title: T cell reactivity to P0, P2, PMP-22, and myelin basic protein in patients with Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neuroimmunology Research Centre, School of Medicine, The University of Queensland, Brisbane, Australia.
authors.forename: P A
authors.initials: PA
authors.lastname: Csurhes
authors.forename: A-A
authors.initials: AA
authors.lastname: Sullivan
authors.forename: K
authors.initials: K
authors.lastname: Green
authors.forename: M P
authors.initials: MP
authors.lastname: Pender
authors.forename: P A
authors.initials: PA
authors.lastname: McCombe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000276:immunology; D005260:Female; D020275:Guillain-Barre Syndrome / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000276:immunology*; D018993:Myelin P0 Protein / Q000276:immunology*; D018996:Myelin P2 Protein / Q000276:immunology*; D009185:Myelin Proteins / Q000276:immunology*; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D015848:Interleukin-5; D004676:Myelin Basic Protein; D018993:Myelin P0 Protein; D018996:Myelin P2 Protein; D009185:Myelin Proteins; C073687:PMP22 protein, human; D007371:Interferon-gamma