论文标题：Control of lupus activity during pregnancy via the engagement of IgG sialylation: novel crosstalk between IgG sialylation and pDC functions

期刊： Frontiers of Medicine

作者：You Wang, Sihan Lin, Jiayue Wu, Meng Jiang, Jianhua Lin, Yu Zhang, Huihua Ding, Haibo Zhou, Nan Shen, Wen Di

发表时间：15 Jun 2023

DOI：10.1007/s11684-022-0965-7

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导 读

上海交通大学医学院附属仁济医院周海波、沈楠和狄文等在Frontiers of Medicine发表研究论文《通过IgG唾液酸化调控孕期狼疮活动：IgG唾液酸化与浆细胞样树突状细胞（pDC）功能的新型交互作用》（Control of lupus activity during pregnancy via the engagement of IgG sialylation: novel crosstalk between IgG sialylation and pDC functions）。本研究发现，系统性红斑狼疮（SLE）孕妇的IgG唾液酸化水平显著降低，导致其对浆细胞样树突状细胞（pDC）的免疫抑制功能减弱；这种功能缺陷通过削弱SYK信号通路的关键磷酸化过程，进一步促进pDC过度分泌I型干扰素，最终加剧了孕期狼疮活动性并显著增加了胎儿的流失风险。

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G（IgG）糖基化通过调控其效应功能参与多种生物学过程，且与包括系统性红斑狼疮（SLE）在内的多种自身免疫性疾病密切相关，这提示糖基化异常在自身免疫中的致病作用。本研究旨在探究IgG唾液酸化与狼疮患者妊娠之间的关系。与对照组血清样本相比，SLE患者的血清样本在四个阶段（从孕前到妊娠晚期）中的IgG唾液酸化水平出现了异常下调，且与妊娠期间的狼疮活动和胎儿丢失显著相关。患有SLE的妊娠患者的I型干扰素特征与IgG唾液酸化水平呈负相关。缺乏唾液酸化会削弱IgG对浆细胞样树突状细胞（pDC）功能的抑制作用。RNA测序分析进一步表明，在IgG和去唾液酸化IgG（deSia-IgG）处理的pDCs中，与脾酪氨酸激酶（SYK）信号通路相关的基因表达存在显著差异。这一结果通过deSia-IgG对SYK及BLNK磷酸化能力的减弱得到了验证。最后，从患有SLE的妊娠患者中分离出的pDCs与IgG/deSia-IgG的共培养实验证明了IgG具有依赖唾液酸化的抗炎功能。本研究表明，IgG通过以唾液酸依赖的方式调节SYK信号通路来调控pDCs的功能，进而影响狼疮活动。

期刊介绍

Frontiers of Medicine专注于发表临床医学和基础医学领域的最新研究成果，旨在通过全球医疗专业人员之间的交流促进健康和医疗保健的发展。该刊采用严格的同行评审和编辑流程，确保发表的文章的科学准确性、新颖性和重要性。

原文信息

标题

Control of lupus activity during pregnancy via the engagement of IgG sialylation: novel crosstalk between IgG sialylation and pDC functions

作者

You Wang^1,2,3, Sihan Lin^1,2,3, Jiayue Wu^1,2,3, Meng Jiang^1,2,3, Jianhua Lin^1,2,3, Yu Zhang^1,2,3, Huihua Ding⁴, Haibo Zhou⁴, Nan Shen^4,5,6, Wen Di^1,2,3

机构

1. Department of Obstetrics and Gynaecology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China

2. Shanghai Key Laboratory of Gynaecologic Oncology, Shanghai 200127, China

3. State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China

4. Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China

5. Center for Autoimmune Genomics and Etiology (CAGE), Cincinnati Children’s Hospital Medical Center, Cincinnati Ohio 45229, USA

6. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Ohio 45267, USA

通讯作者

Haibo Zhou, Nan Shen, Wen Di

引用这篇文章

You Wang, Sihan Lin, Jiayue Wu, Meng Jiang, Jianhua Lin, Yu Zhang, Huihua Ding, Haibo Zhou, Nan Shen, Wen Di. Control of lupus activity during pregnancy via the engagement of IgG sialylation: novel crosstalk between IgG sialylation and pDC functions. Front. Med., 2023, 17(3): 549–561

https://doi.org/10.1007/s11684-022-0965-7

https://journal.hep.com.cn/fmd/EN/10.1007/s11684-022-0965-7

https://link.springer.com/article/10.1007/s11684-022-0965-7

感谢作者对Frontiers of Medicine的信任和支持。

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