Release of Sulfidoleukotrienes In Vitro: A Novel test system in the Diagnosis of Pseudo-Allergy to Acetylsalicylic Acid

Abstract

Pseudo-allergic reactions (PAR) may be caused by acetylsalicylic acid (ASA) and other nonsteroidal antiinflammatory drugs. The clinical symptoms consist of anaphylactic shock, bronchospasm, urticaria, angioedema and thereby resemble immediate type hypersensitivity. Antigen specific immune mechanisms, however, are not involved. In general, skin tests are not reliable and the diagnosis of PAR is mainly based on risky provocation tests. Therefore, the purpose of this study was to establish procedures for in vitro diagnosis of PAR to ASA. A controlled study was performed including patients with PAR to ASA based on history and positive oral provocation test and healthy controls. In this in vitro study the production of sulfidoleukotrienes (sLT) by isolated leukocytes was measured using the cellular allergen stimulation test

enzyme-linked immunosorbent assay (CAST-ELISA), which is based on detection of LTC₄, LTD₄ and LTE₄ by a monoclonal antibody. In patients with PAR to ASA, C5a-induced generation of sLT was significantly increased as compares o controls (Fig. 1). In contrast, there was no difference in the spontaneous release of sLT in vitro in patients and controls. Preincubation of leukecyteswith ASA did not exert a significant modulatory effects on the spontaneuos or the C5a-induced production of sLT in patients and controls. In summary, the present study provides a novel in vitro test sysrem for the diagnosis of PAR to ASA, suitable for routine use, by measurement of sLT release. in leukocytes. Moreover, it is tempting to speculate that C5a induced production of sLT might be a crucial step in the pathogenesis of PAR to ASA in vivo.