title: Translocator protein 18 kDa (TSPO) expression in multiple sclerosis patients.
abstract: Translocator protein (18 kDa) (TSPO) is a marker of inflammation in the brain. Positron emission tomography (PET) scans with ligands for this receptor show increased expression of TSPO in many neuropathologic conditions. However, expression of TSPO in the periphery and its possible correlation to central nervous system (CNS) inflammation has been largely unstudied. In this paper PBR28, a recently synthesized ligand for TSPO that is shown to have 80-fold higher specific binding than its predecessor PK11195, is used to quantify peripheral TSPO. Data presented in this study show that monocytes account for the majority of TSPO measured in peripheral blood mononuclear cells (PBMC), and that TSPO expression is stable over time in healthy individuals. Previous studies show that areas of increased PBR28 binding in the brains of multiple sclerosis (MS) patients correlate with active demylinating lesions found during magnetic resonance imaging (MRI). To measure peripheral TSPO expression in an inflammatory disease of the CNS, PBR28 is used in an in vitro radioligand binding assay to measure the amount of TSPO in the PBMC of MS and healthy donor cohorts. Surprisingly, MS patients are found to have a significantly lower amount of peripheral TSPO than healthy donors. We suggest that TSPO protein expression is a potential peripheral biomarker of MS, more research is needed to determine if peripheral TSPO expression may also be altered in other neuroinflammatory conditions.
authors.affiliation: Neuroimmunology Branch, National Institute of Neurological Disease and Stroke, National Institutes of Health, Building 10, Room 5C103, 10 Center Drive, MSC 1400, Bethesda, MD 20892-1400, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Harberts
authors.forename: Dibyadeep
authors.initials: D
authors.lastname: Datta
authors.forename: Selby
authors.initials: S
authors.lastname: Chen
authors.forename: Jillian E
authors.initials: JE
authors.lastname: Wohler
authors.forename: Unsong
authors.initials: U
authors.lastname: Oh
authors.forename: Steven
authors.initials: S
authors.lastname: Jacobson
mesh_terms: D000081:Acetamides; D000328:Adult; D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging; D002469:Cell Separation; D005260:Female; D006801:Humans; D007546:Isoquinolines; D007963:Leukocytes, Mononuclear / Q000502:physiology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008279:Magnetic Resonance Imaging; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011725:Pyridines; D011869:Radioligand Assay; D019275:Radiopharmaceuticals; D060888:Real-Time Polymerase Chain Reaction; D018079:Receptors, GABA / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000081:Acetamides; D015415:Biomarkers; D007546:Isoquinolines; D018950:Lipopolysaccharide Receptors; C526798:N-(2-methoxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide; D011725:Pyridines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human; C037850:PK 11195