title: Loxoprofen sodium induces the production of complement C5a in human serum.
abstract: Basophil activation test (BAT) is an in vitro allergy test that is useful to identify allergens that cause IgE-dependent allergies. The test has been used to detect not only food allergies and allergies caused by environmental factors but also to detect drug hypersensitivity, which has been known to include IgE-independent reactions. In our preliminary studies in which BAT was applied to detect hypersensitivity of loxoprofen, a non-steroidal anti-inflammatory drug (NSAID), conventional BAT with incubation for 30min did not show basophil activation by means of increased CD203c expression. In this study, we extended the incubation time to 24h on the basis of the hypothesis that loxoprofen indirectly activates basophils. Basophils from healthy control donors as well as allergic patients showed up-regulation of CD203c after incubation with loxoprofen for 24h. Activation was induced using loxoprofen-treated serum. Proteomic and pharmacologic analyses revealed that serum incubation with loxoprofen generated an active complement component C5a, which induced CD203c expression via binding to the C5a receptor on basophils. Because C3a production was also detected after incubation for 24h, loxoprofen is likely to stimulate the complement classical pathway. Our findings suggest that the complement activation is involved in drug hypersensitivity and the suppression of this activation may contribute to the elimination of false positive of BAT for drug allergies.
authors: BML, Inc., 1361-1 Matoba, Kawagoe, Saitama 350-1101, Japan; Human Gene Sciences Center, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors: Tomoaki
authors: T
authors: Kumagai
authors: BML, Inc., 1361-1 Matoba, Kawagoe, Saitama 350-1101, Japan.
authors: Nozomi
authors: N
authors: Yamaguchi
authors: BML, Inc., 1361-1 Matoba, Kawagoe, Saitama 350-1101, Japan. Electronic address: hhirai@bml.co.jp.
authors: Hiroyuki
authors: H
authors: Hirai
authors: BML, Inc., 1361-1 Matoba, Kawagoe, Saitama 350-1101, Japan.
authors: Shigeyuki
authors: S
authors: Kojima
authors: BML, Inc., 1361-1 Matoba, Kawagoe, Saitama 350-1101, Japan.
authors: Yoshiko
authors: Y
authors: Kodani
authors: BML, Inc., 1361-1 Matoba, Kawagoe, Saitama 350-1101, Japan.
authors: Akihiko
authors: A
authors: Hashiguchi
authors: Hanzomon Hospital, 1-10, Kojimachi, Chiyoda-ku, Tokyo 102-0083, Japan.
authors: Michiko
authors: M
authors: Haida
authors: Human Gene Sciences Center, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
authors: Masataka
authors: M
authors: Nakamura
mesh_terms: D000485:Allergens / Q000276:immunology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000276:immunology* / Q000627:therapeutic use; D015549:Basophil Degranulation Test; D001491:Basophils / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D003167:Complement Activation / Q000187:drug effects*; D015926:Complement C3a / Q000096:biosynthesis; D003182:Complement C5 / Q000096:biosynthesis*; D004342:Drug Hypersensitivity / Q000175:diagnosis*; D005189:False Positive Reactions; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D010666:Phenylpropionates / Q000276:immunology* / Q000627:therapeutic use; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011755:Pyrophosphatases / Q000378:metabolism
chemical_list: D000485:Allergens; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003182:Complement C5; C427944:ENPP3 protein, human; D010666:Phenylpropionates; C040656:loxoprofen; D007073:Immunoglobulin E; D015926:Complement C3a; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases
keywords: Basophil activation test; CD203c; Complement C5a, C3a; Drug hypersensitivity; Loxoprofen sodium