BACKGROUND Progressive multifocal leukoencephalopathy (PML) among multiple sclerosis (MS) patients receiving dimethyl fumarate (DMF) is associated with iatrogenic lymphopenia, predominating on CD8+ T-cells. OBJECTIVES AND METHODS We report an unusual case of DMF-related PML in a 66-year-old MS patient with preserved lymphocyte count (nadir: 810/mm3) and normal CD8+ T-cells count. RESULTS A massive overexpression of the inhibitory receptor Programmed Cell Death 1 (PD-1) on CD8+ and memory effector T-cells together with an impaired anti-JC virus (JCV) specific T-cells response were found, compatible with exhaustion. Following DMF withdrawal, PML progressively regressed, PD-1 was downregulated, and a functional anti-JCV response was established. CONCLUSION T-cells exhaustion may favor PML onset on DMF independently of lymphocyte count.

中文翻译：

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富马酸二甲酯进行性多灶性白质脑病，淋巴细胞计数保持不变，但深部 T 细胞耗竭

背景 接受富马酸二甲酯 (DMF) 治疗的多发性硬化症 (MS) 患者的进行性多灶性白质脑病 (PML) 与医源性淋巴细胞减少症有关，主要发生在 CD8+ T 细胞上。目的和方法 我们报告了一名 66 岁 MS 患者的异常 DMF 相关 PML 病例，其淋巴细胞计数（最低点：810/mm3）和正常 CD8+ T 细胞计数正常。结果 发现 CD8+ 和记忆效应 T 细胞上抑制性受体程序性细胞死亡 1 (PD-1) 的大量过度表达以及抗 JC 病毒 (JCV) 特异性 T 细胞反应受损，与衰竭相容。停用 DMF 后，PML 逐渐消退，PD-1 下调，并建立了功能性抗 JCV 反应。结论 T 细胞耗竭可能有利于 DMF 的 PML 发病，而与淋巴细胞计数无关。