Abstract
A catalog of common, intermediate and well‐documented (CIWD) HLA‐A, ‐B, ‐C, ‐DRB1, ‐DRB3, ‐DRB4, ‐DRB5, ‐DQB1 and ‐DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two‐field) and G group assignments are divided into one of four frequency categories: common (≥1 in 10 000), intermediate (≥1 in 100 000), well‐documented (≥5 occurrences) or not‐CIWD. Overall 26% of alleles in IPD‐IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two‐field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well‐documented alleles. Full‐field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole.
Highlights
Identification of the highly polymorphic HLA genes (HLA-A, -B, -C, -DR, -DQ, and -DP) in the clinical laboratory ensures that hematopoietic stem cell donor and recipient are HLA matched at high-resolution, enabling engraftment of donor cells and avoiding detrimental immune responses.[1,2] In solid organ transplantation, evaluation of HLA differences is used to select donors who will not react with or induce donor-specific antibodies to avoid graft rejection.[3,4,5] Other uses of HLA typing are to guide immunotherapies,[6] prevent adverse drug reactions,[7] diagnose autoimmune diseases,[8] and inform HLA population genetics.[9]
Ancestry categorization was defined by each registry and converted into seven population groups for this study: AFA (African/African American), API (Asian/Pacific Islands), EURO (European/European descent), Middle East/North coast of Africa (MENA) (Middle East/North Coast of Africa), HIS (South or Central America/Hispanic/Latino), Native American populations (NAM) (Native American) and Unknown/Not asked/Multiple ancestries/Other (UNK)
This update to the common and well-documented (CWD) allele catalog evaluates the frequency of over 15.2 million two-field P group assignments at each locus of HLA-A, -B, -DRB1, and -DQB1 in over 8 million individuals whose HLA types are found in 20 worldwide hematopoietic stem cell registries listing their ancestries in seven categories (Tables 1, 2a and 2b)
Summary
Identification of the highly polymorphic HLA genes (HLA-A, -B, -C, -DR, -DQ, and -DP) in the clinical laboratory (ie, HLA “typing”) ensures that hematopoietic stem cell donor and recipient are HLA matched at high-resolution, enabling engraftment of donor cells and avoiding detrimental immune responses (eg, graft vs host disease).[1,2] In solid organ transplantation, evaluation of HLA differences is used to select donors who will not react with or induce donor-specific antibodies to avoid graft rejection.[3,4,5] Other uses of HLA typing are to guide immunotherapies,[6] prevent adverse drug reactions,[7] diagnose autoimmune diseases,[8] and inform HLA population genetics.[9]. The almost exponential increase in the known HLA alleles over time[10,11] has been paralleled by changes in the methods used to type those alleles. Serologic typing of HLA proteins was replaced by DNA-based methods that identified the presence or absence of specific polymorphisms through the binding of oligonucleotide probes or primers. Variation in the ability to assign polymorphic residues to one haplotype vs the other has varied with the reagents and methods used producing, in many cases, ambiguity in the specific genotype carried by an individual. The history of all of these changes in the known allele database and the typing methods is reflected in the wide variety of HLA assignments found in the millions of individuals listed in donor registries around the world.[12,13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
