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

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

机构地区：[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

出　　处：《Frontiers of Medicine》2023年第3期549-561,共13页医学前沿（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(Nos.82172918,81901494,82101768,82171767,and 81974252);the Science and Technology Commission of Shanghai Municipality(No.18441904800);the Medical-Engineering Joint Funds of Shanghai Jiao Tong University(No.YG2021GD01);the Shanghai Key Laboratory of Gynecologic Oncology(No.FKZL-2021-02);Shanghai Health Commission(No.201940284);the Clinical Scientific Research Innovation Cultivation Fund of Renji Hospital(No.PYI20-03).

摘　　要：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.

关 键 词：PREGNANCY IgG glycome typeⅠinterferon systemic lupus erythematosus 

分 类 号：R714[医药卫生—妇产科学]