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1.
Immunobiology ; 228(5): 152724, 2023 09.
Article de Anglais | MEDLINE | ID: mdl-37549468

RÉSUMÉ

PDE4D (Phosphodiesterase 4D) gene encodes a hydrolase of cyclic AMP. PDE4D genetic variants have been associated with asthma susceptibility. Therefore, this study aimed to investigate the association between PDE4D variants (and haplotypes) with asthma and atopy in a Brazilian population. The study comprised 1,246 unrelated participants from the SCAALA (Social Changes Asthma and Allergy in Latin America) program. Genotyping was performed using the Illumina 2.5 Human Omni bead chip. Multivariate logistic regression was used to investigate the association between PDE4D variants and asthma/atopy phenotypes in PLINK 1.09 software. Twenty-four SNVs in PDE4D were associated with atopy or asthma. The rs6898082 (A) variant increased asthma susceptibility (OR 2.76; CI 99% 1.26-6.03) and was also related to a greater PDE4D expression in the GTEx database. Also, the variant rs6870632 was further associated with asthma in meta-analysis with a replication cohort. In addition, the variants rs75699812 (C), rs8007656 (G), and rs958851 (T) were positively associated with atopy. Moreover, these variants formed an atopy risk haplotype (OR 1.82; CI 99% 1.15-2.88). Also, these variants were related to lower levels of IL-10. Functional in silico assessment showed that some PDE4D SNVs may have an impact on gene regulation and expression. Variants in the PDE4D are positively associated with asthma and allergy markers. It is possible that these variants lead to alteration in PDE4D expression and therefore impact immunity and pulmonary function.


Sujet(s)
Asthme , Hypersensibilité immédiate , Hypersensibilité , Humains , Enfant , Haplotypes , Brésil/épidémiologie , Prédisposition génétique à une maladie , Asthme/génétique , Hypersensibilité immédiate/génétique , Hypersensibilité/génétique , Polymorphisme de nucléotide simple , Cyclic Nucleotide Phosphodiesterases, Type 4/génétique
2.
Helicobacter ; 28(5): e13008, 2023 Oct.
Article de Anglais | MEDLINE | ID: mdl-37497783

RÉSUMÉ

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.


Sujet(s)
Infections à Helicobacter , Helicobacter pylori , Humains , Enfant , Enfant d'âge préscolaire , Étude d'association pangénomique , Helicobacter pylori/génétique , Amérique latine/épidémiologie , Infections à Helicobacter/épidémiologie , Études transversales
3.
Clin Exp Allergy ; 53(8): 821-832, 2023 08.
Article de Anglais | MEDLINE | ID: mdl-36779555

RÉSUMÉ

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.


Sujet(s)
Hypersensibilité , Humains , Souris , Animaux , Modèles animaux de maladie humaine , Hypersensibilité/thérapie , Allergènes , Inflammation , Cytokines , Désensibilisation immunologique , Immunoglobuline E
4.
Clin Exp Allergy ; 53(2): 198-209, 2023 02.
Article de Anglais | MEDLINE | ID: mdl-36176209

RÉSUMÉ

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.


Sujet(s)
Antigènes de Dermatophagoides , Déterminants antigéniques des lymphocytes T , Hypersensibilité , Animaux , Humains , Souris , Allergènes , Antigènes de Dermatophagoides/immunologie , Antigènes de Dermatophagoides/pharmacologie , Antigènes de Dermatophagoides/usage thérapeutique , Protéines d'arthropode , Dermatophagoides pteronyssinus , Déterminants antigéniques des lymphocytes T/composition chimique , Déterminants antigéniques des lymphocytes T/usage thérapeutique , Hypersensibilité/traitement médicamenteux , Immunoglobuline E , Interleukine-10 , Interleukine-4 , Interleukine-5 , Agranulocytes , Pyroglyphidae , Protéines recombinantes/génétique , Protéines recombinantes/métabolisme , Immunothérapie/méthodes
5.
Transbound Emerg Dis ; 69(5): e2994-e3006, 2022 Sep.
Article de Anglais | MEDLINE | ID: mdl-35801561

