Association of food allergy and atopic dermatitis exacerbations.

BACKGROUND: Atopic dermatitis (AD) and food allergy frequently coexist in children. OBJECTIVE: To examine the association between food allergy and AD. METHODS: Between 2001 and 2011, children referred to our tertiary care center underwent double-blind, placebo-controlled food challenges (DBPCFCs) for one or more suspected food allergies as part of regular care. Immediate reactions were observed and recorded by allergy nursing staff, whereas late reactions were ascertained by semistructured telephone interview 48 hours after challenge. To test to which degree specific IgE results were predictive in the outcome of DBPCFCs in children with and without (previous and current) AD, logistic regression analysis was performed. RESULTS: A total of 1186 DBPCFCs were studied. Sensitization to foods occurred significantly more often in children with previous AD. The association between specific IgE results and the outcome of DBPCFCs was significant for children with and without (previous and current) AD but stronger for children without current AD. The positivity rate of DBPCFCs in children with mild, moderate, and severe AD was 53.3%, 51.7%, and 100%, respectively. Children with AD and a history of worsening AD as their only symptom reacted as often to placebo as to challenge food. CONCLUSION: Children with current AD are more frequently asymptomatically sensitized to the foods in question than those without AD. In addition, children suspected of food allergy should be considered for testing, regardless of the severity of their AD. Our results suggest that children with exacerbation of AD in the absence of other allergic symptoms are unlikely to be food allergic.

Metalloproteinase Profiling in Lung Transplant Recipients With Good Outcome and Bronchiolitis Obliterans Syndrome.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS), the major cause of death on lung transplantation, is characterized by bronchiolar inflammation and tissue remodeling. Matrix metalloproteinases (MMPs) have been implicated in these processes, although it is still unclear whether MMP activity and binding to their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs), is abnormal in BOS. METHODS: We studied total MMP-1,-2,-3,-7,-8,-9,-12,-13 levels, their activity state using activity-based extraction and their binding to TIMP-1, -2, -3, and -4 in bronchoalveolar lavage (BAL) of lung transplant recipients with good outcome and BOS using a multiplex immunoassay. RESULTS: The BAL levels of TIMP-1 and -2 and MMP-2, -3, -7, -8, and -9 were significantly increased in BOS compared to good outcome recipients. Interestingly, activity of MMP-7, but none of the other MMPs, was detected in good outcome recipients, whereas no active MMPs were observed in BOS recipients. However, BAL levels of TIMP-bound MMP-8 and -9 were higher in BOS than in good outcome recipients, suggesting activity of these MMPs in an earlier stage. CONCLUSIONS: We demonstrate that development of BOS is associated with increased levels of TIMP-1 and -2 and total MMP-2, -3, -7, -8, and -9. Although active MMP-7 was only observed in good outcome recipients, levels of TIMP-bound MMP-8 and -9 were higher in BOS. By enabling profiling of active and TIMP-bound MMPs, our novel method may open opportunities for the screening of early predictors for BOS.

Diminished reliability of tryptase as risk indicator of mastocytosis in older overweight subjects.

BACKGROUND: Currently, measurement of serum tryptase level is the most commonly used test to estimate the need for bone marrow biopsy in patients suspected to have indolent systemic mastocytosis (ISM). Yet tryptase levels do not solely reflect the mast cell load and can be elevated by overweight, older age, and impaired renal function. The influence of these factors on urinary methylhistamine (MH) and methylimidazole acetic acid (MIMA) is still unknown. OBJECTIVE: We investigated the impact of age, body mass index (BMI), and kidney function on the diagnostic accuracy of tryptase, MH, and MIMA to select the most optimal test indicating the necessity of a bone marrow biopsy in ISM-suspected patients. METHODS: Retrospective data analysis of all adults in whom bone marrow investigations were performed because of high clinical suspicion and/or elevated tryptase, MH, or MIMA. RESULTS: 194 subjects were included. ISM was present in 112 and absent in 82 subjects (non-ISM). Tryptase was elevated by age and body weight in non-ISM subjects and by BMI in ISM subjects; however, these factors did not influence MH or MIMA. In the total study population, the diagnostic accuracy of tryptase, MH, and MIMA were comparable (area under the curve 0.80, 0.80, and 0.83). In subjects >50 years with a BMI >25 kg/m(2), the diagnostic accuracy of MIMA was higher compared with that of tryptase (area under the curve 0.93 vs 0.74; P = .011). CONCLUSION: In ISM-suspected patients >50 years with a BMI of >25 kg/m(2), MIMA has a greater value compared with tryptase in estimating the need for bone marrow biopsy.

