Proteomic identification of potential protein markers in cerebrospinal fluid of GBS patients T. Jin a,b , L.-S. Hu a , M. Chang a , J. Wu a , B. Winblad c and J. Zhu a,b a Department of Neurology, the First Hospital, Jilin University, Changchun, China; b Division of Neurodegeneration and Neuroinflammation, Department of Neurobiology, Care Sciences and Society, Karolinska University Hospital Huddinge, Stockholm, Sweden; c Alzheimer Disease Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska University Hospital Huddinge, Stockholm, Sweden Keywords: cerebrospinal fluid, Guillain–Barre´ syndrome, mass spectrometry, proteomics, two-dimensional difference gel electrophoresis Received 30 September 2006 Accepted 29 January 2007 Increased protein level in the cerebrospinal fluid (CSF) is a characteristic of patients with Guillain–Barre´ syndrome (GBS), an acute inflammatory autoimmune disorder in the peripheral nervous system (PNS). However, the molecular mechanisms underlying the disease remain poorly understood and so far no reliable disease-related markers are available. By comparing the CSF proteome of GBS patients with control subjects suffering from other neurological disorders, it may be possible to identify proteins that involve in the disease process and thus to study the pathogenesis of GBS. We used two-dimensional difference gel electrophoresis (2D DIGE) technique, in combination with matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), to determine the abnormal CSF proteins in GBS patients. Our data showed that the levels of six proteins and their isoforms in CSF were significantly altered in GBS patients compared with controls. Haptoglobin, apolipoprotein A-IV and PRO2044 (unnamed protein) were considerably increased in the CSF of GBS patients, whereas transthyretin, apolipoprotein E and fibrinogen were considerably decreased. We concluded that these six proteins may be involved in the pathogenesis of GBS and call for further studying the role of these proteins in the pathogenesis of the disease. Introduction Guillain–Barre´ syndrome (GBS) is an immune- mediated inflammatory disease of the peripheral nerves, involving both the myelin sheath and the axons. GBS occurs worldwide and the incidence ranges from 0.6 to 4 per 100 000 per year [1]. Even when patients are treated in well-equipped intensive care units, mortality rates are still 3–7%. Moreover, about 7–15% of patients have permanent neurological sequelae including bilateral footdrop, intrinsic hand muscle wasting, sensory ataxia and dysesthesia [2], which severely affect human daily life. Because some patients suffer from the gastrointes- tinal or upper respiratory infections 1–2 weeks before the onset of clinical signs of GBS, it has been suggested that molecular mimicry between microbial antigens and host tissue might explain the pathogenesis of GBS [3]. Increased protein without pleocytosis in cerebrospinal fluid (CSF) is a characteristic of GBS. CSF examination may be normal during the first days after the onset of symptoms, but protein levels usually increase after 1 week. It is therefore important to determine the cause and function of these abnormal levels of disease related proteins. Proteomics, the study of identifying the entire protein components (proteome) of a cell, tissue or fluid at a given point in time, can provide insight into the mechanisms of diseases. Since proteins play a central role in the life of an organism, the study of proteome of the organism is helpful in discovery of biomarkers, especially such markers that may designate a particular disease. In this study, we used proteomics to identify the components of the abnormal protein levels in the CSF of GBS patients. Understanding of their expression and function may enable us to identify these disease-related proteins as markers to both aid in the diagnosis of GBS and possibly its treatment and prognosis. Materials and methods CSF samples Lumbar puncture was performed in the L4–L5 verteb- ral interspace to collect CSF samples from five GBS (according to Asbury diagnostic criterion [4]) and five Correspondence: Dr Jie Zhu, MD, PhD, Division of Neurodegener- ation and Neuroinflammation (Novum, plan 5), Department of Neurobiology, Care Sciences and Society, Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden (tel.: +46 8 58585494; fax: +46 8 58585470; e-mail: jie.zhu@ki.se). Ó 2007 EFNS 563 European Journal of Neurology 2007, 14: 563–568 doi:10.1111/j.1468-1331.2007.01761.x