Histocompatibility Committee Review of HLA Tables (2016) Histocompatibility Committee

What problem will the proposal solve? Members need updated antigens in UNetSM As a result of the naming process for DPB1 alleles, there is no relationship between the allele designation and the protein structure. Only a small number of DPB1 antigens are present on commercial antibody testing kits. Hence, the possibility exists that an incompatible organ may be inappropriately offered to a candidate. The downstream impact ranges from an unexpected positive crossmatch to early AMR and graft loss. Nomenclature in tables is out of date Current policy requires the Histocompatibility Committee to review the HLA tables in policy on an annual basis and recommend updates to the equivalences. During the 2016-2017 review, the Committee identified the need to include a DPB1 equivalency table as part of the annual update. The presence of HLA-DP donor specific antibodies can affect graft survival, organ allocation, and patient safety. Research shows the prevalence of DPB1 in highly sensitized candidates; in one study among candidates with CPRA greater than 98%, well over 50% possess DPB1 antibodies. As of July 10th 2017, 5,339 registrations had DPB1 unacceptable antigens listed. In November 2014, UNOS added DPB1 to the match-run algorithm, allowing DPB1 antigens to be listed as unacceptable. Though this is helpful, there are problems unique to DPB1. The problems are two-fold: First, DPB1 naming convention does not allow one to easily determine the structural relationship between two alleles. Second, only a small number of DPB1 alleles are available for HLA antibody identification via the commercial kits. As a result of these two issues, a donor’s DPB1 type may not correlate with a DPB1 antigen listed as “unacceptable”. Members are unable to choose DPB1 antigens that may be equivalent/similar to the donor’s DPB1 phenotype. This shortcoming could result in inappropriate organ allocation, unexpected positive crossmatches, increased cold ischemia time, and the potential for transplanting incompatible organs. In order to provide better correlation between donor DPB1 types and listed DPB1 unacceptable antigens, the Histocompatibility Committee proposes the creation of an equivalency table defining the relationships between certain DPB1 alleles, specifically the “G” alleles. These relationships could then be applied to the match-run algorithm to help ensure appropriate organ allocation. The Committee is also proposing some updates to the HLA nomenclature in the equivalency tables that will better align the tables in Policy 4.10 with the language used in the HLA community. This can help improve member usability and understanding of the content in the tables.

What are the proposed solutions? Update existing equivalency tables Add HLA-DPB1 unacceptable antigen table, including G alleles Update nomenclature in all equivalency tables to reflect proper WHO designations. HLA-A 101  HLA- A*01:01 In order to provide members with more up to date equivalency tables, the Committee reviewed and updated the existing tables. The Committee also created a DPB1 unacceptable antigen equivalency table, which will allow members to easily see DPB1 equivalences that include the G alleles. By providing members with this table, they will have more knowledge at their disposal when making transplantation decisions. To make the tables more in line with current HLA nomenclature, the Committee added colons for all specific alleles and a zero in front of single digit allele groups with specific alleles. For example, HLA-A101 would be changed to HLA-A01:01. This change will make the antigens easier to read when members are interpreting the contents of the equivalency tables.

How will members implement this proposal? Members should: familiarize themselves with updates to tables review and modify unacceptable antigens for candidates based on changes to tables Members must update their references and reporting methods to reflect changes in nomenclature Members will implement this proposal as they have with past equivalency table updates. Labs and centers will need to be aware of the additional alleles listed in the tables, as well as any that were taken out due to no longer being detectable. Members will also need to become familiar with the changes in nomenclature when reporting antigens for candidates and donors.

How will the OPTN implement this proposal? Anticipated Board of Directors Review: Dec. 2017 Programming – IT will update tables in Policy 4.10 with changes to nomenclature and antigens Committee will evaluate 1 year post-implementation The projected board date for this proposal is the upcoming December board meeting. If approved, the updates to the tables should go live within a year from the approval date. The UNOS IT department will update the equivalency tables, including updates to the nomenclature. The Committee will review the frequencies for alleles in the equivalency tables one year post-implementation.

Questions? Robert A. Bray, Ph.D., D(ABHI), HCLD/CC(ABB) Committee Chair rbray@emory.edu Alison Wilhelm Committee Liaison alison.wilhelm@unos.org