Donor-specific antibody (DSA) responses against human leukocyte antigen (HLA) proteins mismatched between kidney transplant donors and recipients cause allograft loss. The rules governing the immunogenicity of non-self donor HLA are poorly understood. Using single-cell, molecular, structural, and proteomic techniques, we profiled the HLA-specific B cell response in the kidney and blood of a transplant recipient with antibody-mediated rejection (AMR).
View Article and Find Full Text PDFExperience from human renal allotransplantation informs us that disturbances in serum calcium and phosphate levels are relatively common. Post-transplant hypercalcemia is associated with an increased risk of recipient mortality, but not of graft loss or nephropathy, and post-transplant hyperphosphatemia with an increased risk of both recipient mortality and death-censored graft failure, but neither post-transplant hypocalcemia nor hypophosphatemia is associated with adverse outcome. Studies after pig-to-nonhuman primate kidney xenotransplantation have demonstrated consistent supranormal serum calcium and subnormal serum phosphate levels.
View Article and Find Full Text PDFCurr Opin Organ Transplant
December 2021
Purpose Of Review: Murine studies have established that uterine natural killer (uNK) cells are critical regulators of normal placentation and fetal development in mammals. However, the biology of uNK cells in humans remains poorly understood. This ignorance represents a costly knowledge gap, as disordered placentation is thought to underpin a variety of pregnancy complications that impact maternal and neonatal health.
View Article and Find Full Text PDFPig kidney xenotransplantation has the potential to alleviate the current shortage of deceased and living human organs and provide patients with end-stage renal disease with a greater opportunity for long-term survival and a better quality of life. In recent decades, advances in the genetic engineering of pigs and in immunosuppressive therapy have permitted the resolution of many historical obstacles to the success of pig kidney transplantation in nonhuman primates. Pig kidney xenotransplantation may soon be translated to the clinic.
View Article and Find Full Text PDFExpression of and is tightly regulated in developing T cells to mediate TCR gene assembly. Here we have investigated the molecular mechanisms governing the assembly and disassembly of a transcriptionally active RAG locus chromatin hub in CD4CD8 thymocytes. and gene expression in CD4CD8 thymocytes depends on and promoter activation by a distant antisilencer element (ASE).
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