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Background: Few genome‐wide association studies (GWAS) on Helicobacter pylori infection susceptibility have been conducted for admixed populations from developing countries. Here, we performed a GWAS to identify genetic factors associated with H. pylori serostatus in a cohort of admixed children from a large Latin American urban center. Methods: A cross‐sectional study involving 1161 children from 4 to 11 years old living in poor areas of Salvador, in northeastern Brazil. Logistic regression analysis was performed to detect associations between single‐nucleotide variants (SNVs) and H. pylori seropositivity, assuming an additive genetic model. Enrichment analyses were conducted using the MAGMA v1.10 software. Results: We found 22 SNVs to be suggestively associated (p < 10−5) with H. pylori seropositivity. The most suggestive SNV was the rs77955022 (p = 4.83e‐07) located in an intronic region of EXOC3 at 5p15.33. The second most suggestively associated SNV was rs10914996 (p = 8.97e‐07), located in an intergenic region at 1p34.3. Furthermore, we were able to replicate three SNVs (p < 0.05) in the Study of Health in Pomerania (SHIP) cohort: the rs2339212 and rs4795970, both located at 17q12 near TMEM132E, as well as the rs6595814, an intronic variant of FBN2 at 5q23.3. The enrichment analysis indicated the participation of genes and metabolic pathways related to the regulation of the digestive system and gastric acid secretion in the risk of seropositivity for H. pylori. Conclusions: Additional studies are required to validate these association findings in larger population samples and to get insight into the underlying physiological mechanisms. [ABSTRACT FROM AUTHOR]

Background: Allergen‐specific immunotherapy (AIT) is the only disease‐modifying treatment approach to change disease‐causing allergens. Hypoallergenic derivatives show promise as potential therapeutics, amongst which BTH2 was designed to induce tolerance against Blomia tropicalis allergy. Our aim was to investigate the hypoallergenicity and immunoregulatory activity of BTH2 in vitro and its therapeutic potential in a mouse model of AIT. Methods: Recombinant Blo t 5 and Blo t 21 allergens and their hybrid derivatives (BTH1 and BTH2) were expressed and purified. IgE binding capacity was tested by ELISA using sera from Brazilian, Colombian, and Ecuadorian subjects. Secretion of cytokines in supernatants from human cell cultures was measured following stimulation with the four recombinants and controls. The capacity of BTH2 to ameliorate allergic airway inflammation induced by B. tropicalis extract was evaluated in a murine model of AIT. Results: rBlo t 5 and rBlo t 21 were identified as major allergens in Latin American patients, and BTH2 had the lowest IgE binding. In vitro stimulation of human cells induced greater levels of IL‐10 and IFN‐γ and reduced the secretion of Th2 cytokines. BTH2 ameliorated allergic airway inflammation in B. tropicalis‐challenged A/J mice, as evidenced by the histopathological and humoral biomarkers: decreased Th2 cytokines and cellular infiltration (especially eosinophils), lower activity of eosinophil peroxidase, an increase in IgG blocking antibodies and strong reduction of mucus production by goblet cells. Conclusions: Our study shows that BTH2 represents a promising candidate for the treatment of B. tropicalis allergy with hypoallergenic, immune regulatory and therapeutic properties. Further pre‐clinical studies are required in murine models of chronic asthma to further address the efficacy and safety of BTH2 as a vaccine against B. tropicalis‐induced allergy. [ABSTRACT FROM AUTHOR]

Background: Allergen‐specific immunotherapy (AIT) is the only clinical approach that can potentially cure some allergic diseases by inducing immunological tolerance. Dermatophagoides pteronyssinus is considered as the most important source of mite allergens worldwide, with high sensitization rates for the major allergens Der p 1, Der p 2 and Der p 23. The aim of this work is to generate a hypoallergenic hybrid molecule containing T‐cell epitopes from these three major allergens. Methods: The hybrid protein termed Der p 2231 containing T‐cell epitopes was purified by affinity chromatography. The human IgE reactivity was verified by comparing those with the parental allergens. The hybrid was also characterized immunologically through an in vivo mice model. Results: The hybrid rDer p 2231 stimulated in peripheral blood mononuclear cells (PBMCs) isolated from allergic patients with higher levels of IL‐ 2, IL‐10, IL‐15 and IFN‐γ, as well as lower levels of IL‐4, IL‐5, IL‐13, TNF‐α and GM‐CSF. The use of hybrid molecules as a therapeutic model in D. pteronyssinus allergic mice led to the reduction of IgE production and lower eosinophilic peroxidase activity in the airways. We found increased levels of IgG antibodies that blocked the IgE binding to the parental allergens in the serum of allergic patients. Furthermore, the stimulation of splenocytes from mice treated with rDer p 2231 induced higher levels of IL‐10 and IFN‐γ and decreased the secretion of IL‐4 and IL‐5, when compared with parental allergens and D. pteronyssinus extract. Conclusions: rDer p 2231 has the potential to be used in AIT in patients co‐sensitized with D. pteronyssinus major allergens, once it was able to reduce IgE production, inducing allergen‐specific blocking antibodies, restoring and balancing Th1/Th2 immune responses, and inducing regulatory T‐cells. [ABSTRACT FROM AUTHOR]

