Antiglycolipid antibodies in Guillain-Barré syndrome and related diseases: Review of clinical features and antibody specificities

Abstract

Guillain-Barré syndrome (GBS) is an acute inflammatory polyradiculoneuropathy that usually develops following a respiratory or intestinal infection. Although the pathogenic mechanisms of GBS have not been fully established, both humoral and cell-mediated immune factors have been shown to contribute to the disease process. Several antiglycosphingolipid (anti-GSL) antibodies have been found in the sera of patients with GBS or related diseases. Measurements of these antibody titers are very important in the diagnosis of GBS and in evaluating the effectiveness of treatments in clinical trials. The most common treatment strategies for these disorders involve plasmapheresis and the use of steroids for reducing anti-GSL antibody titers to ameliorate patients' clinical symptoms. Administration of intravenous immunoglobulin may also be beneficial in the treatment of neuropathies by suppressing the immune-mediated processes that are directed against antigenic targets in myelin and axons. In certain demyelinating neuropathies, the destruction or malfunctioning of the blood-nerve barrier, which results in the leakage of circulating antibodies into the peripheral nerve parenchyma, has been considered to be an initial step in development of the disease process. In addition, anti-GSL antibodies, such as anti-GM1, may cause nerve dysfunction and injury by interfering with the ion channel function at the nodes of Ranvier, where carbohydrate epitopes of glycoconjugates are located. These malfunctions thus contribute to the pathogenic mechanisms of certain demyelinating neuropathies.

Ganglioside Molecular Mimicry and Its Pathological Roles in Guillain-Barré Syndrome and Related Diseases

“…The sensitized animals developed clear clinical signs of neuropathies characterized by signs of delayed conduction velocity and conduction block. These models are extremely interesting and have been used extensively for studying the pathogenetic mechanisms of GBS (9).…”

“…In fact, Simon-Haldi et al (74) isolated peptide mimics of the L2/HNK-1 carbohydrate epitope. The use of recombinant DNA techniques to obtain small peptide mimics that regulate carbohydrate epitopes may offer an alternative strategy for the treatment of certain GSL antibody-mediated neurological disorders (9).…”

“…Much of the research into GBS over the last decade has focused on the forms mediated by antiganglioside antibodies (8,9,88). The sera of approximately 60% of patients with GBS contain a variety of anti-glycosphingolipid (GSL) antibodies.…”

“…Thus, in sera that are antibody negative it is necessary to examine the antibody activity by appropriate ganglioside complexes and suitable methods, such as the use of liposome-incorporated GSLs. Nonetheless, measurements of these GSL antibody titers remain the most effective and reliable means for the diagnosis of GBS and in evaluating the effectiveness of treatments in clinical trials (8,9,87).…”

Chemical validation of molecular mimicry: interaction of cholera toxin with Campylobacter lipooligosaccharides

“…Although the etiological mechanism for generating anti-GM1 antibodies has not been fully clarified, Campylobacteriosis is a potential risk factor for GBS, causing the production of high-titer anti-GM1 antibodies [4][5][6]. Campylobacter jejuni (C. jejuni) is a gram-negative bacterium expressing two components of strain-specific lipooligosaccharides (LOSs), a lipid A (or endotoxin) portion and a polysaccharide portion [7,8].…”