The 2021 extramural meeting was the second virtual extramural meeting, which had over 170 registered attendants. The meeting was held on the 26th of November and was organised by the ETRL.
The extramural meeting was opened by Sebastiaan Heidt (ETRL). He welcomed everyone to the second virtual extramural meeting, and he expressed the hope to be able to meet in person the next time.
The first topic on the agenda was the discussion of the three patient-based cases of 2020, presented by Yvonne Zoet (ETRL). A summary of the results is published on the EPT website. The first case was about a non-immunized male, whose crossmatch unexpectedly turned strongly positive (serum from most recent screening; 4 months before transplantation). The cause turned out to be administration of Rituximab 8 months before the organ offer. Single antigen bead testing was repeated on freshly drawn serum and remained negative. The patient was transplanted, and the organ still is functioning. So far, no DSA formation has been detected.
The second case was about the consequences of delisting unacceptable antigens and adding those to the acceptable antigens for patients active in the AM program. This can sporadically be done to improve the chance to receive a compatible donor offer. However, one should be aware that removal of unacceptable antigens can lead to a drop in vPRA below the inclusion criteria for AM. Therefore, it is important to discuss removal of unacceptable antigens with the ETRL.
The last case involved a female AM recipient whose chance for a donor within the AM program was below 0.1%, so reduced minimal match criteria were applicable. Please note that minimal match criteria will be changed to 1 DR match on the broad antigen level. For recipients with a chance lower than 0.1% within the AM program or status HU no minimal match criteria will be applied. This change will be implemented end of January 2022.
Finally, there was a request for all participants of the patient-based case EPT to send their interesting cases to the ETRL.
News from the TTAC
The meeting continued with Sebastiaan Heidt, who showed the issues discussed during the virtual TTAC meeting on the 9th of November 2021. He discussed the following issues:
- Possible Imlifidase usage within Eurotransplant
Imlifidase is an IgG degrading enzyme that can turn a positive crossmatch into a negative crossmatch usually within 6 hours. The EMA conditionally approved its use for HLA incompatible adult kidney transplantation in August 2020. The EMA stated that it should be reserved for patients who are unlikely to obtain a transplant under the available kidney allocation system. The possible use of Imlifidase in Eurotransplant was discussed in the ETKAC. A dedicated ETKAC subcommittee, including the ETRL, will discuss this further, starting 7th of December this year.
- AM program recommendation R-TTAC02.20
Several changes have previously been discussed and agree upon in the TTAC and ETKAC. These include the median waiting time per country before becoming eligible for AM inclusion, as well as the chance of <2% within ETKAS. One point remained open, which was the group of patients for whom no immunizing events is known. These patients are disadvantaged since they are currently not eligible for inclusion in the AM program. A uniform and transparent way to deal with this was proposed by the ETRL and accepted by the TTAC. The recommendation will be put forward for approval by the ETKAC.
- Data required for vPRA panel extension to HLA-DQA, DPB and DPA
The current ETRL vPRA panel v3.0 consists of 10000 deceased donors with a complete typing for HLA-A, -B, -C, -DR and -DQ at split antigen level (except B14/Cw3), used for renal transplantation between 2012 and 2018 within the Eurotransplant area.
For virtual crossmatch purposes a panel with 11 loci (HLA-A, -B, -C, DRB1, DRB3/4/5, DQB1, DQA1, DPB1, DPA1) second field unambiguous typing is needed.
Request to all ET centers: How many actual ET donors (from all over ET) have you typed at 11-loci second field (re-typing, study purposes). An inventory will be done by the TTAC representatives.
Toward virtual cross matching
After a short break Sebastiaan continued with the last point discussed in the TTAC: Future HLA data communication within Eurotransplant, which will be changed to make virtual crossmatching possible. As communicated earlier, in the near future the virtual crossmatch will be implemented to replace the current donor center crossmatch. This will result in the “serum exchange program” no longer being necessary, a higher specificity and decreased cold ischemia times.
The use of the vPRA was already implemented in january 2020 and with this the definition of unacceptable antigens already improved, as shown by the positive donor center crossmatch inventory. Finally, the introduction of more extensive HLA typing (i.e. HLA-A, -B, -C, -DRB1, DRB3/4/5, -DQB1, -DQA1, -DPB1, -DPA1) must be implemented.
For the virtual crossmatch it will be possible to enter antibodies and unacceptable antigens both on antigen evel (broad and split) and on allele level for HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQB1, -DQA1, -DPB1, -DPA1. This makes it possible to calculate the vPRA including HLA-DQA1, DPB1 and DPA1.
For recipient typing intermediate resolution typing including all ambiguities is sufficient. In case of allele specific antibodies high resolution HLA typing is required for proper interpretation and registration. For donor typing intermediate resolution typing including all ambiguities is currently the best we can do with regards to resolution.
For all HLA typing data to be transferred to ET, HML (Histoimmunogenetics Markup Languagewill be used. This data standard developed by the NMDP is a standardized way of reporting HLA typing data, and allows for ambiguous typing data to be correctly transferred. One of the elements of HML is the GL (Genotype List) string. A GL String is a collection of alleles parsed with character delimiters that organize the alleles in terms of loci, alleles, lists of possible alleles, phased genes, genotypes, and lists of possible genotypes.
Suppliers of HLA typing kits have indicated that they will adapt their software so that the export in HML will be possible. For the current overview of suppliers and the status of HML implementation see the presentation of Sebastiaan Heidt. In case other suppliers need to be aprroached, please contact the ETRL.
The final speaker of the day was Suzanne Bezstarosti from the Transplant Immunology research group of Leiden University Medical Center who showed a critical evaluation of the antibody-verified status of eplets listed in the HLA Epitope Registry. Once published, the newly defined list of verified eplets will be used by the ETRL for AM inclusion eligibility.