BACKGROUND: The beneficial off-target effects of Bacille Calmette-Guérin (BCG) vaccination potentially include protection against allergy.
OBJECTIVE: In the MIS BAIR trial, we aimed to determine whether neonatal BCG vaccination reduces atopic sensitisation and clinical food allergy in infants.
METHODS: In this randomised controlled trial, 1272 neonates were allocated to BCG-Denmark vaccine (0.05 mL intradermal dose) or no BCG at birth. Randomisation was stratified by recruitment site, mode of delivery and plurality of birth. The primary outcome was the incidence of atopic sensitisation determined by skin prick test at 1 year of age. Food allergy was determined by 3-monthly online questionnaires and oral food challenges. Data were analysed by intention-to-treat using binary regression.
RESULTS: gov (NCT01906853).
RESULTS: Atopic sensitisation during the first year of life was 22.9% among infants in the BCG group and 18.9% in the control group (adjusted risk difference (aRD) 3.8% (95% CI -1.5 to 9.1) after multiple imputation). Clinical food allergy was similar between infants in the BCG and control groups (9.8% vs. 9.6%; aRD 0.2, 95% CI -3.4 to 3.8). An interaction was observed between the primary outcome and maternal history of BCG vaccination. No interaction was observed for the additional prespecified potential effect modifiers tested (sex, delivery mode, family history of any allergy, season of birth, hepatitis B vaccination at randomisation, BCG scar and age at BCG administration).
CONCLUSIONS: Neonatal BCG-Denmark vaccination does not protect against atopic sensitisation or clinical food allergy in the first year of life.

BACKGROUND: Celery root is known to cause severe allergic reactions in patients sensitized to mugwort pollen.
OBJECTIVE: We studied clinically well-characterized patients with celery allergy by IgE testing with a comprehensive panel of celery allergens to disentangle the molecular basis of what is known as the celery-mugwort syndrome.
METHODS: Patients with suspected food allergy to celery underwent a standardized interview. Main inclusion criteria were a positive food challenge with celery or an unambiguous case history of severe anaphylaxis. IgE to celery allergens (rApi g 1.01, rApi g 1.02, rApi g 2, rApi g 4, nApi g 5, rApi g 6, rApi g 7) and to mugwort allergens (rArt v 1, rArt v 3, rArt v 4) were determined. IgE levels ≥0.35 kUA/L were regarded positive.
RESULTS: Seventy-nine patients with allergy to celery were included. Thirty patients had mild oral or rhinoconjunctival symptoms, and 49 had systemic reactions. Sixty-eight percent had IgE to celery extract, 80% to birch pollen, and 77% to mugwort pollen. A combination of Api g 1.01, 1.02, 4, 5, and 7 increased the diagnostic sensitivity for celery allergy to 92%. The lipid transfer proteins Api g 2 and Api g 6 were not relevant in our celery-allergic population. IgE to Api g 7, detected in 52% of patients, correlated closely (r = 0.86) to Art v 1 from mugwort pollen. Eleven of 12 patients with monosensitization to Api g 7 were IgE negative to celery extract. The odds ratio for developing a severe anaphylactic reaction rather than only mild oral symptoms was about 6 times greater (odds ratio, 5.87; 95% confidence interval, 1.08-32.0; P = .0410) for Api g 7-sensitized versus -nonsensitized subjects.
CONCLUSIONS: There is an urgent need for routine diagnostic tests to assess sensitization to Api g 7, not only to increase test sensitivity but also to identify patients at risk of a severe allergic reaction to celery.

BACKGROUND: The basophil activation test is an emerging clinical tool in the diagnosis of cow\'s milk allergy (CMA). The aim was to assess the association between the basophil allergen threshold sensitivity to the major milk protein casein (casein-specific CD-sens), the levels of milk- and casein-specific Immunoglobulin E antibodies (IgE-ab), and the severity of allergic reactions at milk challenges.
METHODS: We enrolled 34 patients aged 5-15 (median 9) years who underwent a double-blind placebo-controlled milk-challenge (DBPCMC) as screening before inclusion in an oral immunotherapy study for CMA. The severity of the allergic reaction at the DBPCMC was graded using Sampson\'s severity score. Venous blood was drawn before the DBPCMC. Milk- and casein-specific IgE-ab were analyzed. Following in vitro stimulation of basophils with casein, casein-specific CD-sens, was determined.
RESULTS: Thirty-three patients completed the DBPCMC. There were strong correlations between casein-specific CD-sens and IgE-ab to milk (rs = 0.682, p < .001), and between casein-specific CD-sens and IgE-ab to casein (rs = 0.823, p < .001). There was a correlation between the severity of the allergic reaction and casein-specific CD-sens level (rs = 0.395, p = .041) and an inverse correlation between casein-specific CD-sens level and the cumulative dose of milk protein to which the patient reacted at the DBPCMC (rs = -0.418, p = .027). Among the 30 patients with an allergic reaction at the DBPCMC, 67% had positive casein-specific CD-sens, 23% had negative casein-specific CD-sens, and 10% were declared non-responders.
CONCLUSIONS: Two thirds of those reacting at the DBPMC had positive casein-specific CD-sens, but reactions also occurred despite negative casein-specific CD-sens. The association between casein-specific CD-sens and the severity of the allergic reaction and cumulative dose of milk protein, respectively, was moderate.

