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

Author

Listed:
  • Chia-Jung Chang

    (Institute of Biomedical Sciences, Academia Sinica)

  • Chien-Hsiun Chen

    (Institute of Biomedical Sciences, Academia Sinica
    School of Chinese Medicine, China Medical University)

  • 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
    Geisinger Health System)

  • Tian-Lu Cheng

    (Kaohsiung Medical University)

  • Yuan-Tsong Chen

    (Institute of Biomedical Sciences, Academia Sinica
    Duke University Medical Center)

  • Steve R. Roffler

    (Institute of Biomedical Sciences, Academia Sinica
    Kaohsiung Medical University)

  • Jer-Yuarn Wu

    (Institute of Biomedical Sciences, Academia Sinica
    School of Chinese Medicine, China Medical University)

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.

Suggested Citation

  • 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 & Jer-Yuarn Wu, 2017. "A genome-wide association study identifies a novel susceptibility locus for the immunogenicity of polyethylene glycol," Nature Communications, Nature, vol. 8(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00622-4
    DOI: 10.1038/s41467-017-00622-4
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