Comparative Proteomics Analysis Of Serum Of Patients With Guillain-Barré Syndrome

Objectives:Guillain-Barrésyndrome (GBS) is an acute inflammatory polyneuropathy . It is now the most common cause of acute flaccid paralysis in the world. Based on electrophysiologic and pathologic findings, GBS has two predominant forms: acute inflammatory demyelinating polyneuro- pathy (AIDP) and acute motor axonal neuropathy (AMAN). In North America and Europe, GBS is usually caused by AIDP, with electrophysiologic evidence of demyelination in both motor and sensory nerve fibers. In contrast, a considerable number of GBS patients have AMAN in China and Japan. The cause and etiopathogenisis of GBS is not completely clear. It is considered to be an autoimmune disease at present. The crossreactivity between microbial and neural antigens partly explains the pathophysiology of the disease and the possible detection of antiganglioside antibodies. However, the molecular mechanisms underlying the disease remain poorly understood and so far no reliable disease-related markers are available. There is antibody, complement and cytokine relative to GBS in the blood and cerebrospinal fluid (CSF) of GBS patients. The immunomodulatory therapy like IVIg or plasmapheresis is proved efficacious. The global analysis of cellular proteins has recently been termed proteomics and is a key area of research that is developing in the post-genome era. Proteomics offers scientists the possibility of identifying disease- associated protein markers to assist in diagnosis or prognosis and to select potential targets for specific drug therapy. Proteomics, the study of identifying the entire protein components (proteome) of a cell, tissue or fluid at agiven point in time."Clinical proteomics"have appeared following the application and development of proteomics in the human disease and clinical medicine.Comparative proteomics analysis between normal and abnormal individual may discover some special disease- related protein. We plan to use comparative proteomics to research serum proteins in GBS patients and control subjects which may discover potential proteins about the disease. It may be a way to study the molecular mechanisms of GBS.Methods:1 Objects: The serum samples from GBS patients ( according to Asbury diagnostic criterion ) and control subjects.All of subjects from the Department of Neurology, the second hospital affiliated Hebei Medical University. 2 Empirical procedures: The blood sample were centrifuged and then stored under -80℃; The rich-abundance protein were removed; The serum proteins extracted with mixture of urea, CHAPS, DTT, IPG buffer and protease inhibitors were run immobilized pH gradient (IPG) isoelectric focusing electrophoresis as the first dimension, and then run vertical SDS-PAGE as the second dimension. The map is visualized by silver staining or colloidal coomassive blue and analysised with ImageMaster 2D Elite software. The proteins of interest were in-gel digested and identified using MALDI-TOF mass spectrometry or MALDI-TOF/TOF tandem mass spectrometry.Results: Our data showed that the levels of fourteen proteins and their isoforms or their precursor in serum were significantly altered in GBS patients compared with controls.There are fourteen proteins that were up-regulated in serum of GBS patients: alpha-1-antichymotrypsin precursor, gelsolin isoform a precursor, Chain A Crystal Structure Of Uncomplexed Vitamin D-Binding Protein, complement component C4B, Chain A Crystal Structure Of Human Beta-2-Glycoprotein-I (Apolipoprotein-H), ceruloplasmin, Chain A Crig Bound To C3c, Human Complement Factor B, Chain B Human Complement Component C3, Alpha-2-macroglobulin precursor (Alpha-2-M) and complement component 1, s subcomponent. And there are three proteins that were down-regulated: plasminogen, apolipoprotein E precursor, Chain A A Covalent Dimer Of Transthyretin.Conclusions:Nowadays, there is no report about serologic proteomics analysis between GBS patients and control subjects. We concluded that these fourteen proteins detected from our experiment may be involved in the pathogenesis of GBS. It may provide potential biomarkers for the diagnosis and evaluation of the treatment and prognosis of the disease. It will offer us a new direction to study and research GBS tomorrow.