Definitions of histocompatibility typing terms

Abstract

Histocompatibility testing for stem cell and solid organ transplantation has become increasingly complex as newly discovered HLA alleles are described. HLA typing assignments reported by laboratories are used by physicians and donor registries for matching donors and recipients. To communicate effectively, a common language for histocompatibility terms should be established. In early 2010, representatives from Clinical, Registry, and Histocompatibility organizations joined together as the Harmonization of Histocompatibility Typing Terms Working Group to define a consensual language for laboratories, physicians, and registries to communicate histocompatibility typing information. The Working Group defined terms for HLA typing resolution, HLA matching, and a format for reporting HLA assignments. In addition, definitions of verification typing and extended typing were addressed. The original draft of the Definitions of Histocompatibility Typing Terms was disseminated to colleagues from each organization to gain feedback and create a collaborative document. Commentary gathered during this 90-day review period were discussed and implemented for preparation of this report. Histocompatibility testing continues to evolve; thus, the definitions agreed on today probably will require refinement and perhaps additional terminology in the future.

A perspective on the selection of unrelated donors and cord blood units for transplantation

“…Current high-resolution techniques focus only on alleles that code for proteins that are found on the cell surface (and so are immunologically "active") and on genes encoding the antigen recognition site of HLA molecules. 31 The antigen recognition site is the "active" portion of the HLA molecule that binds peptide antigens and interacts with T-cell receptors. Available data indicate that alleles that are identical in the antigen recognition site domain do not have immunologic differences.…”

Effects of transmembrane region variability on cell surface expression and allorecognition of HLA-DP3

“…The results reported here are compatible with the current notion to regard the two HLA-DP3 variants, DPB1 Ã 03:01 and DPB1 Ã 104:01, as a functional entity in unrelated stem cell donor searches. Although this piece of evidence might also be considered as new biological support for international guidelines limiting the requirements for high resolution typing of expressed HLA alleles to those differing inside the antigen binding groove [7], care should be taken in making generalizations (Table S1). Results are reported as mean ± SD of 3 independent experiments.…”

“…DPB1 Ã 03:01 and DPB1 Ã 104:01, the two allelic variants encoding HLA-DP3 beta-chain, are not discriminated by most laboratories following the international guidelines for high resolution histocompatibility typing [7], and their relative frequency in different ethnic groups is unknown. We show that in a population of unrelated stem cell donors selected for patients mostly of Caucasian origin, the two HLA-DP3 variants occur with a relative frequency of 4.2:1.…”

“…In line with this notion, numerous studies have found an association between the clinical outcome of volunteer unrelated donor (VUD)-hematopoietic stem cell transplantation (HSCT) and disparity for mismatches inside the antigen binding groove [3][4][5][6]. Based on these findings, the internationally accepted definitions of histocompatibility typing terms limit the requirements for high resolution typing in VUD searches for HSCT to expressed alleles that encode the same protein sequence for the antigen binding groove [7]. As a consequence, for the majority of newly reported HLA alleles, the outside-the-groove sequence is unknown.…”

Impact of HLA Diversity on Donor Selection in Organ and Stem Cell Transplantation

“…patient and donor are both HLA-A2, but the patient is A * 02: 01 and the donor A * 02: 06. The analysis of the serotype A2 (by serology) or of the allele group A * 02 (by DNA typing) is usually referred to as 'low-resolution typing' [10] . The assignment of the A * 02: 01 and A * 02: 06 alleles is commonly referred to as 'high-resolution typing' [10] and is mandatory in HSCT, at least for unrelated donor matching, because alloreactive T cells are even able to recognize mismatched alleles which differ in a single amino acid.…”