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2023 9

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糖基化 3

N-糖组 1

N-糖链 1

IgG 1

IgG抗体 1

N-糖基化 1

N-糖基心血管年龄 1

免疫球蛋白 G 1

免疫球蛋白G 1

全基因组关联研究 1

全血清 1

前沿技术与中医药创新发展 1

哈夫病 1

基因组学 1

多孔石墨化碳液相色谱-质谱 1

心血管年龄 1

抗体反应 1

机器学习 1

消化道癌症 1

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

《医学前沿（英文）》 2023年第17卷第3期页码 549-561 doi: 10.1007/s11684-022-0965-7

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 type I interferon systemic lupus erythematosus

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基于正交质谱的N-糖组谱揭示哈夫病潜在病原学 Article

刘思, 刘圆圆, 林佳静, 刘笔锋, 何振宇, 吴晓旻, 刘欣

《工程（英文）》 2023年第26卷第7期页码 63-73 doi: 10.1016/j.eng.2022.09.012

摘要：本文中，采用基于高通量的正交质谱对HD中血清和血清衍生的IgG的N-糖组谱进行了表征。数据显示，HD与总血清糖蛋白的核心岩藻糖基化和单半乳糖醇化升高有关。血清IgG水平是HD患者的良好指标。此外，IgG的差异半乳糖基化和唾液酸化与HD密切相关。值得注意的是，IgG1和IgG2的半乳糖基化和唾液酸化的变化具有亚类特异性。有意义的是，IgG2或IgG3/4的唾液酸化和半乳糖基化改变与HD的临床标志物密切相关。本研究表明差异化IgG N-糖基化与HD的关联，为这种罕见疾病的病因提供了新的见解。

关键词：哈夫病全血清 IgG抗体糖基化疾病病原学

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Proteomics study of Mycoplasma pneumoniae pneumonia reveals the Fc fragment of the IgG-binding protein

《医学前沿（英文）》 2022年第16卷第3期页码 378-388 doi: 10.1007/s11684-021-0840-y

摘要： Macrolide and corticosteroid resistance has been reported in patients with Mycoplasma pneumoniae (MP) pneumonia (MPP). MP clearance is difficult to achieve through antibiotic treatment in sensitive patients with severe MPP (SMPP). SMPP in children might progress to airway remodeling and even bronchiolitis/bronchitis obliterans. Therefore, identifying serum biomarkers that indicate MPP progression and exploring new targeted drugs for SMPP treatment require urgency. In this study, serum samples were collected from patients with general MPP (GMPP) and SMPP to conduct proteomics profiling. The Fc fragment of the IgG-binding protein (FCGBP) was identified as the most promising indicator of SMPP. Biological enrichment analysis indicated uncontrolled inflammation in SMPP. ELISA results proved that the FCGBP level in patients with SMPP was substantially higher than that in patients with GMPP. Furthermore, the FCGBP levels showed a decreasing trend in patients with GMPP but the opposite trend in patients with SMPP during disease progression. Connectivity map analyses identified 25 possible targeted drugs for SMPP treatment. Among them, a mechanistic target of rapamycin kinase (mTOR) inhibitor, which is a macrolide compound and a cell proliferation inhibitor, was the most promising candidate for targeting SMPP. To our knowledge, this study was the first proteomics-based characterization of patients with SMPP and GMPP.

关键词： severe Mycoplasma pneumoniae pneumonia children proteomics Fc fragment of the IgG-binding protein mechanistic target of rapamycin kinase inhibitor

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High-level expression of recombinant IgG1 by CHO K1 platform

Ningning Xu, Jianfa Ou, Al-Karim (Al) Gilani, Lufang Zhou, Margaret Liu

《化学科学与工程前沿（英文）》 2015年第9卷第3期页码 376-380 doi: 10.1007/s11705-015-1531-5

摘要： The Chinese Hamster Ovary (CHO K1) cell was used to express a targeted anti-cancer monoclonal antibody by optimizing the platform of the construction of production cell line in this study. The adherent CHO K1 was first adapted to suspension culture in chemical defined medium. Then the glutamine synthetase (GS) vector was applied to construct a single plasmid to overexpress a monoclonal antibody IgG1. Post transfection, the production of cell pool was optimized by glutamine-free selection and amplification using various concentrations of methionine sulfoximine. The best cell pool of CHO K1/IgG1 was used to screen the top single clone using the limiting dilution cloning. Finally, a high IgG1 production of 780 mg/L was obtained from a batch culture. This study demonstrated that the construction of high producing cell line, from gene to clone, could be completed within six month and the gene amplification improved protein production greatly.