Basophil activation test in the diagnosis and monitoring of mastocytosis patients with wasp venom allergy on immunotherapy.

BACKGROUND: There is need for an accurate diagnostic test in mastocytosis patients with wasp venom allergy (WVA) and monitoring of these patients during immunotherapy (IT). In this study, we aimed to evaluate sensitivity and specificity of the Basophil Activation Test (BAT) as a diagnostic and monitoring test in patients with mastocytosis and WVA. METHODS: Seventeen patients with mastocytosis and WVA and six mastocytosis patients without WVA were included. BAT was performed before the start of IT (first visit) and at 6 weeks (second visit) and 1 year (third visit), after reaching the maintenance dose. Of 17 patients included, 11 completed the third visit. In mastocytosis patients with WVA, dose-dependent wasp-venom induced upregulation of CD63 and CD203c expression on basophils was observed compared with mastocytosis patients without WVA. Serum specific IgE, IgG4, and tryptase levels were measured in all patients. RESULTS: BAT had a sensitivity of 87% and specificity of 100% in diagnosing WVA in mastocytosis patients. Basophil allergen threshold sensitivity with respect to CD63 and CD203c was significantly decreased in the second visit compared with the first visit and increased significantly in the third visit compared with the second visit. Specific IgE levels increased significantly in the second visit compared with first and decreased significantly in the third visit compared with the second. Specific IgG4 levels rose significantly in the second visit compared with the first and on the third visit compared with the second. Tryptase levels did not change significantly during the study. CONCLUSIONS: BAT represents a diagnostic test with 100% specificity in allergic patients with mastocytosis and these patients are better to be monitored for a longer period during IT.

Higher mast cell load decreases the risk of Hymenoptera venom-induced anaphylaxis in patients with mastocytosis.

BACKGROUND: Increased basal serum tryptase (bsT) levels are a well-described risk factor for Hymenoptera venom-induced anaphylaxis (HVAn) in patients allergic to Hymenoptera venom. Increased bsT levels might also indicate the presence of mastocytosis. In this study we evaluated whether the risk of HVAn increases with increasing mast cell load in patients with mastocytosis. METHODS: Consecutive patients with different subtypes of mastocytosis (n = 329) admitted to the University Medical Center Groningen were retrospectively assessed. As markers for mast cell load, levels of both bsT and the urinary histamine metabolites methylhistamine and methylimidazole acetic acid (MIMA) were used. RESULTS: In the entire patient group, irrespective of disease subtype and Hymenoptera venom exposure, HVAn prevalence gradually increased with increasing marker levels to a maximum of 36% to 47% at a bsT level of 28.0 µg/L, a methylhistamine level of 231.0 µmol/mol creatinine, and a MIMA level of 2.7 mmol/mol creatinine but decreased thereafter with a further increase in these levels. In patients with indolent systemic mastocytosis with a history of Hymenoptera venom exposure after age 15 years or greater (n = 152), MIMA and age at the most recent Hymenoptera sting were independent predictors for HVAn (odds ratios of 0.723 [P = .001] and 1.062 [P < .001], respectively). CONCLUSIONS: In patients with mastocytosis, HVAn prevalence does not increase constantly with increasing levels of mast cell load parameters: after a gradual increase to a maximum of near 50%, it decreases with a further increase in these levels. In the indolent systemic mastocytosis population, all mast cell load markers were independent negative predictors of HVAn. These findings suggest a complex pathophysiologic association between mast cell load and HVAn risk in patients with mastocytosis.

Threshold dose distributions for 5 major allergenic foods in children.

