Immunological Predictors of Dimethyl Fumarate-Induced Lymphopenia

Martin Diebold; Edoardo Galli; Andreas Kopf; Nicholas Sanderson; Ilaria Callegari; Florian Ingelfinger; Nicolás Gonzalo Núñez; Pascal Benkert; Ludwig Kappos; Jens Kuhle; Burkhard Becher; Manfred Claassen; Tobias Derfuss

doi:10.1002/ana.26328

Immunological Predictors of Dimethyl Fumarate-Induced Lymphopenia

Ann Neurol. 2022 May;91(5):676-681. doi: 10.1002/ana.26328. Epub 2022 Mar 4.

Authors

Martin Diebold^#^{1

2}, Edoardo Galli^#^{1

3}, Andreas Kopf^#^{4

5

6}, Nicholas Sanderson¹, Ilaria Callegari¹, Florian Ingelfinger^{2

7}, Nicolás Gonzalo Núñez², Pascal Benkert^{1

8}, Ludwig Kappos¹, Jens Kuhle¹, Burkhard Becher^#³, Manfred Claassen^#⁹, Tobias Derfuss^#¹

Affiliations

¹ Multiple Sclerosis Center, Neurologic Clinic and Policlinic, Department of Biomedicine and Research Center for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel, University of Basel, Basel, Switzerland.
² Institute of Neuropathology, Neurocenter, University Hospital Freiburg, Freiburg, Germany.
³ Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
⁴ Institute of Molecular Systems Biology, Swiss Federal Institute of Technology in Zurich, Zurich, Switzerland.
⁵ Swiss Institute of Bioinformatics, Zurich, Switzerland.
⁶ Life Science Graduate School Zurich, PhD Program in Systems Biology, Zurich, Switzerland.
⁷ Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
⁸ Clinical Trial Unit, University Hospital Basel, University of Basel, Basel, Switzerland.
⁹ Division of Clinical Bioinformatics, Department of Internal Medicine I, University of Tübingen, Tübingen, Germany.

^# Contributed equally.

Abstract

Treatment with dimethyl fumarate (DMF) leads to lymphopenia and infectious complications in a subset of patients with multiple sclerosis (MS). Here, we aimed to reveal immune markers of DMF-associated lymphopenia. This prospective observational study longitudinally assessed 31 individuals with MS by single-cell mass cytometry before and after 12 and 48 weeks of DMF therapy. Employing a neural network-based representation learning approach, we identified a CCR4-expressing T helper cell population negatively associated with relevant lymphopenia. CCR4-expressing T helper cells represent a candidate prognostic biomarker for the development of relevant lymphopenia in patients undergoing DMF treatment. ANN NEUROL 2022;91:676-681.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Dimethyl Fumarate / adverse effects
Humans
Immunosuppressive Agents / adverse effects
Lymphopenia* / chemically induced
Multiple Sclerosis* / chemically induced
Multiple Sclerosis* / drug therapy
Multiple Sclerosis, Relapsing-Remitting* / drug therapy
Prospective Studies

Substances

Immunosuppressive Agents
Dimethyl Fumarate