CTS Collaborative Transplant Study
Dear Colleague
I hope you are all in good health in these critical days during which our transplant programs severely suffer under the Covid-19 pandemic. Your continued support of the Collaborative Transplant Study is therefore all the more appreciated.
In this Newsletter, I would like to share with you preliminary findings that can be generated from the CTS database regarding the impact of donor-specific HLA antibodies (DSA) in kidney transplantation. Four years ago, we started asking you about data on pre- and post-transplant DSA detected by sensitive single antigen bead technology. Many of you supplied us with this information, also on transplantations from previous years. Approximately three quarters of the pre-transplant and two thirds of the post-transplant DSA data are from the last four years.
As illustrated in Figure 1, pre-transplant DSA have a substantial impact on survival of deceased donor kidney transplants. Although statistically significant, a less pronounced DSA effect is visible in living donor transplantations, most probably due to better organ quality and the possibility of detailed compatibility testing and careful evaluation of the related rejection risk.
Desensitization is practiced widely in DSA-positive cases and appears to be useful in deceased donor kidney transplantation, whereas a positive influence of desensitization cannot be demonstrated in DSA-positive recipients of living donor kidneys with the so far available limited data (Figure 2).
Both in recipients of first and re-transplants, the pre-transplant presence of DSA is associated with significantly impaired survival of deceased donor kidney transplants (Figure 3). Please note the high incidence of DSA-positive cases among recipients of re-transplants compared to first transplants (27.4% versus 6.0%).
As shown in Figure 4, there is a strong influence of pre-transplant DSA in patients with panel reactive cytotoxic antibodies (PRA) whereas the DSA effect does not reach statistical significance in patients without PRA. This finding is in agreement with a previous CTS Serum Study report in which pre-transplant DSA detected in the highly sensitive single-antigen testing were not associated with kidney graft loss, if the patient did not possess, in addition, cytotoxic or ELISA-reactive HLA antibodies in his serum (Transplantation 91:883, 2011; doi: 10.1097/TP.0b013e3182100f77). A further CTS publication indicated that, even in patients with cytotoxic or ELISA-reactive HLA antibodies, the pre-transplant DSA harm renal transplants only if the patient has a pre-activated immune system as measured by high serum levels of soluble CD30 (EBioMedicine 9:366, 2016; doi: 10.1016/j.ebiom.2016.06.006). Altogether these findings suggest that exclusion of donor organs carrying ‘unacceptable’ HLA based exclusively on single antigen testing is not justified; additional information on the patient’s immune state is necessary.
In contrast to pre-transplant testing, previous data from the CTS Serum Study indicated that monitoring of post-transplant DSA by single antigen methodology is of great clinical relevance (Transplantation 99:1976, 2015; doi: 10.1097/TP.0000000000000672), whereas cytotoxicity and no longer available ELISA proved to be of limited value in clinical routine due to insufficient sensitivity. The information received through the CTS forms confirms that post-transplant DSA is a strong predictor of impaired outcome (Figure 5).
The findings presented in this Newsletter are another example of the strength of the cooperation within the Collaborative Transplant Study. Within a relatively short time period, valuable information on the impact of DSA was obtained in more than 15,000 kidney transplantations. Please continue to contact us with proposals for CTS analysis. During the last years, several CTS publications could be accomplished with suggestions from your side.
The next shipping date of Serum and DNA is
June 15/16.
Thank you very much for your continued support of the CTS.
Sincerely yours,
Caner Süsal