Longitudinal Examination of Basophil Functional Phenotypes and Disease Activity in Chronic Idiopathic Urticaria (CIU)

Abstract

RATIONALE: Previously, we demonstrated that 50% of CIU patients' basophils have a “nonresponder” (CIU-NR) functional phenotype, defined as <10% histamine release (HR), with optimal anti-IgE stimulation. CIU-NR basophils also require a ten-fold higher anti-IgE concentration to reach maximal HR when compared to CIU “responder” (CIU-R) basophils and those from non-CIU donors. In the present study, we have examined the persistence of the CIU basophil functional phenotype relative to CIU disease activity. METHODS: Since 2002, 66 CIU subjects were recruited from university allergy and dermatology clinics. After informed consent, basophils were isolated by dextran sedimentation and stimulated with polyclonal goat anti-human IgE (0.01-3 μg/mL) and FMLP (10-6 M), and HR was measured by automated fluorimetry. The majority of subjects (55 of 66) also completed a disease severity questionnaire. RESULTS: Of the 66 subjects sampled, 57 were initially classified by basophil functional phenotype (29 CIU-NR and 28 CIU-R), and 9 specimens were indeterminate due to basopenia. Twenty-four of 57 classified subjects had a second sample an average of 17.2 ± 3.8 months from the initial sample (range 0.5-53 months). Basophil functional phenotype remained stable in subjects with persistent CIU disease activity (n = 18). In contrast, subjects with remission of CIU disease were noted to have heightened sensitivity (CIU-R and CIU-NR) and magnitude of HR (CIU-NR) to anti-IgE. CONCLUSIONS: CIU basophil functional phenotypes (CIU-NR and CIU-R) persist with continued CIU disease activity but shift in disease remission. These findings suggest that basophil HR patterns may be useful markers of CIU disease activity.