Loxoprofen sodium induces the production of complement C5a in human serum.

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.

Close Positive Correlation between the Lymphocyte Response to Hen Egg White and House Dust Mites in Infants with Atopic Dermatitis.

BACKGROUND: It was recently hypothesized that food allergens sensitize infants with atopic dermatitis (AD) via the skin. If this is the case, an intimate positive correlation should be observed between immune responses to both food and indoor allergens. METHODS: One hundred and seven infants with AD and 32 controls were enrolled. The proliferation of lymphocytes stimulated with hen egg white (EW) or house dust mite (HDM) allergens was measured by means of an allergen-specific lymphocyte stimulation test (ALST). Cytokine production was measured in 13 patients and 4 controls. RESULTS: ALST responses for EW (EW-ALST) were significantly higher in AD infants than in control subjects (stimulation index: 7.98 vs. 2.54, p < 0.0001). HDM-ALST responses were also significantly higher in AD infants than in controls (stimulation index: 5.09 vs. 1.44, p < 0.0001). A significant positive correlation was seen between HDM-ALST and EW-ALST responses in AD infants aged 5-6 months (rs = 0.77, p < 0.000001). Serum levels of EW-specific IgE (EW-IgE) were significantly correlated with both EW-ALST (rs = 0.43, p < 0.05) and HDM-ALST levels (rs = 0.47, p < 0.05) in AD patients aged 3-4 months. Serum EW-IgE levels in AD infants were significantly correlated with the ratio of IL-4/IFN-γ production from lymphocytes stimulated with EW (rs = 0.62, p < 0.01) and with HDM (rs = 0.67, p < 0.005). CONCLUSIONS: This study describes the close positive correlation between EW- and HDM-specific immune responses in infants with AD. These results may support the hypothesis that both food and indoor allergens concurrently sensitize infants via the skin.

[Evaluation of the allergenicity of ß-casein in Japanese children with cow milk allergy by using the basophil activation test].

BACKGROUND: Among the casein components, αs-casein (αs-CAS) is considered the major allergen in Japan, and there are very few reports on the allergenicity of ß-casein (ß-CAS). In this study, we compared the allergenicity of ß-CAS with that of αs-CAS in Japanese children with cow milk allergy (CMA). METHOD: The allergenicity of αs-CAS and ß-CAS in 29 CMA patients and 11 control subjects was assessed using the basophil activation test (BAT). The accuracy of the BAT to distinguish the patients with CMA from the control subjects was estimated using a receiver operating characteristic (ROC) analysis and was expressed as the area under the curve (AUC). RESULTS: BAT results for CM were positive in 93.1% of the CMA patients. The results of the ß-CAS-BAT and αs-CAS-BAT were found to be positive in 86.2% and 69.0% of the CMA patients, respectively, however, the difference was not significant. The AUC for the ß-CAS-BAT was 0.893, which was not significantly different from that for the αs-CAS-BAT (0.859). CONCLUSIONS: These results suggest that the allergenicities of ß-CAS and αs-CAS are similar in Japanese patients with CMA.

Biomarkers for allergen immunotherapy in cedar pollinosis.

To initiate, monitor, and complete effective immunotherapy, biomarkers to predict and visualize the immune responses are needed. First, we need to identify the right candidate for immunotherapy. Secondly, the immune responses induced by immunotherapy should be monitored. For the first objective, analysis of polymorphisms of candidate genes may be helpful, but still be in development. Regarding biomarkers for immune responsese, there are numerous reports that evaluate immunotherapy-induced immune changes such as suppression of effector cells, deviation to Th1 cytokine production, and induction of regulatory T cells. No standardized methods, however, have been established. Among them, a functional assay of blocking IgG activity, the IgE-facilitated allergen binding assay, may be useful. We quantitated induced expression of an activation marker, CD203c, on basophils and found that the assay efficiently predicts sensitivity to particular allergen and severity of the allergen-induced symptoms. In patients who received rush immunotherapy for Japanese cedar pollinosis, reduction in CD203c expression after the therapy was observed, suggesting the utility of the test for monitoring immunotherapy.