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多发性硬化症自体造血干细胞移植后新的自身免疫性疾病。

New autoimmune diseases after autologous hematopoietic stem cell transplantation for multiple sclerosis.

机构信息

Division of Immunotherapy, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Neuroimmunology and Immunotherapy, Department of Brain Sciences, Imperial College London, London, UK.

出版信息

Bone Marrow Transplant. 2021 Jul;56(7):1509-1517. doi: 10.1038/s41409-021-01277-y. Epub 2021 Apr 28.

Abstract

Secondary autoimmune diseases (2ndADs), most frequently autoimmune cytopenias (AICs), were first described after allogeneic hematopoietic stem cell transplantation (HSCT) undertaken for malignant and hematological indications, occurred at a prevalence of ~5-6.5%, and were attributed to allogeneic immune imbalances in the context of graft versus host disease, viral infections, and chronic immunosuppression. Subsequently, 2ndADs were reported to complicate roughly 2-14% of autologous HSCTs performed for an autoimmune disease. Alemtuzumab in the conditioning regimen has been identified as a risk for development of 2ndADs after either allogeneic or autologous HSCT and is consistent with the high rates of 2ndADs when using alemtuzumab as monotherapy. Due to the significant consequences but variable incidence, depending on conditioning regimen, of 2ndADs and similarity in known immune reconstitution kinetics after autologous HSCT for autoimmune diseases and after alemtuzumab monotherapy, we propose that an imbalance between B and T lineage regeneration early after HSCT may underlie the pathogenesis of 2ndADs.

摘要

继发性自身免疫性疾病(2 型自身免疫性疾病),最常见的是自身免疫性血细胞减少症(AIC),最初是在为恶性和血液学指征进行同种异体造血干细胞移植(HSCT)后描述的,其患病率约为 5-6.5%,并归因于移植物抗宿主病、病毒感染和慢性免疫抑制背景下的同种异体免疫失衡。随后,报道称自身免疫性疾病的大约 2-14%的自体 HSCT 会并发 2 型自身免疫性疾病。在同种异体或自体 HSCT 后,预处理方案中的阿仑单抗已被确定为发生 2 型自身免疫性疾病的风险因素,并且与阿仑单抗单药治疗时发生的 2 型自身免疫性疾病的高发生率一致。由于 2 型自身免疫性疾病的后果严重但发生率存在差异(取决于预处理方案),以及自身免疫性疾病自体 HSCT 后和阿仑单抗单药治疗后已知的免疫重建动力学相似,我们提出 HSCT 后早期 B 和 T 谱系再生失衡可能是 2 型自身免疫性疾病发病机制的基础。

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