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HLA Equivalency Tables Update 2020

Proposal Overview

Status: Public Comment

Sponsoring Committee: Histocompatibility

Strategic Goal: Improve waitlisted patient, living donor, and transplant recipient outcomes

Read the proposal (PDF; 01/2020)

Contact: Betsy Gans

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eye iconAt a glance

What is current policy and why change it?

Histocompatibility laboratories use commercially available kits to test transplant recipient and potential organ donor tissues for compatibility. This matching helps lower the risk that the recipient’s body will reject the transplant. The values used in this testing are included in tables in OPTN policy, so these values can be programmed into the OPTN computer system. As the science changes, the values used in the test kits need to be updated. This proposal updates the tables and adds an additional table with a new element that can further improve efficiency of tissue matching.   

What’s the proposal?

  • Updates to existing reference tables in OPTN Policy 4.10: Reference Tables of HLA Antigen Values and Split Equivalences.
  • Add new reference tables to be programmed into the OPTN computer systems, including the option for transplant hospital or histocompatibility labs to use an additional method that may make it easier to match candidate and donor tissue.
  • Set up future updates to these tables to go through an expedited policy process which allows these routine updates to be made quickly.

What’s the anticipated impact of this change?

  • What it’s expected to do
    • Update the existing reference tables to match the updated test kits.
    • Add an option to use a new element that can provide easier and more-efficient matching.
    • Shorten the length of time required to routinely update the reference tables.
  • What it won’t do
    • Change the Calculated Panel Reactive Antibodies (CPRA) calculation or frequency data used for the calculation.

Themes to consider

  •  Appropriateness of using expedited process for future updates.
  •  Addition of optional new element that increases efficiency and makes it easier to match tissues.

Terms you need to know

  • Calculated Panel Reactive Antibodies – Calculation that shows the percentage chance a recipient will not match with a donor’s tissue.  The higher the percentage the more “sensitized” a recipient is.
  • Human leukocyte antigen (HLA) complex – a group of genes that helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.
  •  Click here to search the OPTN glossary.

Comments

Valia Bravo-Egana | 01/24/2020

This proposal is particularly important in current times when more and more labs have access to higher resolution HLA typing to assess matching between donors and recipients. With the advent of new technologies that provide a much deeper understanding of the HLA genes and proteins, it is very important that, the histocompatibility community has an efficient and quick way to include this information to be considered by the Programs when assessing matching and compatibility. I think this is long due and feel glad and thankful for this initiative.

Geof Land | 01/25/2020

These are welcome changes to listing patient and donor typings in UNOS, I support them.

Steven Geier | 01/27/2020

The proposed HLA Equivalency Tables Updates are very important to keep the tables up to date.

Marcelo FernandezVina | 01/27/2020

a) For DPB1 tables recommend using P groups that are accepted by the W.H.O. official nomenclature. The P groups include alleles with identical structure om the beta-1 domain. These are W.H.O. Nomenclature Committee and UNOS would not have to go through the approval process when new alleles are described. b) Why some DPB1* alleles are crossed and others are not? e.g. 104:01, 105:01, 124:01. 126:01 are not crossed while 350 and 351:01 are. These are equivalent to DPB1*03:01, 04:01, 04:02. The use of P equivalencies would make the application uniform. c) The DPB1 epitopes 55=57 EAE and AAE are equivalent and indistinguishable. It is worth focusing at residues 56-57 and just have the epitopes AE, EE and ED. This is a simpler way for listing DP avoids based on epitopes. d) It would be even more simple if DPB1 serotypes were reduced to DP1, 2, 3, and 4 as suggested by Cano P, Fernández-Viña M. (Two sequence dimorphisms of DPB1 define the immunodominant serologic epitopes of HLA-DP. Hum Immunol. 2009 Oct;70(10):836-43. doi: 10.1016/j.humimm.2009.07.011. Epub 2009 Jul 25. PubMed PMID: 19635517). The addition of DP10 would account for almost all DP serotypes. f) DPA1 is not taken into consideration although the DPA1 encoded epitopes are as immunogenic or more immunogenic than some DPB1 epitopes. g) B*48:02 has a close serotype corresponding to B71 (see HLA Dictionary; https://www.ebi.ac.uk/ipd/imgt/hla/). Listing as B48 is misleading since the allele lacks the most immundominat epitopes present in B48 (B*48:01 being the prototype).

