Progressive multifocal leukoencephalopathy on dimethyl fumarate with preserved lymphocyte count but deep T-cells exhaustion-Reference-Cited by-同舟云学术

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

Published:2020-07-20 Issue:4 Volume:27 Page:640-644
ISSN:1352-4585
Container-title:Multiple Sclerosis Journal
language:en
Short-container-title:Mult Scler

Author:

Garcia Jeanne¹^ORCID,Hendel-Chavez Houria²,De-Goer Marie-Ghislaine²,L’Honneur Anne Sophie³,Dubessy Anne Laure¹,Taoufik Yassine⁴,Stankoff Bruno⁵

Affiliation:

1. Saint Antoine Hospital, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France

2. Paris Sud Medecine University, INSERM U1184, Kremlin Bicêtre Hospital, Le Kremlin-Bicêtre, France

3. Department of Virology, Cochin Hospital, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France

4. Paris Sud Medecine University, INSERM U1184, Kremlin Bicêtre Hospital, Bicêtre, France/Hematology Department, Kremlin Bicêtre Hospital, Le Kremlin-Bicêtre, France

5. Saint Antoine Hospital, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France/Sorbonne University, UPMC, Brain and Spinal Cord Institute (ICM), INSERM UMR-S 1127, CNRS UMR 7225, Paris, France

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.

Publisher

SAGE Publications

Subject

Neurology (clinical),Neurology

Link

http://journals.sagepub.com/doi/pdf/10.1177/1352458520942201

Reference10 articles.

1. Classifying PML risk with disease modifying therapies

2. Progressive multifocal leukoencephalopathy in patients treated with fumaric acid esters: a review of 19 cases

3. Immunological Hallmarks of JC Virus Replication in Multiple Sclerosis Patients on Long-Term Natalizumab Therapy

4. A case of progressive multifocal leukoencephalopathy under dimethyl fumarate treatment without severe lymphopenia or immunosenescence

5. Detection of JC virus archetype in cerebrospinal fluid in a MS patient with dimethylfumarate treatment without lymphopenia or signs of PML

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