Guillain-Barre' syndrome (GBS) is an immune-mediated, inflammatory, demyelinating polyneuropathy. In serum of GBS patients, complement fixing antibodies against peripheral nerve myelin can be found, which correlate with the clinical course and precede the appearance of activated complement components in CSF, serum and peripheral nerve. A significant portion of this Ab activity in some GBS patients is directed against a neutral glycolipid of peripheral nerve myelin that cross-reacts with Forssman antigen. Forssman is a component of several viruses and bacteria, and heterophile responses accompanying many infections are partly directed against Forssman antigen. In this proposal we want to study the role of antibody and complement in peripheral nerve demyelination in experimental allergic neuritis (EAN), an animal model of GBS.
Our specific aims are: 1) To study the development of experimental allergic neuritis in the Lewis rat, following immunization with Forssman antigen. 2) To determine which epitope on Forssman is recognized by serum Ab from Forssman induced EAN animals. 3) To determine if affinity-purified Ab from EAN serum can cause demyelination following intraneural injection in Lewis rat sciatic nerve. 4) To study the effect of complement depletion on blood-nerve barrier integrity in EAN induced by peripheral nerve myelin. Electrophysiologic testing and histologic studies will be done to assess peripheral nerve demyelination in EAN, and after intraneural injection. Immunological techniques to be used include ELISA, C1 fixation-transfer assay and HPTLC.
|Vriesendorp, F J; Flynn, R E; Malone, M R et al. (1998) Systemic complement depletion reduces inflammation and demyelination in adoptive transfer experimental allergic neuritis. Acta Neuropathol (Berl) 95:297-301|
|Vriesendorp, F J (1997) Insights into Campylobacter jejuni-induced Guillain-Barre syndrome from the Lewis rat model of experimental allergic neuritis. J Infect Dis 176 Suppl 2:S164-8|
|Vriesendorp, F J; Quadri, S M; Flynn, R E et al. (1997) Preclinical analysis of radiolabeled anti-GD2 immunoglobulin G. Cancer 80:2642-9|
|Vriesendorp, F J; Flynn, R E; Khan, M et al. (1996) Oral administration of type I interferon modulates the course of experimental allergic neuritis. Autoimmunity 24:157-65|
|Vriesendorp, F J; Triggs, W J; Mayer, R F et al. (1995) Electrophysiological studies in Guillain-Barre syndrome: correlation with antibodies to GM1, GD1B and Campylobacter jejuni. J Neurol 242:460-5|
|Vriesendorp, F J; Flynn, R E; Pappolla, M A et al. (1995) Complement depletion affects demyelination and inflammation in experimental allergic neuritis. J Neuroimmunol 58:157-65|
|Vriesendorp, F J; Mishu, B; Blaser, M J et al. (1993) Serum antibodies to GM1, GD1b, peripheral nerve myelin, and Campylobacter jejuni in patients with Guillain-Barre syndrome and controls: correlation and prognosis. Ann Neurol 34:130-5|