Source: https://www.nature.com/articles/nrg.2017.12?error=cookies_not_supported&code=8d81f21e-e62d-4c7b-8ccd-d5bfb03098ea
Timestamp: 2019-04-20 19:36:17+00:00

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Joshua Y. C. Yang completed his B.S. in Bioengineering and Biotechnology at the University of California San Diego (USA) and his Master of Translational Medicine degree at the University of California Berkeley and the University of California San Francisco. He is now an M.D.–Ph.D. student at the Johns Hopkins University School of Medicine (Maryland, USA), where he works with Minnie M. Sarwal on the study of and the development of diagnostic biomarkers for transplant-associated outcomes. Joshua Y. C. Yang's homepage.
Minnie M. Sarwal is a professor in the Department of Surgery at the University of California San Francisco (USA) where she is the Director of the Precision Transplant Medicine Initiative. She received her M.D. from Calcutta Medical College, India, and her Ph.D. in Molecular Genetics from the University of Cambridge, Cambridge, UK, where she worked with the Nobel Laureate Sydney Brenner. She also obtained a Diploma in Child Health from the Royal College of Physicians (London, UK), is a member of the Royal College of Physicians (MRCP) and has been honoured with a Fellowship from the Royal College of Physicians (FRCP). Her research focuses on the immunological basis of graft dysfunction and acceptance using genomic and proteomic approaches. Minnie M. Sarwal's homepage.
Ever since the discovery of the major histocompatibility complex, scientific and clinical understanding in the field of transplantation has been advanced through genetic and genomic studies. Candidate-gene approaches and recent genome-wide association studies (GWAS) have enabled a deeper understanding of the complex interplay of the donor–recipient interactions that lead to transplant tolerance or rejection. Genetic analysis in transplantation, when linked to demographic and clinical outcomes, has the potential to drive personalized medicine by enabling individualized risk stratification and immunosuppression through the identification of variants associated with immune-mediated complications, post-transplant disease or alterations in drug-metabolizing genes.
Allograft transplantation is a genetically complex medical scenario that requires the consideration of the genomes of two individuals: those of the donor and the recipient.
Alloimmunity and histocompatibility are dependent on human leukocyte antigen (HLA) variants, but the role of non-HLA factors has been increasingly recognized in recent years.
The majority of genetic studies in the transplantation field have focused on variants in candidate genes, while genome-wide association studies (GWAS) and exome sequencing have just begun to be used in this field.
Diagnostic technologies in the transplant field have become increasingly sophisticated alongside the advances in genetic technologies, and they are starting to be used by clinicians.
Much larger genetic studies than have previously been conducted will be needed to identify associations with the wide variety of post-transplant outcomes in the many types of organ transplants. Initiatives to collect tissue and data from multiple centres, such as iGeneTRAiN, have been started to address the issue of low sample numbers and non-uniform characterization.
The integration of multiple omics technologies will be needed to gain a deeper understanding of the mechanisms and pathways underlying transplant outcomes.
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Division of Transplant Surgery, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143, USA.
M.M.S. is the founder of ORGAN-I (California, USA), a spin-out company from Stanford University (California, USA) that developed the kSORT assay for the assessment of acute kidney transplant rejection using a blood test. M.M.S. is a scientific advisory board member for Immucor (Georgia, USA), a diagnostic company that is commercializing the kSORT assay.
Correspondence to Minnie M. Sarwal.
A state of immune unresponsiveness and quiescence towards specific antigens. In the case of transplantation, tolerance is directed towards donor-specific antigens.
A term that describes tissues that are of distinct genetic origins and thus often immunologically incompatible.
An episode of sudden deterioration in allograft function as a result of either antibody-mediated rejection or T cell-mediated rejection, which result from different molecular processes.
A graft between two individuals who are genetically identical, such as in the case of monozygotic twins.
Grafts from another member of the same species, such as in the case of organ transplantation, as opposed to grafts from a member of a different species (xenograft) or from the recipient themselves (autograft).
Damage to an organ as a result of a transient inadequate blood supply.
A state in which renal failure persists after transplantation, thus necessitating dialysis.
(NODAT). The occurrence of diabetes mellitus after transplantation in a patient who did not have the disease before. This occurs in 2–53% of all solid-organ transplants and is due in part to the immunosuppressive medications that are used to prevent transplant rejection.
An immune response to antigens that are both non-self and from the same species.
The ability of a host to recognize allogeneic tissue as distinct from its own.
A component of the innate immune system that can be activated by antigen-bound antibodies.
The mechanisms by which T cells and B cells are rendered non-reactive to an antigen, typically a self-antigen, in the primary lymphoid organs.
The mechanisms by which T cells and B cells are rendered non-reactive to an antigen outside the primary lymphoid organs.
(Treg cells). A subpopulation of T cells that are generally immunosuppressive rather than pro-inflammatory.
The quality of being able to induce immunological tolerance.
In the context of this Review, an outcome measured as the time until either graft failure (when referring to allograft survival) or patient mortality (when referring to recipient survival).
The rates at which sequenced regions have a low level of confidence in excluding possible allelic variations.
Sequencing of all protein- coding regions in the genome.
Sequencing of the complete DNA genetic material in a cell or organism.
(GVHD). Largely specific to haematopoietic stem cell transplantation, it is a medical complication in which immune cells in the donated tissue reject and attack the host cells.
(KIRs). Receptors that are expressed on the surface of natural killer cells and modulate their cytotoxic activity by recognizing major histocompatibility complex class I allelic variants.
(MICA). A cell-surface antigen that is recognized by the receptor NKG2D, which is found on natural killer cells, T cells and macrophages.
(miHAs). The distinct peptide products of polymorphic genes that distinguish the recipient from the donor.
Self-antigens that are not clonally deleted in the thymus owing to low surface presentation on antigen-presenting cells (APCs). These self-antigens can be expressed by APCs following differential processing by inflammatory proteases.
The lowest levels of a pharmaceutical present in the blood before the next dose.
Refers to the functional characteristics of the transplanted organ, which typically decrease over time owing to immune injury and subsequent fibrosis. Biomarkers of function include serum creatinine levels for kidney transplants, pulmonary function tests for lung transplants, and bile or specific enzyme levels for liver transplants.
An analytical condition in which association tests are confined to subgroups that share common HLA alleles.
The single-nucleotide polymorphism (SNP) within any given locus in a genome-wide association study that has the strongest statistical significance.
(IFTA). Historically called chronic allograft nephropathy, it is the most common cause of long-term renal graft failure and is characterizedby the gradual deterioration of graft function.
The study of how an organism affects a pharmaceutical agent, one aspect of which is the metabolism of the drug. The levels of immunosuppressive drugs are highly affected by individual variability in specific metabolizing enzymes.
A bacterial infection of the kidney. Individuals who are taking immunosuppressive medication are at an increased risk of developing this condition.
Grafts from one species to a different species, such as in the case of heart valve replacement, which often involves the transplantation of heart valves from pigs into humans.
A class of proteins implicated in processes such as ageing, apoptosis and inflammation.

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