人类 T 细胞白血病病毒 1 型相关脊髓病 (HAM) 是一种慢性、进行性炎症性疾病，发病机制尚不清楚，且无有效治疗方法。我们的目的是研究一种新的机制理论并用利妥昔单抗治疗 HAM 患者，利妥昔单抗可以消耗循环中的 CD20 B 淋巴细胞。分析单细胞 RNA 测序 (scRNA-seq) 数据以鉴定 HTLV-1 相关 B 细胞及其对T 细胞。我们对 HAM 队列进行了观察分析，以阐明这些患者免疫微环境的变化。分离 HAM 患者的外周血单核细胞 (PBMC)，以探索体外 B 细胞去除的功效。为了评估 B 细胞耗竭对 HAM 患者的影响，我们队列中符合条件的参与者接受了利妥昔单抗治疗 (NCT04004819)。ScRNA-seq 结果表明 HTLV-1 相关 B 细胞对 T 细胞有显着影响。此外，还发现 HTLV-1 会感染 B 细胞，而 B 细胞的耗竭会抑制 T 细胞的增殖。 HAM患者的B细胞数量与前病毒载量和感染细胞计数呈正相关。 B 细胞的耗竭导致体外 HTLV-1 前病毒载量减少。此外，在临床试验中，还招募了 14 名 HAM 患者。接受利妥昔单抗治疗的 3 名患者 (21.4%) 未能获得缓解，而接受任何其他治疗的患者中有 24 名 (85.7%) 未能获得缓解。由于循环 B 细胞水平较低，CD4 T 细胞中 Ki67 阳性细胞的比例下降。这项研究提供了证据，证明清除 B 淋巴细胞是治疗 HAM 患者的创新策略，并拓宽了对 B 细胞作用的理解在传染性免疫方面。© 2024 作者。 《Annals of Clinical and Translational Neurology》由 Wiley periodicals LLC 代表美国神经病学协会出版。

Human T-cell leukemia virus type 1-associated myelopathy (HAM) is a chronic, progressive, inflammatory disease with unclear pathogenesis and no effective treatments. We aimed to investigate a novel mechanistic theory and treat HAM patients with rituximab, which can deplete CD20+ B lymphocytes in circulation.Single-cell RNA sequencing (scRNA-seq) data was analyzed to identify HTLV-1-associated B cells and their effect on T cells. An observational analysis of our HAM cohort was conducted to elucidate changes in the immunological microenvironment of these patients. Peripheral blood mononuclear cells (PBMC) from HAM patients were isolated to explore the efficacy of B cell depletion in vitro. To assess the effect of B-cell depletion on HAM patients, eligible participants in our cohort received rituximab therapy (NCT04004819).ScRNA-seq results suggest a significant effect of HTLV-1-associated B cells on T cells. Additionally, HTLV-1 was found to infect B cells and depletion of B cells inhibited the proliferation of T cells. Number of B cells in HAM patients had positive correlation with the proviral load and infected cell counts. Depletion of B cells led to a reduction in HTLV-1 proviral load in vitro. Furthermore, in clinical trial, 14 HAM patients were enrolled. Three patients (21.4%) who received rituximab failed to achieve remission, compared to 24 (85.7%) patients received any other therapy that failed to achieve remission. With a low level of circulating B cells, the proportion of Ki67-positive cells in CD4+ T cells fell.This study provided evidence that depleting B-lymphocytes is an innovative strategy for treating patients with HAM and broadens the understanding of the role of B cells in infectious immunity.© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.