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The 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.

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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.

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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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Umbilical cord blood (UCB) represents a valuable graft source in the absence of a human leukocyte antigen (HLA)-matched donor for hematopoietic cell transplantation (HCT). Donor-specific anti-HLA antibodies (DSAs), targeting grafts with mismatched HLA antigens, pose a significant obstacle by increasing the risk of primary graft failure, delayed engraftment, and decreased survival. Existing literature on HLA desensitization has primarily focused on haploidentical transplants, and there is a lack of experience regarding the optimal strategy in UCB transplantation.

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Background: Antibody-mediated rejection (ABMR) has become one of the leading causes of chronic lung graft dysfunction. However, in lung transplantation, this entity is sometimes difficult and controversial to diagnose. It is mainly caused by the appearance of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA), although there are situations with C4d deposits in biopsy in the absence of circulating DSA.

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