title: Upregulation of CD74 and its potential association with disease severity in subjects with ischemic stroke.
abstract: Macrophage migration inhibitory factor (MIF) is a key cytokine/chemokine in the activation and recruitment of inflammatory T lymphocytes known to exacerbate experimental stroke severity. MIF effects are mediated through its primary cellular receptor, CD74, the MHC class II invariant chain present on all class II expressing cells, including monocytes, macrophages and dendritic cells (DC). We demonstrated previously that partial MHC class II/peptide constructs (pMHC) can effectively treat mice with experimental stroke, in part through their ability to competitively inhibit MIF/CD74 interactions and downstream signaling. However, the role of MIF and CD74 in human ischemic stroke is not yet well established. To evaluate the therapeutic potential for pMHC, we assessed MIF and CD74 expression levels and their association with disease outcome in subjects with ischemic stroke. MIF levels were assessed in blood plasma by ELISA and CD74 expression was quantified by flow cytometry and qRT-PCR in peripheral blood mononuclear cells (PBMCs) obtained from subjects with ischemic stroke and age and sex-matched healthy controls (HC). MIF levels were increased in plasma and the number of CD74+cells and CD74 mRNA expression levels were significantly increased in PBMC of subjects with ischemic stroke versus HC, mainly on CD4+T cells, monocytes and DC. Greater increases of CD74+cells were seen in subjects with cortical vs. subcortical infarcts and the number of CD74+cells in blood correlated strongly with infarct size and neurological outcomes. However, differences in MIF and CD74 expression were not affected by age, gender or lesion laterality. Increased CD74 expression levels may serve as a useful biomarker for worse stroke severity and predicted outcomes in subjects with ischemic stroke and provide a rationale for potential future treatment with pMHC constructs.
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Minshu
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Chang-Juan
authors.initials: CJ
authors.lastname: Wei
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Elaine
authors.initials: E
authors.lastname: Shi
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Jin
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Hao
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA; Department of Neurology, Oregon Health & Science University, Portland, OR, USA; Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Vandenbark
authors.affiliation: Neuroimmunology Research, VA Portland Health Care System, Portland, OR, USA; Department of Neurology, Oregon Health & Science University, Portland, OR, USA; Department of Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA. Electronic address: offnerva@ohsu.edu.
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
mesh_terms: D000368:Aged; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000000981:diagnostic imaging* / Q000453:epidemiology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000097:blood*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D020521:Stroke / Q000097:blood* / Q000000981:diagnostic imaging* / Q000453:epidemiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D015415:Biomarkers; D000949:Histocompatibility Antigens Class II; C045084:invariant chain
keywords: CD74; Inflammation; Macrophage Migration Inhibitory Factor; Partial MHC class II constructs; Stroke