Infection, Rejection, and the Connection

Abstract

Solid organ transplantation is a life-saving treatment for people with end-stage organ disease. Immune-mediated transplant rejection is a common complication that decreases allograft survival. Although immunosuppression is required to prevent rejection, it also increases the risk of infection. Some infections, such as cytomegalovirus and BK virus, can promote inflammatory gene expression that can further tip the balance toward rejection. BK virus and other infections can induce damage that resembles the clinical pathology of rejection, and this complicates accurate diagnosis. Moreover, T cells specific for viral infection can lead to rejection through heterologous immunity to donor antigen directly mediated by antiviral cells. Thus, viral infections and allograft rejection interact in multiple ways that are important to maintain immunologic homeostasis in solid organ transplant recipients. Better insight into this dynamic interplay will help promote long-term transplant survival.

Human hypoimmune primary pancreatic islets avoid rejection and autoimmunity and alleviate diabetes in allogeneic humanized mice

“…However, critical challenges to allogeneic islet transplantation include an unsolved regulatory framework ( 19 ), early loss of transplanted islets from instant blood-mediated inflammatory reaction ( 20 , 21 ), and the need for life-long immunosuppression to protect the islet grafts from allo- and autoimmunity. Immunosuppression causes most side effects, including β cell toxicity ( 22 ), kidney toxicity ( 23 , 24 ), infections ( 25 ), and cancer ( 26 ), and limits the more widespread use of this strategy. We here report the concept of human allogeneic, gene-engineered hypoimmune (HIP) islets for transplantation without the need for immunosuppression.…”

Optimizing the approach to monitoring allograft inflammation using serial urinary CXCL10/creatinine testing in pediatric kidney transplant recipients

“…Elevated uCXCL10/Cr levels that persist or appear following infection resolution may identify an increased risk for acute rejection. This rejection risk has been previously reported following both CMV and BK infection 49,66,67 and is likely associated with increased trafficking of immune cells to the allograft with parenchymal inflammation or as the result of decreasing immunosuppression medications during the active infection phase 68 . There is disagreement on the extent to which allograft pyelonephritis contributes to subsequent rejection 69–71 .…”

“…ing both CMV and BK infection 49,66,67 and is likely associated with increased trafficking of immune cells to the allograft with parenchymal inflammation or as the result of decreasing immunosuppression medications during the active infection phase. 68 There is disagreement on the extent to which allograft pyelonephritis contributes to subsequent rejection. [69][70][71] This may be due in part to whether there is actual parenchymal involvement with UTI, since histologically documented pyelonephritis is associated with similar histological 72 and molecular 73 features of acute rejection.…”

Hematopoietic stem cells and betaherpesvirus latency

“…This regulation varies depending on the cell type or model system hosting the virus ( Crawford et al., 2022 ) and is specific to cell fate and viral lifecycle stage, setting up precisely tuned regulatory mechanisms by the virus. While fewer specific details are known about the role of HHV-6 or HHV-7 proteins in latency and cellular control, betaherpesvirus infection has implications in complex disease, including during transplant ( Higdon et al., 2023 ) and latent viral proteins have promise as novel therapeutics ( Perera et al., 2021 ; Berg and Rosenkilde, 2023 ).…”