interpreting Haplotypes

The HLA genes reside close together on chromosome 6 and are inherited in a haplotype block from each parent. HLA typing aims to infer these haplotypes, reported as a series of closely linked HLA alleles. For example, a person may have an HLA-A01~-~B08~-~C07 haplotype inherited from their mother and an HLA-A02~-~B44~-~C05 haplotype from their father. Understanding haplotypes is useful for Hematopoietic Cell Transplantation donor selection.

Handling Ambiguities

Despite advancing HLA typing methods, many individuals still have HLA typing ambiguities where a genotype cannot be definitively resolved to a single allele pair. This occurs when mutations distinguishing alleles are located outside typed exons or when a rare allele is absent from the testing database. Ambiguities are denoted with “/” (e.g. A*01:01/01:02) and should be considered in downstream data interpretations.