myelin-basic-protein and Guillain-Barre-Syndrome

Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy affecting the myelin-protein sheathing and the axons themselves to various degrees. Damage to these structures causes biomarkers to be released into the adjacent body fluid compartment. In case of the proximal nerve roots these biomarkers diffuse into the cerebrospinal fluid (CSF). Here we review the literature on CSF biomarkers in GBS, including a discussion of CSF basic findings, myelin sheath-associated markers (myelin basic protein), axonal damage markers (neurofilaments, tau, anti-ganglioside antibodies), glial and neuronal markers (neuron specific enolase, 14-3-3 proteins, S100B, hypocretin-1), immunological markers (different chemokines and complement factors, cystatin C, tumor necrosis factor-alpha) as well as recent advances in the field of CSF proteome analysis in GBS. Second, the different pathophysiological mechanisms reflected by these biomarkers are discussed. Finally, candidate biomarkers are reviewed with regard to their clinical relevance to act as a surrogate for the disease process, their value for improving prognostic accuracy and their potential to be used as predictors of treatment response.

Topics: 14-3-3 Proteins; Axons; Biomarkers; Cerebrospinal Fluid Proteins; Guillain-Barre Syndrome; Humans; Myelin Basic Protein; Neuroglia; Neurons; Phosphopyruvate Hydratase; Predictive Value of Tests; Prognosis

Since the worldwide spread of the novel influenza type A virus in 2009, trivalent vaccines against H1N1 (pandemic) 09 and seasonal influenza have been used. We describe a 33-year-old woman who presented with hypoesthesia below the Th7 level fifteen days after vaccination without any preceding infection. Cerebrospinal fluid showed an increased level of myelin basic protein and positive oligoclonal IgG bands. Magnetic resonance imaging revealed disseminated lesions in the brain and thoracic cord. Steroid therapy improved her symptoms. She was diagnosed as having acute disseminated encephalomyelitis (ADEM) possibly related to the vaccination. As a potential adverse effect of the influenza vaccine, in addition to Guillain-Barré syndrome, ADEM should also be recognized.

Topics: Adult; Encephalomyelitis, Acute Disseminated; Female; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Japan; Magnetic Resonance Imaging; Myelin Basic Protein

The clinical characteristics of five (22%) of 23 patients with Guillain-Barré syndrome (GBS), whose serum contained immunoglobulin G (IgG) antibodies to the ganglioside N-acetylgalactosaminyl GD1a (GalNAc-GD1a), included pure motor weakness of the axonal type. These patients had a relatively good prognosis, but displayed higher serum tumor necrosis factor-alpha (TNF-alpha) titers than the other GBS patients. We examined the effect of serum from these patients with IgG anti-GalNAc-GD1a antibodies on neurites from cultured rat dorsal root ganglia (DRG) and found it to damage the myelin in well-elongated DRG neurites and monolayer cultures of Schwann cells and neurons. In the regeneration model, serum from these patients delayed neurite extension and inhibited Schwann cell proliferation. Neurons in cultured monolayers showed vacuolation and decreased rapidly in number. Schwann cells were also vacuolated and readily detached from the substratum. The effects of IgG anti-GalNAc-GD1a antibodies purified from one of the patients, rabbit serum after immunization with GalNAc-GD1a, and recombinant TNF-alpha were also examined. IgG anti-GalNAc-GD1a antibodies mainly inhibited the regeneration and preservation of neurons, while TNF-alpha mainly induced morphological changes in well-proliferated Schwann cells and myelin.

Topics: Adolescent; Adult; Animals; Animals, Newborn; Antibodies, Anti-Idiotypic; Child; Chromatography, Thin Layer; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique; Ganglia, Spinal; Gangliosides; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Myelin Basic Protein; Myelin Sheath; Neurites; Neurofilament Proteins; Organ Culture Techniques; Rats; S100 Proteins; Schwann Cells; Time Factors; Tumor Necrosis Factor-alpha

It has been suggested that autoimmunity to peripheral myelin proteins is involved in the pathogenesis of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We aimed to compare reactivity of peripheral blood mononuclear cells (PBMC) to antigens of peripheral myelin proteins in patients with GBS and patients with CIDP with that of healthy controls and patients with other non-immune mediated neuropathies (ON).. We prepared PBMC from blood from 83 healthy controls and from 64 patients with GBS, 54 with CIDP, and 62 with ON. PBMC were tested in antigen specific proliferation assays against peptides from myelin proteins P0, P2, PMP22, and myelin basic protein (MBP), which is identical to myelin P1, and against whole human MBP. Interferon-gamma (IFN-gamma) and interleukin (IL)-5 enzyme linked immunospot (ELISPOT) assays were also performed in some subjects to assess spontaneous and peripheral myelin antigen specific PBMC cytokine secretion.. Antigen specific PBMC proliferation assays showed no significant elevation of peptide specific T cell responsiveness in patients with GBS or CIDP compared with healthy controls or patients with ON. Levels of spontaneous ELISPOT IFN-gamma secretion were increased in patients with GBS and significantly increased in those with CIDP compared with healthy controls and patients with ON. No convincing differences in antigen specific ELISPOT IFN-gamma secretion levels to individual peptides were detectable in patients with GBS. The proportion of patients with CIDP with an increased number of PBMC producing IFN-gamma in response to peptide PMP-22(51-64) was significantly increased compared with healthy controls and patients with ON. No significant differences in antigen specific ELISPOT IL-5 secretion levels were detectable in patients with GBS or CIDP compared with controls, but levels of spontaneous IL-5 secretion were significantly higher in patients with CIDP than in healthy controls or patients with ON.. Although the lack of significantly increased antigen specific PBMC proliferation in GBS and CIDP does not support a role for T cells, the more sensitive ELISPOT technique detected increased numbers of PBMC secreting IFN-gamma spontaneously in 25% of patients with GBS, providing further evidence for a role of T cells in the immunopathology of GBS. Increased numbers of spontaneous IFN-gamma and IL-5 secreting cells, and increased IFN-gamma secretion in response to PMP-22(51-64), in patients with CIDP provide further evidence for a role of myelin specific T cells in CIDP.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cytokines; Female; Guillain-Barre Syndrome; Humans; Interferon-gamma; Interleukin-5; Male; Middle Aged; Myelin Basic Protein; Myelin P0 Protein; Myelin P2 Protein; Myelin Proteins; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; T-Lymphocytes; Th1 Cells; Th2 Cells