OBJECTIVE: To determine whether genetic variants in and around SPINK5 are associated with IgE-mediated food allergy.
METHOD: We genotyped 71 "tag" single nucleotide polymorphisms (tag-SNPs) within a region spanning ~263 kb including SPINK5 (~61 kb) in n=722 (n=367 food-allergic, n=199 food-sensitized-tolerant and n=156 non-food-allergic controls) 12-month-old infants (discovery sample) phenotyped for food allergy with the gold standard oral food challenge. Transepidermal water loss (TEWL) measures were collected at 12 months from a subset (n=150) of these individuals. SNPs were tested for association with food allergy using the Cochran-Mantel-Haenszel test adjusting for ancestry strata. Association analyses were replicated in an independent sample group derived from four paediatric cohorts, total n=533 (n=203 food-allergic, n=330 non-food-allergic), mean age 2.5 years, with food allergy defined by either clinical history of reactivity, 95% positive predictive value (PPV) or challenge, corrected for ancestry by principal components.
RESULTS: SPINK5 variant rs9325071 (A⟶G) was associated with challenge-proven food allergy in the discovery sample (P=.001, OR=2.95, CI=1.49-5.83). This association was further supported by replication (P=.007, OR=1.58, CI=1.13-2.20) and by meta-analysis (P=.0004, OR=1.65). Variant rs9325071 is associated with decreased SPINK5 gene expression in the skin in publicly available genotype-tissue expression data, and we generated preliminary evidence for association of this SNP with elevated TEWL also.
CONCLUSIONS: We report, for the first time, association between SPINK5 variant rs9325071 and challenge-proven IgE-mediated food allergy.
OBJECTIVES: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis.
METHODS: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles ("immunoallertypes"), were determined.
MEASUREMENTS AND MAIN RESULTS: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. "Sensitized bronchiectasis" was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome.
CONCLUSIONS: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a "treatable trait" permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.
DESIGN: Retrospective study.
METHODS: Results from 108 intradermal allergy tests, 25 IgE serological assays and immunotherapy outcomes in 37 dogs were retrospectively analysed. Immunotherapy outcomes were determined as excellent, good, modest or failure using a global assessment of efficacy matrix which incorporated pruritus scores, lesion severity, medication requirements, and owner and clinician opinion.
RESULTS: The most common positive reactions in intradermal allergy tests were Red clover (59%), Dermatophagoides farinae (29%), Tyrophagus putrescentiae (28%), Yellow dock (25%) and Malassezia pachydermatis (24%). In the IgE serological tests, Yorkshire fog grass (40%), Yellow dock (36%), Kentucky bluegrass (36%) and T. putrescentiae (36%) were the most commonly reported positive results. The outcome of allergen-specific immunotherapy was judged to be excellent in 20% of dogs, good in 15%, modest in 18% and a failure in 47%.
CONCLUSION: As has been reported in other geographical areas, environmental mites and plant pollens frequently gave positive reactions in allergy tests in South Australia. However, the prevalence of individual allergen reactions differed between intradermal and IgE serological tests, with M. pachydermatis being identified as a common cause of hypersensitivity in intradermal tests but not in IgE serological assays. Immunotherapy was judged to be a beneficial treatment in 35% of dogs but was essentially unsuccessful in 65%.
METHODS: A cross-sectional study was performed in 150 children aged 12-36 months.
EXCLUSION CRITERIA: recurrent infections, moderate to severe asthma, recent systemic steroid, other diseases affecting growth/nutrition. Growth parameters, SCORing Atopic Dermatitis (SCORAD), hemoglobin, hematocrit, sodium, potassium, albumin, protein, calcium, phosphate, B12, iron, and folate values were determined. Parents completed a 3-day food diary.
RESULTS: The prevalence of food restriction was 60.7%. Commonly restricted foods were shellfish 62.7%, nuts 53.3%, egg 50%, dairy 29.3%, and cow's milk 28.7%. Food-restricted children have significantly lower calorie, protein, fat, riboflavin, vitamin B12, calcium, phosphorus and iron intakes and lower serum iron, protein and albumin values. Z scores of weight-for-age (-1.38 ± 1.02 vs -0.59 ± 0.96, P = .00), height-for-age (-1.34 ± 1.36 vs -0.51 ± 1.22, P = .00), head circumference-for-age (-1.37 ± 0.90 vs -0.90 ± 0.81, P = .00), mid-upper arm circumference (MUAC)-for-age (-0.71 ± 0.90 vs -0.22 ± 0.88, P = .00), and BMI-for-age (-0.79 ± 1.15 vs -0.42 ± 0.99, P = .04) were significantly lower in food-restricted compared to non-food-restricted children. More food-restricted children were stunted, underweight with lower head circumference and MUAC. Severe disease was an independent risk factor for food restriction with OR 5.352; 95% CI, 2.26-12.68.
CONCLUSION: Food restriction is common in children with AD. It is associated with lower Z scores for weight, height, head circumference, MUAC, and BMI. Severe disease is an independent risk factor for food restriction.