Department of Obstetrics and Gynaecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Shanghai Key Laboratory of Gynaecologic Oncology, Shanghai, 200127, China.
Front Med. 2023 Jun;17(3):549-561. doi: 10.1007/s11684-022-0965-7. Epub 2023 Apr 3.
Immunoglobulin (IgG) glycosylation affects the effector functions of IgG in a myriad of biological processes and has been closely associated with numerous autoimmune diseases, including systemic lupus erythematosus (SLE), thus underlining the pathogenic role of glycosylation aberration in autoimmunity. This study aims to explore the relationship between IgG sialylation patterns and lupus pregnancy. Relative to that in serum samples from the control cohort, IgG sialylation level was aberrantly downregulated in serum samples from the SLE cohort at four stages (from preconception to the third trimester of pregnancy) and was significantly associated with lupus activity and fetal loss during lupus pregnancy. The type I interferon signature of pregnant patients with SLE was negatively correlated with the level of IgG sialylation. The lack of sialylation dampened the ability of IgG to suppress the functions of plasmacytoid dendritic cells (pDCs). RNA-seq analysis further revealed that the expression of genes associated with the spleen tyrosine kinase (SYK) signaling pathway significantly differed between IgG- and deSia-IgG-treated pDCs. This finding was confirmed by the attenuation of the ability to phosphorylate SYK and BLNK in deSia-IgG. Finally, the coculture of pDCs isolated from pregnant patients with SLE with IgG/deSia-IgG demonstrated the sialylation-dependent anti-inflammatory function of IgG. Our findings suggested that IgG influences lupus activity through regulating pDCs function via the modulation of the SYK pathway in a sialic acid-dependent manner.
免疫球蛋白 (IgG) 的糖基化作用会影响 IgG 在众多生物过程中的效应功能，并且与许多自身免疫性疾病密切相关，包括系统性红斑狼疮 (SLE)，因此凸显了糖基化异常在自身免疫中的致病作用。本研究旨在探讨 IgG 唾液酸化模式与狼疮妊娠之间的关系。与对照组血清样本相比，SLE 组在妊娠前、妊娠早期、妊娠中期和妊娠晚期四个阶段的血清样本中 IgG 唾液酸化水平异常下调，并且与狼疮妊娠期间的狼疮活动和胎儿丢失显著相关。SLE 妊娠患者的 I 型干扰素特征与 IgG 唾液酸化水平呈负相关。缺乏唾液酸化会降低 IgG 抑制浆细胞样树突状细胞 (pDC) 功能的能力。RNA-seq 分析进一步表明，与 SYK 信号通路相关的基因在 IgG 和去唾液酸化 IgG 处理的 pDC 之间的表达存在显著差异。这一发现得到了去唾液酸化 IgG 降低 SYK 和 BLNK 磷酸化能力的证实。最后，从 SLE 妊娠患者中分离的 pDC 与 IgG/去唾液酸化 IgG 的共培养显示 IgG 依赖唾液酸化的抗炎功能。我们的研究结果表明，IgG 通过调节 SYK 通路，以唾液酸依赖的方式调节 pDCs 功能，从而影响狼疮的活动。
