Organ transplantation, an accepted treatment for end stage organ failure, is often complicated by allograft rejection and disease recurrence. In this review we will discuss the potential role of microRNAs in allograft immunity especially leading to rejection of the transplanted organ. microRNAs (miRNAs), originally identified in C. elegans, are short non-coding 21-24 nucleotide sequences that bind to its complementary sequences in functional messenger RNAs and inhibits post-translational processes through RNA duplex formation resulting in gene silencing (Lau et al., 2001). Gene specific translational silencing by miRNAs regulates pathways for immune responses such as development of innate immunity, inflammation, T-cell and B-cell differentiation and signaling that are implicated in various stages of allograft rejection. miRNAs also play a role in development of post-transplant complicacies like fibrosis, cirrhosis, carcinogenesis often leading to graft loss and poor patient outcome. Recent advancements in the methods for detecting and quantifying miRNA in tissue biopsies, as well as in serum and urine samples, has led to identification of specific miRNA signatures in patients with allograft rejection and have been utilized to predict allograft status and survival. Therefore, miRNAs play a significant role in post-transplant events including allograft rejection, disease recurrence and tumor development impacting patient outcome.
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http://dx.doi.org/10.1016/j.yexmp.2012.09.020 | DOI Listing |
Clin Transplant Res
December 2024
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Solid organ transplantation has significantly improved the survival rate of patients with terminal organ failure. However, its success is often compromised by allograft rejection, a process in which T helper 17 (Th17) cells play a crucial role. These cells facilitate rejection by enhancing neutrophil infiltration into the graft and by activating endothelial cells and fibroblasts.
View Article and Find Full Text PDFJ Heart Lung Transplant
December 2024
Van Cleve Cardiac Regenerative Medicine Program, Mayo Clinic, Rochester MN, 55905; Deparment of Cardiovascular Medicine, Mayo Clinic, Rochester MN, 55905. Electronic address:
Background: Although recommended in International Society for Heart and Lung Transplantation (ISHLT) guidelines, transition to mammalian targets of rapamycin (mTOR) inhibitors in heart transplant recipients is not routinely performed, in part due to perceived risk of rejection. This study sought to evaluate the incidence and risk factors for biopsy-proven, clinically relevant rejection following conversion from calcineurin inhibitor (CNI) to sirolimus (SRL) immunosuppression.
Methods: A single center retrospective study was conducted of all consecutive adult patients who underwent orthotopic heart transplantation (OHT) and CNI-free SRL conversion from January 1999 to January 2023.
Sci Transl Med
January 2025
Duke Transplant Center, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Current desensitization and maintenance immunosuppression regimens for kidney transplantation in sensitized individuals show limited ability to control the posttransplant humoral response, resulting in high rates of antibody-mediated rejection (ABMR) and graft failure. Here, we showed that anti-CD154 monoclonal antibody (mAb)-based immunosuppression more effectively controlled allograft rejection and humoral rebound in a highly sensitized nonhuman primate kidney transplantation model compared with tacrolimus-based standard-of-care (SOC) immunosuppression. Desensitization with an anti-CD154 mAb (5C8) and a proteasome inhibitor led to decreased donor-specific antibodies (DSAs) and disruption of lymph node germinal centers with reduction of proliferating, memory, and class-switched B cells as well as T follicular helper cells.
View Article and Find Full Text PDFTranspl Int
January 2025
Université Paris Cité, Institut national de la santé et de la recherche médicale (INSERM) U970, Paris Institute for Transplantation and Organ Regeneration PITOR, Paris, France.
Donor-derived cell-free DNA (dd-cfDNA) is an emerging non-invasive biomarker for allograft injury detection. This study aimed to evaluate a new, decentralized dd-cfDNA testing kit against a centralized dd-cfDNA testing service broadly utilized in the United States. Kidney transplant recipients with decentralized and centralized dd-cfDNA measurements and concomitant kidney allograft biopsies were included in the study.
View Article and Find Full Text PDFBMC Pulm Med
December 2024
Department of Thoracic Surgery, Kartal Kosuyolu High Specialization Education & Research Hospital, Istanbul, Turkey.
Objective: Bronchoscopy plays a critical role in the diagnosis and management of lung transplant recipients. We retrospectively evaluated the safety, complications, and efficacy of transbronchial biopsy (TBB) in detecting and grading early rejection.
Materials And Methods: We retrospectively assessed the complications associated with TBB and the adequacy of pathological diagnoses in patients who underwent lung transplantation at Koşuyolu Yüksek İhtisas Training and Research Hospital from December 1, 2016, to April 30, 2023.
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