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DOI | 10.1038/s41467-019-09149-2 |
A genome-wide association study identifies a novel susceptibility locus for the immunogenicity of polyethylene glycol | |
Chang, Chia-Jung1; Chen, Chien-Hsiun1,2; Chen, Bing-Mae1; Su, Yu-Cheng1; Chen, Ying-Ting1; Hershfield, Michael S.3; Lee, Ming-Ta Michael1,4; Cheng, Tian-Lu5; Chen, Yuan-Tsong1,6; Roffler, Steve R.1,7; Wu, Jer-Yuarn1,2 | |
2019-03-21 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | Taiwan; USA |
英文摘要 | Conjugation of polyethylene glycol (PEG) to therapeutic molecules can improve bioavailability and therapeutic efficacy. However, some healthy individuals have pre-existing antiPEG antibodies and certain patients develop anti-PEG antibody during treatment with PEGylated medicines, suggesting that genetics might play a role in PEG immunogenicity. Here we perform genome-wide association studies for anti-PEG IgM and IgG responses in Han Chinese with 177 and 140 individuals, defined as positive for anti-PEG IgM and IgG responses, respectively, and with 492 subjects without either anti-PEG IgM or IgG as controls. We validate the association results in the replication cohort, consisting of 211 and 192 subjects with anti-PEG IgM and anti-PEG IgG, respectively, and 596 controls. We identify the immunoglobulin heavy chain (IGH) locus to be associated with anti-PEG IgM response at genome-wide significance (P = 2.23 x 10(-22)). Our findings may provide novel genetic markers for predicting the immunogenicity of PEG and efficacy of PEGylated therapeutics. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000410452800004 |
WOS关键词 | MEMORY B-CELLS ; ANTI-PEG IGM ; BLOOD CLEARANCE ; PEGYLATION ; ANTIBODIES ; PROTEIN |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204278 |
专题 | 资源环境科学 |
作者单位 | 1.Acad Sinica, Inst Biomed Sci, Taipei 11529, Taiwan; 2.China Med Univ, Sch Chinese Med, Taichung 40447, Taiwan; 3.Duke Univ, Med Ctr, Dept Med, Box 3049, Durham, NC 27710 USA; 4.Geisinger Hlth Syst, Genom Med Inst, Danville, PA 17822 USA; 5.Kaohsiung Med Univ, Ctr Biomarkers & Biotech Drugs, Dept Biomed Sci & Environm Biol, Kaohsiung 80708, Taiwan; 6.Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA; 7.Kaohsiung Med Univ, Coll Med, Grad Inst Med, Kaohsiung 80708, Taiwan |
推荐引用方式 GB/T 7714 | Chang, Chia-Jung,Chen, Chien-Hsiun,Chen, Bing-Mae,et al. A genome-wide association study identifies a novel susceptibility locus for the immunogenicity of polyethylene glycol[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Chang, Chia-Jung.,Chen, Chien-Hsiun.,Chen, Bing-Mae.,Su, Yu-Cheng.,Chen, Ying-Ting.,...&Wu, Jer-Yuarn.(2019).A genome-wide association study identifies a novel susceptibility locus for the immunogenicity of polyethylene glycol.NATURE COMMUNICATIONS,8. |
MLA | Chang, Chia-Jung,et al."A genome-wide association study identifies a novel susceptibility locus for the immunogenicity of polyethylene glycol".NATURE COMMUNICATIONS 8(2019). |
条目包含的文件 | 条目无相关文件。 |
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