IgG and IgM cooperate in coating of intestinal bacteria in IgA deficiency
Carsten Eriksen, Janne Marie Moll, Pernille Neve Myers, Ana Pinto, Niels Banhos Danneskiold‐Samsøe, Rasmus Ibsen Dehli, Lisbeth Buus Rosholm, Marlene Dalgaard, John Penders, Daisy Jonkers, Qiang Pan‐Hammarström, Lennart Hammarström, Karsten Kristiansen, Susanne Brix
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.