CTS Collaborative Transplant Study
August 1, 2003
We would like to share with you a very interesting observation that we made recently in the context of the sCD30 project. As you may recall, HLA matching has traditionally shown a strong influence in immunized patients with pretransplant anti-HLA antibodies, but the impact of matching in nonsensitized patients has been relatively small. We have now discovered that patients with high sCD30 show a very strong HLA matching effect even in the absence of preformed antibodies (Figure 1, right half, p=0.0001). In patients with low pretransplant sCD30 (left half), the correlation of matching with graft outcome is only of borderline statistical significance.
This finding suggests that patients on the transplant waiting list should be tested for sCD30, and that the pretransplant sCD30 status should be considered when cadaver kidneys are allocated. Evidently, recipients with a high pretransplant sCD30 benefit greatly from HLA well matched grafts whereas those with a low sCD30, in the absence of anti-HLA antibodies, can tolerate relatively poor match grades.
We have reported previously on the overall impact of sCD30, and on the influence of ELISA-detected anti-HLA antibodies as well as IgG-anti-Fab antibodies. A recent multivariate analysis showed that these three factors act largely independently and additively. The combined consideration of sCD30 and ELISA-reactive antibodies against HLA class I and HLA class II is illustrated in Figure 2.
There is an impressive difference in outcome between patients with low sCD30 (indicated on the graph as sCD30-) and a negative ELISA result against both HLA class I and II (I-, II-), compared to recipients with a high pretransplant sCD30 (sCD30+) and positive ELISA anti-HLA class I and II reactivity (I+, II+). Patients who are positive for anti-HLA and negative for sCD30, or vice versa, have an intermediate graft outcome (Figure 2).
A maximal differentiation of results is achieved when, in addition to the sCD30 and anti-HLA results, IgG-anti-Fab activity of the last pretransplant serum is considered. High IgG-anti-Fab activity has been found previously to be associated with excellent graft outcome. As shown in Figure 3, although results are available only for relatively small numbers of patients, those in whom all indicators predict a favorable graft outcome enjoy an exceedingly good 5-year graft survival rate of nearly 90%, in contrast to a 40% rate in recipients with uniformly unfavorable predictive indicators (p=0.0001).
For an exact definition of the relative impact of each of these indicators, it will be necessary to analyze larger numbers of transplants. One goal of the prospective CTS Serum Project is therefore to obtain a better definition of the relative weights of these factors. Your support and cooperation in providing patient sera for these studies is greatly appreciated.
At the May shipping date, we received more than 2,500 samples for the DNA project and 700 samples for the serum project. The cooperative spirit of the CTS community remains remarkably strong. Thanks are due to all colleagues in the clinical units and laboratories who continue to support the CTS laboratory projects. Please join if you are not yet participating.
The next shipping date for the DNA and serum studies is
Thank you very much for your cooperation.
In order to make the new serum testing assays available to all CTS-associated transplant laboratories, we have developed a combination ELISA kit which allows the simultaneous investigation of sCD30, anti-HLA class I, anti-HLA class II, and IgG-anti-Fab. As with all CTS reagents, the reagent kits will be made available at self-cost.
We anticipate that the upgraded software for analysis of your own transplant results via the CTS website will be functional by the time of the next sendout (November 1, 2003). This improved feature will allow for more flexibility. Please let us know your needs and comments.
In a couple of months it will be time again for the yearly "Cancer Confirmation Questionnaire". May I remind you, therefore, to routinely include a check on malignancies in your transplant follow up procedure. If this is done regularly, no extra effort will be required when the completeness of cancer data has to be confirmed.
Thank you for your continued cooperation.
Sincerely yours,