title: Antibodies to heteromeric glycolipid complexes in Guillain-Barré syndrome.
abstract: Autoantibodies are infrequently detected in the sera of patients with the demyelinating form of Guillain-Barré syndrome most commonly encountered in the Western world, despite abundant circumstantial evidence suggesting their existence. We hypothesised that antibody specificities reliant on the cis interactions of neighbouring membrane glycolipids could explain this discrepancy, and would not have been detected by traditional serological assays using highly purified preparations of single gangliosides. To assess the frequency of glycolipid complex antibodies in a Western European cohort of patients GBS we used a newly developed combinatorial glycoarray methodology to screen against large range of antigens (11 gangliosides, 8 other single glycolipids and 162 heterodimeric glycolipid complexes). Serum samples of 181 patients from a geographically defined, Western European cohort of GBS cases were analysed, along with 161 control sera. Serum IgG binding to single gangliosides was observed in 80.0% of axonal GBS cases, but in only 11.8% of cases with demyelinating electrophysiology. The inclusion of glycolipid complexes increased the positivity rate in demyelinating disease to 62.4%. There were 40 antigens with statistically significantly increased binding intensities in GBS as compared to healthy control sera. Of these, 7 complex antigens and 1 single ganglioside also produced statistically significantly increased binding intensities in GBS versus neurological disease controls. The detection of antibodies against specific complexes was associated with particular clinical features including disease severity, requirement for mechanical ventilation, and axonal electrophysiology. This study demonstrates that while antibodies against single gangliosides are often found in cases with axonal-type electrophysiology, antibodies against glycolipid complexes predominate in cases with demyelinating electrophysiology, providing a more robust serum biomarker than has ever been previously available for such cases. This work confirms the activation of the humoral immune system in the dysimmune disease process in GBS, and correlates patterns of antigen recognition with different clinical features.
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Rinaldi
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Brennan
authors.affiliation: Bioinformatics, Beatson Institute for Cancer Research, Glasgow, United Kingdom.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Kalna
authors.affiliation: Department of Neurology, Erasmus Medical Centre, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Christa
authors.initials: C
authors.lastname: Walgaard
authors.affiliation: Department of Neurology, Erasmus Medical Centre, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: van Doorn
authors.affiliation: Department of Neurology, Erasmus Medical Centre, University Medical Center, Rotterdam, The Netherlands ; Department of Immunology, Erasmus Medical Centre, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Bart C
authors.initials: BC
authors.lastname: Jacobs
authors.affiliation: Institute of Molecular Medicine and Genetics, Medical College of Georgia, Georgia Health Sciences University, Augusta, Georgia, United States of America.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Yu
authors.affiliation: Laboratory Medicine/Clinical Chemistry, Sahlgren's University Hospital, Molndal, Sweden.
authors.forename: Jan-Eric
authors.initials: JE
authors.lastname: Mansson
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Carl S
authors.initials: CS
authors.lastname: Goodyear
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Hugh J
authors.initials: HJ
authors.lastname: Willison
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D005260:Female; D005732:Gangliosides / Q000276:immunology*; D006017:Glycolipids / Q000276:immunology*; D020275:Guillain-Barre Syndrome / Q000097:blood / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D005732:Gangliosides; D006017:Glycolipids; D007074:Immunoglobulin G; D007075:Immunoglobulin M