Global availability and uptake of psychological services for adults, caregivers and children with food allergy.

BACKGROUND: Food allergy (FA) is associated with poor health-related quality of life and high levels of psychological distress. Psychological support is extremely important but not always available. As part of the Global Access to Psychological Services for Food Allergy (GAPS) study, we aimed to assess psychological distress and service use among adults, caregivers and children with FA in a global survey. METHODS: Participants (n = 1329 adults with FA; n = 1907 caregivers of children with FA) from >20 countries were recruited through patient organisations, social media advertisements and online survey panels to complete an online survey. Surveys were available in six languages. RESULTS: A total of 67.7% of adults and 77.2% of caregivers reported direct experience, and 51.6% of caregivers said their child had experienced FA-related psychological distress. The most commonly reported issue was anxiety about having an allergic reaction. Less than 20% had been assessed for FA-related psychological distress. There were significant differences across countries for levels of distress, screening for distress, seeing a mental health professional and being diagnosed with a FA-related mental health disorder (all p < .001). The United Kingdom, Australia and Brazil had the highest number of participants reporting distress. The most commonly reported barrier to seeing a mental health professional was cost. CONCLUSIONS: FA-related distress is common across countries, but with substantial country-to-country variability. Allergy providers are encouraged to routinely assess families for psychological distress and provide access to appropriate mental health resources. Development and implementation of evidence-based, patient-informed accessible, affordable FA interventions in multiple languages is urgently needed.

Component-resolved analysis of IgA, IgE, and IgG4 during egg OIT identifies markers associated with sustained unresponsiveness.

BACKGROUND: In a previously reported CoFAR study, 55 subjects with egg allergy underwent randomized, placebo-controlled egg oral immunotherapy (eOIT). Active treatment induced desensitization in most and sustained unresponsiveness (SU) in a smaller subset. We hypothesized that component-resolved analysis of IgE, IgG4, IgA, IgA1, and IgA2 may identify potential biomarkers of SU in OIT subjects. METHODS: Longitudinal samples for 51 egg-allergic subjects (37 active and 14 placebo) were available. Egg white (EW)-, ovalbumin (OVA)-, and ovomucoid (OVM)-specific levels of IgA, IgA1, and IgA2 were quantified by ELISA. IgE and IgG4 to these antigens were quantified using ImmunoCAP® . Clinical responders achieved SU to egg; all others were considered nonresponders. Between-group comparisons were made among active and placebo, as well as responders and nonresponders. RESULTS: No placebo subjects achieved responder status. Through month 48, among the 37 active subjects, baseline IgE-OVM was lower in responders (median 3.97 kU/l, n = 19) than in nonresponders (10.9 kU/l, n = 18, P = 0.010). Logistic regression analysis revealed that lower baseline IgE-EW (P = 0.038), IgE-OVM (P = 0.032), and a higher IgG4/IgE-OVM ratio (P = 0.013) were associated with clinical response. Relative increases in IgG4-EW, IgA-EW, and IgA2-EW were observed in responders (P = 0.024, 0.024, and 0.029, respectively). IgG4/IgE, IgA/IgE, and IgA2/IgE ratios for EW and IgA/IgE ratio for OVA were found to be significantly elevated among responders (P = 0.004, 0.009, 0.028, and 0.008, respectively). CONCLUSIONS: Increased IgG4-EW, IgA-EW, and IgA2-EW during eOIT are associated with clinical response to eOIT. Lower pretreatment IgE-EW and IgE-OVM are also associated with SU. Future studies are needed to evaluate and validate these potential biomarkers.

Utility of component analyses in subjects undergoing sublingual immunotherapy for peanut allergy.

