July 1, 2002
The discovery that soluble CD30 (sCD30), a Th2 immune response activation marker, is a strong pretransplant indicator for graft rejection risk, is another example of successful collaboration within the CTS study. Without the support of the colleagues at the 41 transplant centers, who contributed pretransplant sera to the CTS serum testing project, we would not have been able to elucidate the relevance of this important factor. The most current update on sCD30 in cadaver kidney transplantation is illustrated in Figure 1.
Figure 1
Patients with low sCD30 (<100) have a strikingly better graft survival rate than patients with high sCD30 (=100) (p<0.0001). In contrast to preformed lymphocytotoxic antibodies (PRA), which indicate an increased risk of acute rejection, sCD30 is an indicator of both acute and chronic rejection. Additional analysis resulted in evidence that sCD30 affects graft rejection but not patient survival. Most importantly, sCD30 can be used to identify "high responders" even among recipients who do not possess any preformed lymphocytotoxic antibodies (Figure 2).
Figure 2
The combined use of PRA and sCD30 allows a much improved pretransplant risk assessment (Figure 3).
Figure 3
In the future, it will be of interest to determine whether certain immunosuppressive regimens can overcome the high rejection rate in high immunological responders.
An important difference compared to the influence of PRA is that the sCD30 effect is not influenced by the degree of HLA matching. The CTS data have shown consistently that the deleterious effect of PRA does not apply to transplants that are well-matched for HLA-A, -B, -DR. sCD30, however, maintains a strong influence on graft survival even in transplants with 0 or 1 HLA-A+B+DR mismatches (Figure 4).
Figure 4
Additionally, we have obtained preliminary evidence showing that testing for sCD30 may be equally informative in the posttransplant period. It will become very important, in the next stage, to confirm these preliminary findings by expanding testing to larger numbers of patients.
Many CTS participants have responded positively to my appeal for a collaborative serum testing project that will seek to clarify the pre- and posttransplant relationships between PRA, sCD30, HLA, and graft rejection. One can view this as a classical example for the necessity of multicenter collaboration. Because interactions of multiple factors must be analyzed, a very large data set must be established. I would therefore like to make an appeal for your active support. We continue to be interested in all pretransplant sera on transplants performed during the last 10 years. Because sCD30 is a relatively large biological molecule, it is not easily degraded and longterm frozen storage is well tolerated. If you have sera (e.g., "old" crossmatch sera) stored in your freezer, please make them available for testing. As a bonus, you will receive the test results free of charge. In the second part of the serum project, we are focusing on prospective transplants with the aim of testing both pre- and posttransplant serum samples. A schedule for obtaining sera at certain intervals is attached to this newsletter. I would be grateful if you would discuss the new project with the members of your transplant team. Your active participation will be most welcome.
In addition to kidney transplants, the study will include heart, liver, and pancreas transplants. If available, please send frozen-stored pretransplant sera for testing. We would also be grateful if you would arrange for participation in the prospective study.
It has been gratifying to see that the new PowerPoint feature on the CTS website has motivated many more users to include CTS graphs in their conference presentations. We welcome any further suggestions you may have for improvement of the website. Currently, we are working on an upgraded layout which will become operative in a few weeks. The individual center statistics have been updated for this newsletter release so that your own center's website graphs are up-to-date again. Please be sure to provide updates on transplant follow up in a timely fashion, otherwise your website center analysis will be out of date
Because so much space has been devoted to the serum testing project, I would like to stress that the DNA project is of course still being continued and is proceeding very well. More than 2000 samples for DNA testing were sent in during the May 2002 cycle. We have obtained very interesting results and are currently performing confirmation studies and various subset analyses. We will be reporting on the recent DNA findings in a forthcoming newsletter.
The next shipping date, both for the DNA project and the serum testing project, will be
November 19/20, 2002.
Please start collecting material for these studies now!
Thank you for your continued support of the CTS study. I look forward to seeing many of you at the Miami transplant congress in August.
Sincerely yours,
Sera for the sCD30 project were provided by the following centers: Barcelona, Spain (Dr. Martorell); Berlin, Germany (Dr. Schönemann); Budapest, Hungary (Dr. Padanyi); Cape Town, South Africa (Dr. Du Toit); Cardiff, United Kingdom (Dr. Rees); Dallas, USA (Dr. Stastny); Essen, Germany (Dr. Vögeler); Freiburg, Germany (Dr. Lang); Geneva, Switzerland (Dr. Jeannet); Giessen, Germany (Dr. Weimer); Glasgow, United Kingdom (Dr. Farrell); Goteborg, Sweden (Dr. Rydberg); Heidelberg, Germany (Dr. Wiesel); Helsinki, Finland (Dr. Koskimies); Lausanne, Switzerland (Dr. Aubert); Leicester, United Kingdom (Dr. Horsburgh); Leuven, Belgium (Dr. Vanrenterghem); Lexington, USA (Dr. Thompson); Liege, Belgium (Dr. Bouillenne); Ljubljana, Slovenia (Dr. Bohinjec); Mannheim, Germany (Dr. Schnülle); Marburg, Germany (Dr. Lange); Medellin, Columbia (Dr. Garcia); Mexico City, Mexico (Dr. Alberu); Munich, Germany (Dr. Scholz); New York, USA (Dr. Fotino); Phoenix, USA (Dr. Vyvial); Portland, USA (Dr. Norman); Prague, Czech Republic (Dr. Ivaskova); Quebec, Canada (Dr. Roy); Reims, France (Dr. Cohen); Rijeka, Croatia (Dr. Vujaklija-Stipanovic); Rio de Janeiro, Brazil (Dr. Goncalves De Freitas); Seoul, South Korea (Dr. Park); Strasbourg, France (Dr. Tongio); Sydney, Australia (Dr. Doran); Tehran, Iran (Dr. Simforoosh); Turin, Italy (Dr. Curtoni); Ulm, Germany (Dr. Goldmann); Zagreb, Croatia (Dr. Kastelan); Zuerich, Switzerland (Dr. Binswanger).