Evaluation of CSF and serum Fetuin-A, CSF S100B and GFAP as predictive markers in multiple sclerosis (P5.211)

OBJECTIVE: To evaluate the biomarkers Fetuin-A, S100B and GFAP in cerebrospinal fluid (CSF) and serum for their utility as biomarkers to predict conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) and to differentiate between relapsing and progressive subytpes of MS. BACKGROUND: Despite the possibility to establish early diagnosis of MS on the basis of the revised McDonald 2010 criteria, there is still a need for more reliable biomarkers as predictors for disease progression after first clinical manifestation. DESIGN/METHODS: The study comprised treatment-naive, newly diagnosed CIS (n=23), relapsing-remitting (RR) (n=22) and primary-progressive (PP) MS (n=7) patients.Samples were collected following a relapse (CIS and RRMS) within one month. Age and gender-matched pseudotumour cerebri patients (n=10) were choosen as controls. Demographic, clinical and radiologic data of each patient were recorded. Besides routine CSF-serum analysis; the candidate biomarkers Fetuin-A (inflammatory activity), S100B (astrocytic activity) and glial-fibrillary-acidic-protein[GFAP] (astrogliosis) were assessed via quantitative immunoassays (ELISA). CIS-group was followed-up for a median time of two years. Median disease duration of PPMS was 4.5 (3.75-6) years. RESULTS: The Qalb (CSFalb/serumalb) and IgG-index were found significantly higher in PPMS (p=0.001; p=0.020). Fetuin-antibody-index[AI] (Qfetuin/Qalb) differentiated between controls and MS (p=0.0001), and within MS subgroups there was a non-significant gradual decrease from CIS, RRMS to PPMS. CSF-GFAP and S100B were significantly increased in patients with severe disability (EDSS>6) compared to those with moderate (EDSS3-6) and mild (EDSS 0.05). CONCLUSIONS: While all investigated biomarkers are not helpful to predict conversion from CIS to MS, Fetuin-AI shows a weak correlation between the MS subtypes with highest levels in PPMS patients. CSF-GFAP and S100B are associated with severe disability independently of the disease subtype. Disclosure: Dr. Altintas has received research support from The Scientific and Technological Research Council Of Turkey. Dr. Akkas-Yazici has nothing to disclose. Dr. Tumani has received personal compensation for activities with Bayer Pharmaceuticals, Inc., Biogen Idec, Merck Serono, Teva Neuroscience, Roche Diagnostics Corporation, Genzyme Corporation, and Virotech. Dr. Lehmensiek has nothing to disclose.