RÉSUMÉ

Toxocariasis is an infection caused by the round worms Toxocara canis and Toxocara cati. It occurs worldwide though it is more prevalent in developing countries. For the diagnosis of toxocariasis, the most used method is the indirect enzyme-linked immunosorbent assay (indirect ELISA), based on the detection of specific antibodies using the excreted/secreted products from T. canis larvae (TES) as antigens, but it cross-reacts with several helminth infections. For this reason, there is a need to investigate species-specific immunoreactive proteins, which can be used for the development of a more sensitive and specific diagnosis. This study aims to investigate immunoreactive protein candidates to be used for the development of a more sensitive and specific diagnosis of Toxocara spp. infection in humans. We have used immunoblotting and mass spectrometry to select four Toxocara canis immunoreactive proteins that were recombinantly expressed in bacteria and evaluated as potential new diagnostic antigens (rMUC3, rTES 26, rTES32 and rCTL4). The recognition of these recombinant proteins by total serum IgG and IgG4 was assayed using the purified proteins in an isolated manner or in combination. The IgG ELISAs performed with individual recombinant antigens reached values of sensitivity and specificity that ranged from 91.7% to 97.3% and 94.0% to 97.9%, respectively. Among the analyses, the IgG4 immunoassay was proven to be more effective, revealing a sensitivity that ranged from 88.8% to 98.3% and a specificity of 97.8%-97.9%. The IgG4 ELISA was shown to be more effective and presented no cross-reactivity when using combinations of the rTES 26 and rCTL4 recombinant proteins. The combination of these two molecules achieved 100% sensitivity and specificity. The use of only two recombinant proteins can contribute to improve the current panorama of toxocariasis immunodiagnosis for, with a better optimization and reduced cost.


Sujet(s)
Toxocara canis , Toxocarose , Animaux , Antigènes d'helminthe , Test ELISA/méthodes , Test ELISA/médecine vétérinaire , Humains , Immunotransfert/médecine vétérinaire , Immunoglobuline G , Tests immunologiques/médecine vétérinaire , Protéomique , Protéines recombinantes , Toxocara , Toxocarose/diagnostic
6.
Gene ; 838: 146706, 2022 Sep 05.
Article de Anglais | MEDLINE | ID: mdl-35772656

RÉSUMÉ

BACKGROUND: Polymorphisms in genes related to the activation and development of regulatory T cells (Tregs), such as FOXP3, may be associated with asthma and atopy development. Additionally, environmental factors such as exposure to infections can modify the effect of these associations. This study evaluated the impact of polymorphisms in the FOXP3 on the risk of asthma and atopy as also gene-environment interactions in these outcomes. METHODS: This study included 1,246 children from the SCAALA program, between 4 and 11 years of age. DNA was extracted from peripheral blood and eight SNPs (rs2280883, rs11465476, rs11465472, rs2232368, rs3761549, rs3761548, rs2232365 and rs2294021) were genotyped using the 2.5 HumanOmni Beadchip from Illumina (San Diego, California, USA) or TaqMan qRT-PCR. RESULTS: The rs2232368 (Allele T) was positively associated with asthma symptoms (OR = 1.95, CI = 1.04 to 3.66, p = 0.040) and skin prick test (SPT) reactivity to aeroallergens (OR = 2.31, CI = 1.16 to 4.59, p = 0.017). The rs3761549 (Allele T) was positively associated with SPT reactivity (OR = 1.44, CI = 1.03 to 2.02, p = 0.034). The rs2280883 (Allele C) was negatively associated with specific IgE to aeroallergens (OR = 0.83, CI = 0.70 to 0.99, p = 0.040). Furthermore, the rs2280883 played a protective role in the development of atopy only in individuals seropositive to Epstein-Barr virus (EBV) infection (OR = 0.74, CI = 0.60 to 0.92, p = 0.003 and OR = 0.74; 95% CI = 0.61-0.91, p = 0.007 for SPT and slgE respectively), but not in individuals without EBV infection. CONCLUSION: Polymorphisms in the FOXP3 gene were associated with the risk of atopy and asthma development in our population. In addition, EBV infection had an effect modifier of the observed association for rs2280883 variant.


Sujet(s)
Asthme , Infections à virus Epstein-Barr , Hypersensibilité immédiate , Asthme/génétique , Brésil , Enfant , Facteurs de transcription Forkhead/génétique , Interaction entre gènes et environnement , Prédisposition génétique à une maladie , Herpèsvirus humain de type 4 , Humains , Hypersensibilité immédiate/génétique , Polymorphisme de nucléotide simple
7.
Gene ; 828: 146478, 2022 Jun 20.
Article de Anglais | MEDLINE | ID: mdl-35390444

RÉSUMÉ

BACKGROUND: Obesity is a chronic complex disease with great prevalence for children all over the world. Characterized for low-grade inflammation associated with several comorbidities such as resistance and type 2 diabetes mellitus (T2DM). OBJECTIVES: To investigate whether genetic variants in IL10, IL1RL1, IL1B, IRF4, TNF, IL6, and IL33 genes are associated with being overweight in children. METHODS: We performed the genotyping of 1004 children using Illumina 2.5 Human Omni bead chip, and association analysis on the genetic variants and the overweight through logistic regression adjusted for sex, age and components principal. RESULTS: Of the seven genes analyzed, 16 SNVs significantly associated. Eleven variants in IL1RL1, two in IL1B and one in IRF4 genes increased overweight risk and two SNVs in IL1RL1 were associated with protection against overweight. The rs2287047-A was negatively associated (OR: 0.66, CI95%: 0.19-0.45) and had a reduced IL1RL1 expression in whole blood (p 0.033) in silico eQTL. The rs12203592-T, in IRF4, was positively associated with being overweight, and led to an increased gene expression in whole blood (p < 0.001) and adipose tissue (p < 0.001). CONCLUSION: These results suggest that genetic variants in inflammatory genes may play an important role in the development of overweight in children.


