Pancreas transplant rejection

UNLABELLED: Regulatory T cells (Tregs) have potential as a cell-based therapy to prevent or treat transplant rejection and autoimmunity. Using an HLA-A2-specific chimeric antigen receptor (A2-CAR), we previously showed that adoptive transfer of A2-CAR Tregs limited anti-HLA-A2 alloimmunity. However, it was unknown if A2-CAR Tregs could also limit immunity to autoantigens. Using a model of HLA-A2 + islet transplantation into immunodeficient non-obese diabetic mice, we investigated if A2-CAR Tregs could control diabetes induced by islet-autoreactive (BDC2...

The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality. Spike messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 may contribute to immune-mediated injuries. Here we present a case of a previously healthy 47-year-old man, who developed progressive jaundice 2 weeks after receiving his 3rd COVID-19 vaccination (1st mRNA-based vaccine). Apart from elevated serum total bilirubin levels (peaked at >70 mg/dL), deteriorating renal (blood urea nitrogen: peak, 108...

BACKGROUND: Pancreas transplant biopsy practices for the diagnosis of rejection or other pathologies are not well described. METHODS: We conducted a survey of staff at US pancreas transplant programs (March 22, 2022, to August 22, 2022) to assess current program practices and perceptions about the utility and challenges in the performance and interpretation of pancreas allograft biopsies. RESULTS: Respondents represented 65% (76/117) of active adult pancreas transplant programs, capturing 66% of recent pancreas transplant volume in the United States...

Introduction: Avascular necrosis is a debilitating osseous complication in transplant recipients. Project Aim: This program evaluation sought to describe risk factors and adverse outcomes of avascular necrosis in kidney transplant recipients. Design: This was a retrospective evaluation of all recipients of kidneys and simultaneous pancreas and kidneys between 2001 and 2018 from a single center. Controls were selected based on the incidence density, sampling at a 1:3 ratio based on the post-transplant interval...

Tixagevimab/cilgavimab (tix/cil) received emergency use authorization in December 2021 for pre-exposure prophylaxis against COVID-19 in moderately to severely immunocompromised patients. Our study aimed to describe the incidence of COVID-19 infection and assess the immunologic risks associated with tix/cil in kidney, pancreas, liver, and heart transplant recipients. Retrospective chart review was completed to provide descriptive analysis. Outcomes data included COVID-19 infection, severity of COVID-19 infection, graft function, and rejection...

Kidney transplant is not only the best treatment for patients with advanced kidney disease, but it also reduces health-care expenditure. The management of transplant patients is complex as they require special care by transplant nephrologists who have expertise in assessing transplant candidates, understand immunology and organ rejection, have familiarity with peri-operative complications, and have the ability to manage the long-term effects of chronic immunosuppression. This skill set at the intersection of multiple disciplines necessitates additional training in Transplant Nephrology...

SUMMARY: Kabuki syndrome is a genetic disorder characterised by distinctive facial features, developmental delays, and multisystem congenital anomalies. Endocrine complications such as premature thelarche and short stature are common, whereas disorders of glycaemic control are less frequent. We describe a 23-year-old white female referred to the diabetes clinic for hyperglycaemia during haemodialysis. She was subsequently diagnosed with Kabuki syndrome based on characteristic clinical features, confirmed by detecting a heterozygous pathogenic variant in KMT2D...

We present a unique case of pancreatic panniculitis (PP) in a 42-year-old male with a history of pancreas-after-kidney (PAK) transplant. The patient developed PP due to acute pancreas allograft rejection. Clinical manifestations included fevers, myalgias, arthralgias, and tender erythematous subcutaneous nodules on the lower extremities. A recent hospital admission was noted for acute pancreas allograft rejection related to low tacrolimus levels. Rheumatological and infectious disease workups were negative...

Tacrolimus is one of the calcineurin inhibitors used for maintaining immuno-suppression in thoracic and abdominal transplantations including heart, lung, liver, intestine, pancreas, and renal transplants. It has a narrow therapeutic window requiring therapeutic drug monitoring (TDM). Genetic polymorphism in the expression of cytochrome P3A5 enzyme plays a significant role in the bioavailability of tacrolimus in patients, leading to toxicity or rejection. In this case, we studied a renal transplant patient who received a standard dose of tacrolimus and experienced toxicity related to the poor expression of cytochrome P450 3A5 (CYP3A5), which required the withholding of tacrolimus and cutting the dose for several days with more frequent TDM...

Type-1 diabetes mellitus (T1DM) is characterized by damage of beta cells in pancreatic islets. Cell-sheet engineering, one of the newest therapeutic approaches, has also been used to create functional islet systems by creating islet/beta cell-sheets and transferring these systems to areas that require minimally invasive intervention, such as extrahepatic areas. Since islets, beta cells, and pancreas transplants are allogeneic, immune problems such as tissue rejection occur after treatment, and patients become insulin dependent again...

