Large-scale profiling of antibody reactivity to glycolipids in patients with Guillain-Barré syndrome.
Journal
Brain : a journal of neurology
Journal Volume
148
Journal Issue
11
Start Page
4000
End Page
4015
ISSN
1460-2156
Date Issued
2025-11-04
Author(s)
Thomma, Robin C M
Halstead, Susan K
de Koning, Laura C
Wiegers, Eveline J A
Gourlay, Dawn S
Tio-Gillen, Anne P
van Rijs, Wouter
Andersen, Henning
Antonini, Giovanni
Arends, Samuel
Attarian, Shahram
Barroso, Fabio A
Bateman, Kathleen J
Benedetti, Luana
Van den Bergh, Peter
Bürmann, Jan
Busby, Mark
Casasnovas, Carlos
Dardiotis, Efthimios
Davidson, Amy
Feasby, Thomas E
Fehmi, Janev
Galassi, Giuliana
Garcia-Sobrino, Tania
Granit, Volkan
Gutiérrez-Gutiérrez, Gerardo
Hadden, Robert D M
Harbo, Thomas
Hartung, Hans-Peter
Hasan, Imran
Holt, James K L
Islam, Zhahirul
Karafiath, Summer
Katzberg, Hans D
Kolb, Noah
Kusunoki, Susumu
Kuwabara, Satoshi
Kuwahara, Motoi
Lehmann, Helmar C
Leonhard, Sonja E
Martín-Aguilar, Lorena
Monges, Soledad
Nobile-Orazio, Eduardo
Pardo, Julio
Pereon, Yann
Querol, Luis
Reisin, Ricardo C
Rinaldi, Simon
Ripellino, Paolo
Roberts, Rhys C
Scheidegger, Olivier
Shahrizaila, Nortina
Sheikh, Kazim A
Silvestri, Nicholas J
Sindrup, Soren H
Stein, Beth
Tan, Cheng Y
Tankisi, Hatice
Visser, Leo H
Waheed, Waqar
Huizinga, Ruth
Jacobs, Bart C
Willison, Hugh J
Abstract
Guillain-Barré syndrome is an acute polyradiculoneuropathy in which preceding infections often elicit the production of antibodies that target peripheral nerve antigens, principally gangliosides. Anti-ganglioside antibodies are thought to play a key role in the clinical diversity of the disease and can be helpful in clinical practice. Extensive research into clinical associations of individual anti-ganglioside antibody specificities has been performed. Recent research has highlighted glycolipid complexes, glycolipid combinations that may alter antibody binding, as targets. In this study, we investigated antibody reactivity patterns to glycolipids and glycolipid complexes using combinatorial array, in relation to clinical features in Guillain-Barré syndrome. In total, 1413 patients from the observational International Guillain-Barré syndrome Outcome Study (0-91 years, 60.3% male) and 1061 controls (healthy, family, infectious, vaccination, other neurological disease) were included. Acute-phase sera from patients were screened for IgM, IgG, and IgA reactivity against 15 glycolipids and one phospholipid and their heteromeric complexes, similarly to archived control sera. Antibody specificities and reactivity patterns were analysed in relation to clinical features. Of all patients, 1309 (92.6%) were positive for at least one anti-glycolipid (complex) antibody. Anti-GM1 and anti-GQ1b (complex) antibodies best distinguished motor Guillain-Barré syndrome and Miller Fisher syndrome from controls, with antibodies to glycolipid complexes outperforming antibodies to single glycolipids. Three models consisting of anti-glycolipid (complex) antibodies distinguished patients with Guillain-Barré syndrome, the motor variant, and Miller Fisher syndrome from controls with high sensitivity and specificity, performing better than antibodies to single glycolipids used in clinical practice. Seven patient clusters with particular antibody reactivity patterns were identified. These clusters were distinguished by geographical region, clinical variants, preceding Campylobacter jejuni infection, electrophysiological subtypes, the Medical Research Council sum score at study entry, and the ability to walk 10 m unaided at 26 weeks. Two patient clusters with distinct anti-GM1 (complex) reactivity (broad versus restricted) differed in frequency of the axonal subtype. In cumulative incidence analyses, 15 anti-glycolipid (complex) antibodies were associated with the time required to regain the ability to walk 10 m unaided. After adjustment for known prognostic factors, IgG anti-GQ1b:GM4, GQ1b:PS and GQ1b:Sulfatide remained associated with faster recovery. Addition of anti-glycolipid antibodies to clinical prognostic models slightly improved their discriminative capacity, though insufficiently to improve the models. Measurement of anti-glycolipid antibodies by combinatorial array increases the diagnostic yield compared to assaying single glycolipids, identifies clinically relevant antibody reactivity patterns to glycolipids and glycolipid complexes, and may be useful in outcome prediction in Guillain-Barré syndrome.
Subjects
autoantibody
peripheral neuropathy
SDGs
Type
journal article