Serum 25-hydroxyvitamin D deficiency is associated with atopy, and sex may be an effect modifier of its association with asthma in teenagers from northeast Brazil.

OBJECTIVE: Sufficient vitamin D (25-hydroxyvitamin D [25(OH)D]) serum levels are associated with decreased asthma symptoms. Our aim was to investigate associations between vitamin D and atopy, asthma, asthma severity, and asthma phenotypes in Brazilian teenagers. METHODS: This cross-sectional study involved 942 individuals (11-19 years old) engaged in an asthma cohort. The ISAAC questionnaire was employed to diagnosis asthma and asthma severity. Serum allergen-specific immunoglobulin E (sIgE) was measured by ImmunoCap and serum 25(OH)D was measured by ELISA. We calculated the correlation between sIgE and 25(OH)D. We used multivariate logistic regression analysis to assess associations of interest. RESULTS: We found that 25(OH)D deficiency was positively associated with atopy (OR 1.45, confidence interval [CI] 1.05-2.00) and high levels of this vitamin negatively correlated with sIgE to Dermatophagoides pteronyssinus (r = -0.11, p = 0.019). The average 25(OH)D serum level was 27.0 ± 9.5 ng/ml; 366 individuals (38.8%) had a sufficient level. There was no association between 25(OH)D and asthma, asthma severity or asthma phenotypes in the population. However, sex was a possible effect modifier of the association between vitamin D and asthma: insufficiency in asthmatic women (86%) was higher than in asthmatic men (42%), and there was an association between insufficient vitamin D levels and greater asthma risk only in women (OR = 3.06, 95% CI 1.16-8.07). CONCLUSION: We have shown that vitamin D deficiency was associated with greater risk of atopy in both sexes and vitamin D insufficiency was associated with asthma only in women. There was no association between vitamin D levels and asthma phenotypes or asthma severity.

Toxocara canis extract fractions promote mainly the production of Th1 and regulatory cytokines by human leukocytes in vitro.

Helminths possibly down-modulate immune responses to airborne allergens through the induction of a regulatory network. The identification of helminths bioactive molecules is highly desirable, given their immunomodulatory potential which could be used in immunotherapies for allergy and autoimmune diseases. To investigate the immunoregulatory potential of the adult Toxocara canis crude extract and ten protein fractions of its extract, human peripheral blood mononuclear cells (PBMC) from 10 allergic and 9 non-allergic individuals were cultivated, in vitro, in the presence or absence of these antigens, and their supernatants were evaluated for cytokine production (TGF-ß, IL-10, IL-12, TNF-α, IL-6, IL-5, IL13, and IL-17). To determine the cell viability, the PBMC were cultivated for 24 h in the presence of the antigens and, following, they were subjected to a cytotoxicity assay. The viability of the PBMC was not affected by incubation with the T. canis antigens. As some fractions stimulated the production of immunoregulatory (TGF-ß and/or IL-10), IL-12 and Th1 (TNF-α) cytokines, without stimulating Th2 cytokines (IL-5 and IL13) and IL-17, it was proposed that they would be potential candidates for further studies, especially involving the purification and characterization of specific proteins, which could be tested separately to evaluate their specific role as adjuvants in immunotherapy for inflammatory diseases.

WSB1 and IL21R Genetic Variants Are Involved in Th2 Immune Responses to Ascaris lumbricoides.

Genetic and epigenetic factors are considered to be critical for host-parasite interactions. There are limited data on the role of such factors during human infections with Ascaris lumbricoides. Here, we describe the potential role of genetic factors as determinants of the Th2 immune response to A. lumbricoides in Brazilian children. Stool samples were collected from the children to detect A. lumbricoides by microscopy and peripheral blood leukocytes (PBLs) were cultured in whole blood cultures for detection of cytokines (IL-5, IL-10, and IL-13) in vitro. Levels of anti-A. lumbricoides IgE and IgG4 were measured in plasma. DNA was extracted from PBLs and genotyped using Illumina 2.5 Human Omni Beadchip. Candidate genes associated with A. lumbricoides responses were identified and SNVs in these selected genes associated with the Th2 immune response to A. lumbricoides. Haplotype, gene expression, and epigenetic analyses were done to identify potential associations with Th2 immune responses. GWAS on samples from 1,189 children identified WSB1 as a candidate gene, and IL-21R was selected as a biologically relevant linked gene for further analysis. Variants in WSB1 and IL21R were associated with markers of Th2 immune responses: increased A. lumbricoides-specific IgE and IL-5/IL-13 by PBLs from infected compared to uninfected individuals. In infected children, WSB1 but not IL21R gene expression was suppressed and increased methylation was observed in the WSB1 promoter region. This is the first study to show an association between genetic variants in WSB1 and IL21R and Th2 immune responses during A. lumbricoides infections in children. WSB1/IL21R pathways could provide a potential target for the treatment of Th2-mediated diseases.

Genetic polymorphisms in vitamin D pathway influence 25(OH)D levels and are associated with atopy and asthma.

BACKGROUND: Vitamin D deficiency or insufficiency, has been associated with atopy and lack of asthma control. Our objective was to investigate associations between variants in genes of vitamin D pathway with serum levels of 25-hydroxyvitamin D (25(OH)D), atopy, asthma and asthma severity in teenagers from Northeast Brazil. METHODS: This is a cross sectional study nested in a cohort population of asthma. 25(OH)D was quantified from 968 of 11-17 years old individuals by ELISA. Asthma diagnosis was obtained by using the ISAAC Phase III questionnaire. Specific IgE was determined by ImmunoCAP; genotyping was performed using the 2.5 HumanOmni Biochip from Illumina. Statistical analyses were performed in PLINK 1.07 and SPSS 22.1. RESULTS: After quality control, 104 Single Nucleotides Variants (SNVs) in vitamin D pathway genes, typed in 792 individuals, were included in the analysis. The allele A of rs10875694 on VDR was positively associated with atopy (OR = 1.35; 95% CI 1.01-1.81). The allele C of rs9279 on VDR, was negatively associated with asthma risk (OR = 0.66; 95% CI 0.45-0.97), vitamin D insufficiency (OR = 0.78; 95% CI 0.70-0.96) and higher VDR expression. Two variants in VDR were associated with asthma severity, the allele A of rs2189480 (OR = 0.34; 95% CI 0.13-0.89) and the allele G of rs4328262 (OR = 3.18; 95% CI 1.09-9.28). The combination of variants in CYP2R1 and CYP24A1 (GAC, to rs10500804, rs12794714 and rs3886163, respectively) was negatively associated with vitamin D production (ß = - 1.24; 95% CI - 2.42 to - 0.06). CONCLUSIONS: Genetic variants in the vitamin D pathway affect vitamin D serum levels and, thus, atopy and asthma.