Although the male epididymal fat pad is an effective site for islet transplantation, females lack this tissue. Here, we present a protocol to assess the parametrial fat pad (PFP) adjacent to the uterine horn in females as an alternative site for islet transplantation. We describe steps for islet isolation from the pancreas, counting, transplantation into PFP, and monitoring for engraftment. Transplantation into PFP is minimally invasive, time efficient, and supports long-term engraftment of syngeneic islets and rejection of allogeneic islets...

BACKGROUND: Solid organ transplantation is a life-saving medical operation that has progressed greatly because of developments in diagnostic tools and histocompatibility tests. Crossmatching for complement-dependent cytotoxicity (CDC) and human leukocyte antigen (HLA) typing are two important methods for checking graft compatibility and reducing the risk of graft rejection. HLA typing and CDC crossmatching are critical in kidney, heart, lung, liver, pancreas, intestine, and multi-organ transplantation...

Type 1 diabetes (T1D) presents a persistent medical challenge, demanding innovative strategies for sustained glycemic control and enhanced patient well-being. Beta cells are specialized cells in the pancreas that produce insulin, a hormone that regulates blood sugar levels. When beta cells are damaged or destroyed, insulin production decreases, which leads to T1D. Allo Beta Cell Transplantation has emerged as a promising therapeutic avenue, with the goal of reinstating glucose regulation and insulin production in T1D patients...

Organ transplantation is an innovative field that was pioneered in the middle of the last century with the development of surgical techniques, advances in the understanding of immunological processes that cause rejection, introduction of drugs to prevent rejection and improved methods for organ preservation. In Israel, the first heart transplantation and kidney transplantation were performed in the mid-1960's followed by pancreas, lung and liver transplantation that were conducted for the first time in the late 1980's and early 1990's...

BACKGROUND: Pig islet xenotransplantation is a potential treatment for type 1 diabetes. We have shown that maintenance immunosuppression is required to protect genetically modified (GM) porcine islet xenografts from T cell-mediated rejection in baboons. Local expression of a depleting anti-CD2 monoclonal antibody (mAb) by the xenograft may provide an alternative solution. We have previously reported the generation of GGTA1 knock-in transgenic pigs expressing the chimeric anti-CD2 mAb diliximab under an MHC class I promoter (MHCIP)...

BACKGROUND: Invasive fungal infections (IFIs) remain a rare yet dreaded complication following pancreas transplantation. Current guidelines recommend antifungal prophylaxis in patients with 1 or more risk factors. At our center, single-dose antifungal prophylaxis is administered in the operating room but none subsequently, regardless of risk factors. Here we evaluate the 1-year incidence, outcome, and risk factors associated with IFI following pancreas transplantation. METHODS: A retrospective, single-center cohort study was conducted in patients who underwent pancreas transplantation between 1 January 2009 and 31 December 2019...

INTRODUCTION: An increased midnight cortisol (MC) has been described in end-stage kidney disease (ESKD) and type 1 diabetes (T1D). Lower circulating levels of the cytokine soluble tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) have been found in T1D and ESKD and associated with cardiovascular (CV) events in the latter. We aimed to study MC and sTWEAK in simultaneous pancreas-kidney transplant (SPKT) recipients, and the association of these markers with CV risk factors and transplant outcomes...

The Banff pancreas working schema for diagnosis and grading of rejection is widely used for treatment guidance and risk stratification in centers that perform pancreas allograft biopsies. Since the last update, various studies have provided additional insight regarding the application of the schema and enhanced our understanding of additional clinicopathologic entities. This update aims to clarify terminology and lesion description for T cell-mediated and antibody-mediated allograft rejections, in both active and chronic forms...

Cytomegalovirus (CMV) is a common cause of infection after transplantation, but few studies have evaluated its epidemiology, risk factors, and outcomes among pancreas transplant recipients. We performed a retrospective cohort study of adults who underwent pancreas transplantation from January 1, 2010, through December 31, 2020, at 3 sites in Arizona, Florida, and Minnesota. The primary outcome was clinically significant CMV infection (csCMVi), defined as CMV disease or infection requiring antiviral therapy...

Outcomes analyzing conversion from IR-tacrolimus (IR) to LCP-tacrolimus (LCP) in obesity are limited. This was a retrospective longitudinal cohort study of patients converted from IR to LCP from June 2019 to October 2020. Primary outcomes were conversion ratios for weight-based dose at a steady-state therapeutic level and identification of appropriate dosing weight. Other outcomes included tacrolimus coefficient of variation (CV), time in therapeutic range (TITR), adverse events, infections, donor specific antibodies (DSAs), and acute rejection...