Progressive multifocal leukoencephalopathy on dimethyl fumarate with preserved lymphocyte count but deep T-cells exhaustion.

ABSTRACT

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.