BACKGROUND: For most allergenic foods, insufficient threshold dose information within the population restricts the advice on levels of unintended allergenic foods which should trigger precautionary labeling on prepackaged foods. OBJECTIVE: We wanted to derive threshold dose distributions for major allergenic foods and to elaborate the protein doses at which a proportion of the allergic population is likely to respond. METHODS: For 7 allergenic foods double-blind, placebo-controlled food challenges (DBPCFCs) with a positive outcome for allergic reactions were selected from the clinical database of children routinely tested to diagnose food allergy at the University Medical Center Groningen. For each allergen 2 population threshold distributions were determined with the individual minimal eliciting dose and the preceding dose of each DBPCFC for objective symptoms and any symptom (either subjective or objective). RESULTS: Individual positive DBPCFCs were available for peanut (n = 135), cow's milk (n = 93), hen's egg (n = 53), hazelnut (n = 28), and cashew nut (n = 31). Fewer children were challenged with soy (n = 10) or walnut (n = 13). Threshold dose distributions showed a good statistical and visual fit. The protein dose at which 5% of the allergic population is likely to respond with objective reactions was 1.6 mg for peanut, 1.1 mg for cow's milk, 1.5 mg for hen's egg, 7.4 mg for cashew nut, and 0.29 mg for hazelnut. Thresholds for any symptom were on average 2 to 6 times lower than for objective symptoms. The 95% upper and lower confidence intervals of the threshold distributions were overlapping. The peanut threshold distribution on objective symptoms was similar to the distribution of another European center. CONCLUSIONS: Threshold distribution curves and eliciting doses are a powerful tool to compare different allergenic foods and for informing policy on precautionary labeling.

Enzymatic treatment of whey proteins in cow's milk results in differential inhibition of IgE-mediated mast cell activation compared to T-cell activation.

BACKGROUND: Cow's milk (CM) hydrolysates are frequently used as milk substitutes for children with CM allergy. In hydrolysates, allergenic epitopes within CM proteins are diminished by enzymatic treatment. The aim of this study was to examine the allergenic and immunogenic properties of whey proteins during hydrolysis. METHODS: During hydrolysis, samples were obtained at 0, 10, 15, 30, 45, 60, 75 and 90 min. Degradation was checked by HPLC and SDS-PAGE. Allergenic potential was analyzed by IgE crosslinking capacity of human Fcε receptor type 1-transduced rat basophilic leukemia cells sensitized with serum of CM-allergic patients. Whey-sensitized C3H/HeOuJ mice were ear challenged intracutaneously with the hydrolysates. Immunogenicity was tested using whey-specific human T-cell clones and T-cell lines at the level of proliferation and release of IL-4, IL-10, IL-13 and IFN-γ. RESULTS: After 15 min of hydrolysis, the majority of the proteins were degraded. Hydrolysis for 15 min resulted in 92% inhibition of mast cell degranulation and in 82% reduction of ear swelling in the mouse model. In contrast, T-cell-stimulatory capacity was less affected by hydrolysis: reduction of human T-cell proliferation was only 9%. This was further reduced to 57 and 74% after 30 and 45 min of hydrolysis, respectively. Cytokine production followed the pattern of T-cell proliferation. CONCLUSION: Via differential analysis of allergenic versus immunogenic properties of the time kinetics of hydrolysis of whey proteins, we have demonstrated specific hydrolysis conditions with reduced IgE-crosslinking responses but retained T-cell activating properties. This approach might be useful in better defining CM hydrolysates.

Anaphylaxis and severe systemic reactions caused by skin contact with persulfates in hair-bleaching products.

BACKGROUND: Persulfates have been reported to cause both delayed-type and immediate skin reactions. They may also cause immediate reactions of the mucous membranes of the bronchial system through inhalation, leading to asthma and rhinitis. Anaphylactic reactions caused by contact with persulfates are rare. The mechanism of immediate reactions caused by persulfates is unclear. OBJECTIVES: To report 2 cases with systemic reactions after skin contact with persulfates, and to propose a test protocol for diagnosing immediate reactions caused by persulfates. METHODS: Prick tests with serial dilutions of ammonium and potassium persulfate were performed. Patch tests were also performed with the two agents. Persulfate-specific IgE was detected with two different IgE immunoblotting techniques. RESULTS: Prick tests were positive with ammonium and potassium persufate, but no specific IgE was detected in the serum. Patch tests showed early positive reactions to both persulfates in 1 patient. CONCLUSIONS: Prick tests and patch tests can be valuable in the testing of patients with a suspicion of an immediate-type reaction caused by persulfates. The mechanism of these reactions remains unclear.

Quantification of matrix metalloprotease-9 in bronchoalveolar lavage fluid by selected reaction monitoring with microfluidics nano-liquid-chromatography-mass spectrometry.