Danny Youngs | 01/27/2020

Overall the changes are good, and the Epitope-based Unacceptable Antigen Assignment for DPB1 is very useful, but there is an omission: DPB1*99:01 is missing from both the 55AAE and 84GGPM sections of Table 4-15. It's unfortunate that the Additional Unacceptable Antigen Equivalences to be used in CPRA (Table 4-17) still exists. When will CPRA be based on actual DR51/52/53 results, and not on associated DRB1 typing?

Olga Charnaya | 01/29/2020

Highly support this change and looking forward to studying the effectiveness of DPB1 eplet based UA designation. As technology advances and more labs are moving to high-resolution HLA typing for solid organ transplant we should make every effort to utilize the new information being generated to optimize patient care and outcomes.

Idoia Gimferrer | 01/29/2020

DQB1*03:04 allele is missing from table 4-13. Although DQB1*03:04 is a DQ7 by WHO, it has epitope 55PPA shared with DQB1*03:02 (8).

Massimo Mangiola | 02/03/2020

I want to first extend my thank you to the Histocompatibility Committee members for working on this very much needed update and especially for their willingness to take the first steps needed to introduce the eplet concept into the UNOS system. I have few comments on the eplet component of this proposal. 1) Name. I would refer to these polymorphic residues as to EPLETS, not epitopes, since the epitope is a mostly unknown and much larger area which contains the eplet(s) but also includes several self-residues. Since you are planning on using an "eplet nomenclature" you should refer to these as eplets, not epitopes. 2) Nomenclature. I think we need to start this project by using current nomenclature. Although I can agree that the Epitope Registry (https://www.epregistry.com.br) has not been yet officially approved as the "current nomenclature", to date it is the only eplet database and, in the interim, is virtually the official HLA eplet nomenclature. Three (3) of the eplets in the residues area 55-57 are listed with a name that reflects the polymorphic residues, not the eplet: 55AAE = 55A 55DED = 57D 55DEE = 56EE The possible downside of NOT using the nomenclature as it appears in the Epitope Registry is that many users may not find the eplet in the UAs list. In fact, for the common 57D eplet, I would probably look for that, not 55DED. 3) Residues Used (two questions) I was wondering why you are limiting yourself to the polymorphic areas between AA55-AA57 and AA84-AA87? If you want to start with something, why not start with at least including the antibody-verified eplets? There are several known eplets on either side of these regions with some that have been verified by an antibody. I would recommend to add 35FV, 56A, 56E, 69E, 85GPM and 96K. I believe that, by adding at least all the 9 antibody-verified eplets, you will also have the opportunity to collect data on DP antibody patterns and their occurrence in the patient population.

OPTN Operations and Safety Committee | 02/14/2020

HLA Equivalency Table Update 2020 The Operations and Safety Committee (OSC) thanks the OPTN Histocompatibility Committee for their efforts in developing this public comment proposal for the HLA Equivalency Table Update. The Committee indicated the following sentiments for the proposal: 46% Strongly Support, 54% Support, 0% Neutral/Abstain, 0% Oppose, 0% Strongly Oppose

Region 4 | 02/20/2020

Strongly support (11), Support (9), Neutral/Abstain (2), Oppose (0), Strongly Oppose (0)

Region 8 | 02/20/2020

8 Strongly Support, 10 Support, 2 Neutral/Abstain, 0 Oppose, 0 Strongly Oppose

Region 6 | 02/21/2020

Strongly support (8), Support (9), Neutral/Abstain (0), Oppose (0), Strongly Oppose (0)

Region 5 | 02/21/2020

Strongly support (13), Support (8), Neutral/Abstain (1), Oppose (0), Strongly Oppose (0)