{"title":"The preclinical data and immunologic rationale for hematopoietic stem cell transplantation in autoimmunity.","authors":"Dimitrios Karussis, Panayiota Petrou","doi":"10.1016/B978-0-323-90242-7.00013-4","DOIUrl":null,"url":null,"abstract":"<p><p>The development of autoimmune diseases (ADs) is thought to be caused by a dysfunction of the intrinsic ability of our immune system for \"self-nonself\" discrimination. Following the breakdown of \"self-tolerance,\" an orchestrated immune cascade develops, involving B- and T-lymphocytes and autoantibodies that target self-antigens. An imbalance of the regulatory immune network and a suitable genetic background, along with external (infectious and environmental) triggers, are all important contributors to the outbreak of clinical autoimmunity. Immunotherapies for ADs can be classified into treatments that are given continuously (chronic treatments) and therapies that are applied only once or intermittently, aiming to induce partial or complete reconstitution of the immune system [immune reconstitution therapies (IRTs)]. The principle underlying IRTs is based on the depletion of mature immune cells and the rebuilding of the immune system. During this process of immune reconstitution, a substantial change in the lymphocyte repertoire occurs, which may explain the impressive and long-term beneficial effects of IRTs, including the possibility of induction of tolerance to self-antigens. Hematopoietic (or bone marrow) stem cell transplantation (HSCT or BMT) represents the prototype-and the most radical type-of IRT therapy. The rationale for HSCT or BMT for the treatment of severe ADs is based on convincing proof in preclinical studies, utilizing various animal models of autoimmunity. More than 30 years' worth of pioneering experiments in various models of ADs have shown that HSCT can lead to substantial improvement or even cure of the autoimmune syndromes and induction of long-term tolerance to autoantigens. The success of treatment depends on how completely the autoantigen-reactive lymphocytes and memory cells are eradicated by the conditioning chemotherapy, which is administered in a single dose before the transplantation. The most successful conditioning methods in animal models of ADs are total body irradiation (TBI) and high-dose cyclophosphamide (CY). These preclinical studies, summarized in this review, have provided important data about the therapeutic potential of HSCT in human ADs and the associated mechanisms of action and have contributed to the formulation of guidelines for clinical applications of autologous or allogeneic HSCT/BMT in refractory autoimmunity.</p>","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Handbook of clinical neurology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/B978-0-323-90242-7.00013-4","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
The development of autoimmune diseases (ADs) is thought to be caused by a dysfunction of the intrinsic ability of our immune system for "self-nonself" discrimination. Following the breakdown of "self-tolerance," an orchestrated immune cascade develops, involving B- and T-lymphocytes and autoantibodies that target self-antigens. An imbalance of the regulatory immune network and a suitable genetic background, along with external (infectious and environmental) triggers, are all important contributors to the outbreak of clinical autoimmunity. Immunotherapies for ADs can be classified into treatments that are given continuously (chronic treatments) and therapies that are applied only once or intermittently, aiming to induce partial or complete reconstitution of the immune system [immune reconstitution therapies (IRTs)]. The principle underlying IRTs is based on the depletion of mature immune cells and the rebuilding of the immune system. During this process of immune reconstitution, a substantial change in the lymphocyte repertoire occurs, which may explain the impressive and long-term beneficial effects of IRTs, including the possibility of induction of tolerance to self-antigens. Hematopoietic (or bone marrow) stem cell transplantation (HSCT or BMT) represents the prototype-and the most radical type-of IRT therapy. The rationale for HSCT or BMT for the treatment of severe ADs is based on convincing proof in preclinical studies, utilizing various animal models of autoimmunity. More than 30 years' worth of pioneering experiments in various models of ADs have shown that HSCT can lead to substantial improvement or even cure of the autoimmune syndromes and induction of long-term tolerance to autoantigens. The success of treatment depends on how completely the autoantigen-reactive lymphocytes and memory cells are eradicated by the conditioning chemotherapy, which is administered in a single dose before the transplantation. The most successful conditioning methods in animal models of ADs are total body irradiation (TBI) and high-dose cyclophosphamide (CY). These preclinical studies, summarized in this review, have provided important data about the therapeutic potential of HSCT in human ADs and the associated mechanisms of action and have contributed to the formulation of guidelines for clinical applications of autologous or allogeneic HSCT/BMT in refractory autoimmunity.
期刊介绍：
The Handbook of Clinical Neurology (HCN) was originally conceived and edited by Pierre Vinken and George Bruyn as a prestigious, multivolume reference work that would cover all the disorders encountered by clinicians and researchers engaged in neurology and allied fields. The first series of the Handbook (Volumes 1-44) was published between 1968 and 1982 and was followed by a second series (Volumes 45-78), guided by the same editors, which concluded in 2002. By that time, the Handbook had come to represent one of the largest scientific works ever published. In 2002, Professors Michael J. Aminoff, François Boller, and Dick F. Swaab took on the responsibility of supervising the third (current) series, the first volumes of which published in 2003. They have designed this series to encompass both clinical neurology and also the basic and clinical neurosciences that are its underpinning. Given the enormity and complexity of the accumulating literature, it is almost impossible to keep abreast of developments in the field, thus providing the raison d''être for the series. The series will thus appeal to clinicians and investigators alike, providing to each an added dimension. Now, more than 140 volumes after it began, the Handbook of Clinical Neurology series has an unparalleled reputation for providing the latest information on fundamental research on the operation of the nervous system in health and disease, comprehensive clinical information on neurological and related disorders, and up-to-date treatment protocols.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
