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

• Published in: Brain communications Vol. 5; no. 4; p. fcad206
• Main Authors: Tsaktanis, Thanos, Linnerbauer, Mathias, Lößlein, Lena, Farrenkopf, Daniel, Vandrey, Oliver, Peter, Anne, Cirac, Ana, Beyer, Tobias, Nirschl, Lucy, Grummel, Verena, Mühlau, Mark, Bussas, Matthias, Hemmer, Bernhard, Quintana, Francisco J, Rothhammer, Veit
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 2023
• Subjects: Original; checkpoint; autoimmunity; neuroinflammation; PBMCs; co-regulation
• ISSN: 2632-1297; 2632-1297
• DOI: 10.1093/braincomms/fcad206

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. Tsaktanis et al. reveal distinct expression patterns of membrane-bound and soluble programmed cell death ligand 1 in relapsing–remitting multiple sclerosis, correlating with disease severity. These findings demonstrate regulation of programmed cell death protein 1/programmed cell death ligand 1 signalling and emphasize its potential as a disease surveillance and therapeutic target. Graphical Abstract Graphical Abstract