Analysis of Pre-existing IgG and IgM Antibodies against Polyethylene Glycol (PEG) in the General Population.
Circulating antibodies (Ab) that specifically bind polyethylene glycol (PEG), a biocompatible polymer routinely used in protein and nanoparticle therapeutics, have been associated with reduced efficacy of and/or adverse reactions to therapeutics modified with or containing PEG. Unlike most antidrug antibodies that are induced following initial drug dosing, anti-PEG Ab can be found in treatment-naïve individuals (i.e., individuals who have never undergone treatment with PEGylated drugs but most likely have been exposed to PEG through other means). Unfortunately, the true prevalence, quantitative levels, and Ab isotype of pre-existing anti-PEG Ab remain poorly understood. Here, using rigorously validated competitive ELISAs with engineered chimeric anti-PEG monoclonal Ab standards, we quantified the levels of anti-PEG IgM and different subclasses of anti-PEG IgG (IgG1-4) in both contemporary and historical human samples. We unexpectedly found, with 90% confidence, detectable levels of anti-PEG Ab in ∼72% of the contemporary specimens (18% IgG, 25% IgM, 30% both IgG and IgM). The vast majority of these samples contained low levels of anti-PEG Ab, with only ∼7% and ∼1% of all specimens possessing anti-PEG IgG and IgM in excess of 500 ng/mL, respectively. IgG2 was the predominant anti-PEG IgG subclass. Anti-PEG Ab's were also observed in ∼56% of serum samples collected during 1970-1999 (20% IgG, 19% IgM, and 16% both IgG and IgM), suggesting that the presence of PEG-specific antibodies may be a longstanding phenomenon. Anti-PEG IgG levels demonstrated correlation with patient age, but not with gender or race. The widespread prevalence of pre-existing anti-PEG Ab, coupled with high Ab levels in a subset of the population, underscores the potential importance of screening patients for anti-PEG Ab levels prior to administration of therapeutics containing PEG.
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy; ‡Lineberger Cancer Center, Biostatistics Shared Resource; §UNC/NCSU Joint Department of Biomedical Engineering; ∥Department of Microbiology & Immunology, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
Qi
Q
Yang
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy; ‡Lineberger Cancer Center, Biostatistics Shared Resource; §UNC/NCSU Joint Department of Biomedical Engineering; ∥Department of Microbiology & Immunology, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
Timothy M
TM
Jacobs
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy; ‡Lineberger Cancer Center, Biostatistics Shared Resource; §UNC/NCSU Joint Department of Biomedical Engineering; ∥Department of Microbiology & Immunology, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
Justin D
JD
McCallen
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy; ‡Lineberger Cancer Center, Biostatistics Shared Resource; §UNC/NCSU Joint Department of Biomedical Engineering; ∥Department of Microbiology & Immunology, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
Dominic T
DT
Moore
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy; ‡Lineberger Cancer Center, Biostatistics Shared Resource; §UNC/NCSU Joint Department of Biomedical Engineering; ∥Department of Microbiology & Immunology, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
Justin T
JT
Huckaby
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy; ‡Lineberger Cancer Center, Biostatistics Shared Resource; §UNC/NCSU Joint Department of Biomedical Engineering; ∥Department of Microbiology & Immunology, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
Jasmine N
JN
Edelstein
Division of Molecular Pharmaceutics, Eshelman School of Pharmacy; ‡Lineberger Cancer Center, Biostatistics Shared Resource; §UNC/NCSU Joint Department of Biomedical Engineering; ∥Department of Microbiology & Immunology, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
Samuel K
SK
Lai
D000328:Adult; D000368:Aged; D000937:Antigen-Antibody Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000032:analysis*; D055815:Young Adult
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011092:Polyethylene Glycols