关键词： Chinese hamster ovary (CHO) monoclonal antibody IgG1 amplification cell line development

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糖组与糖医学

王嵬, 杨宝峰

《工程（英文）》 2023年第26卷第7期页码 1-2 doi: 10.1016/j.eng.2023.05.007

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IgG N-糖基心血管年龄独立于真实年龄精准表征心血管事件风险 Article

武志远, 郭政, 郑雨露, 王玉涛, 张海平, 潘慧颖, 李志伟, Lois Balmer, 李霞, 陶丽新, 郭秀花, 王嵬

《工程（英文）》 2023年第26卷第7期页码 99-107 doi: 10.1016/j.eng.2022.12.004

摘要：

亚临床动脉粥样硬化和代谢紊乱是心血管健康的重要风险因素，应用免疫球蛋白G（IgG）N-聚糖模式作为炎症指标表征其发病风险已有研究报道然而，对于IgG N-糖基谱在心血管疾病（CVD）风险分层中的能力仍然未知。本研究旨在利用IgG N-糖基标志物开发追踪心血管疾病风险的年龄指数。使用机器学习递归特征消除和惩罚回归算法逐步筛选特征糖基，并开发IgG N-糖基化心血管年龄（GlyCage）指数，以反映归因于心血管风险的与真实年龄间的偏差。因此，本研究开发的GlyCage指数利用IgG N-糖基谱追踪心血管健康水平。GlyCage和真实年龄之间的差距能够独立地表征心血管风险，提示IgG N-糖基化在心血管疾病的发病机制中起作用。

关键词： IgG N-糖基心血管年龄心血管年龄免疫球蛋白G 糖基化炎症特征选择机器学习

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Real time monitoring of bioreactor mAb IgG3 cell culture process dynamics via Fourier transform infrared

Huiquan Wu, Erik Read, Maury White, Brittany Chavez, Kurt Brorson, Cyrus Agarabi, Mansoor Khan

《化学科学与工程前沿（英文）》 2015年第9卷第3期页码 386-406 doi: 10.1007/s11705-015-1533-3

摘要： Compared to small molecule process analytical technology (PAT) applications, biotechnology product PAT applications have certain unique challenges and opportunities. Understanding process dynamics of bioreactor cell culture process is essential to establish an appropriate process control strategy for biotechnology product PAT applications. Inline spectroscopic techniques for real time monitoring of bioreactor cell culture process have the distinct potential to develop PAT approaches in manufacturing biotechnology drug products. However, the use of inline Fourier transform infrared (FTIR) spectroscopic techniques for bioreactor cell culture process monitoring has not been reported. In this work, real time inline FTIR Spectroscopy was applied to a lab scale bioreactor mAb IgG3 cell culture fluid biomolecular dynamic model. The technical feasibility of using FTIR Spectroscopy for real time tracking and monitoring four key cell culture metabolites (including glucose, glutamine, lactate, and ammonia) and protein yield at increasing levels of complexity (simple binary system, fully formulated media, actual bioreactor cell culture process) was evaluated via a stepwise approach. The FTIR fingerprints of the key metabolites were identified. The multivariate partial least squares (PLS) calibration models were established to correlate the process FTIR spectra with the concentrations of key metabolites and protein yield of in-process samples, either individually for each metabolite and protein or globally for all four metabolites simultaneously. Applying the 2 derivative pre-processing algorithm to the FTIR spectra helps to reduce the number of PLS latent variables needed significantly and thus simplify the interpretation of the PLS models. The validated PLS models show promise in predicting the concentration profiles of glucose, glutamine, lactate, and ammonia and protein yield over the course of the bioreactor cell culture process. Therefore, this work demonstrated the technical feasibility of real time monitoring of the bioreactor cell culture process via FTIR spectroscopy. Its implications for enabling cell culture PAT were discussed.

关键词： process analytical technology (PAT) Fourier-transform infrared (FTIR) spectroscopy partial least squares (PLS) regression mouse IgG3 bioreactor cell culture process real time process monitoring

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系统性红斑狼疮患者的血清IgG糖链特征 Article

潘胡丹, 王静蓉, 梁勇, 王灿坚, 田瑞敏, 叶华, 张晓, 吴沅皞, 邵苗, 张瑞军, 肖瑶, 李智, 张光峰, 周华, 王艺霖, 王晓双, 栗占国, 刘维, 刘良

《工程（英文）》 2023年第26卷第7期页码 89-98 doi: 10.1016/j.eng.2023.01.006

摘要：在本研究中，通过对389例SLE患者及304例健康对照者进行深入的糖组学分析，鉴定出血清免疫球蛋白G（IgG）上的两种N-糖链能够作为SLE的诊断生物标志物。基于片段特异性糖链分析和糖肽分析，发现这两种N-糖链生物标志物位于IgG上的Fc区域，并与疾病活动性密切相关。而酶学分析结果则提示，SLE患者体内一系列糖转移酶的失调可能是观察到的糖链产生变化的原因。研究结果为基于血清IgG糖基化的高效人群筛查和SLE潜在的新致病因素提供了新的思路。

关键词：系统性红斑狼疮 N-糖链诊断指标

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人类蛋白质N-糖基化的十二年全基因组关联研究 Review