Quantitative protein analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the selected reaction monitoring (SRM) mode was used to quantify matrix metalloprotease-9 (MMP-9; ∼90 kDa) in bronchoalveolar lavage fluid (BALF) from patients having undergone lung transplantation. We developed an SRM assay for microfluidics-based nanoLC-MS/MS on a triple quadrupole mass spectrometer based on two signature peptides. Samples were prepared by chloroform-methanol precipitation followed by trypsin digestion in the presence of stable-isotope-labeled internal peptide standards. The method allows accurate quantification of MMP-9 in BALF with an LLOQ of 2.9 ng/mL and an LLOD of 0.25 ng/mL without the use of extensive fractionation or antibodies.

Parental eczema increases the risk of double-blind, placebo-controlled reactions to milk but not to egg, peanut or hazelnut.

BACKGROUND: While genetic factors are known to be important in the development of sensitization to foods, it is not known whether they also play a role in clinical allergic reactivity to foods. OBJECTIVE: We aimed to determine whether parental atopic diseases are associated with a higher risk of a reaction to common allergenic foods when tested in a double-blind, placebo-controlled food challenge (DBPCFC). METHODS: Parents of children suspected of being food allergic were interviewed about their own and their child's atopic history. Specific IgE and skin prick tests to food allergens and the outcome of food challenges in the child were recorded. RESULTS: Data from 553 double-blind food challenges performed in 396 children were analyzed. The foods tested were milk (n = 185), egg (n = 110), peanut (n = 198) and hazelnut (n = 60). Only parental eczema was significantly associated with positive outcomes for food challenges with milk after correction for age, sex, atopic comorbidity in the child and milk-specific IgE test results (odds ratio 3.1, 95% confidence interval 1.5-6.3). CONCLUSIONS: Children with a positive DBPCFC to milk more frequently have parents with eczema than children with a negative test. This effect of parental eczema was not seen in children challenged with egg, peanut or hazelnut. Clinical reactivity to milk may be caused by genetic factors which are shared with parental eczema to a greater extent than clinical reactivity to other foods.

Acute respiratory effects in firefighters.

BACKGROUND: Associations between acute respiratory inflammatory responses, changes in bronchial hyperresponsiveness, serum pneumoprotein levels, and exposure to fire smoke were studied. METHODS: The study comprised 51 firefighters. Blood samples were taken within 24 hr following exposure to fire smoke, and after a week and 3 months. Sputum was induced within 5 days post-exposure and subjects underwent spirometry and methacholine provocation one week post-exposure. Exposure was registered by a questionnaire. RESULTS: No changes were observed following smoke exposure in bronchial hyperresponsiveness and serum pneumoprotein levels. Nevertheless, in a sizable proportion of the firefighters (44%) elevated sputum neutrophil levels (≥60%) were found. Serum IL-8 concentrations were higher 24 hr post-exposure compared to pre-exposure. Elevated neutrophil levels in sputum were associated with elevated serum IL-8 (ß = 0.010, P = 0.004) and TNFα (ß = 0.005, P = 0.034) levels within 24 hr post-exposure and IL-8 elevation lasted up to 3 months. CONCLUSIONS: Acute exposure to fire smoke induces acute neutrophilic airway and long-lasting systemic inflammation in healthy firefighters in the absence of bronchial hyperresponsiveness.

The eliciting dose of peanut in double-blind, placebo-controlled food challenges decreases with increasing age and specific IgE level in children and young adults.

BACKGROUND: Several risk factors for severe anaphylactic reactions to food in daily life are known. However, to date, it is not possible to predict the severity of allergic reactions to food in the individual patient with accuracy. Some studies show that a history of severe reactions is associated with a lower eliciting dose in double-blind, placebo-controlled food challenges (DBPCFCs). Therefore, in this study, the eliciting dose was used as a measure of clinical sensitivity. OBJECTIVES: To study whether risk factors for severe allergic reactions to food in daily life such as age, degree of sensitization, and coexistent atopic disease influence the eliciting dose in DBPCFCs in children allergic to peanut. METHODS: Data from children who had clinical reactions to peanut during DBPCFCs at the University Medical Center Groningen (2001-2009) were analyzed. A Cox regression model was used to analyze the association of the determinants with the eliciting dose. RESULTS: One hundred twenty-six positive DBPCFCs with peanut were analyzed. Age older than 10 years, a specific IgE level above the lowest tertile (≥ 5.6 kU/L), and the absence of atopic dermatitis were associated with reactions to lower doses: respective hazard ratios 1.89 (95% CI, 1.28-2.81; P = .001), 2.03 (95% CI, 1.37-3.00; P < .0001), and 0.45 (95% CI, 0.29-0.71; P = .001) present versus absent. No significant associations with the eliciting dose were found for sex, the presence of asthma and rhinitis, and the severity of food reactions by history. CONCLUSIONS: Using the eliciting dose as a measure of clinical sensitivity, greater clinical sensitivity in DBPCFCs to peanut was found to be associated with increasing age, higher specific IgE level, and the absence of atopic dermatitis. This finding may explain why adolescents experience severe allergic reactions in daily life to peanut more often than do younger children.