Keywords: allergens and epitopes; IgE; immunotherapy vaccines and mechanisms EN allergens and epitopes IgE immunotherapy vaccines and mechanisms 1503 1507 5 06/01/20 20200601 NES 200601 Studies demonstrated that among the identified I B tropicalis i allergens, Blo t 5 is a major allergen,[[1], [3]] which makes the protein a target for diagnosis and allergen-specific immunotherapy (AIT). Cross-inhibition results showed that rBlo t 5 SB short sb cannot always inhibit the rDer p 5-specific IgE, but rDer p 5 possesses a moderate inhibitory capacity on rBlo t 5 SB short sb -specific IgE binding (Figure S4F). Blomia tropicalis Blo t 5 and Blo t 21 recombinant allergens might confer higher specificity to serodiagnostic assays than whole mite extract. [Extracted from the article]

Toxoplasma gondii (T gondii) infection has been associated with protection against allergy and autoimmune diseases. We investigated the effects of T gondii infection on cytokine and antibody responses in atopic and nonatopic Brazilian subjects. We have measured in whole‐blood cultures, Th1 (IFN‐γ and IL‐12), Th2 (IL‐5) and regulatory cytokine IL‐10 in blood cells unstimulated and stimulated with pokeweed mitogen or T gondii soluble tachyzoites antigen (STAg) or Dermatophagoides pteronyssinus antigen. A significant negative association was found between high levels of anti‐dust mite IgE and T gondii seropositivity (OR = 0.46; 95%CI = 0.25‐0.85). STAg stimulation induced a mixed profile of Th1 and Th2 cytokines (IFN‐γ, IL‐12 and IL‐5) in Tg‐positive atopic individuals compared with Tg‐negative atopic individuals (P <.0001, P =.033 and P =.003, respectively). In contrast, IL‐10 production was not different between these groups. No association was found between T gondii infection and asthma. We hypothesized that the protective effect on atopy might be related to the strong Th1 immune response to T gondii found on the seropositive subjects. From our knowledge, this is the first study to investigate the association between atopy and T gondii infection in Brazilian subjects, analysing the cellular immune responses. [ABSTRACT FROM AUTHOR]

Background Helicobacter pylori infection is a strong risk factor for gastric cancer, likely due to the extensive inflammation in the stomach mucosa caused by these bacteria. Many studies have reported an association between IL10 polymorphisms, the risk of gastric cancer, and IL-10 production. The aim of the study was to evaluate the association between IL10 genetic variants, Helicobacter pylori infection, and IL-10 production by peripheral blood leukocytes in children. Materials and Methods We genotyped a total of 12 single nucleotide polymorphisms in IL10 in 1259 children aged 4-11 years living in a poor urban area in Salvador, Brazil, using TaqMan probe based, 5′ nuclease assay minor groove binder chemistry. Association tests were performed by logistic regression for Helicobacter pylori infection and linear regression for IL-10 spontaneous production (whole-blood cultures) including sex, age, and principal components for informative ancestry markers as covariates, using PLINK. Results Our results shown that IL10 single nucleotide polymorphisms rs1800896 ( OR = 1.63; 95% CI = 1.11-2.39), rs3024491 ( OR = 1.71; 95% CI = 1.14-2.57), rs1878672 ( OR = 1.79; 95% CI = 1.19-2.68), and rs3024496 ( OR = 1.48; 95% CI = 1.05-2.08) were positively associated with Helicobacter pylori infection. Eight single nucleotide polymorphisms were associated with spontaneous production of IL-10 in culture, of which three (rs1800896 and rs1878672, p = .04; rs3024491, p = .01) were strongly associated with infection by Helicobacter pylori. Conclusions Our results indicate that IL10 variants rs1800896, rs3024491, rs1878672, and rs3024496 are more consistently associated with the presence of anti- H. pylori IgG by inducing increased production of IL-10. Further studies are underway to elucidate the role of additional genetic variants and to investigate their impact on the occurrence of gastric cancer. [ABSTRACT FROM AUTHOR]