Predictive value of levels of cerebrospinal fluid cytokines on relapse and conversion to multiple sclerosis of patients with clinical isolated syndrome
Objective To investigate the predictive value of levels of ten cerebrospinal fluid( CSF) cytokines including interleukin-6( IL-6) on relapse and conversion to multiple sclerosis( MS) of patients with clinical isolated syndrome( CIS). Methods A total of 33 patients with acute CIS admitted to Beijing Tiantan Hospital Affiliated to Capital Medical University from January 2015 to August 2017 were retrospectively enrolled, including 9 males and 24 females, with a median age of 35 years old. The CSF levels of IL-6, IL-4, IL-2, IL-10, IL-13, IL-17A, IL-21, IL-23, and interferon-γ( IFN-γ) were detected by Luminex liquid chip method. The level of transforming growth factor beta 1( TGF-β1) was detected by enzyme-linked immunosorbent assay( ELISA). The patients were followed up in outpatient service, and the relapse and conversion to MS were recorded. The difference of CSF cytokines between relapse and non relapse patients was compared. Receiver operating characteristic( ROC) curve and Cox regression models were used to analyze the predictive value of CSF cytokines on the the relapse and conversion to MS of CIS patients. Results The median follow-up time of the enrolled patients was 23.4( 17.6, 29.1) months. 11 CIS cases( 33.3%) had clinical relapse during the follow-up period, and 4 cases were diagnosed as MS. Although no clinical recurrence was found in other 2 patients, follow-up MR revealed new lesions, which were diagnosed as MS. The level of CSF IL-6 in patients with relapse was significantly higher than that in patients without relapse[ 1.9( 1.4,7.9) ng/L vs. 1.1( 0.9,1.5) ng/L; Z=-2.904,P=0.003]. ROC curve analysis showed that the optimal cut-off value of IL-6 was 1.37 ng/L. However, Uni-variate Cox regression showed that CSF IL-6 > 1.37 ng/L could not predict the relapse of CIS (HR=1.54, 95%CI: 0.40-5.92,P=0.533). There was no significant difference in CSF IL-6 and the other 9 cytokines between the patients with conversion to MS and those without conversion to MS( all P > 0.05). Conclusions Ten cytokines such as IL-6 in CIF investigated in this study may not be markers for predicting the relapse or conversion to MS of CIS patients.