Basophil Activation to Gluten and Non-Gluten Proteins in Wheat-Dependent Exercise-Induced Anaphylaxis.

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a cofactor-induced wheat allergy. Gluten proteins, especially ω5-gliadins, are known as major allergens, but partially hydrolyzed wheat proteins (HWPs) also play a role. Our study investigated the link between the molecular composition of gluten or HWP and allergenicity. Saline extracts of gluten (G), gluten with reduced content of ω5-gliadins (G-ω5), slightly treated HWPs (sHWPs), and extensively treated HWPs (eHWPs) were prepared as allergen test solutions and their allergenicity assessed using the skin prick test and basophil activation test (BAT) on twelve patients with WDEIA and ten controls. Complementary sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE), high-performance liquid chromatography (HPLC), and mass spectrometry (MS) analyses revealed that non-gluten proteins, mainly α-amylase/trypsin inhibitors (ATIs), were predominant in the allergen test solutions of G, G-ω5, and sHWPs. Only eHWPs contained gliadins and glutenins as major fraction. All allergen test solutions induced significantly higher %CD63+ basophils/anti-FcεRI ratios in patients compared with controls. BAT using sHWPs yielded 100% sensitivity and 83% specificity at optimal cut-off and may be useful as another tool in WDEIA diagnosis. Our findings indicate that non-gluten proteins carrying yet unidentified allergenic epitopes appear to be relevant in WDEIA. Further research is needed to clarify the role of nutritional ATIs in WDEIA and identify specific mechanisms of immune activation.

The basophil activation test differentiates between patients with wheat-dependent exercise-induced anaphylaxis and control subjects using gluten and isolated gluten protein types.

BACKGROUND: Oral food challenge using gluten and cofactors is the gold standard to diagnose wheat-dependent exercise-induced anaphylaxis (WDEIA), but this procedure puts patients at risk of an anaphylactic reaction. Specific IgE to ω5-gliadins as major allergens and skin prick tests to wheat may yield negative results. Thus, we designed a proof-of-principle study to investigate the utility of the basophil activation test (BAT) for WDEIA diagnosis. METHODS: Different gluten protein types (GPT; α-, γ-, ω1,2- and ω5-gliadins, high-molecular-weight glutenin subunits [HMW-GS] and low-molecular-weight glutenin subunits [LMW-GS]) and gluten were used in different concentrations to measure basophil activation in 12 challenge-confirmed WDEIA patients and 10 control subjects. The results were compared to routine allergy diagnostics. Parameters analyzed include the percentage of CD63+ basophils, the ratio of %CD63+ basophils induced by GPT/gluten to %CD63+ basophils induced by anti-FcεRI antibody, area under the dose-response curve and test sensitivity and specificity. RESULTS: GPT and gluten induced strong basophil activation for %CD63+ basophils and for %CD63+/anti-FcɛRI ratio in a dose-dependent manner in patients, but not in controls (p < 0.001, respectively). BAT performance differed from acceptable (0.73 for LMW-GS) to excellent (0.91 for ω5-gliadins) depending on the specific GPT as evaluated by the area under the receiver operating characteristic curve. Patients showed individual sensitization profiles. After determination of the best cut-off points, ω5-gliadins and HMW-GS showed the best discrimination between patients and controls with a sensitivity/specificity of 100/70 and 75/100, respectively. CONCLUSION: This study shows the alternative role of BAT in better defining WDEIA and the causative wheat allergens. The best BAT parameters to distinguish WDEIA patients from controls were %CD63+ basophil values for ω5-gliadins and HMW-GS.

Health-Related Quality of Life and Influencing Factors in Adults with Nonadvanced Mastocytosis-A Cross-Sectional Study and Qualitative Approach.

BACKGROUND: Mastocytosis comprises a heterogeneous group of disorders characterized by an accumulation of mast cells in 1 or more organs. Symptoms range from mild complaints to severe and life-threatening events. Impact on quality of life seems to vary widely, but influencing factors are poorly understood so far. OBJECTIVE: To examine impairments, psychological burden, health-related quality of life (HRQOL), and possible influencing factors in patients with mastocytosis. METHODS: In semistructured telephone interviews, patients provided information on impairments in everyday life and psychological burden caused by mastocytosis. HRQOL was measured using the Mastocytosis Quality of Life (MC-QoL) questionnaire. Clinical data were collected from patient files. RESULTS: A total of 101 adult patients with mastocytosis (74.3% women; mean age, 47.7 ± 13.5 years) were included. Half of the interviewed patients (50.6%) reported disease-related impairments in everyday life, and 42.4% stated a psychological burden. MC-QoL questionnaire scores showed a broad distribution, with a mean total score at a "mild" impairment level (mean total score, 34.7 ± 22.5). One-third of patients felt moderately (22.8%) or severely (13.9%) impaired, whereas one-third reported no impairment at all (30.7%). Symptoms of mast cell activation and perceived food intolerance had the highest impact on HRQOL. Higher age, higher body mass index, higher tryptase level, and longer duration of symptoms, as well as current drug therapy and pathological bone density, were each associated with reduced HRQOL. CONCLUSIONS: A high level of suffering and strong associations between impairments and symptom-related factors indicate the importance of addressing patients' concerns and adequate symptom management in mastocytosis.