IgG and IgM cooperate in coating of intestinal bacteria in IgA deficiency

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 and Susanne Brix ()
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Carsten Eriksen: Technical University of Denmark
Janne Marie Moll: Technical University of Denmark
Pernille Neve Myers: Technical University of Denmark
Ana Rosa Almeida Pinto: Technical University of Denmark
Niels Banhos Danneskiold-Samsøe: University of Copenhagen
Rasmus Ibsen Dehli: Technical University of Denmark
Lisbeth Buus Rosholm: Technical University of Denmark
Marlene Danner Dalgaard: Technical University of Denmark
John Penders: Maastricht University Medical Centre
Daisy MAE Jonkers: Maastricht University Medical Centre+
Qiang Pan-Hammarström: Karolinska Institutet
Lennart Hammarström: Karolinska Institutet
Karsten Kristiansen: Aalborg University
Susanne Brix: Technical University of Denmark

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-44007-2

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