A5011634251- Renal Transplantation Outcomes and Treatments
- Organ Transplantation Techniques and Outcomes
- Transplantation: Methods and Outcomes
- Xenotransplantation and immune response
- Renal Diseases and Glomerulopathies
- Organ and Tissue Transplantation Research
- Organ Donation and Transplantation
- T-cell and B-cell Immunology
- Complement system in diseases
- Immune Cell Function and Interaction
- Animal Genetics and Reproduction
- Nephrotoxicity and Medicinal Plants
- Hematopoietic Stem Cell Transplantation
- Pancreatic function and diabetes
- Reconstructive Surgery and Microvascular Techniques
- Tissue Engineering and Regenerative Medicine
- Chronic Kidney Disease and Diabetes
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Renal and Vascular Pathologies
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Vasculitis and related conditions
- Liver Disease and Transplantation
- Drug-Induced Hepatotoxicity and Protection
- Diabetes and associated disorders
Massachusetts General Hospital
2016-2025
Harvard University
2016-2025
Mass General Brigham
2018-2024
Harvard University Press
2024
University of Fribourg
2023
Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital
2023
UCLouvain
2023
The University of Sydney
2023
Hudson Institute
2023
Experimental Pathology Laboratories
2022
The XV. Banff conference for allograft pathology was held in conjunction with the annual meeting of American Society Histocompatibility and Immunogenetics Pittsburgh, PA (USA) focused on refining recent updates to classification, advances from working groups, standardization molecular diagnostics. This report kidney transplant details clarifications refinements criteria chronic active (CA) T cell–mediated rejection (TCMR), borderline, antibody-mediated (ABMR). main focus sessions how address...
Significance Statement Kidney involvement may occur in coronavirus disease 2019 (COVID-19), and can be severe among Black individuals. In this study of collapsing glomerulopathy six patients with COVID-19, the authors found that all had variants gene encoding apo L1 (APOL1) are more common those African descent linked by past research to susceptibility non–COVID-19 patients. They no evidence direct kidney viral infection but observed changes expression biopsy samples suggesting mechanism is...
This meeting report from the XV Banff conference describes creation of a multiorgan transplant gene panel by Molecular Diagnostics Working Group (MDWG). Human Organ Transplant (B-HOT) is culmination previous work MDWG to identify broadly useful based on whole transcriptome technology. A data-driven process distilled list peer-reviewed comprehensive microarray studies that discovered and validated their use in kidney, liver, heart, lung biopsies. These were supplemented genes define relevant...
Abstract Recent human decedent model studies 1,2 and compassionate xenograft use 3 have explored the promise of porcine organs for transplantation. To proceed to studies, a clinically ready donor must be engineered its successfully tested in nonhuman primates. Here we describe design, creation long-term life-supporting function kidney grafts from genetically transplanted into cynomolgus monkey model. The was carry 69 genomic edits, eliminating glycan antigens, overexpressing transgenes...
Porcine cells devoid of three major carbohydrate xenoantigens, αGal, Neu5GC, and SDa (TKO) exhibit markedly reduced binding human natural antibodies. Therefore, it is anticipated that TKO pigs will be better donors for xenotransplantation. However, previous studies on using old world monkeys (OWMs) have been disappointing because higher anti-TKO pig antibodies in OWMs than humans. Here, we show long-term survival renal xenografts from express additional transgenes (hTGs) can achieved...
Significance Statement Although corticosteroids are an effective first-line therapy for minimal change disease, relapse, steroid dependence, and intolerance common in this podocytopathy of unknown etiology. The efficacy B cell–targeted therapies some patients suggests autoantibody-mediated This study describes the novel discovery both adults children with disease autoantibodies targeting nephrin, a critical component podocyte slit diaphragm that ensures integrity glomerular filtration...
