Antibodies to heteromeric glycolipid complexes in guillain-barré syndrome

Simon Rinaldi, Kathryn M. Brennan, Gabriela Kalna, Christa Walgaard, Pieter Van Doorn, Bart C. Jacobs, Robert K Yu, Jan Eric Mansson, Carl S. Goodyear, Hugh J. Willison

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere82337
JournalPloS one
Volume8
Issue number12
DOIs
StatePublished - Dec 16 2013

Fingerprint

glycolipids
Glycolipids
gangliosides
Gangliosides
Electrophysiology
electrophysiology
antibodies
Antibodies
Serum
antigens
Antigens
Disease control
Western World
autoantibodies
Antibody Specificity
Immune system
Demyelinating Diseases
Biomarkers
antibody detection
Artificial Respiration

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Rinaldi, S., Brennan, K. M., Kalna, G., Walgaard, C., Van Doorn, P., Jacobs, B. C., ... Willison, H. J. (2013). Antibodies to heteromeric glycolipid complexes in guillain-barré syndrome. PloS one, 8(12), [e82337]. https://doi.org/10.1371/journal.pone.0082337

Antibodies to heteromeric glycolipid complexes in guillain-barré syndrome. / Rinaldi, Simon; Brennan, Kathryn M.; Kalna, Gabriela; Walgaard, Christa; Van Doorn, Pieter; Jacobs, Bart C.; Yu, Robert K; Mansson, Jan Eric; Goodyear, Carl S.; Willison, Hugh J.

In: PloS one, Vol. 8, No. 12, e82337, 16.12.2013.

Research output: Contribution to journalArticle

Rinaldi, S, Brennan, KM, Kalna, G, Walgaard, C, Van Doorn, P, Jacobs, BC, Yu, RK, Mansson, JE, Goodyear, CS & Willison, HJ 2013, 'Antibodies to heteromeric glycolipid complexes in guillain-barré syndrome', PloS one, vol. 8, no. 12, e82337. https://doi.org/10.1371/journal.pone.0082337
Rinaldi S, Brennan KM, Kalna G, Walgaard C, Van Doorn P, Jacobs BC et al. Antibodies to heteromeric glycolipid complexes in guillain-barré syndrome. PloS one. 2013 Dec 16;8(12). e82337. https://doi.org/10.1371/journal.pone.0082337
Rinaldi, Simon ; Brennan, Kathryn M. ; Kalna, Gabriela ; Walgaard, Christa ; Van Doorn, Pieter ; Jacobs, Bart C. ; Yu, Robert K ; Mansson, Jan Eric ; Goodyear, Carl S. ; Willison, Hugh J. / Antibodies to heteromeric glycolipid complexes in guillain-barré syndrome. In: PloS one. 2013 ; Vol. 8, No. 12.
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