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

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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.
OriginalsprogEngelsk
Artikelnummer8124
TidsskriftNature Communications
Vol/bind14
Udgave nummer1
Antal sider12
ISSN2041-1723
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
We thank Renée Engqvist at Karolinska Instituttet for help during sample collection. This research was supported by Technical University of Denmark providing a PhD scholarship to CE in the group of SB, the Swedish Research Council (2019-0132, QPH), and the Knut and Alice Wallenberg Foundation (KAW 2020-0102, LH and QPH). SB is the incumbent of the FII institute Research Chair at DTU in Immune-based Prediction of Disease.

Funding Information:
We thank Renée Engqvist at Karolinska Instituttet for help during sample collection. This research was supported by Technical University of Denmark providing a PhD scholarship to CE in the group of SB, the Swedish Research Council (2019-0132, QPH), and the Knut and Alice Wallenberg Foundation (KAW 2020-0102, LH and QPH). SB is the incumbent of the FII institute Research Chair at DTU in Immune-based Prediction of Disease.

Publisher Copyright:
© 2023, The Author(s).

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