Upregulation Of CD74 And Its Potential Association With Disease Severity In Subjects With Ischemic Stroke

Background and purpose In early stages of clinical trials,T cells were known to exacerbate experimental stroke severity.Macrophage migration inhibitor factor(MIF)is a key cytokine/chemokine in the activation and recruitment of inflammatory T lymphocytes.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(p MHC)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 p MHC,we assessed MIF and CD74 expression levels and their association with disease outcome in subjects with ischemic stroke.Methods From May 2016 to August 2016,20 eligible consecutive patients with ischemic stroke hospitalized in the Department of Neurology of Tianjin Medical University General Hospita were recruited into this study,male13,female7,average age 66.60±1.44 years old.14 age-matched healthy subjects were recruited into this study as controls,male 8,female 6,average age 63.71±0.95 years old.Flow cytometry and q RT-PCR were used to measure CD74 expression in peripheral blood mononuclear cells(PBMCs)obtained from patients with ischemic stroke and healthy controls(HC).ELISA was performed to measure the plasma level of MIF.Results MIF levels were increased in plasma and the number of CD74+ cells and CD74 m RNA 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.Conclusions 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 p MHC constructs.