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

Published online

Journal Article

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.Some individuals develop antibodies against the polyethylene glycol that is commonly used in therapeutic preparations. Here the authors conduct a GWAS in Han Chinese and find the IGH locus is associated with anti-PEG IgM.

Full Text

Duke Authors

Cited Authors

  • Chang, C-J; Chen, C-H; Chen, B-M; Su, Y-C; Chen, Y-T; Hershfield, MS; Lee, M-TM; Cheng, T-L; Chen, Y-T; Roffler, SR; Wu, J-Y

Published Date

  • September 12, 2017

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • 522 -

PubMed ID

  • 28900105

Pubmed Central ID

  • 28900105

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-017-00622-4

Language

  • eng

Conference Location

  • England