Xenotransplantation offers a potential solution to the organ shortage crisis. A 62-year-old hemodialysis-dependent man with long-standing diabetes, advanced vasculopathy, and marked dialysis-access challenges received gene-edited porcine kidney 69 genomic edits, including deletion of three glycan antigens, inactivation endogenous retroviruses, insertion seven human transgenes. The xenograft functioned immediately. patient's creatinine levels decreased promptly progressively, dialysis was no...
Since the first attempt of pig-to-primate liver xenotransplantation (LXT) in 1968, survival has been limited. We evaluated a model utilizing α-1,3-galactosyltransferase knockout donors, continuous posttransplant infusion human prothrombin concentrate complex, and immunosuppression including anti-thymocyte globulin, FK-506, methylprednisone, costimulation blockade (belatacept, n = 3 or anti-CD40 mAb, 1) to extend survival. Baboon 1 remained well until postoperative day (POD) 25, when...
Successful xenotransplantation will likely depend, in part, on the induction of immunological tolerance, because high levels immunosuppression otherwise required would have unacceptable side effects. Rapid clearance administered porcine hematopoietic stem cells by primate macrophages has hampered previous attempts to induce tolerance through mixed chimerism across a pig-to-primate barrier. Phagocytosis is normally inhibited binding cell surface protein CD47 macrophage signal regulatory α...
Significance Statement Biomarkers for noninvasive diagnosis of subclinical acute rejection are needed to enable risk-stratification and tailoring immunosuppression kidney transplant recipients. Using RNA sequencing analyses whole blood collected from a cohort recipients at the time surveillance biopsy, authors identified transcriptional signature on basis set 17 genes that accurately detects ongoing rejection. After extensive validation, they developed sequencing-based targeted expression...
Islet transplantation to treat insulin-dependent diabetes is greatly limited by the need for maintenance immunosuppression. We report a strategy through which cotransplantation of allogeneic islets and streptavidin (SA)–FasL–presenting microgels omentum under transient rapamycin monotherapy resulted in robust glycemic control, sustained C-peptide levels, graft survival diabetic nonhuman primates >6 months. Surgical extraction prompt hyperglycemia. In contrast, animals receiving without...
To seek insights into the pathogenesis of chronic active antibody-mediated rejection (CAMR), we performed mRNA analysis and correlated transcripts with pathologic component scores graft outcomes.We utilized NanoString nCounter platform Banff Human Organ Transplant gene panel to quantify on 326 archived renal allograft biopsy samples. This system allowed correlation pathology from same tissue block long-term outcomes.The only score that AMR pathways in CAMR was peritubular capillaritis (ptc)....
BackgroundAcute tubulointerstitial nephritis (AIN) is one of the few causes acute kidney injury with diagnosis-specific treatment options. However, due to need obtain a biopsy for histological confirmation, AIN diagnosis can be delayed, missed, or incorrectly assumed. Here, we identify and validate urinary CXCL9, an IFN-γ-induced chemokine involved in lymphocyte chemotaxis, as diagnostic biomarker AIN.MethodsIn prospectively enrolled cohort pathologist-adjudicated diagnoses, termed discovery...
The XVI-th Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from 19th-23rd September 2022, as a joint meeting with the Canadian Society of Transplantation. In addition to key focus on impact microvascular inflammation and biopsy-based transcript analysis Classification, further sessions were devoted other aspects kidney transplant pathology, particular T cell-mediated rejection, activity chronicity indices, digital xenotransplantation, clinical trials, surrogate...
Backgournd. Peritransplant ischemia/reperfusion injury (IRI) plays a central pathogenic role in nondelayed or delayed kidney allograft function immediately after transplantation and increases the risk of subsequent rejection. Potential therapies targeting specific cytokines complement proteins to limit IRI have failed clinical trials. Monoclonal antibody 107 (mAb107), “pure” (nonactivating) inhibitor archetypal innate immune receptor integrin CD11b, has been shown extend survival nonhuman...
