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)

Adhesion molecules are important in T-cell trafficking to sites of inflammation. We determined levels of circulating vascular cell adhesion molecule-1 (VCAM-1), L-selectin, and E-selectin in the serum of 147 patients with definite multiple sclerosis of the remitting-relapsing or secondary progressive type. Soluble VCAM-1 and L-selectin concentrations were increased compared to levels in a large group of control subjects. Levels were highest in patients with gadolinium-enhancing lesions on magnetic resonance imaging (VCAM-1: 1,011 +/- 276 vs 626 +/- 87 ng/ml; L-selectin: 1,130 +/- 272 vs 793 +/- 207 ng/ml [mean +/- standard deviation]; p < 0.0001 vs patients without enhancing lesions). Serum levels of soluble tumor necrosis factor receptor (60 kd) were also raised (2.64 +/- 1.23 vs 2.17 +/- 0.69 ng/ml in subjects with other neurological diseases and 2.1 +/- 0.77 ng/ml in healthy control subjects; p < 0.05). Soluble VCAM-1 and L-selectin levels were correlated to concentrations of soluble tumor necrosis factor receptor. In 13 patients with viral encephalitis, similar observations were made. Raised levels of soluble VCAM-1 and L-selectin probably reflect cytokine-induced endothelial cell and T-lymphocyte/monocyte activation occurring in the process of T-cell migration into the central nervous system. Tumor necrosis factor-alpha may be critically involved.

In this uncontrolled study, 104 patients with generalized myasthenia gravis treated with azathioprine for a median period of 29 months (range, 1 month to 12 years) were surveyed for possible adverse reactions. These occurred in 36 patients (35%) in the following order of frequency: hematologic (18%), gastrointestinal (13%), infectious diseases (13%), and elevation of liver enzymes (6%). No allergic skin reactions were observed. Azathioprine had to be discontinued temporarily in a total of 11 patients (11%) because of possible side effects. The cause of death in the nine patients who died during the period of observation (up to 12 years) was related to myasthenic crisis in two patients. In five patients, a malignant tumor was diagnosed (two carcinoma of the prostate, one ovarian carcinoma, one bronchial carcinoma, and one renal lymphoma) after 2.5 years, 6 months, 3 months, 5 years, and 6 years of treatment, respectively. A causal relationship seems unlikely in the first four cases, but cannot be excluded in the one case of late lymphoma.

Intercellular adhesion molecule ICAM-1 has a crucial role in the induction of an immune response and is instrumental in migration of T cells into inflamed tissue. We studied soluble ICAM-1 concentrations in patients with multiple sclerosis (MS), viral encephalitis, and other immunologic diseases, and compared results with those in other noninflammatory, nondemyelinating neurologic disorders as well as in healthy controls. MS patients with clinically active disease or enhancing lesions on MRI had elevated serum levels of soluble ICAM-1. Concentrations of soluble ICAM-1 were also increased in some patients with viral encephalitis. These findings raise the possibility that circulating ICAM-1 serves as a marker of acute inflammatory events in the brain and add to evidence implicating this adhesion molecule in the pathogenesis of MS.

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.