Search for antibodies to neutral glycolipids in sera of patients with Guillain-Barré syndrome

doi:10.1016/0022-510X(91)90095-O

Journal of the Neurological Sciences

Volume 102, Issue 1, March 1991, Pages 67-75

https://doi.org/10.1016/0022-510X(91)90095-O Get rights and content

Abstract

Sera from 54 patients with Guillain-Barré syndrome (GBS), 34 patients with other neurological diseases (OND) and 32 healthy controls were tested for antibodies to total lipid fractions and higher neutral glycolipid fractions isolated from human and dog nerves, purified Forssman glycolipid and a panel of purified neutral glycolipids by both an enzyme-linked immunosorbent assay (ELISA) and a thin-layer chromatogram (TLC)-overlay technique. IgM and IgG antibodies to total lipid fractions, as well as to galactocerebroside, ceramide dihexoside, ceramide trihexoside, and globoside were not significantly elevated in the sera of GBS patients as compared to controls. High levels of anti-asialo-GM1 IgG antibodies, however, were detected in 6 of 54 (11%) GBS patients and 1 of 30 (3%) OND patients. Intense reactivity with purified Forssman glycolipid and a number of glycolipid antigens in higher neutral glycolipid enriched fractions of human cauda equina and dog sciatic nerves was noted by TLC-immunostaining in many GBS and control sera. Although the levels of anti-Forssman IgM were significantly decreased in GBS sera compared with normal sera (P < 0.05) and OND sera (P < 0.02), the levels of anti-Forssman IgG antibodies were not significantly different. With the possible exception of IgG antibodies to asialo-GM1, our results suggest that serum antibodies against Forssman glycolipid and neutral glycolipids are not significantly elevated in GBS patients and, thus, are unlikely to play an important role in the pathogenesis of this disease.

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High titers of anti-GA₁ antibodies have been associated with neurological syndromes. In most cases, these antibodies cross-react with the structurally related glycolipids GM₁ and GD_1b, although specific anti-GA₁ antibodies have also been reported. The role of specific anti-GA₁ antibodies is uncertain since the presence of GA₁ in the human nervous system has not been clarified. A rabbit was immunized with GD_1a and its sera were screened for antibody reactivity by standard immunoassay methods (HPTLC-immunostaining and ELISA). Anti-GD_1a antibodies were not detected but, unexpectedly, anti-GA₁ IgG-antibodies were found. Antibody binding to GA₁ was inhibited by soluble GA₁ but also by GD_1a. These results indicate that the rabbit produced antibodies that recognize epitopes present on the glycolipids, that are absent or not exposed on solid phase adsorbed GD_1a. We investigated the presence of these unusual anti-ganglioside antibodies in normal and neurological patient sera. Approximately, 10% of normal human sera contained low titer of specific anti-GA₁ IgG-antibodies but none of them recognized soluble GD_1a. High titers of IgG-antibodies reacting only with GA₁ were detected in 12 patient sera out of 325 analyzed. Of these, 6 sera showed binding that was inhibited by soluble GD_1a and four of them also by GM₁. This new type of anti-ganglioside antibodies should be considered important elements for understanding of the pathogenesis of these diseases as well as their diagnosis.
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Recent neurophysiological and pathological studies have led to a reclassification of the diseases that underlie Guillain-Barré syndrome (GBS) into acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor and sensory axonal neuropathy (AMSAN) and acute motor axonal neuropathy (AMAN). The Fisher syndrome of ophthalmoplegia, ataxia and areflexia is the most striking of several related conditions. Significant antecedent events include Campylobacter jejuni (4–66%), cytomegalovirus (5–15%), Epstein-Barr virus (2–10%), and Mycoplasma pneumoniae (1–5%) infections. These infections are not uniquely associated with any clinical subtype but severe axonal degeneration is more common following C. jejuni and severe sensory impairment following cytomegalovirus. Strong evidence supports an important role for antibodies to gangliosides in pathogenesis. In particular antibodies to ganglioside GM1 are present in 14–50% of patients with GBS, and are more common in cases with severe axonal degeneration associated with any subtype. Antibodies to ganglioside GQ1b are very closely associated with Fisher syndrome, its formes frustes and related syndromes. Ganglioside-like epitopes exist in the bacterial wall of C. jejuni. Infection by this and other organisms triggers an antibody response in patients with GBS but not in those with uncomplicated enteritis. The development of GBS is likely to be a consequence of special properties of the infecting organism, since some strains such as Penner O:19 and O:41 are particularly associated with GBS but not with enteritis. It is also likely to be a consequence of the immunogenetic background of the patient since few patients develop GBS after infection even with one of these strains. Attempts to match the subtypes of GBS to the fine specificity of anti-ganglioside antibodies and to functional effects in experimental models continue but have not yet fully explained the pathogenesis. T cells are also involved in the pathogenesis of most or perhaps all forms of GBS. T cell responses to any of three myelin proteins, P2, PO and PMP22, are sufficient to induce experimental autoimmune neuritis. Activated T cells are present in the circulation in the acute stage, up-regulate matrix metalloproteinases, cross the blood-nerve barrier and encounter their cognate antigens. Identification of the specificity of these T cell responses is still at a preliminary stage. The invasion of intact myelin sheaths by activated macrophages is difficult to explain according to a purely T cell mediated mechanism. The different patterns of GBS are probably due to the diverse interplay between antibodies and T cells of differing specificities.

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Research paperSearch for antibodies to neutral glycolipids in sera of patients with Guillain-Barré syndrome

Abstract

Brain Res.

J. Biol. Chem.

J. Neuroimmunol.

Brain Res.

J. Neurol. Sci.

Chem. Phys. Lipids

Trends Biochem. Sci.

Acute inflammatory demyelinating polyradiculo-neuropathies

Criteria for the diagnosis of Guillain-Barré syndrome

Ann. Neurol.

Isolation and characterization of a protein from sciatic nerve myelin responsible for experimental allergic neuritis

Nat. New Biol.

The role of autoantibody and immune complexes in the pathogenesis of Guillain-Barré syndrome

Ann. Neurol

Infection and autoimmunity in the Guillain-Barré syndrome

Antibodies to glycosphingolipids in patients with multiple sclerosis and SLE

J. Immunol.

Passive transfer studies in Guillain-Barré polyneuropathy

Neurology

Efficiency of plasma exchange in Guillain-Barré syndrome: role of replacement fluid

Ann. Neurol.

Plasmapheresis and acute Guillain-Barré syndrome

Neurology

Demyelination induced by serum from patients with Guillain-Barré syndrome

Ann. Neurol.

Anti-glycolipid autoantibody detected in the sera from systemic lupus erythematosus patients

J. Clin. Invest.

IgM in a human neuropathy related to paraproteinemia binds to a carbohydrate determinant in the myelin-associated glycoprotein and to a ganglioside

Research paper
Search for antibodies to neutral glycolipids in sera of patients with Guillain-Barré syndrome