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Background Peanut allergy (PA) is a complex disease with both environmental and genetic risk factors. Previously, PA loci were identified in filaggrin (FLG) and HLA in candidate gene studies, and loci in HLA were identified in a genome-wide association study and meta-analysis. Objective We sought to investigate genetic susceptibility to PA. Methods Eight hundred fifty cases and 926 hyper-control subjects and more than 7.8 million genotyped and imputed single nucleotide polymorphisms (SNPs) were analyzed in a genome-wide association study to identify susceptibility variants for PA in the Canadian population. A meta-analysis of 2 phenotypes (PA and food allergy) was conducted by using 7 studies from the Canadian, American (n = 2), Australian, German, and Dutch (n = 2) populations. Results An SNP near integrin α6 (ITGA6) reached genome-wide significance with PA ( P  = 1.80 × 10 −8 ), whereas SNPs associated with Src kinase–associated phosphoprotein 1 (SKAP1) , matrix metallopeptidase 12 (MMP12)/MMP13 , catenin α3 (CTNNA3) , rho GTPase–activating protein 24 (ARHGAP24) , angiopoietin 4 (ANGPT4) , chromosome 11 open reading frame (C11orf30/EMSY) , and exocyst complex component 4 (EXOC4) reached a threshold suggestive of association ( P  ≤ 1.49 × 10 −6 ). In the meta-analysis of PA, loci in or near ITGA6 , ANGPT4 , MMP12/MMP13 , C11orf30 , and EXOC4 were significant ( P  ≤ 1.49 × 10 −6 ). When a phenotype of any food allergy was used for meta-analysis, the C11orf30 locus reached genome-wide significance ( P  = 7.50 × 10 −11 ), whereas SNPs associated with ITGA6 , ANGPT4 , MMP12/MMP13 , and EXOC4 and additional C11orf30 SNPs were suggestive ( P  ≤ 1.49 × 10 −6 ). Functional annotation indicated that SKAP1 regulates expression of CBX1 , which colocalizes with the EMSY protein coded by C11orf30. Conclusion This study identifies multiple novel loci as risk factors for PA and food allergy and establishes C11orf30 as a risk locus for both PA and food allergy. Multiple genes ( C11orf30 / EMSY , SKAP1 , and CTNNA3 ) identified by this study are involved in epigenetic regulation of gene expression. [ABSTRACT FROM AUTHOR]

Background: Sublingual immunotherapy (SLIT) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care. Most efficacy studies in children lack power to be conclusive, and all have been performed in referral centers. Objective: To investigate the efficacy of SLIT with grass pollen allergen in children and adolescents with rhinoconjunctivitis in a primary care setting. Methods: Youngsters aged 6-18 years with hay fever were enrolled from general practices and randomly assigned to receive placebo or grass pollen mix for 2 years. The primary outcome was the mean daily total symptom score (scale 0-15) comprising sneezing, itching nose, watery running nose, nasal blockage, and itching eyes during the months May-August of the second treatment year. Results: Out of 204 youngsters randomized, 168 entered the intention-to-treat analysis (91 verum, 77 placebo). The mean daily total symptom score did not differ between participants allocated to verum and those allocated to placebo (difference for verum minus placebo: −0.08, 95%CI, −0.66-0.50; P = .78). No differences were found for rescue medication–free days, disease-specific quality of life, and overall evaluation of the treatment effect. Local side effects were more frequent in the verum group (39% vs 17% of participants; P = .001). Conclusion: Sublingual immunotherapy with grass pollen in a primary care setting is not effective in children and adolescents. Clinical implications: Currently, SLIT cannot be recommended for general practitioners as a therapeutic modality in youngsters with grass pollen allergy. [Copyright &y& Elsevier]

Background BM32 is a grass pollen allergy vaccine based on recombinant fusion proteins consisting of nonallergenic peptides from the IgE-binding sites of the 4 major grass pollen allergens and the hepatitis B preS protein. Objective We sought to study the safety and clinical efficacy of immunotherapy (allergen immunotherapy) with BM32 in patients with grass pollen–induced rhinitis and controlled asthma. Methods A double-blind, placebo-controlled, multicenter allergen immunotherapy field study was conducted for 2 grass pollen seasons. After a baseline season, subjects (n = 181) were randomized and received 3 preseasonal injections of either placebo (n = 58) or a low dose (80 μg, n = 60) or high dose (160 μg, n = 63) of BM32 in year 1, respectively, followed by a booster injection in autumn. In the second year, all actively treated subjects received 3 preseasonal injections of the BM32 low dose, and placebo-treated subjects continued with placebo. Clinical efficacy was assessed by using combined symptom medication scores, visual analog scales, Rhinoconjunctivitis Quality of Life Questionnaires, and asthma symptom scores. Adverse events were graded according to the European Academy of Allergy and Clinical Immunology. Allergen-specific antibodies were determined by using ELISA, ImmunoCAP, and ImmunoCAP ISAC. Results Although statistical significance regarding the primary end point was not reached, BM32-treated subjects, when compared with placebo-treated subjects, showed an improvement regarding symptom medication, visual analog scale, Rhinoconjunctivitis Quality of Life Questionnaire, and asthma symptom scores in both treatment years. This was accompanied by an induction of allergen-specific IgG without induction of allergen-specific IgE and a reduction in the seasonally induced increase in allergen-specific IgE levels in year 2. In the first year, more grade 2 reactions were observed in the active (n = 6) versus placebo (n = 1) groups, whereas there was almost no difference in the second year. Conclusions Injections of BM32 induced allergen-specific IgG, improved clinical symptoms of seasonal grass pollen allergy, and were well tolerated. [ABSTRACT FROM AUTHOR]

Background: Subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are safe and effective treatments of allergic rhinitis, but high levels of compliance and persistence are crucial to achieving the desired clinical effects. Objective: Our objective was to assess levels and predictors of compliance and persistence among grass pollen, tree pollen, and house dust mite immunotherapy users in real life and to estimate the costs of premature discontinuation. Methods: We performed a retrospective analysis of a community pharmacy database from The Netherlands containing data from 6486 patients starting immunotherapy for 1 or more of the allergens of interest between 1994 and 2009. Two thousand seven hundred ninety-six patients received SCIT, and 3690 received SLIT. Time to treatment discontinuation was analyzed and included Cox proportional hazard models with time-dependent covariates, where appropriate. Results: Overall, only 18% of users reached the minimally required duration of treatment of 3 years (SCIT, 23%; SLIT, 7%). Median durations for SCIT and SLIT users were 1.7 and 0.6 years, respectively (P < .001). Other independent predictors of premature discontinuation were prescriber, with patients of general practitioners demonstrating longer persistence than those of allergologists and other medical specialists; single-allergen immunotherapy, lower socioeconomic status; and younger age. Of the persistent patients, 56% were never late in picking up their medication from the pharmacy. Direct medication costs per nonpersistent patient discontinuing in the third year of treatment were €3800, an amount that was largely misspent. Conclusion: Real-life persistence is better in SCIT users than in SLIT users, although it is low overall. There is an urgent need for further identification of potential barriers and measures that will enhance persistence and compliance. [Copyright &y& Elsevier]