Multiple sclerosis (Houndmills, Basingstoke, England) · 2020
Progressive multifocal leukoencephalopathy on dimethyl fumarate with preserved lymphocyte count but deep T-cells exhaustion.
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Garcia Jeanne, Hendel-Chavez Houria, De-Goer Marie-Ghislaine, L'Honneur Anne Sophie, Dubessy Anne Laure, Taoufik Yassine, Stankoff Bruno
Аннотация
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.
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.