Objective: We describe the first successful penis transplant in United States a patient with history of subtotal penectomy for penile cancer. Background: Penis transplantation represents new paradigm restoring anatomic appearance, urine conduit, and sexual function after genitourinary tissue loss. To date, only 2 transplants have been performed worldwide. Methods: After institutional review board approval, extensive medical, surgical, radiological evaluations were performed. His candidacy...
Fibrosis underlies the loss of renal function in patients with chronic kidney disease (CKD) and transplant recipients allograft nephropathy (CAN). Here, we studied effect an intronic SNP SHROOM3, which has previously been linked to CKD, on development CAN a prospective cohort recipients. The presence rs17319721 allele at SHROOM3 locus donor correlated increased expression allograft. In vitro, determined that sequence containing risk is transcription factor 7–like 2–dependent...
Export Primary renal tubulointerstitial disease resulting from proximal tubule antigen–specific antibodies and immune complex formation has not been well characterized in humans. We report a cohort of patients with distinct, underappreciated kidney by antibrush border failure (ABBA disease). identified ten ABBA who had combination damage, IgG-positive deposits the tubular basement membrane, circulating reactive normal human brush border. All but one also segmental glomerular on biopsy...
Extracellular hemoglobin and cell-free heme are toxic breakdown products of hemolyzed erythrocytes. Mammals synthesize the scavenger proteins haptoglobin hemopexin, which bind extracellular heme, respectively. Transfusion packed red blood cells is a lifesaving therapy for patients with hemorrhagic shock. Because erythrocytes undergo progressive deleterious morphological biochemical changes during storage, transfusion that have been stored prolonged intervals (SRBCs; 35-40 days in humans or...
Interstitial fibrosis, tubular atrophy, and inflammation are major contributors to kidney allograft failure. Here we sought an objective, quantitative pathological assessment of these lesions improve predictive utility constructed a deep-learning-based pipeline recognizing normal vs. abnormal tissue compartments mononuclear leukocyte infiltrates. Periodic acid- Schiff stained slides transplant biopsies (60 training 33 testing) were used quantify specific for interstitium, tubules...
Non-invasive biomarkers of immune checkpoint inhibitor-associated acute tubulointerstitial nephritis (ICI-nephritis) are urgently needed. Because ICIs block pathways that include cytotoxic T lymphocyte antigen 4 (CTLA4), we hypothesized dysregulationpreviously defined in patients with congenital CTLA4 deficiency, including elevated soluble interleukin-2 receptor alpha (sIL-2R) and flow cytometric cell-based markers B cell dysregulation peripheral blood may aid the diagnosis ICI-nephritis.
The renal actions of parathyroid hormone (PTH) promote 1,25-vitamin D generation; however, the signaling mechanisms that control PTH-dependent vitamin activation remain unknown. Here we demonstrated Salt Inducible Kinases (SIKs) orchestrated production downstream PTH signaling. inhibited SIK cellular activity by cAMP-dependent PKA phosphorylation. Whole tissue and single cell transcriptomics both pharmacologic inhibitors regulated a gene module in proximal tubule. increased Cyp27b1 mRNA...
Kidney transplant (KTx) biopsies showing glomerulopathy (TG) (glomerular basement membrane double contours (cg) > 0) and microvascular inflammation (MVI) in the absence of C4d staining donor-specific antibodies (DSAs) do not fulfill criteria for chronic active antibody–mediated rejection (CA-AMR) diagnosis fit into any other Banff category. To investigate this, we initiated a multicenter intercontinental study encompassing 36 cases, comparing immunomic transcriptomic profiles 14 KTx...
The transplanting islets to the liver approach suffers from an immediate posttransplant loss of more than 50%, progressive graft dysfunction over time, and precludes recovery grafts should there be serious complications such as development teratomas with that are stem cell-derived (SC-islets). omentum features attractive extrahepatic alternative site for clinical islet transplantation. We explore in which allogeneic transplanted onto omentum, is bioengineered a plasma-thrombin biodegradable...