Transplant Tolerance 'Signature' Identified
It is hoped that the research will lead to doctors being able to deliver more personalized care to kidney transplant patients in the future, by safely modifying the amount of medication patients take while preventing rejection of the donor organ.
A team of researchers at King's College London and across Europe have identified a ‘full set’ of immunological markers in the blood, which could be used to predict whether an individual’s kidney transplant will be a long-term success or whether it will fail.
It is hoped that the research will lead to doctors being able to deliver more personalized care to kidney transplant patients in the future, by safely modifying the amount of medication patients take while preventing rejection of the donor organ.
The research was led by King's College London with its MRC Centre for Transplantation and the National Institute for Health Research comprehensive Biomedical Research Centre, a partnership between King's and Guy’s and St Thomas’ NHS Foundation Trust. Seven European institutions collaborated in this multicenter study: King’s College London, Imperial College London and Oxford University in the UK, Institut de Transplantation et de Recherche en Transplantation (ITERT) in France, Université Libre de Bruxelles in Belgium, and Charité - Universitätsmedizin Berlin and Miltenyi Biotec in Germany.
The team of European researchers studied kidney transplant tolerance - how accepting the body is of a foreign organ. They studied 11 kidney transplant patients from across Europe who had seemed to develop tolerance of the donor organ naturally, as well as stable transplant patients who were taking varying amounts of immunosuppression (drugs to control their immune response), patients who were taking such drugs but showing signs of chronically rejecting the donor organ, and a group of healthy volunteers. They carried out a range of detailed laboratory tests to see if they could identify any characteristics in the blood that differentiated the group who were not taking medication and had become tolerant of their transplanted organ.
Dr. Maria Hernandez-Fuentes, senior author of the study, at King’s said, “Astonishingly there are rare individuals who seem to develop tolerance naturally after a kidney transplant. This is usually only revealed when unexpectedly organ rejection does not take place if they have to stop taking their immunosuppressive drugs for some reason. We worked with renal units across Europe to identify this small number of patients and then sought to involve them in our research.”
'Tolerance fingerprint'
Dr. Hernandez-Fuentes and the team were able to demonstrate that these individuals share a ‘tolerance fingerprint,’ a specific ‘full set’ of immunological markers in the blood. This group displayed an expansion of peripheral blood B and NK lymphocytes, fewer activated CD4+ T cells, absence of donor-specific antibodies, direct-pathway donor-specific hyporesponsiveness, and a high ratio of FoxP3/αmannosidase gene expression. In addition, microarray analysis revealed tolerant recipients have a B cell bias in differentially expressed genes and their associated molecular pathways.
The European team’s findings were subsequently corroborated in another cohort of kidney transplant recipients that was independently recruited by the Immune Tolerance Network in the United States.
Every year, approximately 3,500 organ transplants take place in the UK, 1,550 of these are kidney transplants. The average lifespan of a transplanted kidney is 12 years, rising to around 20 years in some cases if the kidney is from a living donor.
Dr. Rachel Hilton, a renal consultant at Guy’s Hospital, home to the UK’s second largest kidney transplant service, and co-author in the study said, “Recipients of kidney transplants take immunosuppression drugs for the rest of their lives to prevent their own immune systems from rejecting the transplanted organ, even though these drugs may also bring serious health complications.”
“The findings of this study are really exciting, and we hope now that they have been validated, we will be able to screen patients for these markers, and perhaps identify small numbers who can safely withdraw or reduce their use of immunosuppressants. It is vitally important though, that transplant recipients do not stop taking their immunosuppression on the back of these research findings, as any reduction in medication needs to be very carefully managed and clinically monitored.”
This study is part of an exciting and wide ranging program of liver, kidney, and bone marrow transplantation research taking place across King’s Health Partners. Professor Robert Lechler, Executive Director of King’s Health Partners and also a senior author of the study said, “'At King’s Health Partners we are at the leading-edge of transplant research internationally, with a strong focus on translational research. We are studying a number of areas, ranging from ways to improve the matching of patients to donor organs to improve the lifespan of donated organs, ways to better predict transplant outcomes, and to personalize the amount of immunosuppression individual transplant patients need to take. This translational research will bring real benefits to our patients and others more further afield.”
Illustration: King’s College London.
