The 2023 extramural meeting was the first in-person meeting since the pandemic. To get in line with the original meeting schedule, the 2022 extramural meeting was skipped.
Opening
The 2023 extramural meeting was opened by Marie-Paule Emonds (HILA, Mechelen) and Sebastiaan Heidt (ETRL).
External proficiency testing
The first part of the program was the presentation of the EPT results of 2022 by Yvonne Zoet (ETRL). For HLA typing, a discrepancy rate of 1.97% was observed. For cross-matching (all results included) discrepancy rates of 3.5% and 3.0% for respective donor centers and recipient centers were observed.
To complete the overview, data from screening detection and screening identification scheme were also shown. For screening detection, a discrepancy rates of 1.9% for HLA class I antibodies, and 2.4% for HLA class II antibodies were observed. For screening identification, CDC and SPA Single Antigen techniques were assessed. In CDC, 11 consensus specificities were found and in SPA SA 302 consensus specificities were found. Finally, she showed the changes in the Eurotransplant EPT and EPT website that followed the introduction of the virtual crossmatch. A discussion followed as to why the ETRL had chosen for the option to enter ET match determinants in the HLA-typing EPT. This was done because the ETRL would like to retain the interpretation of HLA typing data, and because of current technical possibilities. For the future to the ETRL will explore alternative options using HML-based data transfer.
The next topic on the agenda was the discussion of the three patient-based cases of 2022, also presented by Yvonne Zoet. A summary of the results is published on the EPT website. The first case was about a female with donor- specific antibodies detectable in Luminex only, with a negative CDC crossmatch both without and with DTT. Most participants argued that the organ was suitable. The patient was transplanted and two years later the kidney functions well.
The second case was about a female patient with a consistently positive autologous CDC crossmatch. Upon organ offer, the crossmatch results without DTT were positive and with DTT negative, as could be expected with a positive autologous crossmatch. Most participants accepted this organ offer for this patient. She was transplanted and has good graft function, 4 years after transplantation.
The last case involved a female patient with an allele-specific DRB3*02 antibody and DQA1 antibodies. Unacceptable antigen definition before and after the introduction of the virtual crossmatched was requested as well as the options for this patient. From 24th of January this year onwards it is possible to enter allelic unacceptable antigens on the allelic level, as well as for DQA, DPB and DPA in ENIS.
Virtual crossmatch
The meeting continued with Cynthia Kramer (ETRL) who informed the participants about the first experiences with the virtual donor center crossmatch within Eurotransplant.
On the 24th of January 2023 Eurotransplant switched to the use of the virtual donor center crossmatch, with a shadow phase of a physical donor center crossmatch until April 24, 2023. The virtual crossmatch was introduced to overcome the following issues:
- Mandatory serum exchange program required
- No immunological history known at donor center
- False positive crossmatches due to irrelevant antibodies not directed against HLA
- Low sensitivity for HLA class II antibodies (only unseparated or T cell crossmatches are valid)
- Long(er) cold ischemia times
Cynthia led us through all changes the registration of unacceptable antigens in ENISNext, HLA typing requirements, data transfer through HML files by ET immunology service, the filtering process of HML files, and the actual virtual crossmatch.
At time of the Extramural Meeting 80% of the HLA typing data was transmitted through HML files, of which 87% did not require any adjustment. She also showed the details per country and discussed some reasons for manual adjustment of the generated phenotype upon HML submission.
It was clear that still positive donor center crossmatches occur due to incomplete unacceptable antigen registration. All labs were encouraged to update the unacceptable antigens for their recipients as soon as possible.
CDC screening inventory
The meeting continued with the results of the CDC screening inventory, presented by Cynthia Kramer. All 44 Eurotransplant affiliated tissue typing laboratories were asked to complete a survey about status and future of CDC screening for detection and identification of HLA-specific antibodies, of which 37 responded.
Some remarks:
- In case you are interested in joining the Amsterdam laboratory of Junior Lardy for the possible joint acquisition of new cell dispensers for CDC, please contact the ETRL (etrl@eurotransplant.org). The Amsterdam laboratory already is in contact with a company that could provide such dispensers.
- The possibilities to have in-house panels IVDR approved was also discussed. This can easiest be done when companies will not certify their CDC tests, which for now seems to be the case.
- In case you like to have the coverage of your (in house) panel checked, or when you like to have protocols for freezing and storage of cells for the screening panel, please contact the ETRL (etrl@eurotransplant.org).
News from the TTAC
The meeting continued with Sebastiaan Heidt, who showed the topics discussed during the TTAC meeting on the 9th of March 2023, in Mechelen, Belgium. Some of the major topics discussed were similar to those discussed at the extramural meeting, namely the virtual crossmatch and the future of CDC screening. For the virtual crossmatch, it was discussed that the frequently occurring issues with HML to genotype conversion would be made available to the ET community to raise awareness.
For CDC crossmatching, a policy will be drafted in which CDC screening will be made mandatory at listing of a patient, but no longer mandatory to subsequently screen with CDC every year for non-sensitized patients. A policy for mandatory pre-treatment of sera for Luminex SAB testing was approved by the TTAC and will be put forward to the Council of Medicine and Science. Finally, the use of DQA, DPB and DPA for inclusion into the AM program was discussed. It was agreed that in case of missing data on these loci from immunizing events, DQB1-DQA1 linkage will be used for assigning the most probable DQA1 typing for the immunizer, and for DP, the strongest reactions in Luminex will be used for deducting the most probable immunizing DP antigens.
As a last point Sebastiaan asked for a volunteer center that would like to organize together with the ETRL, the extramural meeting of 2024.
Scientific lecture
The final speaker of the day was Maarten Naessens from the University Hospitals Leuven, Belgium, who took us along in the ‘Bermuda triangle’ between HLA-specialist, pathologists, and nephrologists when it comes to post-transplant rejection diagnostics.
Get-together with drinks and dinner on Thursday evening in the Belgian beer brewery “het Anker”, where the locally brewed beer was extensively tested.