A genome-wide association study identifies a novel susceptibility locus for the immunogenicity of polyethylene glycol

Chia-Jung Chang, Chien-Hsiun Chen, Bing-Mae Chen, Yu-Cheng Su, Ying-Ting Chen, Michael S. Hershfield, Ming-Ta Michael Lee, Tian-Lu Cheng, Yuan-Tsong Chen (), Steve R. Roffler () and Jer-Yuarn Wu ()
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Chia-Jung Chang: Institute of Biomedical Sciences, Academia Sinica
Chien-Hsiun Chen: Institute of Biomedical Sciences, Academia Sinica
Bing-Mae Chen: Institute of Biomedical Sciences, Academia Sinica
Yu-Cheng Su: Institute of Biomedical Sciences, Academia Sinica
Ying-Ting Chen: Institute of Biomedical Sciences, Academia Sinica
Michael S. Hershfield: Duke University Medical Center
Ming-Ta Michael Lee: Institute of Biomedical Sciences, Academia Sinica
Tian-Lu Cheng: Kaohsiung Medical University
Yuan-Tsong Chen: Institute of Biomedical Sciences, Academia Sinica
Steve R. Roffler: Institute of Biomedical Sciences, Academia Sinica
Jer-Yuarn Wu: Institute of Biomedical Sciences, Academia Sinica

Nature Communications, 2017, vol. 8, issue 1, 1-7

Abstract: Abstract Conjugation of polyethylene glycol (PEG) to therapeutic molecules can improve bioavailability and therapeutic efficacy. However, some healthy individuals have pre-existing anti-PEG 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 × 10−22). Our findings may provide novel genetic markers for predicting the immunogenicity of PEG and efficacy of PEGylated therapeutics.

Date: 2017
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DOI: 10.1038/s41467-017-00622-4

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