Dear Editor,Hyperactivation of the type I interferon(IFN)signature has been observed in several systemic autoimmune conditions,and the type I IFN receptor antagonist Saphnelo(anifrolumab-fnia)has been approved in 2021...Dear Editor,Hyperactivation of the type I interferon(IFN)signature has been observed in several systemic autoimmune conditions,and the type I IFN receptor antagonist Saphnelo(anifrolumab-fnia)has been approved in 2021 by the Food and Drug Administration(FDA)in the US.The launch of Saphnelo marked the only new treatment approved for systemic lupus erythematosus(SLE)in more than 10 years.展开更多
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),...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.展开更多
基金the National Natural Science Foundation of China(Grant Number:81903882,81871240,82001709)the Science and Technology Commission of Shanghai Municipality(Grant Number:22ZR1473700,21S11907700)"Science and Technology Innovation Action Plan"medicine innovation fund by Science and Technology Commission of Shanghai Municipality(Grant Number:21Y31900200).
文摘Dear Editor,Hyperactivation of the type I interferon(IFN)signature has been observed in several systemic autoimmune conditions,and the type I IFN receptor antagonist Saphnelo(anifrolumab-fnia)has been approved in 2021 by the Food and Drug Administration(FDA)in the US.The launch of Saphnelo marked the only new treatment approved for systemic lupus erythematosus(SLE)in more than 10 years.
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)+3 种基金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).
文摘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.
