TY - JOUR
T1 - A genome-wide association study identifies a novel susceptibility locus for the immunogenicity of polyethylene glycol
AU - Chang, Chia Jung
AU - Chen, Chien Hsiun
AU - Chen, Bing Mae
AU - Su, Yu-Cheng
AU - Chen, Ying Ting
AU - Hershfield, Michael S.
AU - Lee, Ming Ta Michael
AU - Cheng, Tian Lu
AU - Chen, Yuan Tsong
AU - Roffler, Steve R.
AU - Wu, Jer Yuarn
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85029312637&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-00622-4
DO - 10.1038/s41467-017-00622-4
M3 - Article
C2 - 28900105
AN - SCOPUS:85029312637
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 522
ER -