16^th IHIW: Global distribution of extended HLA haplotypes

Abstract

This report describes the project to identify the global distribution of extended HLA haplotypes, a component of 16th International HLA and Immunogenetics Workshop (IHIW), and summarizes the initial analyses of data collected. The project aims to investigate extended HLA haplotypes, compare their distribution among different populations, assess their frequency in hematopoietic stem cell unrelated donor registries and initiate an international family studies database and DNA repository to be made publicly available. HLA haplotypes compiled in immunogenetics laboratories during the evaluation of transplant candidates and related potential donors were analysed. Haplotypes were determined using the pedigree analysis tool publicly available from the National Marrow Donor Program (NMDP) website. Nineteen laboratories from 10 countries (11 laboratories from North America, five from Asia, two from Latin America and one from Australia) contributed data on a total of 1719 families comprised of 7474 individuals. We identified 10393 HLA haplotypes, of which 1682 haplotypes included high-resolution typing at HLA-A, B, C, DRB1 and DQB1 loci. We also present haplotypes containing MICA and other HLA loci and haplotypes containing rare alleles seen in these families. The project will be extended through the 17th IHIW, and investigators interested in joining the project may communicate with the first author.

JC Polyomavirus Infection Is Strongly Controlled by Human Leucocyte Antigen Class II Variants

“…Several HLA-alleles showed association to anti-JCV antibody status in both Scandinavian MS cases and controls (Table 2). The table is organised based on common established extended haplotypes found in the Caucasian population [19]–[21]. It is noteworthy that the DRB1*15-DQA1*01:02-DQB1*06:02 -haplotype, the most strongly associated MS genetic risk factor, was found to be negatively associated with the positive detection of anti-JCV antibodies.…”

“…Age was included as a continuous covariate. *Multivariate: all nominally significant alleles from the same gene in the same model, adjusted for age and gender. DQB1*06:03 and DQA1*01:03 were not included in the analysis because the allele frequency was below 5%.Common extended HLA haplotypes were selected from those published in the literature for the Caucasian population [19]–[21]. Alternative common DRB1*15 haplotypes DQB1*06:02-DQA1*01:02-DRB1*15-B*07-C*07-A*02 , DQB1*06:02-DQA1*01:02-DRB1*15-B*07-C*07-A*03 , DQB1*06:02-DQA1*01:02-DQB1*15-B*51-C*?-A*02 , DQB1*06:02-DQA1*01:02-DRB1*15-B*51-C*?-A*11 .…”

“…As only alleles on the DQB1*06:02-DQA1*01:02-DRB1*15 haplotype were significant no multivariate analysis was performed. * Median nOD is given among individuals positive or negative for respective HLA allele.Common extended HLA haplotypes were selected from those published in the literature for the Caucasian population [19]–[21]. Alternative common DRB1*15 haplotypes DQB1*06:02-DQA1*01:02-DRB1*15-B*07-C*07-A*02, DQB1*06:02-DQA1*01:02-DRB1*15-B*07-C*07-A*03, DQB1*06:02-DQA1*01:02-DRB1*15-B*51-C*?-A*02, DQB1*06:02-DQA1*01:02-DRB1*15-B*51-C*?-A*11.…”

Genetic Ancestry and Health

“…These systems include HLA, MICA, KIR, blood group, cytokine, HNA and HPA [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. These new datasets not only provide special insights into the ancestry of these people, but also is of significant value in health; as recently reviewed by [21][22].…”

The major histocompatibility complex: a model for understanding graft-versus-host disease

“…MICA is polymorphic, 72 has strong haplotypic associations to HLA-B, 73,74 is inducible by stress, 75 and is a ligand for activating NKG2D receptors. 76 A potential role for MICA in GVHD might involve T cell-or NK-mediated pathways and/or inflammatory and stress mediators.…”