IgA subclasses have different effector functions associated with distinct glycosylation profiles
IgA subclasses have different effector functions associated with distinct glycosylation profiles
复制标题
DOI：
10.1038/s41467-019-13992-8
复制
发表时间：
2020-01-08
影响因子：
16.6
通讯作者：
Schett, Georg
中科院分区：
文献类型：
--
作者：
Steffen, Ulrike;Koeleman, Carolien A.;Schett, Georg
单体血清免疫球蛋白A （IgA）参与多种自身免疫性疾病的发生发展，但其对血清IgA效应物功能的调控尚不明确。本研究表明，由于不同的结合和信号特性，两种IgA亚类（IgA1和IgA2）对免疫细胞的作用不同。虽然IgA2对中性粒细胞和巨噬细胞有促炎作用，但IgA1没有明显的作用。此外，IgA1和IgA2具有不同的糖基化谱，IgA1比IgA2拥有更多的唾液酸。唾液酸的去除增加了IgA1的促炎能力，使其与IgA2相当。值得注意的是，类风湿关节炎患者的疾病特异性自身抗体向促炎IgA2亚类转变，这与较高的疾病活动性相关。综上所述，这些数据表明IgA效应物的功能依赖于亚类和糖基化，而亚类平衡的紊乱与自身免疫性疾病有关。
Monomeric serum immunoglobulin A (IgA) can contribute to the development of various autoimmune diseases, but the regulation of serum IgA effector functions is not well defined. Here, we show that the two IgA subclasses (IgA1 and IgA2) differ in their effect on immune cells due to distinct binding and signaling properties. Whereas IgA2 acts pro-inflammatory on neutrophils and macrophages, IgA1 does not have pronounced effects. Moreover, IgA1 and IgA2 have different glycosylation profiles, with IgA1 possessing more sialic acid than IgA2. Removal of sialic acid increases the pro-inflammatory capacity of IgA1, making it comparable to IgA2. Of note, disease-specific autoantibodies in patients with rheumatoid arthritis display a shift toward the pro-inflammatory IgA2 subclass, which is associated with higher disease activity. Taken together, these data demonstrate that IgA effector functions depend on subclass and glycosylation, and that disturbances in subclass balance are associated with autoimmune disease.