Author Interviews, JAMA, Kidney Disease, Transplantation / 26.08.2019 Interview with: Alexandre Loupy, MD PhD Nephrologist, Department of Nephrology & Kidney Transplantation Necker Hospital, Paris Head of the Paris Transplant Group (Inserm) What is the background for this study? Response: The lack of organs for kidney transplantation is a major public health problem across the world, due to its attributable mortality and excess cost to healthcare systems while waitlisted patients are maintained on chronic dialysis. Nearly 5,000 people in the US and 3,500 people in Europe die each year while waiting for a kidney transplant. Yet in the US, over 3,500 donated kidneys are discarded annually, representing almost 18% of the available organs, while the discard rate in France is only 6,8%, though these countries have similar organ allocation systems and offer the same treatments to patients after transplant. We thus compared the use of donated kidneys in the US to France from 2004-2014 in much more depth, using a new approach based on validated analytic methods and computer simulation.  (more…)
Author Interviews, Microbiome, Transplantation / 23.06.2016 Interview with: Maria-Luisa Alegre, MD, PhD Professor of medicine University of Chicago What is the background for this study? What are the main findings? Response: Most of the research that investigates why/how transplanted organs are rejected has focused on the genetic disparities between the donor and the recipient. Foreign proteins in the donor organ are recognized by the immune system of the host, which becomes activated to reject the transplanted organ. This is why transplant recipients need to take immunosuppressive medications for the rest of their lives. Whether environmental factors, in addition to genetic factors, can also affect how the immune system is activated by the transplanted organ is much less understood. In particular, the microbiota, the communities of microbes that live on and in our body, is distinct in each individual and is known to affect the function of the immune system in diseases ranging from autoimmunity to cancer. Using mouse models of skin and heart transplantation, we investigated if the microbiota was an environmental factor that could affect the speed at which the immune system rejects a transplanted organ. We found that the microbial communities that colonize the donor and the host fine-tune the function of the immune system and control the strength with which the immune system reacts to a transplanted organ. (more…)
Author Interviews, Personalized Medicine, Transplantation, University of Pennsylvania / 05.10.2015 Interview with: Brendan J. Keating, DPhil Assistant professor of Transplant Surgery Penn Medicine Medical Research: What is the background for this study? What are the main findings? Response: Genetic studies in transplantation have been plagued by small samples and very complex phenotypes/outcomes of patients. Transplanted individuals are typically on potent immunosuppression drugs for the rest of their lives, as they have 3.5 million to 10 million variants difference from an unrelated transplanted donor organ. Such populations would certainly benefit from large well-powered genetic studies but only 3 transplant genome-wide genotyping studies comprising a few hundred individuals have been published. The papers outline the resources in hand for the International Genetics & Translational Research in Transplantation Network, comprising 22 studies to date (since the publication it has now expanded to 25 studies and > 32,000 subjects with genome-wide genotyping data). We show significant statistical power in iGeneTRAiN to detect main effect association signals across regions such as the MHC region (which harbors the HLA Class I/II regions which are well established to associate with transplantation outcomes). We also show strong genome-wide power to detect transplant outcomes that span all solid organs including graft survival, acute rejection, new onset of diabetes after transplantation (fast becoming the most common comorbidity post-transplantation), and delayed graft function (to date we have looked at this in kidney transplant patients only). We show that iGeneTRAiN is statistically powered to deliver pioneering insights into the genetic architecture of transplant-related outcomes across a range of different solid-organ transplant studies. The transplant specific GWAS array that we designed (described in depth in the Genome Medicine paper) show that the coverage in key transplant associated regions is much higher than conventional arrays, and we describe the ‘imputation’ pipeline to expand the 780,000 or so variants examined in any given individual to > 15 millions of variants using whole genome sequencing reference datasets. (more…)