title: A novel approach to predict cetuximab-induced hypersensitivity reaction: detection of drug-specific IgE on basophils.
abstract: Cetuximab is remarkable for the relatively high rate and severity of hypersensitivity reactions (HR) being reported in the literature. Screening for cetuximab-specific IgE in serum via immunoassay has been found to be useful in preventing HR; however, these tests are known to have a low positive predictive rate. In an attempt to remedy this, we evaluated the interaction between cetuximab and IgE on basophils for predicting severe cetuximab-induced HR. Twelve head and neck cancer patients were enrolled in this single-institution study: four with a history of cetuximab-induced HR and eight with no such history. Cetuximab-specific and galactose-α-1,3-galactose (α-gal) specific IgEs in serum were measured in vitro using an enzyme-linked immunosorbent assay (ELISA). IgE-cetuximab binding on basophils was also analyzed to evaluate the decrease in cetuximab molecules on basophils after dissociation of IgE from FcεRI. The positive predictive value associated with the presence of cetuximab- or α-gal-specific IgE in serum was found to be only 0.67, whereas the negative predictive value was 1.00. On the other hand, in all four patients who developed HR, the cetuximab molecules on basophils were decreased significantly due to the dissociation of IgE from basophils (P < 0.05). However, this was not the case in patients who did not develop HR. In conclusion, our results strongly imply that the IgE-cetuximab interaction on basophils may be key to developing improved methods for predicting severe cetuximab-induced HR.
authors.affiliation: Department of Pharmacy, Mie University Hospital, Tsu, Mie, 514-8507, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Iwamoto
authors.affiliation: Department of Pharmacy, Mie University Hospital, Tsu, Mie, 514-8507, Japan.
authors.forename: Akiharu
authors.initials: A
authors.lastname: Okamoto
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Ishinaga
authors.affiliation: Department of Oral and Maxillofacial Surgery, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan.
authors.forename: Kasumi
authors.initials: K
authors.lastname: Shimizu
authors.affiliation: Center for Medical and Nursing Education, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan.
authors.forename: Alberto A
authors.initials: AA
authors.lastname: Gayle
authors.affiliation: Department of Oral and Maxillofacial Surgery, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Arai
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Department of Pharmacy, Mie University Hospital, Tsu, Mie, 514-8507, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okuda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity / Q000276:immunology; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D000068818:Cetuximab / Q000009:adverse effects* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006258:Head and Neck Neoplasms / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011379:Prognosis; D011755:Pyrophosphatases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C427944:ENPP3 protein, human; D007073:Immunoglobulin E; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D000068818:Cetuximab
keywords: Antibody drugs; biomarkers; drug allergy; head and neck cancer