The diagnostic utility of determining anti-GM1: GalC complex antibodies in multifocal motor neuropathy: a validation study

Galban-Horcajo, F., Vlam, L., Delmont, E., Halstead, S. K., van den Berg, L., van der Pol, W.-L. and Willison, H. J. (2015) The diagnostic utility of determining anti-GM1: GalC complex antibodies in multifocal motor neuropathy: a validation study. Journal of Neuromuscular Diseases, 2(2), pp. 157-165. (doi: 10.3233/JND-150080) (PMID:27858734) (PMCID:PMC5271459)

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Abstract

Background: Multifocal motor neuropathy (MMN) is associated with IgM antibodies to GM1 ganglioside. The importance of the lipid milieu that might facilitate or inhibit antibody binding to GM1 in immunoassays is well recognised. Existing studies, using a range of different approaches, generally concur that anti-GM1 IgM antibody detection rates are improved by the addition of galactocerebroside (GalC) to the GM1 assay. Objective: The current study sought to formally evaluate the clinical utility of the GM1:GalC complex assay in the diagnosis of MMN. Methods: Anti-GM1 and -GM1:GalC antibodies were examined using ELISA and glycoarray (dot blot) in a fully blinded study design, consisting of 100 MMN patients, 100 ALS cases and 100 healthy controls. Results: The detection of anti-GM1 Abs using glycoarray was 67% sensitive and 85% specific. The addition of GalC to GM1, (1:1 weight to weight ratio), increased the sensitivity to 81% , whilst dropping specificity to 80% . Increasing the GalC content to a 1:5 ratio (or higher) further decreased specificity, and in doing so limited the usefulness of the GM1:GalC assay to the level of GM1 alone. The addition of GalC to the ELISA method also significantly increased sensitivity compared with GM1 alone, albeit with a significant decrease in specificity. Conclusions: This study indicates that the GM1:GalC assay is an advantageous assay adaptation for detecting anti-GM1 antibodies in MMN, using either glycoarray or ELISA, and warrants introduction into clinical diagnostic practice.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Halstead, Dr Susan and Willison, Professor Hugh and Delmont, Dr Emilien
Authors: Galban-Horcajo, F., Vlam, L., Delmont, E., Halstead, S. K., van den Berg, L., van der Pol, W.-L., and Willison, H. J.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Neuromuscular Diseases
Publisher:IOS Press
ISSN:2214-3599
ISSN (Online):2214-3602
Copyright Holders:Copyright © 2015 IOS Press and The Authors
First Published:First published in Journal of Neuromuscular Diseases 2(2):157-165
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
165079The structural and functional diversity of anti-glycolipid antibody repertoires and their nerve binding domains in human autoimmune neuropathyHugh WillisonWellcome Trust (WELLCOTR)092805/Z/10/ZIII - Immunology