Proteomic Analysis in CSF Identified Subtype Specific and Shared Molecular Pathways for Multiple Sclerosis Clinical Phenotypes (P5.216)

Objective: The purpose of this study is to find out molecular pathways associated with the etiopathogenesis of Multiple Sclerosis (MS) and its major subclinical pathways. To this aim proteomic and bioinformatics approaches were used to reveal the differentially expressed proteins and their related pathways in cerebrospinal fluids of patients with clinically isolated syndrome, relapsing remitting MS and progressive MS. Background: Phenotypic heterogeneity of MS appears to be cause by immune-mediated, neuro-inflammatory, demyelinating and neurodegenerative processes harboring complex molecular mechanisms. Design / Methods: CSF samples of 63-CIS, 72-RRMS, 44-PPMS and 42-controls including healthy subjects and other neurological disease samples were analyzed. For all samples, 2D-PAGE analyses were performed. At least four times differently expressed protein spots were identified by PDQuest® software and removed from the gel for MALDI-TOF-MS protein identification analysis. The results of proteomic studies were further confirmed by both ELISA and western blot methods for selected candidate proteins. KEGG pathways analysis was done with genes corresponding the proteins to identify disease relevant specific molecular pathways. Results: Comparison of disease groups with controls identified a total of 151 proteins that are differentially expressed in clinically different MS subtypes. KEGG analysis using PANOGA tool revealed disease related pathways including aldosterone-regulated sodium reabsorption (p=8.02x10-5) which is important in the immune cell migration, renin-angiotensin (p=6.88x10-5) system that induces Th17 dependent immunity, notch signaling (p=1.83x10-10) pathway indicating the activated remyelination and vitamin digestion and absorption pathways (p=1.73x10-5). Conclusions: Proteomic investigation of in CSF samples of different MS phenotypes indicated that all MS clinical forms share common biological pathways such as renin-angiotensin system (RAS) and complement and coagulation cascade (CCC) pathways. There are also clinical subtype specific and pathophysiology related pathways which may have further therapeutic implications. This study was supported by The Scientific and Technological Research Council of Turkey (TUBITAK) fund, numbered 109S070. Disclosure: Dr. Avsar has nothing to disclose. Dr. Durasi has nothing to disclose. Dr. Uygunoglu has nothing to disclose. Dr. Tutuncu has nothing to disclose. Dr. Demirci has nothing to disclose. Dr. Saip has nothing to disclose. Dr. Sezerman has nothing to disclose. Dr. Siva has nothing to disclose. Dr. Turanli has nothing to disclose.