Regulation of the programmed cell death protein 1/programmed cell death ligand 1 axis in relapsing-remitting multiple sclerosis

Thanos Tsaktanis; Mathias Linnerbauer; Lena Lößlein; Daniel Farrenkopf; Oliver Vandrey; Anne Peter; Ana Cirac; Tobias Beyer; Lucy Nirschl; Verena Grummel; Mark Mühlau; Matthias Bussas; Bernhard Hemmer; Francisco J Quintana; Veit Rothhammer

doi:10.1093/braincomms/fcad206

Regulation of the programmed cell death protein 1/programmed cell death ligand 1 axis in relapsing-remitting multiple sclerosis

Brain Commun. 2023 Jul 25;5(4):fcad206. doi: 10.1093/braincomms/fcad206. eCollection 2023.

Authors

Thanos Tsaktanis^{1

2}, Mathias Linnerbauer^{1

2}, Lena Lößlein², Daniel Farrenkopf², Oliver Vandrey², Anne Peter², Ana Cirac¹, Tobias Beyer¹, Lucy Nirschl¹, Verena Grummel¹, Mark Mühlau¹, Matthias Bussas¹, Bernhard Hemmer^{1

3}, Francisco J Quintana^{4

5}, Veit Rothhammer^{1

2}

Affiliations

¹ Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich 81675, Germany.
² Department of Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg, Erlangen 91054, Germany.
³ Munich Cluster for Systems Neurology (SyNergy), Munich 81377, Germany.
⁴ Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁵ Eli and Edythe L Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Abstract

The programmed cell death protein 1/programmed cell death ligand 1 axis plays an important role in the adaptive immune system and has influence on neoplastic and inflammatory diseases, while its role in multiple sclerosis is unclear. Here, we aimed to analyse expression patterns of programmed cell death protein 1 and programmed cell death ligand 1 on peripheral blood mononuclear cells and their soluble variants in multiple sclerosis patients and controls, to determine their correlation with clinical disability and disease activity. In a cross-sectional study, we performed in-depth flow cytometric immunophenotyping of peripheral blood mononuclear cells and analysed soluble programmed cell death protein 1 and programmed cell death ligand 1 serum levels in patients with relapsing-remitting multiple sclerosis and controls. In comparison to control subjects, relapsing-remitting multiple sclerosis patients displayed distinct cellular programmed cell death protein 1/programmed cell death ligand 1 expression patterns in immune cell subsets and increased soluble programmed cell death ligand 1 levels, which correlated with clinical measures of disability and MRI activity over time. This study extends our knowledge of how programmed cell death protein 1 and programmed cell death ligand 1 are expressed in the membranes of patients with relapsing-remitting multiple sclerosis and describes for the first time the elevation of soluble programmed cell death ligand 1 in the blood of multiple sclerosis patients. The distinct expression pattern of membrane-bound programmed cell death protein 1 and programmed cell death ligand 1 and the correlation between soluble programmed cell death ligand 1, membrane-bound programmed cell death ligand 1, disease and clinical factors may offer therapeutic potential in the setting of multiple sclerosis and might improve future diagnosis and clinical decision-making.

Keywords: PBMCs; autoimmunity; checkpoint; co-regulation; neuroinflammation.