BACKGROUND: Sublingual immunotherapy (SLIT) with peanut changes clinical and immune responses in most peanut-allergic individuals, but the response is highly variable. OBJECTIVE: We sought to examine the component-specific effects of peanut SLIT and determine whether peanut component testing could predict the outcome of a double-blind, placebo-controlled food challenge (DBPCFC) after 12 months of peanut SLIT. METHODS: We included 33 subjects who underwent peanut SLIT with a DBPCFC of 2500 mg of peanut protein performed after 12 months of therapy. Plasma samples from baseline and after 12 months of peanut SLIT were assayed using ImmunoCAP for IgE and IgG4 against whole peanut, Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9. RESULTS: Following 12 months of SLIT, 10 subjects (30%) passed the DBPCFC without symptoms and were considered desensitized. Subjects that failed the DBPCFC tolerated a median of 460 mg peanut protein (range: 10-1710 mg). The desensitized group had significantly lower baseline levels of IgE against peanut (median 40.8 vs. 231 kUA /L, P = 0.0082), Ara h 2 (median 17 vs. 113 kUA /L, P = 0.0082), and Ara h 3 (median 0.3 vs. 8.5 kUA /L, P = 0.0396). ROC curves indicated that baseline IgE against peanut and Ara h 2 were equally effective at discriminating between the two groups (AUC = 0.7957, P = 0.007752 for both). CONCLUSION AND CLINICAL RELEVANCE: In this cohort of subjects undergoing SLIT for peanut allergy, lower baseline levels of IgE against Ara h 2, Ara h 3, and peanut were associated with successful desensitization.

Evidence of pathway-specific basophil anergy induced by peanut oral immunotherapy in peanut-allergic children.

BACKGROUND: In Westernized countries, over 1% of the population is allergic to peanuts or tree nuts, which carries a risk of severe allergic reactions. Several studies support the efficacy of peanut oral immunotherapy (OIT) for reducing the clinical sensitivity of affected individuals; however, the mechanisms of this effect are still being characterized. One mechanism that may contribute is the suppression of effector cells, such as basophils. Basophil anergy has been characterized in vitro as a pathway-specific hyporesponsiveness; however, this has not been demonstrated to occur in vivo. OBJECTIVE: To evaluate the hypothesis that basophil anergy occurs in vivo due to chronic allergen exposure in the setting of a clinical oral immunotherapy trial. METHODS: Samples of peripheral blood were obtained from subjects during a placebo-controlled clinical trial of peanut OIT. Basophil reactivity to in vitro stimulation with peanut allergen and controls was assessed by the upregulation of activation markers, CD63 and CD203c, measured by flow cytometry. RESULTS: The upregulation of CD63 following stimulation of the IgE receptor, either specifically with peanut allergen or non-specifically with anti-IgE antibody, was strongly suppressed by active OIT. However, OIT did not significantly suppress this response in basophils stimulated by the distinct fMLP receptor pathway. In the subset of subjects with egg sensitization, active peanut OIT also suppressed CD63 upregulation in response to stimulation with egg allergen. Allergen OIT also suppressed the upregulation of CD203c including in response to stimulation with IL-3 alone. CONCLUSION: Peanut OIT induces a hyporesponsive state in basophils that is consistent with pathway-specific anergy previously described in vitro. This suggests the hypothesis that effector cell anergy could contribute to clinical desensitization.

Pediatric food allergy and mucosal tolerance.

The gastrointestinal (GI) mucosal immune response is characterized by an intricate balance between host defense and immunoregulation. A principal element of this normal response is acquisition of oral tolerance. Aberrations in oral tolerance induction can lead to food allergy, an increasingly prevalent disorder that causes significant medical and psychosocial stressors for patients and families. At present there is no definitive therapy for food allergy and the mainstays of treatment are allergen avoidance, nutritional support, and ready access to emergency medications. Significant progress toward an active therapy for food allergy has been made with the advent of novel therapies such as oral immunotherapy (OIT) and sublingual immunotherapy (SLIT), which modulate the GI mucosal immune response with the goal of promoting oral tolerance. In this review, we will examine the mechanisms of oral tolerance induction and its relation to food allergy and explore novel immunotherapeutic strategies for treatment and prevention of food allergy.