CSF levels of HoxB3 and YKL-40 may predict conversion from clinically isolated syndrome to relapsing remitting multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) often initiates with an acute episode of neurological disturbance, known as clinically isolated syndrome (CIS). There is an unmet need for biomarkers that differentiate patients who will convert to MS and who will remain as CIS after the first attack. METHODS: First attack serum and cerebrospinal fluid (CSF) samples of 33 CIS patients were collected and these patients were divided as those who converted to MS (CIS-MS, n=17) and those who continued as CIS (CIS-CIS, n=16) in a 3-year follow-up period. Levels of homeobox protein Hox-B3 (HoxB3) and YKL-40 were measured by ELISA in samples of CIS-CIS, CIS-MS, relapsing remitting MS (RRMS) patients (n=15) and healthy controls (n=20). RESULTS: CIS-CIS patients showed significantly reduced CSF levels of YKL-40 and increased serum/CSF levels of HoxB3 compared with CIS-MS and RRMS patients. CIS-MS and RRMS patients had comparable YKL-40 and HoxB3 level profiles. Receiver operating characteristic (ROC) curve analysis showed the highest sensitivity for CSF HoxB3 measurements in prediction of CIS-MS conversion. Kaplan-Meier analysis demonstrated that CIS patients with lower CSF HoxB3 (<3.678 ng/ml) and higher CSF YKL-40 (>654.9 ng/ml) displayed a significantly shorter time to clinically definite MS. CONCLUSION: CSF levels of HoxB3 and YKL-40 appear to predict CIS to MS conversion, especially when applied in combination. HoxB3, which is a transcription factor involved in immune cell activity, stands out as a potential candidate molecule with biomarker capacity for MS.

Serum levels of inflammasome pathway factors in clinically isolated syndrome and multiple sclerosis patients: a pilot study.

Pathogenic roles of nuclear factor κB (NF-κB) pathway and NLRP3 inflammasome complex factors are involved in multiple sclerosis (MS) development. Activation of the NF-κB, NLRP3, and caspase-1 cascade results in production of proinflammatory cytokines that lead to stimulation of macrophages, lymphocytes, and glial cells. Although increased levels of inflammasome complex factors are observed in MS, contribution of inflammasome pathway to conversion from clinically isolated syndrome (CIS) to relapsing remitting MS (RRMS) has been scarcely investigated. To examine predictive value of inflammasome factors in CIS-MS conversion, levels of NLRP3, caspase-1, and NFκB are measured by ELISA in sera of age-gender matched CIS (n = 18; 8 converting, 10 non-converting) and RRMS (n = 23) patients. CIS and RRMS patients have comparable serum levels of NLRP3, caspase-1, and NFκB. Similarly, no statistically significant difference can be found among converting and non-converting CIS patients by means of inflammasome complex factor levels. Inflammasome factors are presumably overexpressed at early stages of MS. Therefore, they are unlikely to be used as biomarkers to predict CIS-MS conversion.

Adipokines in Multiple Sclerosis Patients with and without Optic Neuritis as the First Clinical Presentation.

BACKGROUND: Adipocytokines have been implied to be involved in multiple sclerosis (MS) pathogenesis. MS patients whose first clinical episode is optic neuritis (ON) have been reported to display a milder disease course. In this study, we aimed to show whether this milder disease course is related to reduced adipokine production. METHODS: A total of 55 (24 with ON as the first clinical episode) relapsing-remitting MS (RRMS) patients and 40 healthy individuals were recruited. Concentrations of adipokines were measured in sera by ELISA. RESULTS: The levels of adiponectin, leptin, resistin, monocyte chemoattractant protein-1 (MCP-1) and IL-8 were significantly higher in RRMS patients compared with healthy controls. RRMS cases starting with ON had lower expanded disability status scale scores. Serum adiponectin, leptin, resistin and MCP-1 levels were significantly lower in MS patients, whose first clinical episode was ON. CONCLUSIONS: MS patients with ON as the first manifestation display both lower disability scores and reduced serum adipokine levels implying that adipocytokine production is associated with MS progression. Exact mechanisms of this association in MS patients with first episode ON need to be further studied.

Investigation of the prognostic value of adipokines in multiple sclerosis.

BACKGROUND: Adipokines may be involved in multiple sclerosis (MS) as well as other inflammatory diseases. This study aimed to analyze the value of serum adipokine levels as biomarkers in determining the clinical progression of MS. METHODS: A total of 90 subjects including 40 healthy individuals and 50 MS patients [24 with classical clinical course of MS (C-MS), 26 with benign MS (B-MS)] were recruited for this study. The levels of serum adipokines and inflammatory mediators were measured using immunoassay methods. RESULTS: The levels of adiponectin, MCP-1, TNF-α and IL-6 were significantly higher in C-MS patients compared with B-MS patients and healthy controls. Only adiponectin and MCP-1 levels remained significantly high after Bonferroni correction. Adiponectin, MCP-1 and TNF-α levels showed a modest correlation with expanded disability status scale (EDSS) scores, which disappeared after Bonferroni correction. CONCLUSIONS: Our findings suggest the potential role of adipokines in pathogenesis and clinical progression of MS. Adiponectin and MCP-1 might potentially serve as prognostic biomarkers in MS.