title: Measurement of Pre-Existing IgG and IgM Antibodies against Polyethylene Glycol in Healthy Individuals.
abstract: Polyethylene glycol (PEG) is a biocompatible polymer that is often attached to therapeutic molecules to improve bioavailability and therapeutic efficacy. Although antibodies with specificity for PEG may compromise the safety and effectiveness of PEGylated medicines, the prevalence of pre-existing anti-PEG antibodies in healthy individuals is unclear. Chimeric human anti-PEG antibody standards were created to accurately measure anti-PEG IgM and IgG antibodies by direct ELISA with confirmation by a competition assay in the plasma of 1504 healthy Han Chinese donors residing in Taiwan. Anti-PEG antibodies were detected in 44.3% of healthy donors with a high prevalence of both anti-PEG IgM (27.1%) and anti-PEG IgG (25.7%). Anti-PEG IgM and IgG antibodies were significantly more common in females as compared to males (32.0% vs 22.2% for IgM, p < 0.0001 and 28.3% vs 23.0% for IgG, p = 0.018). The prevalence of anti-PEG IgG antibodies was higher in younger (up to 60% for 20 year olds) as opposed to older (20% for >50 years) male and female donors. Anti-PEG IgG concentrations were negatively associated with donor age in both females (p = 0.0073) and males (p = 0.026). Both anti-PEG IgM and IgG strongly bound PEGylated medicines. The described assay can assist in the elucidation of the impact of anti-PEG antibodies on the safety and therapeutic efficacy of PEGylated medicines.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Bing-Mae
authors.initials: BM
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Su
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Burnouf
authors.affiliation: Graduate Institute of Pharmacognosy, Taipei Medical University , Taipei 11031, Taiwan.
authors.forename: Kuo-Hsiang
authors.initials: KH
authors.lastname: Chuang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica , Taipei 11529, Taiwan.|School of Chinese Medicine, China Medical University , Taichung 40447, Taiwan.
authors.forename: Chien-Hsiun
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Biomedical Science and Environmental Biology, Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University , Kaohsiung 80708, Taiwan.
authors.forename: Tian-Lu
authors.initials: TL
authors.lastname: Cheng
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica , Taipei 11529, Taiwan.|Department of Pediatrics, Duke University Medical Center , Durham, North Carolina 27710, United States.
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica , Taipei 11529, Taiwan.|School of Chinese Medicine, China Medical University , Taichung 40447, Taiwan.
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica , Taipei 11529, Taiwan.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung 80708, Taiwan.
authors.forename: Steve R
authors.initials: SR
authors.lastname: Roffler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D044466:Asian People; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood* / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology; D008297:Male; D051379:Mice; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D055815:Young Adult
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016898:Interferon-alpha; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; C100416:peginterferon alfa-2a