Discovery in polyethylene glycol immunogenicity: The characteristic of intergenerational inheritance of anti-polyethylene glycol IgG

• Published in: European journal of pharmaceutics and biopharmaceutics 2022-03, Vol.172, p.89-100
• Main Authors: Gao, Xin, Yan, Xinyang, Wang, Ruoyu, Li, Cong, Qiu, Qiujun, Liu, Mengyang, Tang, Xueying, Yan, Na, Li, Jie, Song, Yanzhi, Deng, Yihui
• Format: Article
• Language: English
• Subjects: Anti-PEG IgG; Intergenerational transmission; PEGylated nanocarriers
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2022.01.008

Scheme 1. Offspring of blank polyethylene glycol (PEG)ylated nanoemulsion-stimulated rats were anti-PEG immunoglobulin (Ig)G positive. [Display omitted] Several studies have reported the prevalence of anti-polyethylene glycol (PEG) antibodies (APAs) in healthy people, highlighting the widespread existence of APAs. The prevalence of anti-PEG immunoglobulin (Ig)G is significantly negatively correlated with age. Here, we used Wistar rats as model organism to examine whether APAs in parental rats can affect the production of antibodies in their offspring. After being pre-stimulated with blank PEGylated nanoemulsions (PE) to induce APAs production, parental rats were paired in cages. The presence of antibodies in the parents and offspring was detected using enzyme-linked immunosorbent assay. The presence of antibodies in the parental rats led to significant anti-PEG IgG positivity in their offspring, indicating that anti-PEG IgG exhibits intergenerational inheritance. Moreover, anti-PEG IgG in the offspring rats could bind to PE and accelerate its blood clearance. To the best of our knowledge, this is the first report on the intergenerational properties of APAs.