Immediate‐type hypersensitivity to pyridoxal 5′‐phosphate: Study of in vivo and in vitro cross‐reactivity and identification of the antigenic determinant
ABSTRACT Background: A case in which a 45-year-old female patient with peritonitis experienced immediate-type hypersensitivity on two occasions after administration of preparations containing six different medications was referred to us for closer inspection.Methods/Results: Skin tests performed on the six medications revealed a positive reaction to the vitamin B6 preparation Biosechs (Wakamoto Pharmaceutical, Tokyo, Japan). Further investigation showed that the principal ingredient, pyridoxal 5′-phosphate (PLP), produced a positive reaction, whereas the injection solvent with the principal ingredient removed produced a negative reaction. When compounds similar to PLP were tested, pyridoxine (PN), pyridoxamine and pyridoxal produced a negative reaction, whereas pyridoxine 5′-phosphate and pyridoxamine 5′-phosphate (PMP) produced a positive reaction. Adenosine 2′-phosphate and adenosine 5′-diphosphate were also tested and these produced a negative reaction. When a histamine-release test was performed, PLP and PMP produced a positive reaction, whereas PN produced a negative reaction. When all tests were performed on three control subjects, the results were all negative.Conclusions: In this very rare case, phosphate radical conjugates with a pyridine nucleus became haptenic-epitope and an immediate-type reaction occurred. In past cases involving hypersensitivity to vitamin B6, two cases involved a photoallergic reaction caused by PN and one case involved an immediate-type hypersensitivity caused by PLP. In the past cases, closely related substances had not been tested and an epitope was not identified.
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ABSTRACT: Anaphylaxis to mannitol present naturally in pomegranate and cultivated mushroom in a sensitized subject has been described recently, and an IgE-mediated mechanism to this sugar alcohol has been proposed. The same subject also experienced severe allergic reactions to a chewable pharmaceutical (cisapride drug). The purpose of the study was to identify allergenic component in the pharmaceutical preparation, and also, to understand the mechanism of immediate hypersensitivity to mannitol. Methodology involved skin prick tests (SPTs), high-performance liquid chromatographic (HPLC) analysis of pharmaceutical preparations, separation of mannitol by Ca++-ion-moderated cation-exchange chromatography, preparation of alditol-protein conjugates by reductive amination, SPT using the conjugates, hapten affinity purification of the allergic serum on D-mannitol-keyhole limpet haemocyanin (KLH)-Sepharose CL-6B, and detection of serum mannitol-specific IgE by ELISA. Component testing by SPT, and HPLC analysis of various pharmaceuticals indicated that the excipient mannitol is the causative allergen. Mannitol separated from Cisapid MPS showed allergenic activity by SPT. Among the several conjugates tested by SPT, D-mannitol-bovine serum albumin and D-mannitol-KLH showed positive weal/flare reaction, demonstrating the presence of cell-bound mannitol-specific IgE in vivo. Negative results with D-glucitol, D-galactitol, meso-erythritol, and L-mannitol protein conjugates clearly showed that the mannitol-specific human IgE is very specific to the D-isomer of mannitol. ELISA using the hapten affinity-purified allergic serum was positive, demonstrating the presence of mannitol-specific serum IgE in the allergic subject. Mannitol, which is widely used as a food and drug additive (excipient), can rarely cause IgE-mediated anaphylaxis. This study is the first one to demonstrate the presence of mannitol-specific human IgE in a sensitized allergic subject to validate an IgE-mediated hypersensitivity mechanism for mannitol.Clinical & Experimental Allergy 11/2004; 34(10):1602-9. · 4.32 Impact Factor