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[Pubmed] Differences in IgG autoantibody Fab glycosylation across autoimmune diseases

Posté : 30 janv. 2023 12:00
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J Allergy Clin Immunol. 2023 Jan 27:S0091-6749(23)00091-X. doi: 10.1016/j.jaci.2022.10.035. Online ahead of print.

ABSTRACT

BACKGROUND: Increased prevalence of autoantibody Fab glycosylation has been demonstrated for several autoimmune diseases.

OBJECTIVE: To study if elevated Fab glycosylation is a common feature of autoimmunity, we investigated Fab glycosylation levels on serum IgG and its subclasses for autoantibodies associated with a range of different B cell-mediated autoimmune diseases, including rheumatoid arthritis, myasthenia gravis subtypes, pemphigus vulgaris, ANCA-associated vasculitis, systemic lupus erythematosus, anti-GBM glomerulonephritis, thrombotic thrombocytopenic purpura and Guillain-Barré syndrome.

METHODS: The level of Fab glycosylated IgG antibodies was assessed by lectin affinity chromatography and autoantigen-specific immunoassays.

RESULTS: In six out of ten autoantibody responses, in five out of eight diseases, we found increased levels of Fab glycosylation on IgG autoantibodies that varied from 86% in RA to 26% in SLE. Elevated autoantibody Fab glycosylation was not restricted to IgG4, which is known to be prone to Fab glycosylation, but also present in IgG1. When autoimmune diseases with a chronic disease course were compared with more acute autoimmune illnesses, increased Fab glycosylation was restricted to the chronic diseases. As a proxy for chronic autoantigen exposure, we determined Fab glycosylation levels on antibodies to common latent herpes viruses, as well as to gp120 in chronically HIV-1-infected individuals. Immunity to these viral antigens was not associated with increased Fab glycosylation levels, indicating that chronic antigen-stimulation as such does not lead to increased Fab glycosylation levels.

CONCLUSION: Our data indicate that in chronic but not acute B cell-mediated autoimmune diseases disease-specific autoantibodies are enriched for Fab glycans.

PMID:36716825 | DOI:10.1016/j.jaci.2022.10.035


Source: https://pubmed.ncbi.nlm.nih.gov/3671682 ... t6+86293ac