In vivo and in vitro evaluation of the residual allergenicity of partially hydrolysed infant formulas.

Hypoallergenic infant formulas are commonly used for genetically predisposed children and infants diagnosed with cow's milk allergy. This study describes both in vitro and in vivo approaches to assess residual allergenicity of partially hydrolysed infant formulas. Electrophoretic patterns indicated that ß-lactoglobulin and other whey proteins were largely degraded. For safety reasons, according to the European commission-guidelines, it is required that the sensitizing capacity of hypoallergenic formulas is tested in an animal model. In contrast to whey sensitization, no elevated levels of whey-specific IgE, anaphylactic reactions or drop in body temperature were observed in sensitized mice exposed to whey hydrolysates. This indicates that the whey hydrolysates lost their putative sensitizing capacity in a mouse model using oral sensitization, which is highly relevant in relation to the human situation. In combination with the lost capacity of hydrolysed infant formulas to cross-link human IgE antibodies on RBL-huFcɛRI in vitro, both the sensitization and the challenge phase of the allergic response were studied. This combination of assays is proposed as a strategy for the screening of new hypoallergenic formulas aimed at preventing sensitization in atopic children and avoiding clinical symptoms in infants suffering from cow's milk allergy.

The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome.

BACKGROUND: Mast cell activation is thought to be involved in visceral hypersensitivity, one of the main characteristics of the irritable bowel syndrome (IBS). A study was therefore undertaken to investigate the effect of the mast cell stabiliser ketotifen on rectal sensitivity and symptoms in patients with IBS. METHODS: 60 patients with IBS underwent a barostat study to assess rectal sensitivity before and after 8 weeks of treatment. After the initial barostat, patients were randomised to receive ketotifen or placebo. IBS symptoms and health-related quality of life were scored. In addition, mast cells were quantified and spontaneous release of tryptase and histamine was determined in rectal biopsies and compared with biopsies from 22 age- and gender-matched healthy volunteers. RESULTS: Ketotifen but not placebo increased the threshold for discomfort in patients with IBS with visceral hypersensitivity. This effect was not observed in normosensitive patients with IBS. Ketotifen significantly decreased abdominal pain and other IBS symptoms and improved quality of life. The number of mast cells in rectal biopsies and spontaneous release of tryptase were lower in patients with IBS than in healthy volunteers. Spontaneous release of histamine was mostly undetectable but was slightly increased in patients with IBS compared with healthy volunteers. Histamine and tryptase release were not altered by ketotifen. CONCLUSIONS: This study shows that ketotifen increases the threshold for discomfort in patients with IBS with visceral hypersensitivity, reduces IBS symptoms and improves health-related quality of life. Whether this effect is secondary to the mast cell stabilising properties of ketotifen or H(1) receptor antagonism remains to be further investigated. Trial Registration Number NTR39, ISRCTN22504486.

Preeclampsia is associated with lower percentages of regulatory T cells in maternal blood.

OBJECTIVE: Immunological mechanisms are involved in the pathophysiology of preeclampsia. During pregnancy there is an increase in regulatory T (Treg) cells, which has an important role in regulating tolerance to the immunologically distinct fetus. We hypothesised that percentages of Treg cells are decreased in preeclamptic patients. METHODS: Peripheral blood was obtained from 26 healthy pregnant controls and 18 preeclamptic patients. Treg cells were measured using flow-cytometry. RESULTS: Women with pregnancies complicated by preeclampsia had significantly lower percentages of CD4(+)FOXP3(+) Treg cells. CONCLUSION: We conclude that a deficiency of regulatory T cells may play a role in the pathophysiology of preeclampsia.

Change in inflammation in out-patient COPD patients from stable phase to a subsequent exacerbation.

