title: Sialylated intravenous immunoglobulin suppress anti-ganglioside antibody mediated nerve injury.
abstract: 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.
authors.affiliation: Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin street, Houston, Texas 77030.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin street, Houston, Texas 77030.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Massaad
authors.affiliation: Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin street, Houston, Texas 77030.
authors.forename: Tong
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin street, Houston, Texas 77030.
authors.forename: Laila
authors.initials: L
authors.lastname: Pillai
authors.affiliation: Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin street, Houston, Texas 77030.
authors.forename: Natalia
authors.initials: N
authors.lastname: Bogdanova
authors.affiliation: Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin street, Houston, Texas 77030.
authors.forename: Sameera
authors.initials: S
authors.lastname: Ghauri
authors.affiliation: Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin street, Houston, Texas 77030.
authors.forename: Kazim A
authors.initials: KA
authors.lastname: Sheikh
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005732:Gangliosides / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D020275:Guillain-Barre Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D000067596:Interleukin-33 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000906:Antibodies; D005732:Gangliosides; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D000067596:Interleukin-33; D012333:RNA, Messenger
keywords: Guillain-Barré syndrome; IL-33; IL-4; IVIg; SIGN-R1; Th2 pathway; sIVIg