Large-scale profiling of antibody reactivity to glycolipids in patients with Guillain-Barré syndrome

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.

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Journal
Brain
Published
2025-03-17
DOI
https://doi.org/10.1093/brain/awaf102
Citations
6
Primary Topic
Peripheral Neuropathies and Disorders
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article
Field-Weighted Citation Impact
8.34

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Large-scale profiling of antibody reactivity to glycolipids in patients with Guillain-Barré syndrome

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Large-scale profiling of antibody reactivity to glycolipids in patients with Guillain-Barré syndrome

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article en
6 citations

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.

BrainVol. 148(11)
University of Bern (CH), University of Modena and Reggio Emilia (IT), Universitat Autònoma de Barcelona (ES), Hospital Británico (UY), The University of Sydney (AU), Allen Institute for Brain Science (US), Cliniques Universitaires Saint-Luc (BE), University Health Network (CA), Montefiore Medical Center (US), University of Thessaly (GR), University of Liverpool (GB), University of Cape Town (ZA), Chiba University (JP), University of Calgary (CA), University of Toronto (CA), Utah Valley University (US), International Centre for Diarrhoeal Disease Research (BD), Leeds Teaching Hospitals NHS Trust (GB), Garrahan Hospital (AR), University Hospital of Bern (CH), Instituto de Salud Carlos III (ES), Odense University Hospital (DK), Hospital de Sant Pau (ES), Erasmus MC (NL), University of Vermont Medical Center (US), Bellvitge University Hospital (ES), Groote Schuur Hospital (ZA), Aarhus University Hospital (DK), Cambridge University Hospitals NHS Foundation Trust (GB), John Radcliffe Hospital (GB), Walton Centre (GB), Centre Hospitalier Universitaire de Nantes (FR), University of Malaya (MY), University of Oxford (GB), Institut d'Investigació Biomédica de Bellvitge (ES), Düsseldorf University Hospital (DE), Azienda Unita' Sanitaria Locale Di Modena (IT), Ospedale regionale di Lugano (CH), Kindai University Hospital (JP), Complejo Hospitalario Universitario de Santiago (ES), Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (AR), University Hospital of Larissa (GR), Centre for Biomedical Network Research on Rare Diseases (ES), Medizinisches Versorgungszentrum Prof. Mathey, Prof. Schofer (DE), Instituto de Neurología Cognitiva (AR), St. Joseph’s University Medical Center (US), Azienda Ospedaliera Sant'Andrea (IT), Centre d'Investigation Clinique de Nantes (FR), St. Joseph Health System (US), Haga Hospital (NL), Ospedale Policlinico San Martino (IT), Hospital Británico de Buenos Aires (AR), Jacobs Institute (US), Elisabeth-TweeSteden Ziekenhuis (NL), King's College Hospital (GB), University Hospital Cologne (DE), Addenbrooke's Hospital (GB), Hospital Universitario Infanta Sofía (ES), Instituto de Investigación de Enfermedades Raras (ES), Hôpital de la Timone (FR), IRCCS Humanitas Research Hospital (IT), Heinrich Heine University Düsseldorf (DE), Università della Svizzera italiana (CH), University at Buffalo, State University of New York (US), Medical University of Vienna (AT), University of Glasgow (GB), Universidad Europea de Madrid (ES), Erasmus University Rotterdam (NL), Kindai University (JP), The University of Texas Health Science Center at Houston (US)
CSL Behring, Wellcome Trust, GBS/CIDP Foundation International, University of Glasgow, Erasmus Medisch Centrum, Grifols
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