Higher levels of IgG3 antibodies in serum, but not in CSF, distinguish multiple sclerosis from other neurological disorders

Kennedy, P. G.E., Graner, M. W., Fringuello, A., Zhou, W., Pointon, T., Alquatli, K., Bisel, S., Langford, D. and Yu, X. (2022) Higher levels of IgG3 antibodies in serum, but not in CSF, distinguish multiple sclerosis from other neurological disorders. Journal of Neuroimmune Pharmacology, (doi: 10.1007/s11481-021-10048-x) (PMID:34989971) (Early Online Publication)

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Abstract

Increased intrathecal IgG and oligoclonal bands (OCB) are seminal features of multiple sclerosis (MS). Although no such differences in MS blood total IgG antibodies have been reported, serum OCB are a common and persistent finding in MS and have a systemic source. Recent studies showed that IgG3+ B cells and higher levels of serum IgG3 are linked to the development of MS. Additionally, intrathecal IgG synthesis in MS is associated with IgG3 heavy chain gene single nucleotide polymorphisms, and there is a strong relationship between susceptibility to MS and an IgG3 restriction fragment length polymorphism. These studies support the role of IgG3 in disease pathogenesis. Using multiple immunoassays, we investigated levels of total IgG, IgG1, and IgG3 in sera and CSF of 102 MS patients (19 paired CSF and sera), 76 patients with other neurological disorders (9 paired CSF and sera), and 13 healthy controls. We show that higher levels of total IgG and IgG3 antibodies were detected in MS serum, but not in CSF, which distinguishes MS from other inflammatory and non-inflammatory neurological disorders, with Receiver Operating Characteristic (ROC) Curves 0.79 for both IgG3 & total IgG. Our data support the notion that IgG3 antibodies may be a potential candidate for MS blood biomarker development.

Item Type:Articles
Additional Information:Funding: This work was supported by the Department of Neurosurgery Research Funds, University of Colorado Anschutz Medical Campus. Additional support was from NIH NIMH (5R21MH118174-02) for MWG & XY.
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kennedy, Professor Peter
Authors: Kennedy, P. G.E., Graner, M. W., Fringuello, A., Zhou, W., Pointon, T., Alquatli, K., Bisel, S., Langford, D., and Yu, X.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Journal of Neuroimmune Pharmacology
Publisher:Springer
ISSN:1557-1890
ISSN (Online):1557-1904
Published Online:06 January 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Journal of Neuroimmune Pharmacology 2022
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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