Nonsteroidal anti‐inflammatory drugs enhance IgE‐mediated activation of human basophils in patients with food anaphylaxis dependent on and independent of nonsteroidal anti‐inflammatory drugs

Abstract

Summary Background Nonsteroidal anti‐inflammatory drugs (NSAIDs) act as cofactors worsening the allergic reactions induced by food allergens. Aim The aim of this study was to evaluate the effect of both lysine acetylsalicylate (L‐ASA) (non‐selective cyclooxygenase (COX) inhibitor) and valdecoxib (selective COX‐2 inhibitor) in basophils activated by peach lipid transfer protein (Pru p 3) in patients with food‐dependent NSAID‐induced anaphylaxis (FDNIA). Methods Twenty Pru p 3‐allergic patients with FDNIA group, eleven peach anaphylaxis not exacerbated by NSAIDs (no‐NSAID group) and 5 healthy volunteers were recruited. Basophil activation (BA) was measured as expression of CD63 (Flow2CAST™; Bühlmann®), after stimulation with Pru p 3, both alone and in combination with L‐ASA (1.13, 3.38 and 6.78 mm) or valdecoxib (0.87, 7.8 and 31.25 μm). Results Basophils from no‐NSAID group were significantly more reactive and sensitive to Pru p 3 than those from the FDNIA group. In both groups, an increase in BA was observed when basophils were exposed to Pru p 3 and L‐ASA. In the FDNIA group, valdecoxib partially terminates the BA induced by Pru p 3, whereas in the no‐NSAID group, a dual effect was observed depending on the concentration tested. Conclusions This study indicates that subjects with food‐induced anaphylaxis differ from FDNIA subjects in the higher reactivity and sensitivity of their basophils to allergen challenge. We have shown a direct effect of NSAIDs on basophils using a human model of FDNIA. Our results also suggest that selective COX2 inhibitors might be a safe alternative. BA test may be a useful tool in the study of the pathogenic mechanism of the cofactor phenomenon.

Progress in understanding hypersensitivity reactions to nonsteroidal anti‐inflammatory drugs

“…The effect is stronger with drugs inhibiting the two COX isoforms compared with selective COX‐2 inhibitors . Another possibility suggests a direct effect of the drug potentiating basophils and mast cells activation/degranulation . The magnitude of the IgE response may depend on the NSAIDs class, the dose and the COX‐1 inhibition potency …”

“…NSAIDs intake has been associated with food-induced anaphylaxis, [75][76][77][78][79] and these drugs can exacerbate food allergy in patients with food-dependent exercise-induced anaphylaxis. [80][81][82][83] [86][87][88] Concerning the association between food allergy and NSAIDs hypersensitivity, NSAIDs have been suggested to increase intestinal barrier permeability, enhancing allergen absorption. 89 The effect is stronger with drugs inhibiting the two COX isoforms compared with selective COX-2 inhibitors.…”

The clinical relevance of lipid transfer protein

“…Another interesting aspect is the frequent association between LTP hypersensitivity and adverse reactions to non‐steroidal anti‐inflammatory drugs (NSAIDs) . It was recently shown that NSAIDs are able to enhance IgE‐mediated activation of basophils, an effect that can be essential for the occurrence of severe reactions in patients who are only slightly sensitized to certain foods …”

“…[33][34][35][36] It was recently shown that NSAIDs are able to enhance IgE-mediated activation of basophils, an effect that can be essential for the occurrence of severe reactions in patients who are only slightly sensitized to certain foods. 37 Along with negative co-factors, "positive" co-factors exist as well.…”

Usefulness of the Basophil Activation Test to Confirm Beer Allergy

“…Hence, ascertaining the effect of cofactors is critical if we are to prevent the development of a severe anaphylactic reaction. The basophil activation test (BAT) has become a reliable diagnostic tool in the evaluation of food allergy [7,8] and can be used before oral challenge testing, especially if a cofactor such as NSAIDs is suspected of being implicated in the reaction [9]. We present a case of beer-induced anaphylaxis confirmed with a positive BAT result to barley and beer, with a negative effect of dexketoprofen (NSAID) as a cofactor.…”