An acute infectious illness frequently precedes the Guillain-Barré syndrome. Recently, Campylobacter jejuni was claimed to be a predominant precipitating agent that may also trigger a humoral immune response to glycoconjugates of peripheral myelin in Guillain-Barré syndrome. Because of conflicting reports, we determined the frequency of a recent infection with C. jejuni in 38 patients with Guillain-Barré syndrome using a highly sensitive and specific immunoblot technique, and of the presence of circulating antibodies to gangliosides. We detected IgM and/or IgG C. jejuni directed antibodies in 15 of 38 patients with Guillain-Barré syndrome. In contrast, only 7 of 39 healthy control subjects, 3 of 20 patients with multiple sclerosis, and 2 of 72 patients with neuroborreliosis showed IgA or IgM antibody responses to C. jejuni. In Guillain-Barré syndrome, C. jejuni-specific antibodies were predominantly directed to outer membrane proteins of one specific serotype, Lior 11, whereas the most common serotype associated with enteritis in Germany is Lior 4. Two of 27 patients with Guillain-Barré syndrome had ganglioside-specific IgA antibodies; 1 of 32 patients, antibodies of IgM; and 4 of 31 patients, antibodies of IgG class. There was no correlation between severity, type (axonal versus demyelinating), and outcome of the disease and the presence or absence of a humoral immune response to C. jejuni or to glycoconjugates. Our findings do not support previous suggestions that a preceding C. jejuni infection heralds a poorer outcome or that antibodies to gangliosides carry prognostic significance.(ABSTRACT TRUNCATED AT 250 WORDS)

We have investigated the functional role of very late antigen-4 [VLA-4 (alpha4/beta1) integrin] and vascular cell adhesion molecule-1 (VCAM-1) in experimental autoimmune neuritis (EAN), an animal model of the Guillain-Barré syndrome, using neutralizing monoclonal antibodies (mAbs) as probes. Disease was induced by intravenous adoptive transfer of P2 specific T cells (AT-EAN), or by immunization with bovine myelin (active EAN). Preventive treatment with 500 microg anti-VLA-4 mAb (TA-2) or with an isotype control antibody was given in AT-EAN 4 h before cell transfer and at day 3. Intravenous injection of 500 microg anti-VCAM-1 mAb (5F10) or a corresponding isotype control was given in AT-EAN 4 h before disease induction, and at days 2, 4 and 6. Preventive treatment of active EAN with mAb to VLA-4 or VCAM-1 was performed at days 5, 9 and 13. On immunohistochemical examination, VCAM-1 in sciatic nerve was found to be upregulated at early stages of EAN (days 3-5 after T-cell transfer), whilst no expression was noted in healthy controls. In both EAN models, blockade of VLA-4 markedly attenuated disease severity. Blockade of VCAM-1 also significantly ameliorated the disease course and diminished T-cell infiltration in sciatic nerve, but to a lesser degree. These experiments demonstrate the critical role of VLA-4 in the pathogenesis of EAN and show that upregulation of VCAM-1 expression contributes, at least in part, to the progression of the disease in the early stages. Future studies are needed to assess the potential contribution of other VLA-4 ligands.

Goodpasture's syndrome is mediated by immunopathogenic autoantibodies to the alpha 3 NC1 domain of type IV collagen. It is not known whether collaborating T-cells participate in this autoreactive response. Here we describe the first T-cell clone isolated from a Goodpasture patient autoreactive to alpha 3 type IV collagen of glomerular basement membrane. To investigate cellular autoreactivity, T-cells from Goodpasture patients or controls were isolated and stimulated by purified native or recombinant type IV collagen proteins and synthetic oligopeptides. Cell surface markers, the T-cell receptor repertoire, and MHC-restriction were analyzed. T-cell clones specific for the alpha 3 (IV) NC1 domain were established in two Goodpasture patients, but not in controls. One of the three CD8+ T-cell clones was characterized further. It was MHC class I restricted (HLA-A11) and expressed the T-cell receptor V beta 5.1. chain. This clone specifically recognized a motif at the N-terminal area of the alpha 3 (IV) NC1 domain (AA 51 to 59: GSPATWTTR). We conclude that autoreactive T-cells exists in Goodpasture patients and may play a crucial role in the inflammatory process. T-cell clones are autoreactive to the alpha 3 (IV) NC1 domain. At least for one of the clones, the T-cell epitope is different from the putative antibody-binding site.

Adhesion molecules are critically involved in inflammatory responses. We studied serum concentrations of the soluble form of E-selectin (endothelial-leukocyte adhesion molecule-1, ELAM-1) in 187 patients with neuropathies of diverse etiology, 54 patients with other noninflammatory, nondemyelinating neurologic disorders, and 15 healthy controls. Serum E-selectin levels, quantitated by a two-site enzyme-linked immunosorbent assay, were significantly increased in 126 patients with Guillain-Barré syndrome (GBS) (mean +/- SD, 45.1 +/- 16.3 ng/ml) and 13 patients with vasculitic neuropathies (47.1 +/- 19.1ng/ml) compared with patients with other neurologic diseases (19.8 +/- 7.4 ng/ml) and healthy controls (21.9 +/- 8.1 ng/ml). In GBS, E-selectin levels were temporally related to disease activity. Cytokine-mediated upregulation of E-selectin may be important in homing and attachment of leukocytes to endoneurial endothelial cells. Raised E-selectin concentrations probably reflect endothelial cell activation occurring early in the sequence of immunopathologic events culminating in peripheral nerve damage.