Hematopoietic stem cell transplantation for neuromyelitis optica spectrum disorder. Can immune tolerance be reestablished?

Q2 Medicine
Richard K Burt, Joachim Burman, Raffaella Greco, John W Rose
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引用次数: 0

Abstract

Neuromyelitis optica (NMO), which is also referred to as Devic's disease, was originally considered an aggressive subtype of multiple sclerosis (MS) presenting as optic neuritis and/or extensive transverse myelitis in which 50% of patients become blind or in a wheelchair within 5 years of onset. Subsequently, NMO was categorized as one of a spectrum of inflammatory and demyelinating autoimmune disorders that are distinct from multiple sclerosis and termed neuromyelitis optica spectrum disorder (NMOSD). NMOSD differs from multiple sclerosis by its clinical course, presentation, magnetic resonance imaging findings, clinical presentation, serum biomarker prognosis, and response to treatment. More recently, NMOSD has been subdivided according to auto-antibody status as aquaporin 4 (AQP4) seropositive NMO, myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), and seronegative NMOSD. The only treatment to date that has resulted in treatment-free remissions, now lasting for more than 5-10 years with posttreatment disappearance of anti-AQP4 antibodies, is hematopoietic stem cell transplantation (HSCT) using either an allogeneic (matched sibling or unrelated) donor with a reduced toxicity conditioning regimen or an autologous stem cell source using a nonmyeloablative conditioning regimen of plasmapheresis (PLEX), cyclophosphamide (Cytoxan®), rabbit antithymocyte (ATG), and rituximab (Rituxan®). Post-HSCT long-term resolution of disease activity and disappearance of AQP4 antibodies is consistent with HSCT-induced immune tolerance.

造血干细胞移植治疗神经脊髓炎视网膜谱系障碍。免疫耐受可以重新建立吗?
神经脊髓炎视网膜病(NMO)又称德维克病,最初被认为是多发性硬化症(MS)的一种侵袭性亚型,表现为视神经炎和/或广泛横贯性脊髓炎,50%的患者在发病 5 年内失明或坐轮椅。后来,NMO 被归类为有别于多发性硬化症的一系列炎症性和脱髓鞘性自身免疫性疾病之一,并被称为神经脊髓炎视神经频谱障碍(NMOSD)。NMOSD 与多发性硬化症的区别在于其临床过程、表现、磁共振成像结果、临床表现、血清生物标志物预后以及对治疗的反应。最近,NMOSD 根据自身抗体状态被细分为水蒸气素 4(AQP4)血清阳性 NMO、髓鞘少突胶质细胞糖蛋白(MOG)抗体相关疾病(MOGAD)和血清阴性 NMOSD。迄今为止,该疗法是唯一一种可实现无治疗缓解的疗法,目前可持续 5-10 年以上,治疗后抗 AQP4 抗体消失、造血干细胞移植(HSCT)是使用异体(匹配的同胞或非亲缘)供体,采用毒性降低的调理方案,或使用自体干细胞来源,采用非蜕膜化调理方案,包括浆细胞分离(PLEX)、环磷酰胺(Cytoxan®)、兔抗胸腺细胞(ATG)和利妥昔单抗(Rituximab®)。造血干细胞移植后,疾病活动长期缓解,AQP4 抗体消失,这与造血干细胞移植诱导的免疫耐受是一致的。
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来源期刊
Handbook of clinical neurology
Handbook of clinical neurology Medicine-Neurology (clinical)
CiteScore
4.10
自引率
0.00%
发文量
302
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.
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