The natural history of persistent peanut allergy.

BACKGROUND: Peanut allergy affects 1% of children, and for those with persistent disease, few data have been published on trends in peanut-specific immunoglobulin E (P-IgE) levels or the value of P-IgE in predicting reaction severity. OBJECTIVE: The primary outcome was the frequency of inadvertent peanut exposure. Secondary outcomes included clinical characteristics, trends in P-IgE, characteristics of accidental exposures, and predictors of reaction severity in patients with persistent peanut allergy. METHODS: Records of patients with persistent peanut allergy were reviewed. Other allergic conditions, P-IgE levels, and peanut exposures were documented. RESULTS: Seven hundred eighty-two patients were studied, 524 of them male. The median age at initial observation was 1.4 years; the median duration of follow-up was 5.3 years. Of the 782 patients, 93.1% were avoiding other foods, 70.8% had atopic dermatitis, 57.3% allergic rhinitis, and 55.8% asthma. The median initial P-IgE was 28.0 kU/L, and the median peak P-IgE was 68.1. Six hundred eighty-five exposures were seen among 455 patients: 75.9% ingestion, 13.6% contact, 4.5% airborne. 73.7% resulted in urticaria/angioedema, 22.2% lower respiratory symptoms, 21.2% gastrointestinal symptoms, and 7.7% oral erythema/pruritus. Treatment included antihistamines (33.4%), emergency department visits (16.5%), epinephrine (13.1%), corticosteroids (7.7%), albuterol (3.2%), no treatment (26.3%), and not recorded (29.6%). The rate of postdiagnosis ingestion was 4.7%/year; exposures with severe reactions, 1.6%/year; reactions treated with epinephrine, 1.1%/year. Reaction severity did not change with repeated exposure. Severe reactions were associated with higher P-IgE, but not with age, sex, or asthma. CONCLUSION: In this referral population, the rates of accidental peanut exposures and severe reactions were low. There was a strong association between higher P-IgE levels and reaction severity.

Effects of omalizumab on basophil and mast cell responses using an intranasal cat allergen challenge.

BACKGROUND: Omalizumab treatment suppresses FcepsilonRI expression faster on blood basophils than skin mast cells. OBJECTIVE: We used omalizumab to elucidate the relative contributions of basophil versus mast cell FcepsilonRI activation in a nasal allergen challenge (NAC) model. METHODS: Eighteen subjects with cat allergy were enrolled in a 3.5-month, double-blind, randomized (3.5:1), placebo-controlled trial of omalizumab using standard dosing. At baseline, subjects underwent NAC with lavage for prostaglandin D(2) measurement, skin prick test titration (SPTT), and blood sampling for basophil histamine release (BHR) and basophil IgE/FcepsilonRI measurements. Basophil studies were repeated at day 3 and then weekly until cat allergen-induced BHR was <20% of baseline or until day 45. Baseline visit procedures were repeated after the BHR reduction (midstudy NAC) and at the treatment period's completion (final NAC). RESULTS: Subjects treated with omalizumab who completed all NACs (n = 12) demonstrated significant mean reduction in BHR to an optimal dose of cat allergen by midstudy NAC compared with baseline (74% decrease; P = .001). In addition, these subjects demonstrated significant decreases in mean combined nasal symptom scores (50% decrease; P = .007) and total sneeze counts (59% decrease; P = .01) by midstudy NAC relative to baseline NAC. In contrast, measures of mast cell response (SPTT and nasal lavage prostaglandin D(2)) were only significantly reduced by the final NAC. Subjects on placebo (n = 4) did not experience a shift in basophil, NAC symptom, or mast cell measures. CONCLUSION: Reduction in nasal symptom scores occurred when the basophil, but not mast cell, response was reduced on omalizumab, implicating a role for basophils in the acute NAC response.

Interleukin-10 and Th2 cytokines differentially regulate osteopontin expression in human monocytes and dendritic cells.

