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Immunoglobulin A (IgA) is acknowledged to play a role in the defence of the mucosal barrier by coating microorganisms. Surprisingly, IgA-deficient humans exhibit few infection-related complications, raising the question if the more specific IgG may help IgM in compensating for the lack of IgA. Here we employ a cohort of IgA-deficient humans, each paired with IgA-sufficient household members, to investigate multi-Ig bacterial coating. In IgA-deficient humans, IgM alone, and together with IgG, recapitulate coating of most bacterial families, despite an overall 3.6-fold lower Ig-coating. Bacterial IgG coating is dominated by IgG1 and IgG4. Single-IgG2 bacterial coating is sparse and linked to enhanced Escherichia coli load and TNF-α. Although single-IgG2 coating is 1.6-fold more prevalent in IgA deficiency than in healthy controls, it is 2-fold less prevalent than in inflammatory bowel disease. Altogether we demonstrate that IgG assists IgM in coating of most bacterial families in the absence of IgA and identify single-IgG2 bacterial coating as an inflammatory marker. © 2023. The Author(s).

Citation

Carsten Eriksen, Janne Marie Moll, Pernille Neve Myers, Ana Rosa Almeida Pinto, Niels Banhos Danneskiold-Samsøe, Rasmus Ibsen Dehli, Lisbeth Buus Rosholm, Marlene Danner Dalgaard, John Penders, Daisy Mae Jonkers, Qiang Pan-Hammarström, Lennart Hammarström, Karsten Kristiansen, Susanne Brix. IgG and IgM cooperate in coating of intestinal bacteria in IgA deficiency. Nature communications. 2023 Dec 08;14(1):8124

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PMID: 38065985

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