Read more…
King’s College London News Release (05/25/10)
EurekAlert! (05/24/10)
Abstract (Journal of Clinical Investigation; 120(6), 1862-1872 (06/01/10))
Abstract (Journal of Clinical Investigation; 120(6), 1848-1861 (06/01/10))
Abstract (Journal of Clinical Investigation; 120(6), 1836-1847 (06/01/10))
Abstract (Journal of Clinical Investigation; 120(6), 1803-1806 (06/01/10))
It is hoped that the research will lead to doctors being able to deliver more personalized care to kidney transplant patients in the future, by safely modifying the amount of medication patients take while preventing rejection of the donor organ.
The research was led by King's College London with its MRC Centre for Transplantation and the National Institute for Health Research comprehensive Biomedical Research Centre, a partnership between King's and Guy’s and St Thomas’ NHS Foundation Trust. Seven European institutions collaborated in this multicenter study: King’s College London, Imperial College London and Oxford University in the UK, Institut de Transplantation et de Recherche en Transplantation (ITERT) in France, Université Libre de Bruxelles in Belgium, and Charité - Universitätsmedizin Berlin and Miltenyi Biotec in Germany.
The team of European researchers studied kidney transplant tolerance - how accepting the body is of a foreign organ. They studied 11 kidney transplant patients from across Europe who had seemed to develop tolerance of the donor organ naturally, as well as stable transplant patients who were taking varying amounts of immunosuppression (drugs to control their immune response), patients who were taking such drugs but showing signs of chronically rejecting the donor organ, and a group of healthy volunteers. They carried out a range of detailed laboratory tests to see if they could identify any characteristics in the blood that differentiated the group who were not taking medication and had become tolerant of their transplanted organ.
Dr. Maria Hernandez-Fuentes, senior author of the study, at King’s said, “Astonishingly there are rare individuals who seem to develop tolerance naturally after a kidney transplant. This is usually only revealed when unexpectedly organ rejection does not take place if they have to stop taking their immunosuppressive drugs for some reason. We worked with renal units across Europe to identify this small number of patients and then sought to involve them in our research.”
'Tolerance fingerprint'
Dr. Hernandez-Fuentes and the team were able to demonstrate that these individuals share a ‘tolerance fingerprint,’ a specific ‘full set’ of immunological markers in the blood. This group displayed an expansion of peripheral blood B and NK lymphocytes, fewer activated CD4+ T cells, absence of donor-specific antibodies, direct-pathway donor-specific hyporesponsiveness, and a high ratio of FoxP3/αmannosidase gene expression. In addition, microarray analysis revealed tolerant recipients have a B cell bias in differentially expressed genes and their associated molecular pathways.
The European team’s findings were subsequently corroborated in another cohort of kidney transplant recipients that was independently recruited by the Immune Tolerance Network in the United States.
Every year, approximately 3,500 organ transplants take place in the UK, 1,550 of these are kidney transplants. The average lifespan of a transplanted kidney is 12 years, rising to around 20 years in some cases if the kidney is from a living donor.
Dr. Rachel Hilton, a renal consultant at Guy’s Hospital, home to the UK’s second largest kidney transplant service, and co-author in the study said, “Recipients of kidney transplants take immunosuppression drugs for the rest of their lives to prevent their own immune systems from rejecting the transplanted organ, even though these drugs may also bring serious health complications.”
“The findings of this study are really exciting, and we hope now that they have been validated, we will be able to screen patients for these markers, and perhaps identify small numbers who can safely withdraw or reduce their use of immunosuppressants. It is vitally important though, that transplant recipients do not stop taking their immunosuppression on the back of these research findings, as any reduction in medication needs to be very carefully managed and clinically monitored.”
This study is part of an exciting and wide ranging program of liver, kidney, and bone marrow transplantation research taking place across King’s Health Partners. Professor Robert Lechler, Executive Director of King’s Health Partners and also a senior author of the study said, “'At King’s Health Partners we are at the leading-edge of transplant research internationally, with a strong focus on translational research. We are studying a number of areas, ranging from ways to improve the matching of patients to donor organs to improve the lifespan of donated organs, ways to better predict transplant outcomes, and to personalize the amount of immunosuppression individual transplant patients need to take. This translational research will bring real benefits to our patients and others more further afield.”
Illustration: King’s College London.
Read more…
King’s College London News Release (05/25/10)
EurekAlert! (05/24/10)
Abstract (Journal of Clinical Investigation; 120(6), 1862-1872 (06/01/10))
Abstract (Journal of Clinical Investigation; 120(6), 1848-1861 (06/01/10))
Abstract (Journal of Clinical Investigation; 120(6), 1836-1847 (06/01/10))
Abstract (Journal of Clinical Investigation; 120(6), 1803-1806 (06/01/10))