What’s Hot, What’s New at WTC—Basic Science

Abstract

The World Transplant Congress of 2014 presented a broad swath of science that touched on many disparate aspects of cell and organ transplantation, molecular and cellular immunology, systems biology, development, technology and translation into humans. A number of themes emerged this year. B cell biology and antibody chemistry were prominent, as they have been for several years. T cells, co-stimulatory blockade and regulatory T cells continue to dominate many aspects of immune research. Many new aspects of monocyte, macrophage, NK cell and NK T cell development, biology and regulation are now being explored. Diverse aspects of organ injury and the acute and chronic responses to injury are being investigated with new techniques, new targets and a resurgent vigor. Novel advances in xenotransplantation and experimental tolerance garnered much attention. Newer investigations in microbiota and nanotechnology promise significant gains in the near future. Lastly the 'omics of DNA, RNA, proteins, metabolites, bacteria and enzyme actions promise new understanding in biological systems and how to control those systems.Abbreviations: AMR, antibody mediated rejection; Breg, regulatory B cell; CyTOF, flow cytometry timeof-flow mass spectroscopy; DC, dendritic cell; HSC, hematopoietic stem cell; iPS, induced pluripotent stem cell; IRI, ischemia reperfusion injury; MDSC, myeloid derived suppressor cell; MSC, mesenchymal stem cell; TLR, Toll-like receptor B CellsB cells have been an obvious focus of transplant immunology for several decades, being the source of alloantibody and a major effector mechanism during acute and chronic graft rejection. However, over recent years, it has become evident that B cells simultaneously perform many other regulatory activities that are pro-or antiinflammatory or immunogenic. A number of reports demonstrate so-called B regulatory cells (Breg) that serve to dampen the immune response. Abstracts #657 (1), #658 (2), #2141 (3), and #2945 (4) demonstrate diverse roles for Breg in T cell effector memory responses, induction of Treg via TGFb, induction and maintenance viaTIM-1 signaling and promoting engraftment of hematopoietic stem cells, respectively. The implications of these reports are that indiscriminate depletion of B cells, such as with anti-CD20 mAbs, may actually be detrimental for graft survival by disrupting important regulatory pathways. These reports also identify potential targets for enhancing Breg presence, numbers and/or function; however, the diversity of Breg phenotypes currently precludes the ability to definitively identify this subset.Conversely, there are B helper subsets that promote inflammation and immunity and are distinguished by the expression of TIM-4 (Abstract #1413 (5)). This report identifies a potential target for depleting or inhibiting B helper function. Conversely, enhancing B helper function may improve immune responses to vaccines, cancer or microbial pathogens.Investigation of antibody function shows that some patients have immunoglobulins that recognize an u...

Moving Biomarkers toward Clinical Implementation in Kidney Transplantation

“…A biomarker comprised of a refined 13-gene set accurately predicted impending fibrosis at 12 months, predicted graft loss, independent of simultaneous ACR was validated in external cohorts, which included for-cause biopsies, 12,16 and was independently associated with histologic progression and graft loss. 116 Together, these genomic analyses suggest that, if transcriptome assessments were performed on surveillance or forcause biopsies, prognostic gene sets could risk stratify allografts for histologic progression or graft loss and thereby, guide treatment decisions. Ultimately, prospective studies will be required to test whether therapeutic interventions on the basis of biopsy-derived molecular signatures will improve outcomes compared with therapeutic interventions driven by results of standard histology.…”