Format

Send to

Choose Destination
Sci Transl Med. 2018 May 2;10(439). pii: eaan1217. doi: 10.1126/scitranslmed.aan1217.

Microbial ecology perturbation in human IgA deficiency.

Author information

1
Sorbonne Université, INSERM, Centre d'Immunologie et des Maladies Infectieuses-Paris (CIMI-Paris), 75013 Paris, France.
2
Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Département d'Immunologie, 75013 Paris, France.
3
UMR1319 Micalis, Institut National de la Recherche Agronomique (INRA), Jouy-en-Josas, France.
4
Center for Bioinformatics and Computational Biology, University of Maryland, Paint Branch Road, College Park, MD 20742, USA.
5
INRA, US1367 MetaGenoPolis, 78350 Jouy en Josas, France.
6
INSERM, LNC UMR866, University Bourgogne Franche-Comté, F-21000 Dijon, France.
7
LIPoprotéines et Santé prévention & Traitement des maladies Inflammatoires et du Cancer (LipSTIC) LabEx, Fondation de Coopération Scientifique Bourgogne-Franche Comté, F-21000 Dijon, France.
8
Département d'Immunologie Clinique, Hôpital Saint-Louis, AP-HP, 75010 Paris, France.
9
INSERM U1126, Université Paris Diderot Paris 7, 75010 Paris, France.
10
Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière, Service de Médecine Interne 2, Institut E3M, 75013 Paris, France.
11
Université Paris Diderot Paris 7, EA3518, 75010 Paris, France.
12
King's College London, Centre for Host-Microbiome Interactions, Dental Institute Central Office, Guy's Hospital, London, UK.
13
Sorbonne Université, INSERM, Centre d'Immunologie et des Maladies Infectieuses-Paris (CIMI-Paris), 75013 Paris, France. martin.larsen@upmc.fr guy.gorochov@upmc.fr.

Abstract

Paradoxically, loss of immunoglobulin A (IgA), one of the most abundant antibodies, does not irrevocably lead to severe infections in humans but rather is associated with relatively mild respiratory infections, atopy, and autoimmunity. IgA might therefore also play covert roles, not uniquely associated with control of pathogens. We show that human IgA deficiency is not associated with massive quantitative perturbations of gut microbial ecology. Metagenomic analysis highlights an expected pathobiont expansion but a less expected depletion in some typically beneficial symbionts. Gut colonization by species usually present in the oropharynx is also reminiscent of spatial microbiota disorganization. IgM only partially rescues IgA deficiency because not all typical IgA targets are efficiently bound by IgM in the intestinal lumen. Together, IgA appears to play a nonredundant role at the forefront of the immune/microbial interface, away from the intestinal barrier, ranging from pathobiont control and regulation of systemic inflammation to preservation of commensal diversity and community networks.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center