Cerebrospinal fluid proteome profile in patients with multiple sclerosis

Aims: Cerebrospinal fluid (CSF) proteins may provide important information about the pathomechanisms present in multiple sclerosis (MS). Although diagnostic criteria for early MS are available, there is still a need for biomarkers predicting disease subtype and progression. Therefore, we intended to analyze the CSF proteome profile of MS patients.

Methods: CSF samples from 12 patients with relapsing remitting MS (RRMS, mean age 40.4 years; median disease duration 24 months) and from 12 patients with clinically isolated syndrome (CIS, mean age 33.8 years; median disease duration 3 weeks) were analyzed and compared to age matched normal controls; all MS and CIS patients received a lumbar puncture during an acute relapse. CSF samples were analyzed by 2-dimensional difference in-gel electrophoresis (2-D-DIGE) technology. Only those protein spots that showed more than 2-fold difference between both groups were selected for further analysis with MALDI-TOF mass spectrometry.

Results: In RRMS, 11 different spots were detected. Only one of them was up-regulated which was identified as Ig kappa chain NIG precursor protein; on the other hand, 10 out of 11 proteins were down-regulated which were identified as transferrin, some serine proteinase inhibitors, alpha-2-HS-glycoprotein, apolipoprotein E and transthyretin. In contrast, 14 different spots were detected in the CSF of CIS patients. Two of the different proteins were up-regulated which were identified as IgG kappa chain and proapo-A-1-protein. Down-regulated proteins included serum albumine precursor, serum albumine, complement factor 3, some serine proteinase inhibitors, vitamin D-binding protein, translation-initiation factor elF-4-gamma, apolipoprotein E precursor and transthyretin. Some of these proteins, serine proteinase inhibitors, alpha-2-HS-glycoprotein and translation-initiation factor eIF-4-gamma, have not been reported in CSF of MS patients yet.

Conclusion: Our preliminary results show clear differences in the proteome profile of patients with RRMS and CIS as compared to normal controls. Though the pathopysiological role of these proteins still remain to be elucidated in detail and further validation of the findings is needed, this non-hypothesis driven approach may have a relevant impact on the identification of disease-specific markers.