Antibodies to single glycolipids and glycolipid complexes in Guillain-Barré syndrome subtypes

Abstract

Objective: To comprehensively investigate the relationship between antibodies to single glycolipids and their complexes and Guillain-Barré syndrome subtypes and clinical features.Methods: In acute sera from 199 patients with Guillain-Barré syndrome, immunoglobulin G (IgG) antibodies to glycolipids and ganglioside complexes were tested using ELISA against individual antigens from single glycolipids including gangliosides (LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GD1b, GT1a, GT1b, GQ1b) and a neutral glycolipid, asialo-GM1 (GA1), and antigens from the combination of 2 different glycolipids. Based on serial nerve conduction studies, the electrodiagnoses were as follows: 69 demyelinating subtype, 85 axonal subtypes, and 45 unclassified.Results: Significant associations were detected between acute motor axonal neuropathy subtype and IgG antibodies to GM1, GalNAc-GD1a, GA1, or LM1/GA1 complex. Reversible conduction failure was significantly associated with IgG antibodies to GM1, GalNAc-GD1a, GD1b, or complex of LM1/GA1. No significant association was demonstrated between acute inflammatory demyelinating polyneuropathy and any of the glycolipids or ganglioside complexes. Antiganglioside complex antibodies alone were detected in 7 patients (5 axonal subtype). Conclusions:The current study demonstrates that antibodies to single glycolipids and ganglioside complexes are associated with acute motor axonal neuropathy or acute motor conduction block neuropathy but not acute inflammatory demyelinating polyneuropathy. Classification of evidence:This study provides Class II evidence that antibodies to glycolipids are increased in patients with acute motor axonal neuropathy and acute motor conduction block neuropathy but not acute inflammatory demyelinating polyneuropathy. Neurology ® 2014;83:118-124 GLOSSARY AIDP 5 acute inflammatory demyelinating polyneuropathy; AMAN 5 acute motor axonal neuropathy; AMCBN 5 acute motor conduction block neuropathy; GBS 5 Guillain-Barré syndrome; GSC 5 ganglioside complex; Ig 5 immunoglobulin; NCS 5 nerve conduction study.Guillain-Barré syndrome (GBS) is an acute immune-mediated polyneuropathy with 2 major subtypes: acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN).1 Within the axonal subtype, there are now recognized variants evident on nerve conduction studies (NCS), which demonstrate early reversible conduction failure, referred to as acute motor conduction block neuropathy (AMCBN).2 There is robust evidence that immunoglobulin G (IgG) anti-ganglioside antibodies are associated with the pathogenesis of AMAN, whereas the target antigens in AIDP remain elusive. The patients who were seronegative for antibodies to single gangliosides were found to have anti-GSC antibodies. The authors have since described further associations between anti-GSC antibodies and variants of GBS. This includes antibodies to LM1 and its complexes in AIDP, 5 to complex of GM1 and GalNAc-GD1a (GM1/GalNAc-GD1a) in AMCBN,6 and to complexes of GD1a/GD1b and GD1b/GT1b in pa...

Prospective study comparing enzyme‐linked immunosorbent assay and glycoarray assay to detect antiglycolipid antibodies in a routine diagnostic neuroimmunology laboratory setting

“…The present study emphasizes the value of measuring antibodies against complexes of glycolipids in the diagnosis of inflammatory neuropathy . In a previous study on a cohort of GBS, the addition of antibodies against complexes of glycolipids improved the sensitivity of the test from 12% to 62% among the cases with demyelinating electrophysiology (acute inflammatory demyelinating polyneuropathy) .…”

Destruction of paranodal architecture in inflammatory neuropathy with anti-contactin-1 autoantibodies

“…Autoantibodies against gangliosides can be found in a subset of patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), and some autoantibodies like GQ1b or diasilosyl antibodies are associated with distinct clinical syndromes 1 2. Nodes of Ranvier are suspected to be an important site of attack in immune-mediated neuropathies.…”

Acute bulbar palsy as a variant of Guillain-Barré syndrome

“…First, some studies have found no significant association between bulbar palsy and anti-GT1a antibodies, with anti-GQ1b antibodies-which are recognized to cross-react with GT1a-being significantly associated with this condition. 17,18 Furthermore, one large study found IgG anti-GT1a antibodies in only 51% of the included PCB patients, and even IgG antiGQ1b antibodies were present in 39% of them. 19 Therefore, the role of IgG anti-GT1a antibodies in ABPp syndrome remains to be elucidated.…”