The International Histocompatibility Working Group (IHWG) is a collaborative international effort to increase the availability and efficacy of hematopoietic cell transplantation (HCT) from alternative donors through an improved understanding of the genetic barrier. The HCT working group is comprised of experts in the fields of histocompatibility and immunogenetics, hematopoietic cell transplantation, and outcomes research. The current working group includes 170 investigators, 42 laboratories, 435 transplant centers, 10 transplant and donor registries from18 countries who have built a genetic and clinical database of 30,099 transplants. Active investigation is in progress in 8 key areas: the impact of HLA matching, role of race and ethnicity, identification of permissible HLA mismatches, haplotype-associated determinants, minor histocompatibility antigens, non-inherited maternal antigens, immune response and cytokine genes, and KIR genetics. New studies for the 17th HLA Workshop will extend to cord blood and haploidentical related donor transplantation.
The 17th workshop studies will include investigation into the role of HLA-DRB3, DRB4, DRB5, DQA1, MICA, MICB, HLA-E and HLA-G in unrelated donor transplantation using workshop genotyping protocols and quality control panels.
Importance of Ethnicity on Transplant Outcomes
In follow-up to the 16th workshop analysis of acute GVHD, relapse and mortality, the working group will investigate the impact of ethnicity on risk of chronic GVHD, and define high-risk HLA haplotypes associated with GVHD.
Novel MHC Variants
Newly defined determinants of outcome identified from SNP and haplotype analyses will be the focus of this study, in which the frequency of high-risk genotypes and of donor-recipient matching will be determined in ethnically diverse transplant populations.
In the 17th HLA workshop, the working group will elucidate the diversity of the TNF region in class III to test the hypothesis that genetic variation within the TNF block influences clinical outcome after transplantation. Testing of TNF block variants will involve workshop quality control panels prior to large-scale testing of patients, donors and cord blood units.
Minor Histocompatibility Antigens
This study will elucidate the synergistic effects of mismatching for minor and major histocompatibility antigens represented by HY and HLA-DP in matched and mismatched transplantation.
Non-inherited Maternal Antigens
Haploidentical related donor and cord blood transplant populations will be newly recruited to address the role of non-inherited maternal antigens and NIMA-matching in transplant outcomes.
The KIR working group will extend their analysis of KIR alleles and haplotypes on transplant outcome for patients with acute leukemia and will expand the trasnplant population to include non-myeloablative transplants, transplants utilizing alternative stem cell donor sources (cord blood allografts, haploidentical donors), and patients with lymphoma.
Component Leader: Effie Petersdorf MD
Liaison: Harriet Noreen CHS