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 re-examined 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.
Highlights
Anti-N-methyl-D-aspartate-receptor encephalitis is newly accepted as an autoimmune neurological disorder mainly affecting young women [1, 2]
We detected a significant increase in cerebrospinal fluid (CSF) OPN, IL-6, tumor necrosis factor (TNF)-α, and IL-10 in anti-NMDAR encephalitis patients in acute stage compared to controls, and both the levels of CSF OPN and its relevant cytokines decrease as the disease develops into the remission stage
We revealed that the CSF levels of OPN, IL-6, IL-10, and TNF-α were obviously higher in antiNMDAR encephalitis patients in acute stage compare to those in remission
Summary
Anti-N-methyl-D-aspartate (anti-NMDA)-receptor encephalitis is newly accepted as an autoimmune neurological disorder mainly affecting young women [1, 2]. Typical clinical manifestation of this disease predominantly involves the progressive development of neurological and psychiatric symptoms, such as movement disorder, seizures, speech disorder, consciousness disturbances, autonomic instability, and central hypoventilation [3]. The production of antibodies to the NMDA receptor is considered to be the main culprit of this disorder, its pathogenesis remains unclear. Patients usually develop from influenza-like symptoms to profound neurological impairments in a short time, and multidisciplinary care becomes essential and urgent [4, 5]. Cytokines mentioned previously like interleukin (IL)-6, tumor necrosis factor (TNF)-α have been proposed to play important roles in the pathogenesis of this disease [9,10,11]. We have reported increased inflammatory cytokines in cerebrospinal fluid (CSF) in the acute stage of anti-NMDAR encephalitis [12, 13]
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