Sialylated intravenous immunoglobulin suppress anti-ganglioside antibody mediated nerve injury
Open accessAbstract
The precise mechanisms underlying the efficacy of intravenous immunoglobulin (IVIg) in autoimmune neurological disorders including Guillain-Barré syndrome (GBS) are not known. Anti-ganglioside antibodies have been reported to be pathogenic in some variants of GBS, and we have developed passive transfer animal models to study anti-ganglioside antibody mediated-endoneurial inflammation and associated neuropathological effects and to evaluate the efficacy of new therapeutic approaches. Some studies indicate that IVIg's anti-inflammatory activity resides in a minor sialylated IVIg (sIVIg) fractions and is dependent on an innate Th2 response via binding to a specific ICAM3-grabbing nonintegrin related 1 receptor (SIGN-R1). Therefore the efficacy of IVIg, IVIg fractions with various IgG Fc sialylation status, and the involvement of Th2 pathway were examined in one of our animal model of antibody-mediated inhibition of axonal regeneration. We demonstrate that both IVIg and sIVIg ameliorated anti-glycan antibody mediated-pathological effect, whereas, the unsialylated fractions of IVIg were not beneficial in our model. Tenfold lower doses of sIVIg compared to whole IVIg provided equivalent efficacy in our studies. Moreover, we found that whole IVIg and sIVIg significantly upregulates the gene expression of IL-33, which itself can provide protection from antibody-mediated nerve injury in our model. Our results support that the SIGN-R1-Th2 pathway is involved in the anti-inflammatory effects of IVIg on endoneurium in our model and elements of this pathway including IL-33 can provide novel therapeutics in inflammatory neuropathies.
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Galactose is required for sialylation with NeuAc, which can improve solubility, anti-inflammatory activity, thermal stability and serum half-life of mAbs.
“On the other hand, galactose is required for sialylation with N-acetylneuraminic acid (NeuAc), which in turn can improve the solubility, anti-inflammatory activity, thermal stability and serum half-life of mAbs [8,23–26].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [26]
The Discussion and Results report that sialylated IVIg had greater anti-inflammatory efficacy than sialic-acid-depleted IVIg in a mouse nerve-injury model (page not provided). The paper does not establish that galactose is required for NeuAc sialylation or that sialylation improves the solubility, thermal stability, or serum half-life of mAbs; its efficacy finding concerns IVIg, not therapeutic mAbs. (LLM, conf=0.84)
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Self-citation
- Authors
- Zhang, G., Massaad, C. A., Gao, T., Pillai, L., Bogdanova, N., Ghauri, S., & Sheikh, K. A.
- Corresponding author
- Sheikh, Kazim A.
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 282
- Pages
- 49-55
- ISSN
- 0014-4886 (ISSN-L)
- PMC
- PMC5351292
- OpenAlex
- W2396047646
- Cited by
- 38
- References
- 40
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 2 · 2022: 1 · 2021: 7 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 2
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01 NS42888, R01 NS54962, R21NS087467)
- Topics
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Keywords
- intravenous immunoglobulin, anti-ganglioside antibodies, Guillain-Barré syndrome, Th2 immune response, IL-33, axon regeneration, autoimmune neuropathy
- MeSH terms
- Interleukin-33, Animals, Antibodies, Disease Models, Animal, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Gangliosides, Gene Expression Regulation, Immunologic Factors, Mice, Inbred C57BL, Nerve Regeneration, RNA, Messenger, Time Factors, Immunoglobulins, Intravenous, Recovery of Function, Guillain-Barre Syndrome, Sciatic Neuropathy, Mice
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