Emilie Lebraud, Maëva Eloudzeri, M. Rabant, B. Lamarthée, D. Anglicheau
{"title":"Microvascular Inflammation of the Renal Allograft: A Reappraisal of the Underlying Mechanisms","authors":"Emilie Lebraud, Maëva Eloudzeri, M. Rabant, B. Lamarthée, D. Anglicheau","doi":"10.3389/fimmu.2022.864730","DOIUrl":null,"url":null,"abstract":"Antibody-mediated rejection (ABMR) is associated with poor transplant outcomes and was identified as a leading cause of graft failure after kidney transplantation. Although the hallmark histological features of ABMR (ABMRh), i.e., microvascular inflammation (MVI), usually correlate with the presence of anti-human leukocyte antigen donor-specific antibodies (HLA-DSAs), it is increasingly recognized that kidney transplant recipients can develop ABMRh in the absence of HLA-DSAs. In fact, 40-60% of patients with overt MVI have no circulating HLA-DSAs, suggesting that other mechanisms could be involved. In this review, we provide an update on the current understanding of the different pathogenic processes underpinning MVI. These processes include both antibody-independent and antibody-dependent mechanisms of endothelial injury and ensuing MVI. Specific emphasis is placed on non-HLA antibodies, for which we discuss the ontogeny, putative targets, and mechanisms underlying endothelial toxicity in connection with their clinical impact. A better understanding of these emerging mechanisms of allograft injury and all the effector cells involved in these processes may provide important insights that pave the way for innovative diagnostic tools and highly tailored therapeutic strategies.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":null,"pages":null},"PeriodicalIF":5.7000,"publicationDate":"2022-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"10","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fimmu.2022.864730","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 10
Abstract
Antibody-mediated rejection (ABMR) is associated with poor transplant outcomes and was identified as a leading cause of graft failure after kidney transplantation. Although the hallmark histological features of ABMR (ABMRh), i.e., microvascular inflammation (MVI), usually correlate with the presence of anti-human leukocyte antigen donor-specific antibodies (HLA-DSAs), it is increasingly recognized that kidney transplant recipients can develop ABMRh in the absence of HLA-DSAs. In fact, 40-60% of patients with overt MVI have no circulating HLA-DSAs, suggesting that other mechanisms could be involved. In this review, we provide an update on the current understanding of the different pathogenic processes underpinning MVI. These processes include both antibody-independent and antibody-dependent mechanisms of endothelial injury and ensuing MVI. Specific emphasis is placed on non-HLA antibodies, for which we discuss the ontogeny, putative targets, and mechanisms underlying endothelial toxicity in connection with their clinical impact. A better understanding of these emerging mechanisms of allograft injury and all the effector cells involved in these processes may provide important insights that pave the way for innovative diagnostic tools and highly tailored therapeutic strategies.
期刊介绍:
Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.