The 2016 extramural meeting was held in Maastricht, the Netherlands, February 26, 2016, organised by Marcel Tilanus and his colleagues.
This year’s extra mural meeting was opened by Sebastiaan Heidt from the ETRL who discussed the pilot on patient-based external proficiency testing (EPT) cases. First, the paper-based EPT that was sent around in July 2015 was discussed. The results from this exercise showed a striking diversity in the advice on whether the transplant could go ahead or not. Some important issues came up, such as what to do in case a crossmatch without DTT is positive, the crossmatch with DTT is negative, and no information is available on autologous crossmatch results. Furthermore, there was lots of discussion on how to deal with HLA antibodies detected by Luminex only in case of a negative crossmatch. Some practical issues, such as how to deal with the prozone effect in Luminex assays were discussed. It was clear that center-specific policies on the value of antibodies detected by Luminex only are quite different. Next, the patient-based EPT on actual samples used for crossmatching was discussed. Also here, it was clear that there was quite some difference in the acceptance of organs on immunological grounds, again mainly based on antibodies detected by Luminex only.
Based on the experience of these two types of patient-based EPT schemes, it was decided that only the paper-based EPT will be part of the ETRL EPT scheme from now on. The lack of patient information in the virtual cases of the sample-based scheme was considered a crucial omission for a proper interpretation of the results. All centers are strongly encouraged to send in their interesting patient cases in an anonymised way for the upcoming paper-based EPT exercises.
Next, Yvonne Zoet of the ETRL showed updates and new functionalities of the web-based tool for EPT data. First she introduced the new calculators, for vPRA, and for donor frequencies for ETKAS, heart and AM patients. These calculators are based on the HLA data of 6870 deceased donors within Eurotransplant between 2010 and 2014. The calculators are available on the ETRL website. Next, some changes in the EPT website were shown. In short: It is now possible to enter HLA-DNA typing techniques. Furthermore, one can enter some extra splits in HLA typing (like DR17, DR18). A new page has been added with all information “about EPT”, including rules, the manual, HLA-typing of serum donors etc. Entering data on PRA categories in Screening Detection has also been changed, in order for CDC (and FCM) analysis to be performed on basis of consensus. Certificates will be adapted further so that a clear difference between technique based (screening detection per technique and screening identification; typing and cross matching per technique) and interpretation based (patient cases and final results of cross match and screening detection) certificates can be issued.
News from the TTAC
The third topic was presented by Sebastiaan Heidt and covered the most important points that were discussed during the Tissue Typers Advisory Committee in January 2016. One policy and one recommendation were proposed to the ET board. Policy P-TTAC01.16 concerned the change of outdated serum after 180 days instead of the current 150 days for logistical reasons, and has already been approved by the ET board. Recommendation R-TTAC02.16 concerned mandatory donor retyping in the recipient center, and was not approved by the board. The TTAC will discuss in the next meeting whether mandatory retyping should be proposed in case of immunized recipients only.
Other points discussed in the TTAC meeting were also shown. In case a retyping is performed in the recipient center, leading to a discrepant tissue typing, ET will notify donor and recipient center, who will have to come to a consensus HLA typing together. The ETRL will perform a reference typing in case the two centers do not come to an agreement. Furthermore, not all changes in HLA will be regarded as an SAE anymore. An SAE will only be filed when the newly found HLA antigen is in the list of unacceptable antigens of the recipient. It is important to realize that the filing of an SAE is merely for registration purposes and not a reprimand in any way.
The forthcoming introduction of the virtual PRA (vPRA) as only indicator for a patient to be sensitized was also discussed. As Yvonne Zoet already showed, the new vPRA calculator has already been published on the ETRL website. This calculator will soon be implemented into ENIS. The vPRA will solely be based on unacceptable antigens registered by the tissue typing center (TTC), and will not be based on antibody specificities. A possibility to send in bulk PRA and HLA data is already available from the ET member site and will soon be complemented by the possibility to transfer unacceptable antigen data in bulk.
A final point that was discussed was what resolution HLA data is minimally required to communicate to ET, and whether Bw4/Bw6 data should be mandatorily registered as well. The minimal requirement for HLA typing to be communicated to ET has been set by the TTAC at the serological split level (with the exception of HLA-B14). During the extramural meeting, the relevance of making reporting of Bw4/Bw6 data mandatory was discussed. Conclusion from this discussion is that Bw4/Bw6 reporting should not become mandatory, and that no Bw4 should be reported in case of HLA-A23, -A24, -A25 or -A32 is found in the typing of this patient or donor. Reporting of Bw4/Bw6 based on HLA-B is recommended.
Towards epitope matching
Next on the program was Frans Claas from the ETRL who showed why the tissue typing community should gradually start to make the transition from HLA antigen or allele typing to HLA epitope typing. It is very important to prevent the formation of HLA-specific antibodies, since many patients will require an additional transplant at some stage in their life. Matching on the level of antibody epitopes will aid in prevention of HLA antibody induction. A second important aspect on HLA epitopes is that it can aid in defining acceptable antigens for those patients who do have circulating HLA-specific antibodies. Frans invited all TTC to join in the upcoming 17th international HLA and immunogenetics workshop, of which one of the components will be mapping of serological HLA epitopes.
The extra mural meeting was completed by two scientific presentations, of which the first was presented by Dave Roelen from Leiden. He presented data on the comparison between single antigen Luminex kits from two vendors, as well as two kits capable of detecting complement-binding antibodies from the same two vendors. The results that were presented showed a rather good concordance between the kits from the two vendors, both the regular HLA antibody kits, as well as the complement-binding antibody kits.
The second scientific lecture was by Joris Vanderlocht from Maastricht who showed exciting ongoing work on the relative immunogenicity of HLA-DRB3 antigens to induce antibody responses. His data suggested that not all HLA-DRB3 antigens are equally immunogenic. Their research further focussed on the expression levels of the different HLA-DRB3 antigens and will in the future also be focussed on the antibody epitopes that are present on the molecules.