Differential mediator release from basophils of allergic and non-allergic asthmatic patients after stimulation with anti-IgE and C5a

Background The differentiation between allergic and non-allergic asthma is a common and important challenge for the clinician. Until now, no in vitro diagnostic characteristics have been described to distinguish between these types. Objective To examine the diagnostic value of a basophil stimulation test, w e compared anti-IgE- and C5a-induced mediator release from peripheral blood leucocytes in different types of bronchial asthma. Methods Peripheral blood leucocytes (PBL) from 10 aspirin-sensitive asthmat ics (ASA), 12 non-allergic asthmatics without aspirin intolerance (NAA), se ven allergic asthmatics (AA), and nine healthy controls were prepared by de xtran sedimentation. After priming with interleukin-3 (IL-3) PBL were stimu lated with anti-IgE and C5a, and the release of histamine (HR) and sulfidol eukotrienes (LTR) in the supernatant was compared. Additionally, purified l eucocyte fractions were studied to determine the cellular source of mediato r release. Results Upon stimulation with anti-IgE LTR was slightly, but not significan tly, lower in ASA and NAA compared to AA and controls. In contrast, C5a-tri ggered LTR was significantly higher in ASA (14.4 +/- 12.88 pg/10(5) cells) and NAA (22.9 +/- 22.61 pg/10(5) cells) than in AA (9.6 +/- 3.29 pg/10(5) c ells) and controls (7.5 +/- 7.19 pg/10(5) cells) (P < 0.05). This differenc e between ASA and NAA vs. AA and controls was even more pronounced when det ermining the quotient C5a-/anti-IgE-induced LTR (P < 0.001). At an optimal cut-off point of 1.0, calculated by relative operating characteristics (ROC ) analysis, the positive predictive value for a donor to belong to ASA or N AA was 0.94. No significant differences could be found in HR between the as thmatic patient groups and healthy controls in either condition. As cellula r source of LTR and HR the basophil could be determined. Conclusion Determination of anti-IgE- and C5a-induced LTR from basophils al lows us to discriminate between allergic and non-allergic asthmatic patient s. For diagnostic purposes the quotient C5a-/anti-IgE-induced LTR is more s ignificant than considering a single parameter. ASA cannot be distinguished from NAA.