BACKGROUND: Inflammation increases during exacerbations of COPD, but only a few studies systematically assessed these changes. Better identification of these changes will increase our knowledge and potentially guide therapy, for instance by helping with quicker distinction of bacterially induced exacerbations from other causes. AIM: To identify which inflammatory parameters increase during COPD exacerbations compared to stable disease, and to compare bacterial and non-bacterial exacerbations. METHODS: In 45 COPD patients (37 male/8 female, 21 current smokers, mean age 65, FEV(1) 52% predicted, pack years 38) sputum was collected during a stable phase and subsequently during an exacerbation. RESULTS: Sputum total cell counts (9.0 versus 7.9 x 10(6)/mL), eosinophils (0.3 versus 0.2 x 10(6)/mL), neutrophils (6.1 versus 5.8 x 10(6)/mL), and lymphocytes (0.07 versus 0.02 x 10(6)/mL) increased significantly during an exacerbation compared to stable disease. A bacterial infection was demonstrated by culture in 8 sputum samples obtained during an exacerbation. These exacerbations had significantly increased sputum total cell and neutrophil counts, leukotriene-B4, myeloperoxidase, interleukin-8 and interleukin-6, and tumor necrosis factor-alpha (TNF-alpha) levels, and were also associated with more systemic inflammation compared to exacerbations without a bacterial infection. Sputum TNF-alpha level during an exacerbation had the best test characteristics to predict a bacterial infection. CONCLUSION: Sputum eosinophil, neutrophil, and lymphocyte counts increase during COPD exacerbations. The increase in systemic inflammation during exacerbations seems to be limited to exacerbations caused by bacterial infections of the lower airways. Sputum TNF-alpha is a candidate marker for predicting airway bacterial infection.

In vitro and in vivo anti-allergic effects of Arctium lappa L.

The discovery of drugs that can be used for the treatment of allergic disease is important in human health. Arctium lappa Linne (Compositae) (AL) has been used as a traditional medicine in Brazil and throughout Asia and is known to have an anti-inflammatory effect. In this study, the inhibitory effects of AL on degranulation and the release of mediators as well as on inhibition of cys-leukotriene biosynthesis by basophils were investigated. AL was selected out of 10,000 herbal extracts in a set-up for high throughput screening in which the degree of degranulation was monitored by the release of beta-hexosaminidase from rat basophil leukemia (RBL-2H3) cells. The AL extract significantly reduced degranulation and biosynthesis of cys-leukotrienes of human basophils in peripheral blood mono-nuclear cells (PBMCs) (50% inhibitory concentration [IC(50)] = 8.3 and 11.4 microg/ml, respectively). Viability and metabolic activity of the PBMCs were not affected. Although arctiin, the active component of AL that has been described in the literature, was not able to reduce degranulation in RBL-2H3 cells, a single high-performance liquid chromatography (HPLC) fraction from the AL extract inhibited beta-hexosaminidase release (IC(50) = 22.2 microg/ml). Topical administration of an aqueous extract of AL (5 mg/ear) on the ear of whey-sensitized mice 4 hrs before challenge with whey in the ear inhibited acute ear swelling by 50% in an in vivo cow's milk allergic model. The extract had no effect in this model when administered orally. In conclusion, the active component present in the active HPLC fraction of the AL extract was able to significantly reduce the release of inflammatory mediators through inhibition of degranulation and cys-leukotriene release in vitro. In addition, this active component was able to inhibit acute skin response in mice in vivo, indicating that AL is a very promising natural component for use in anti-allergic treatment.

Basophil-activation tests in Hymenoptera allergy.

PURPOSE OF REVIEW: Despite recent advances in our understanding of basophil biology and discovery of new markers for basophil activation, tests measuring basophil activation are not widely utilized in Hymenoptera allergy. Studies of the basophil-activation test in Hymenoptera allergy were examined and the clinical utility of this test was assessed. RECENT FINDINGS: It has been demonstrated that the results of basophil-activation tests correlate quite well with those of serum IgE testing or skin-prick tests. Many studies compare test outcomes with history in patients and nonallergic controls, so that specificity in sensitized but clinically nonreactive individuals remains unknown. Although one study showed that the basophil-activation test might predict immunotherapy side effects, this could not be confirmed in a second study, and no role has been established for the basophil-activation test in the monitoring of venom immunotherapy. The basophil-activation test has no extra value in assessing sting challenges, although experience is limited. SUMMARY: The measurement of basophil-activation markers may be useful in detecting IgE-mediated sensitization but the relevance for application of the basophil-activation test in prediction of clinical reactivity in Hymenoptera allergy is very limited. For this reason, this test currently has no established role in the diagnosis and management of patients with insect sting allergy.