Osteopontin (OPN) is a pleiotrophic phosphoprotein involved in homeostatic and pathophysiologic responses. It is known to be a chemotactic cytokine for dendritic cells (DCs), a critical cell type in both innate and adaptive immune responses. We report herein a contrasting role of interleukin-10 (IL-10) and Th2 cytokines in the regulation of OPN expression in human monocytes and monocyte-derived DCs (Mo-DCs). Our results showed first that the expression of OPN in monocytes and Mo-DCs was induced in a time-dependent and dose-dependent manner by IL-10 but was inhibited by IL-4 or IL-13. Further, the basal level of OPN expression was also inhibited by IL-4. This inhibitory effect of IL-4 was associated with a faster decay of OPN transcripts and a decreased proximal promoter activity of OPN in IL-4-treated cells. These results demonstrate a novel role of IL-10 and Th2 cytokines in the regulation of DC function through their contrasting regulatory activities on the expression of OPN.

Bullous systemic lupus erythematosus with milia and calcinosis.

Bullous systemic lupus erythematosus (SLE) is a rare skin manifestation of SLE. It shares many features with epidermolysis bullosa acquisita (EBA). We report on a patient with SLE who developed a vesiculobullous eruption followed by findings not typical in bullous SLE, namely milia, mild scarring, and calcinosis. We discuss the relationship between bullous SLE and EBA.

Basophil phenotypes in chronic idiopathic urticaria in relation to disease activity and autoantibodies.

Potentially pathogenic IgG autoantibodies to IgE or its receptor, Fc epsilonRIalpha, have been detected in approximately 40% of chronic idiopathic urticaria (CIU) patients. CIU patients' basophils display distinct altered Fc epsilonRIalpha-mediated degranulation. CIU patients with basophil histamine release in response to polyclonal goat anti-human IgE > or = 10% are classified as CIU responders (CIU-R) and < 10% are CIU non-responders (CIU-NR). We compared the presence of autoantibodies to basophil degranulation phenotypes and to disease status (active or inactive). Sera were collected from non-CIU subjects and CIU subjects who participated in a longitudinal study of disease severity and had defined basophil degranulation phenotypes. Immunoenzymetric assays (IEMA) quantified IgG anti-Fc epsilonRIalpha and anti-IgE. IgG anti-Fc epsilonRIalpha antibody was detected in 57% of CIU-R (n=35), 55% of CIU-NR (n=29), and 57% of non-CIU subjects (n=23), whereas IgG anti-IgE was present in 43% of CIU-R, 45% of CIU-NR, and 30% of non-CIU subjects. Both the autoantibody levels and the functional basophil phenotype remained stable in subjects with active disease (n=16), whereas there was an enhancement in basophil function as subjects evolved into a state of remission (n=6), which appears independent of the presence of autoantibody. IEMAs detected a similar frequency of autoantibodies in CIU-R, CIU-NR, and non-CIU subjects. Basophil function may be independent of IEMA-detected autoantibodies.

Expression of activation markers on basophils in a controlled model of anaphylaxis.

BACKGROUND: Anaphylaxis has variable clinical presentations and lacks reliable biomarkers. Expression of activation markers on basophils has been useful in assessing sensitization in IgE-mediated diseases but has not been examined in vivo in anaphylaxis. OBJECTIVE: The study's goals were to assess the baseline expression of activation markers on basophils in individuals with a sting reaction history, the degree of change in expression of these markers after intentional sting challenge, and the relationship between in vitro and in vivo activation marker expression. METHODS: Patients allergic to insect venom were enrolled and grouped by clinical category defined by a history of a systemic or large local reaction and use of venom immunotherapy. Blood was collected before and after sting challenge. Enriched basophils were analyzed for activation marker expression. In select subjects, basophils were examined after in vitro stimulation with insect venom for activation marker expression and histamine release. RESULTS: Of 35 sting-challenge participants, 21 provided adequate samples for analysis. Pre-sting basophil CD63 expression was significantly higher in systemic reactors on immunotherapy. Following sting challenge, the rise in basophil CD69 expression and CD203c was significantly higher in systemic reactors on immunotherapy. Levels of activation markers on basophils were greater after in vitro venom stimulation than after in vivo challenge. CONCLUSION: Broader shifts in expression of basophil activation markers after in vivo challenge occurred among subjects with a history of in vivo systemic anaphylaxis despite venom immunotherapy. CLINICAL IMPLICATIONS: Basophil activation markers may be potential biomarkers for anaphylaxis.