Anna Timoshchuk, Sodbo Sharapov, Yurii S. Aulchenko

《工程（英文）》 2023年第26卷第7期页码 17-31 doi: 10.1016/j.eng.2023.03.013

摘要：

Most human-secreted and membrane-bound proteins have covalently attached oligosaccharide chains, or glycans. Glycosylation influences the physical and chemical properties of proteins, as well as their biological functions. Unsurprisingly, alterations in protein glycosylation have been implicated in a growing number of human diseases, and glycans are increasingly being considered as potential therapeutic targets, an essential part of therapeutics, and biomarkers. Although glycosylation pathways are biochemically well-studied, little is known about the networks of genes that guide the cell- and tissue-specific regulation of these biochemical reactions in humans in vivo. The lack of a detailed understanding of the mechanisms regulating glycome variation and linking the glycome to human health and disease is slowing progress in clinical applications of human glycobiology. Two of the tools that can provide much sought-after knowledge of human in vivo glycobiology are human genetics and genomics, which offer a powerful data-driven agnostic approach for dissecting the biology of complex traits. This review summarizes the current state of human populational glycogenomics. In Section 1, we provide a brief overview of the N-glycan's structural organization, and in Section 2, we give a description of the major blood plasma glycoproteins. Next, in Section 3, we summarize, systemize, and generalize the results from current N-glycosylation genome-wide association studies (GWASs) that provide novel knowledge of the genetic regulation of the populational variation of glycosylation. Until now, such studies have been limited to an analysis of the human blood plasma N-glycome and the N-glycosylation of immunoglobulin G and transferrin. While these three glycomes make up a rather limited set compared with the enormous multitude of glycomes of different tissues and glycoproteins, the study of these three does allow for powerful analysis and generalization. Finally, in Section 4, we turn to genes in the established loci, paying particular attention to genes with strong support in Section 5. At the end of the review, in Sections 6 and 7, we describe special cases of interest in light of new discoveries, focusing on possible mechanisms of action and biological targets of genetic variation that have been implicated in human protein N-glycosylation.

关键词：糖组学聚糖 N-糖基化基因组学遗传学全基因组关联研究

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潘胡丹：风湿病IgG糖链结构改变及临床应用价值（2023年6月17日）

2023年06月29日

关键词：前沿技术与中医药创新发展

结直肠癌、基质和正常结肠黏膜显微解剖区域N-糖组的显著多样性 Article

Di Wang, Katarina Madunić , Tao Zhang, Guinevere S.M. Lageveen-Kammeijer, Manfred Wuhrer

《工程（英文）》 2023年第26卷第7期页码 32-43 doi: 10.1016/j.eng.2022.08.016

摘要：

Aberrant glycosylation is considered to be a hallmark of colorectal cancer (CRC), as demonstrated by various studies. While the N-glycosylation of cell lines and serum has been widely examined, the analysis of cancer-associated N-glycans from tissues has been hampered by the heterogeneity of tumors and the complexity of N-glycan structures. To overcome these obstacles, we present a study using laser capture microdissection that makes it possible to largely deconvolute distinct N-glycomic signatures originating from different regions of heterogeneous tissues including cancerous, stromal, and healthy mucosa cells. N-glycan alditols were analyzed by means of porous graphitized carbon liquid chromatography-electrospray ionization tandem mass spectrometry, enabling the differentiation and structural characterization of isomeric species. In total, 116 N-glycans were identified that showed profound differences in expression among cancer, stroma, and normal mucosa. In comparison with healthy mucosa, the cancer cells showed an increase in α2-6 sialylation and monoantennary N-glycans, as well as a decrease in bisected N-glycans. Moreover, specific sialylated and (sialyl-)LewisA/X antigen-carrying N-glycans were exclusively expressed in cancers. In comparison with cancer, the stroma showed lower levels of oligomannosidic and monoantennary N-glycans, LewisA/X epitopes, and sulfation, as well as increased expression of (core-)fucosylation and α2-3 sialylation. Our study reveals the distinct N-glycomic profiles of different cell types in CRC tumor and control tissues, proving the necessity of their separate analysis for the discovery of cancer-associated glycans.

关键词：结直肠癌肿瘤多孔石墨化碳液相色谱-质谱 N-糖组抗体反应

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血清免疫球蛋白G N-糖基的高通量分析——一种消化道癌症的非侵入性生物标志物 Article

刘鹏程, 王小兵, 顿爱社, 李昱潼, 李厚强, 王璐, 张怡春, 李灿灿, 张金霞, 张晓雨, 马立兴, 侯海峰

《工程（英文）》 2023年第26卷第7期页码 44-53 doi: 10.1016/j.eng.2023.02.008

摘要：

免疫球蛋白G (Immunoglobulin G, IgG) 的 N-糖基化在炎症性疾病的发展中起着重要作用。本研究旨在评价IgG N-糖基在消化道癌症亚型中的诊断效能。hydrophilic interaction liquid chromatography using ultra-performance liquid chromatography, HILIC-UPLC）分析血浆中IgGIgG N-糖基的组成与炎症因子相关 (r = 0.556)。这些研究结果表明，IgG N-糖基在调节消化道肿瘤的发病机制中发挥了重要作用。血清IgG N-糖基可以作为潜在的非侵入性辅助消化道癌症临床诊断的方法。