Cerebrospinal Fluid Osteopontin and Inflammation-Associated Cytokines in Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Abstract

Anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune neurological disorder. Osteopontin (OPN) is a secreted multifunctional phosphorylated glycoprotein that regulates various autoimmune and inflammatory diseases, but its diagnostic and prognostic values in anti-NMDAR encephalitis patients remain elusive. This retrospective study aimed to determine the levels of OPN and related cytokines in cerebrospinal fluid (CSF) of anti-NMDAR encephalitis patients and to assess their influence on disease severity so as to evaluate their efficacy as biomarkers for diagnosis and prognosis. CSF samples from 33 anti-NMDAR encephalitis, 13 viral encephalitis, and 21 controls were collected. All CSF were tested for levels of OPN and inflammation-associated cytokines [interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α] via ELISA. In addition, 15 anti-NMDAR encephalitis patients without follow-up relapse were reexamined for these four parameters 3 months later. The clinical status was evaluated by modified Rankin Scale (mRS) scores. Results showed that the CSF levels of these cytokines were increased in anti-NMDAR encephalitis patients compared to controls but not viral encephalitis patients. Their levels were decreased in remission compared with that in acute stage. Moreover, CSF OPN positively correlated with IL-6, white blood cell (WBC) counts, and C-reactive protein (CRP) levels in anti-NMDAR encephalitis patients. However, no associations were found between OPN or related cytokines and mRS scores in acute stage in anti-NMDAR encephalitis patients. Overall, CSF OPN and related cytokines were increased when anti-NMDAR encephalitis patients are in acute stage and decreased in remission, suggesting the underlying neuro-inflammatory process in this disease. However, they are not qualified with diagnostic or prognostic value.

Cytokines and chemokines profile in encephalitis patients: A meta-analysis

“…The full-text article could not be found in 21 studies (_((((xxx))))_)[ 80 , 104 – 123 ]. Based on the inclusion and exclusion criteria, 71 studies (_((((xxx))))_)[ 8 , 23 – 30 , 121 , 124 – 184 ] were considered for this study, of which 23 studies had sufficient quantitative data and were included in the meta-analysis and reported in this study (_((((xxx))))_)[ 25 , 28 – 30 , 125 – 127 , 131 , 134 , 140 – 142 , 144 , 147 , 149 , 152 , 156 , 175 , 178 – 180 , 183 , 184 ]. The remaining 48 studies were not included in the meta-analysis because they mostly reported qualitative data and did not contain sufficient quantitative data.…”

“…Our study does not report qualitative data and only focuses on the meta-analysis of quantitative data. Although Chen et al [ 8 ] study investigated the concentration of cytokines, the reported data overlapped Zou et al [ 184 ] study, published more recently, so we considered the latter in the meta-analysis. The meta-analysis was performed for 12 cytokines and chemokines, each of which was assessed in at least three comparison studies.…”

“…The included studies’ publication time were between 1996 and 2021. CSF was used in 11 studies for evaluating the concentration of the cytokines [ 29 , 30 , 125 , 126 , 134 , 140 , 141 , 149 , 156 , 178 , 184 ], plasma/serum was examined for cytokines concentration in 2 studies [ 28 , 142 ], and both CSF and serum/plasma were investigated in 9 studies [ 25 , 127 , 131 , 144 , 147 , 152 , 175 , 179 , 180 , 183 ]. Twelve cytokines and chemokines were included in the CSF meta-analysis, namely IL-2 [ 149 , 156 , 175 ], IL-4 [ 125 , 126 , 156 , 183 ], IL-6 [ 25 , 125 , 126 , 134 , 141 , 156 , 178 , 184 ], IL-8 [ 29 , 30 , 125 , 126 , 140 , 156 ], IL-10 [ 25 , 125 , 126 , 134 , 149 , 156 , …”

“…Five cytokines, including CXCL10 [ 127 , 147 , 179 , 180 ], CXCL13 [ 25 , 179 , 180 ], IL-6 [ 25 , 131 , 142 ], IL-10 [ 25 , 28 , 131 ], and TNF-α [ 28 , 142 , 144 , 175 ] were encompassed in the serum/plasma meta-analysis. The concentration of the cytokines were measured using enzyme-linked immunosorbent assay (ELISA) (_((((xxx))))_)[ 25 , 28 – 30 , 131 , 134 , 141 , 142 , 147 , 149 , 152 , 175 , 178 – 180 , 183 , 184 ], flowcytometry immunoassay [ 28 , 127 , 140 ], and multiplex assay [ 125 , 126 , 156 ]. The total number of the included subjects in the serum meta-analysis is 421, comprised of 241 patients and 180 controls.…”

Aldosterone is a possible new stimulating factor for promoting vascular calcification

“…We therefore hypothesized that aldosterone could increase vascular calcification, and spriolactone can alleviate vascular calcification. Osteopontin (OPN) is a multifunctional aspartic acid, N-linked glycosylated protein that highly expressed in chronic inflammatory and autoimmune diseases [21]. OPN appears to modulate inflammatory, proliferation [22], migration [23,24], and accumulation of smooth muscle and endothelial cells, all these were involved in the repair and remodeling processes of the vasculature [25].…”