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Food allergy in atopic dermatitis is mediated by complex immune interactions between genetics, diet, environment, and the microbiome. When contact between inflamed skin and food antigens occurs, contact hypersensitivity can develop. Consequently, systemic contact dermatitis (SCD) can occur after ingestion of allergenic foods or food additives in the setting of a Th2 response with CLA-positive T cells, triggering dermatitis where skin resident memory lymphocytes reside. This phenomenon explains food-triggered dermatitis. Atopy patch tests (APTs) detect sensitization to food proteins responsible for SCD, which in turn can be confirmed by oral food challenge with delayed interpretation. We summarize the literature on using APTs to identify foods for oral challenge with dermatitis as an outcome. In dermatitis patients at risk for Th2 skewing based on a history of childhood-onset flexural dermatitis, shared decision-making should include a discussion of identifying and avoiding food and food additive triggers, as well as identifying and avoiding all contact allergens, prior to initiation of systemic therapy for dermatitis.

Delayed hypersensitivity to gluten and milk protein is frequently reported but may be difficult to diagnose.
We aimed to explore if a method of home-based double-blind placebo-controlled food challenges (H-FC) can identify and reduce unnecessary elimination diets in children.
We included 73 of 92 children aged 1 to 17 years referred to a tertiary allergy clinic from 2011 to 2021 due to self-reported, delayed symptoms to gluten or milk. The children were randomized to H-FC, receiving gluten/milk protein or placebo for 5 to 7 days in a double-blind crossover manner, separated by 3 washout weeks. Patients/parents recorded symptoms using standardized forms. Two crossover periods were used from 2011 to 2016 and 3 periods from 2017 to 2021. A positive challenge required significantly more symptoms during the active period versus the placebo period. After the challenge, reintroduction of milk/gluten was assessed by a follow-up interview. The primary outcome was the proportion of children with a positive challenge.
The children, with a mean age of 11 years, had followed a strict gluten-free or milk-protein-free diet for a median duration of 24 months (range: 3-180 months). A positive challenge was observed in 18 of 73 children (25%), more often using 2 (35%) compared with 3 challenge periods (12%). At follow-up, 44 of 55 (80%) children with a negative challenge had successfully reintroduced milk/gluten.
H-FC may be an effective method in avoiding unnecessary elimination diets in children. Only 25% of the challenges were positive, and 80% of the children with negative challenges succeeded in reintroducing the food. Three challenge periods may be necessary to reduce false-positive outcomes.

BACKGROUND: Exposure of the esophageal mucosa to food allergens can cause acute mucosal responses in patients with eosinophilic esophagitis (EoE), but the underlying local immune mechanisms driving these acute responses are not well understood.
OBJECTIVE: We sought to gain insight into the early transcriptomic changes that occur during an acute mucosal response to food allergens in EoE.
METHODS: Bulk RNA sequencing was performed on esophageal biopsy specimens from adult patients with EoE (n = 5) collected before and 20 minutes after intramucosal injection of various food extracts in the esophagus. Baseline biopsy specimens from control subjects without EoE (n = 5) were also included.
RESULTS: At baseline, the transcriptome of the patients with EoE showed increased expression of genes related to an EoE signature. After local food injection, we identified 40 genes with a potential role in the early immune response to food allergens (most notably CEBPB, IL1B, TNFSF18, PHLDA2, and SLC15A3). These 40 genes were enriched in processes related to immune activation, such as the acute-phase response, cellular responses to external stimuli, and cell population proliferation. TNFSF18 (also called GITRL), a member of the TNF superfamily that is best studied for its costimulatory effect on T cells, was the most dysregulated early EoE gene, showing a 12-fold increase compared with baseline and an 18-fold increase compared with a negative visual response. Further experiments showed that the esophageal epithelium may be an important source of TNFSF18 in EoE, which was rapidly induced by costimulating esophageal epithelial cells with the EoE-relevant cytokines IL-13 and TNF-α.
CONCLUSIONS: Our data provide unprecedented insight into the transcriptomic changes that mediate the acute mucosal immune response to food allergens in EoE and suggest that TNFSF18 may be an important effector molecule in this response.

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This case study examines the kinetics of the diamine oxidase levels after challenge with a histamine-rich meal in patients with histamine intolerance as an alternative diagnostic tool to conventional tests combined with the dietary intervention.

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