In recent years, there have been multiple studies published on longitudinal and retrospective analysis of anti-human leukocyte antigen (anti-HLA) antibodies. The focus of these reports was to determine specific characteristics of the impact of donor specific anti-HLA antibodies (DSA) in organ transplantation. There has been a growing concern about DSA in a multitude of organ transplants. Research efforts are attempting to gain a better understanding of DSA and possible treatment implications for patients with DSA. In 2015, many studies confirm and expand upon both the understanding of the humoral theory and the clinical applications of DSA in transplantation. This review highlights some of these publications and their contributions to the humoral theory of transplantation.
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Anti-Human Leukocyte Antigen Antibody Detection from Terasaki's Humoral Theory to Delisting Strategies in 2024.
Int J Mol Sci
January 2025
Immunology Department, University Hospital Marqués de Valdecilla, 39008 Santander, Spain.
The human leukocyte antigen (HLA) system plays a critical role in transplant immunology, influencing outcomes through various immune-mediated rejection mechanisms. Hyperacute rejection is driven by preformed donor-specific antibodies (DSAs) targeting HLAs, leading to complement activation and graft loss within hours to days. Acute rejection typically occurs within six months post-transplantation, involving cellular and humoral responses, including the formation of de novo DSAs.
View Article and Find Full Text PDFAssessment of access and outcomes of kidney transplantation through the reforms of the Swiss organ allocation system.
Front Public Health
January 2025
Transplant Immunology Unit, Geneva University Hospitals, Geneva, Switzerland.
Introduction: The Swiss allocation system for kidney transplantation has evolved over time to balance medical urgency, immunological compatibility, and waiting time. Since the introduction of the transplantation law in 2007, which imposed organ allocation on a national level, the algorithm has been optimized. Initially based on waiting time, HLA compatibility, and crossmatch performed by cell complement-dependent cytotoxicity techniques, the system moved in 2012 to a score including HLA compatibility, waiting time, anti-HLA antibodies detected by the Luminex technology, and a virtual crossmatch.
View Article and Find Full Text PDFThe Clinical Significance of HLA Compatibility Scores in Lung Transplantation.
Transpl Int
January 2025
Department of Chronic Diseases, Metabolism and Ageing, Laboratory for Respiratory Diseases and Thoracic Surgery, Faculty of Medicine, KU Leuven, Leuven, Belgium.
Lung transplantation is a life-saving therapeutic option for many chronic end-stage pulmonary diseases, but long-term survival may be limited by rejection of the transplanted organ. Since HLA disparity between donor and recipient plays a major role in rejection, we performed a single center, retrospective observational cohort analysis in our lung transplant cohort (n = 128) in which we calculated HLA compatibility scores for B-cell epitopes (HLAMatchmaker, HLA-EMMA), T-cell epitopes (PIRCHE-II) and missing self-induced NK cell activation (KIR Ligand Calculator). Adjusted Cox proportional hazards model was used to investigate the association between mismatched scores and time to development of donor-specific antibodies (DSA) post-transplant, time to first biopsy-proven acute rejection episode, freedom from CLAD, graft survival and overall survival.
View Article and Find Full Text PDFDepletion of alloreactive B cells by drug-resistant chimeric alloantigen receptor T cells to prevent transplant rejection.
Mol Ther
January 2025
Institute of Transfusion Medicine and Transplant Engineering, Hannover Medical School, 30625 Hannover, NI, Germany. Electronic address:
Antibody-mediated rejection (AMR) remains a major complication after solid organ transplantation (SOT). Current treatment options are inefficient and result in drastic impairment of the general immunity. To selectively eliminate responsible alloreactive B cells characterized by anti-donor-HLA B cell receptors (BCRs), we generated T cells overcoming rejection by antibodies (CORA-Ts) engineered with a novel chimeric receptor comprising a truncated donor-HLA molecule as antigen recognition domain.
View Article and Find Full Text PDFTumor-Infiltrating Immune Cells and HLA Expression as Potential Biomarkers Predicting Response to PD-1 Inhibitor Therapy in Stage IV Melanoma Patients.
Biomolecules
December 2024
National Tumor Biology Laboratory, National Institute of Oncology, H-1122 Budapest, Hungary.
PD-1 inhibitors are known to be effective in melanoma; however, a considerable proportion of patients fail to respond to therapy, necessitating the identification of predictive markers. We examined the predictive value of tumor cell HLA class I and II expression and immune cell infiltration in melanoma patients treated with PD-1 inhibitors. Pretreatment surgical samples from 40 stage IV melanoma patients were studied immunohistochemically for melanoma cell expression of HLA class I molecules (using four antibody clones with different specificities), HLA-II, and immune cell infiltration (using a panel of 10 markers).
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