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; Susanne Brix

doi:10.1038/s41467-023-44007-2

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
, Susanne Brix^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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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.

Originalsprog	Engelsk
Artikelnummer	8124
Tidsskrift	Nature Communications
Vol/bind	14
Udgave nummer	1
Antal sider	12
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-023-44007-2
Status	Udgivet - 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).

Finansiering

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. 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.

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10.1038/s41467-023-44007-2Licens: CC BY

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Citationsformater

Eriksen, C., Moll, J. M., Myers, P. N., Pinto, A. R. A., Danneskiold-Samsøe, N. B., Dehli, R. I., Rosholm, L. B., Dalgaard, M. D., Penders, J., Jonkers, D. M., Pan-Hammarström, Q., Hammarström, L., Kristiansen, K., & Brix, S. (2023). IgG and IgM cooperate in coating of intestinal bacteria in IgA deficiency. Nature Communications, 14(1), Artikel 8124. https://doi.org/10.1038/s41467-023-44007-2

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title = "IgG and IgM cooperate in coating of intestinal bacteria in IgA deficiency",

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.",

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AU - Eriksen, Carsten

AU - Moll, Janne Marie

AU - Myers, Pernille Neve

AU - Pinto, Ana Rosa Almeida

AU - Danneskiold-Samsøe, Niels Banhos

AU - Dehli, Rasmus Ibsen

AU - Rosholm, Lisbeth Buus

AU - Dalgaard, Marlene Danner

AU - Penders, John

AU - Jonkers, Daisy Mae

AU - Pan-Hammarström, Qiang

AU - Hammarström, Lennart

AU - Kristiansen, Karsten

AU - Brix, Susanne

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N2 - 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.

AB - 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.

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