MSACL Conference Schedule

Differential Neuroproteomics Reveal Characteristic Protein Expression Changes in Fulminant Multiple Sclerosis
Wed 10:30 AM - Session: Disease Markers
Jonas Bergquist

Multiple Sclerosis (MS) is a chronic demyelinating disorder of the central nervous system. In rare fulminant cases rapid progression may lead to death shortly after diagnosis. Currently there is no available diagnostic test to predict disease course and prognosis in individual patients, therefore identification of biomarkers that can differentiate at an early stage between clinical forms and predict severity of the disease is of great importance. The aim of this study was to identify potential biomarkers/proteins related to rapid progression.

Patients and Methods:

We present the case history of a 15-year-old male MS patient diagnosed according to McDonald's criteria. In the course of the disease cerebrospinal fluid (CSF) from lumbar puncture was taken at two time points: (1) at diagnosis and (2) at the time of rapid progression that finally lead to the patient's death within two years from the first symptoms. With a shotgun-proteomic approach based on isobaric tag labeling and nanoflow liquid chromatography (nanoLC) in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry (MALDI TOF MS/MS) we quantitatively analysed the protein content of the following CSF samples: two CSF samples from a patient with fulminant MS, one MS patient with relapsing-remitting (RR) clinical form (disease control) and one control headache patient, whose CSF analysis proved to be normal. Results: 75 proteins have been identified in the CSF samples. The relative abundance of these proteins showed differences across the samples. Seven proteins were found to be more abundant by at least 50% in both fulminant MS samples but not in the RR MS sample compared to control. These proteins are involved in the immune response, regulation of blood coagulation, cell proliferation and cell adhesion. Conclusions: In this pilot study we were able to show differences in the CSF proteome of a rapidly progressing MS patient compared to a more typical clinical form of MS and a control subject. In an ongoing study we aim to verify our results by analyzing more CSF samples from MS patients with different clinical forms of the disease and matched controls.