Search

Background Early progression of chronic histologic lesions in kidney allografts represents the main finding in graft attrition. The objective of this retrospective cohort study was to elucidate whether HLA histocompatibility is associated with progression of chronic histologic lesions in the first year post-transplant. Established associations of de novo donor-specific antibody (dnDSA) formation with HLA mismatch and microvascular inflammation (MVI) were calculated to allow for comparability with other study cohorts. Methods We included 117 adult kidney transplant recipients, transplanted between 2016 and 2020 from predominantly deceased donors, who had surveillance biopsies at 3 and 12 months. Histologic lesion scores were assessed according to the Banff classification. HLA mismatch scores [i.e. eplet, predicted indirectly recognizable HLA-epitopes algorithm (PIRCHE-II), HLA epitope mismatch algorithm (HLA-EMMA), HLA whole antigen A/B/DR] were calculated for all transplant pairs. Formation of dnDSAs was quantified by single antigen beads. Results More than one-third of patients exhibited a progression of chronic lesion scores by at least one Banff grade in tubular atrophy (ct), interstitial fibrosis (ci), arteriolar hyalinosis (ah) and inflammation in the area of interstitial fibrosis and tubular atrophy (i-IFTA) from the 3- to the 12-month biopsy. Multivariable proportional odds logistic regression models revealed no association of HLA mismatch scores with progression of histologic lesions, except for ah and especially HLA-EMMA DRB1 [odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.03–1.18]. Furthermore, the established associations of dnDSA formation with HLA mismatch and MVI (OR = 5.31, 95% CI 1.19–22.57) could be confirmed in our cohort. Conclusions These data support the association of HLA mismatch and alloimmune response, while suggesting that other factors contribute to early progression of chronic histologic lesions. [ABSTRACT FROM AUTHOR]

Analyzing HLA polymorphism in lung transplantation (LTx) is important, given its impact on LTx recipient survival and graft function. Accordingly, we conducted a retrospective study to examine the influence of HLA mismatch and donor-specific antibodies (DSA) on short-term outcomes and early-phase post-LTx complications. HLA antigen or eplet mismatch in LTx patients at Tohoku University Hospital from 2018 to 2023 was determined, and DSA was measured on admission for surgery to identify preformed DSA and at weeks 4 to 12 post-LTx for de novo DSA, respectively. The participants were 45 LTx recipients, HLA-A/B/DR antigen mismatch (5-6 of 6) being identified in 57%, HLA-A/B/Cw/DR/DQ mismatch (8-10 of 10) in 57%, and HLA eplet mismatch (>61) in 46%. The prevalence of preformed DSA was 24%, and persistence (uncleared) was 16%. The incidence of de novo DSA was 16% after LTx. During the study,16 recipients experienced grade 3 primary graft dysfunction (PGD), 8 developed acute rejection, and 5 died. No HLA-related variables were significantly associated with post-LTx mortality and were not risk factors for high-grade PGD or acute rejection. Despite limitations in sample size, resulting in tentative findings, the study serves as a crucial pilot study for an ongoing multicenter prospective trial in Japan. [ABSTRACT FROM AUTHOR]

An editorial delves into the pivotal role of HLA (human leukocyte antigen) in organ transplantation, exploring its historical significance and contemporary challenges. It emphasizes the impact of HLA compatibility on transplant success rates and discusses the emergence of HLA antibodies post-transplantation, particularly in highly sensitized patients.

Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. This paradigm represents a closed genetic system within which donor T cells interact with peptide-major histocompatibility complexes (MHCs), though clonal interrogation remains challenging due to the sparseness of the T cell repertoire. We developed a Bayesian model using donor and recipient T cell receptor (TCR) frequencies in murine stem cell transplant systems to define limited common expansion of T cell clones across genetically identical donor-recipient pairs. A subset of donor CD4+ T cell clonotypes differentially expanded in identical recipients and were microbiota dependent. Microbiota-specific T cells augmented GVHD lethality and could target microbial antigens presented by gastrointestinal epithelium during an alloreactive response. The microbiota serves as a source of cognate antigens that contribute to clonotypic T cell expansion and the induction of GVHD independent of donor-recipient genetics. [Display omitted] • The recipient microbiota dictates clonal selection of donor T cells post HSCT • Microbiota-specific donor T cells augment GVHD in the presence of cognate antigen • Allogeneic T cells promote activation and TNF response in microbiota-specific T cells • Allogeneic T cells facilitate microbial antigen presentation by recipient GI epithelium Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. Yeh et al. found that a subset of donor CD4+ T cell clonal expansion was microbiota dependent and that microbiota-specific T cells augmented GVHD lethality independent of donor-recipient genetics. [ABSTRACT FROM AUTHOR]

Despite its recent decline in volumes, intestinal transplantation remains an important option for patients with irreversible intestinal failures. The long-term outcome of an intestinal transplant has stagnated. The major cause of graft loss is rejection, resulting from mismatches in human leukocyte antigens (HLA) and the presence of antibodies to mismatched donor-specific HLA antigens (DSA). Literature has reported that DSAs, either preformed before transplantation or developed de novo after transplantation, are harmful to intestinal grafts, especially for those without combined liver grafts. A comprehensive assessment of DSA by the histocompatibility laboratory is critical for successful intestinal transplantation and its long-term survival. This paper briefly reviews the history and current status of different methods for detecting DSA and their clinical applications in intestinal transplantation. The focus is on applying different antibody assays to manage immunologically challenging intestinal transplant patients before and after transplantation. A clinical case is presented to illustrate the complexity of HLA tests and the necessity of multiple assays. The review of risk assessment by the histocompatibility laboratory also highlights the need for close interaction between the laboratory and the intestinal transplant program. [ABSTRACT FROM AUTHOR]