Immediate Hypersensitivity to Polyethylene Glycols and Polysorbates: More Common Than We Have Recognized.

BACKGROUND: The most common immediate hypersensitivity to macrogols is associated with polyethylene glycol (PEG) 3350; however, the epidemiology, mechanisms, and cross-reactivity are poorly understood. Thousands of medications contain either PEGs or structurally similar polysorbates. OBJECTIVE: Our objective was to better understand the mechanism, cross-reactivity, and scope of PEG hypersensitivity. METHODS: Two cases with a past history of immediate hypersensitivity to PEG-containing medications were used to study potential mechanisms and cross-reactivity of immediate reactions to PEG 3350. Skin testing and oral challenges with PEG and polysorbate-containing agents were employed to determine clinical reactivity and cross-reactivity between the 2 allergens. Enzyme-linked immunosorbent assay and electrochemiluminescent immunoassay were used to detect anti-PEG specific IgG and IgE, respectively, using PEGylated protein or PEG alone as antigens in 2 cases and 6 PEG 3350 tolerant controls. We searched US Food and Drug Administration (FDA) adverse event reports for immediate reactions to PEG 3350 to determine the potential scope of this problem in the United States. RESULTS: Skin and provocation testing demonstrated symptomatic reactivity in both cases to PEG 3350 and polysorbate 80. Plasma samples were positive for anti-PEG specific IgE and IgG antibodies only in cases and binding increased directly proportional to the molecular weight of PEG tested. FDA adverse event reports revealed 53 additional cases of possible PEG 3350 anaphylaxis. CONCLUSIONS: Immediate hypersensitivity to PEG 3350 with cross-reactive polysorbate 80 hypersensitivity may be underrecognized in clinical practice and can be detected with clinical skin testing. Our studies raise the possibility of an IgE-mediated type I hypersensitivity mechanism in some cases.

The evolving story of human leukocyte antigen and the immunogenetics of peanut allergy.

OBJECTIVE: Peanut allergy (PA) clearly has a heritable component. Specific genetic contributions are unknown, but human leukocyte antigen (HLA) loci are obvious candidates. This review focuses on emerging studies of HLA associations with PA. DATA SOURCES: PubMed was searched with no time limitations using key terms human leukocyte antigen, HLA, MHC, peanut, peanut hypersensitivity, and peanut allergy. STUDY SELECTIONS: Qualifying studies were English-language reports of genetic analyses examining PA and HLA associations. RESULTS: Seven relevant citations were identified, which were published from 1996 to 2015. Early studies using candidate gene approaches found associations between PA and HLA-DR and -DQ alleles (HLA-DRB1*08 and DQB1*06:03P) when comparing subjects with peanut allergy with nonallergic unrelated control groups. No significant associations were found between siblings with and without peanut allergy. However, a recent large genomewide association study of patients with peanut allergy and their family members found 2 PA-associated single-nucleotide polymorphisms (rs9275596 and rs7192) mapping to regions involving the HLA-DR and HLA-DQ genes. Associations with differential DNA methylation partly mediated the associations between PA and single-nucleotide polymorphisms. CONCLUSION: Early studies using candidate gene approaches identified HLA associations with PA compared with the general population, suggesting a link with atopy but failing to identify a PA-specific association. These studies had various limitations that included small samples. The most compelling evidence for a PA-specific HLA association comes from a genomewide association study, which examined the entire genome in large, well-defined, related cohorts. More research is needed to validate and replicate these findings, to perform fine genetic mapping of specific HLA loci, and to demonstrate underlying mechanisms of HLA contributions to PA.