The 2020 extramural meeting was the first (and hopefully last) virtual extramural meeting. The meeting was held on the 27th of November and was organised by the ETRL.
The first virtual extramural meeting was opened by Frans Claas (ETRL). Frans officially stepped down from his ETRL duties in 2020.
The extramural meeting that was originally planned in Mechelen, Belgium in 2020 was intended to be his last extramural as head of the ETRL. With this meeting being cancelled for obvious reasons, the first virtual extramural meeting was Frans’ last extramural meeting in which he officially participated. He handed over his responsibilities to Sebastiaan Heidt and thanked everyone for their contributions over the years.
The first topic on the agenda was an update on the EPT results from 2019, presented by Yvonne Zoet (ETRL). For HLA typing, a discrepancy rate of 1.6% was observed. For cross-matching (all results included) discrepancy rates of 2.8% and 3.6% for respective donor centers and recipient centers were observed.
To complete the overview, data from the screening detection and screening identification schemes were also shown. For screening detection, discrepancy rates of 1.8% for HLA class I antibodies, and 3.2% for HLA class II antibodies were observed. For screening identification, CDC and SPA Single Antigen techniques were assessed. In CDC, 17 consensus specificities were found and in SPA SA 348 consensus specificities were found.
Next, Yvonne discussed the three patient based cases that were sent to all EPT participants in 2019. A summary of the results is published on the EPT website. The first case was about a patient with Waldenströhms Marcoglobulenimia and abundance of IgM type antibodies in the serum turning all CDC tests positive, while in SAB testing no HLA specific antibodies were found. Serum of such patient should not be shipped for crossmatching at the donor center, and SAB results must be taken into account when deciding if a donor organ is suitable for this patient.
The second case was about a patient who received an offer through the AM program, which appeared to be perfectly matched on HLA-A, -B, -C, -DR and -DQ, but nonetheless had a positive crossmatch on spleen cells. Upon donor HLA-DP typing it was clear that, the recipient had strong antibodies against the HLA-DP of the donor. This case showed the need to expand unacceptable antigen registration within ET.
The last case involved a patient that returned to the waiting list after a failed transplant and had a fairly quick new offer. At the time of the new offer, only one serum sample was available after graft failure. The discussion that followed was on what to do when after return on the waiting list only one serum sample has tested for HLA antibodies and is available for crossmatching. It is preferred to have at least two separately drawn samples tested before a patient is re-entered on the waiting list (to exclude clerical errors). When this is not possible, the recipient center crossmatch should include a freshly drawn pre-transplant serum.
News from the TTAC
The meeting continued with Sebastiaan Heidt (ETRL), who discussed the main topics discussed during the virtual TTAC meeting on the 17th of September 2020. He discussed the following topics:
- vPRA and current German guidelines: an interpretation on the current German guidelines to facilitate the vPRA has been drafted and discussed with the BÄK and will be further decided on. This interpretation handles the vPRA similarly yo the other memberstates of ET.
- The AM program 2.0: one policy and two recommendations have been drafted by the TTAC and were presented to the ETKAC. The recommendation on extending HLA-A, -B, and -DR with HLA-C and -DQ at the ET match determinant level for AM program allocation was approved. The recommendation on new inclusion criteria for the AM program was positively received by the ETKAC but required some more underlying data. The policy on reducing the minimal match criteria to one HLA-DR on the broad antigen level was approved by the ETKAC.
- Extended HLA typing: For the introduction of the virtual crossmatch, extended HLA typing data is required. Since second field HLA typing without ambiguities is not yet possible during deceased donor procedures, a temporary solution for using intermediate resolution HLA typing is required. The discussion was on the options to communicate this level of HLA typing data to Eurotransplant.
Two options were put forward: option 1, reporting the most likely HLA alleles at the second field level in a worksheet (not a report as defined by EFI), with the acknowledgement that ambiguities may exist. Option 2, Reporting all ambiguities, for example as P-groups or as a GL-string. In the meantime, a survey was sent to all tissue typing laboratories in ET to further evaluate these options.
Toward virtual cross matching
Sebastiaan continued with a presentation about how to move to virtual crossmatching in ET. This is necessary, because physical donor crossmatches are associated with a number of problems that can be overcome by the use of virtual crossmatching. As a first step, from 28-01-2020 the vPRA was effectuated, which represents the percentage of potential donors within ET to which the patient has made HLA-specific antibodies.
The next step is to introduce a new way of reporting results of HLA typing to Eurotransplant, as described above. New HLA tables to be used in the near future have been developed by the ETRL and approved by the TTAC.
The time path of the steps that have to be taken can be found in the presentation on the ETRL website. At this moment the introduction of virtual crossmatching is scheduled for quarter 4 of 2022.
The final speaker of the day was Cynthia Kramer who showed an elegant overview of HLA epitopes. She made the clear distinction between functional and structural epitopes and their relation with immunogenicity and antigenicity. Furthermore, Cynthia showed data on monoclonal HLA-specific antibodies that showed that not all reactivity towards a structural epitope is clinically relevant.
The meeting ended with thanking Frans Claas for all his work for and contributions to the ETRL and TTAC.