Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark.
Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark.
Nat Commun. 2023 Dec 8;14(1):8124. doi: 10.1038/s41467-023-44007-2.
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.
免疫球蛋白 A（IgA）被认为在通过涂层微生物来防御黏膜屏障方面发挥作用。令人惊讶的是，IgA 缺乏的人类几乎没有与感染相关的并发症，这引发了一个问题，即更具特异性的 IgG 是否可以帮助 IgM 弥补 IgA 的缺乏。在这里，我们利用一组 IgA 缺乏的人类，每个人都与 IgA 充足的家庭成员配对，以研究多 Ig 细菌涂层。在 IgA 缺乏的人类中，IgM 单独，以及与 IgG 一起，可重现大多数细菌家族的涂层，尽管 Ig 涂层总体低 3.6 倍。细菌 IgG 涂层主要由 IgG1 和 IgG4 组成。单 IgG2 细菌涂层稀疏，与大肠杆菌负荷和 TNF-α 升高有关。尽管在 IgA 缺乏症中，单 IgG2 涂层比健康对照组更常见 1.6 倍，但比炎症性肠病中更常见 2 倍。总之，我们证明了 IgG 在 IgA 缺乏时协助 IgM 涂层大多数细菌家族，并确定单 IgG2 细菌涂层是一种炎症标志物。