Sujet(s)
Diabète de type 2 , Facteurs de régulation d'interféron/génétique , Polymorphisme de nucléotide simple , Brésil , Enfant , Diabète de type 2/génétique , Prédisposition génétique à une maladie , Humains , Protéine-1 analogue au récepteur de l'interleukin-1/génétique , Interleukine-1 bêta/génétique , Surpoids/génétique
8.
Mol Biol Rep ; 48(4): 3405-3416, 2021 Apr.
Article de Anglais | MEDLINE | ID: mdl-33914278

RÉSUMÉ

Successful research in the wide-ranging field of allergy is usually achieved by definition not only of physicochemical and immunological properties of natural, but also recombinant allergens. Blomia tropicalis mite is a well-known source for various groups of hypersensitivity-causing proteins. The goal of the present work was to produce, purify and characterise by in silico, biochemical and immunological methods the recombinant group-12 allergen of B. tropicalis. The recombinant Blo t 12 aggregation capacity as well as the affinity to antibodies from BALB/c immunised mice and B. tropicalis-sensitised human donors were investigated through in silico analyses, dynamic light scattering, SDS-PAGE, ELISA and Western blot. The presence of Blo t 12 within B. tropicalis extracts was also determined by ELISA and Western blot. High concentrations of dimeric rBlo t 12 were detected through SDS-PAGE next to other aggregates and the results were confirmed by data from DLS and Western blot. The YITVM peptide was predicted to be the most aggregation-prone region. The IgE-reactivity of rBlo t 12 was not completely abolished by aggregate formation but it was significantly decreased compared to rBlo t 5, or B. tropicalis extracts. Natural Blo t 12 may naturally dimerises, but it was detected in non-delipidified B. tropicalis extracts in low amounts. Given that this allergen may be a specific marker for B. tropicalis allergy, the recombinant Blo t 12 herein obtained is characterised as a mid-tier allergen in Brazilian atopic patients and may be useful for the improvement in precision allergy molecular diagnostic applications.


Sujet(s)
Allergènes/isolement et purification , Mites (acariens)/métabolisme , Allergènes/génétique , Allergènes/immunologie , Animaux , Escherichia coli/génétique , Humains , Souris , Souris de lignée BALB C , Protéines recombinantes
9.
Article de Anglais | MEDLINE | ID: mdl-32834827

RÉSUMÉ

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.

10.
Vaccine ; 38(30): 4762-4772, 2020 06 19.
Article de Anglais | MEDLINE | ID: mdl-32451213

RÉSUMÉ

Toxocariasis, a natural helminth infection of dogs and cats caused by Toxocara canis and T. cati, respectively, that are transmitted to mammals, including humans. Infection control is based currently on periodic antihelmintic treatment and there is a need for the development of vaccines to prevent this infection. MATERIALS AND METHODS: Eight potential vaccine candidate T. canis recombinant proteins were identified by in silico (rTcGPRs, rTcCad, rTcVcan, rTcCyst) and larval proteomics (rTES26, rTES32, rMUC-3 and rCTL-4) analyses. Immunogenicity and protection against infectious challenge for seven of these antigens were determined in a murine model of toxocariasis. C57BL/6 female mice were immunized with each of or combinations of recombinant antigens prior to challenge with 500 T. canis embryonated eggs. Levels of specific antibodies (IgG, IgG1, IgG2a and IgE) in sera and cytokines (IL-5, INF-É£ and IL-10) produced by antigens-stimulated splenocytes, were measured. Presence of specific antibodies to the molecules was measured in sera of T. canis-seropositive dogs and humans. RESULTS: All seven molecules were immunogenic in immunized mice; all stimulated significantly elevated levels of specific IgG, IgG1 or IgG2a and six were associated with elevated levels of specific IgE; all induced elevated production of IFN- É£ and IL-10 by splenocytes, but only the in silico-identified membrane-associated recombinants (rTcCad, rTcVcan, and rTcCyst) induced significantly increased IL-5 production. Vaccination with two of the latter (rTcCad and rTcVcan) reduced larval loads in the T. canis challenged mice by 54.3% and 53.9% (P < 0.0001), respectively, compared to unimmunized controls. All seven recombinants were recognized by T. canis-seropositive dog and human sera. CONCLUSION: The identification of vaccine targets by in silico analysis was an effective strategy to identify immunogenic T. canis proteins capable of reducing larval burdens following challenge with the parasite. Two recombinant proteins, rTcCad and rTcVcan, were identified as promising vaccine candidates for canine toxocariasis.


Sujet(s)
Maladies des chats , Maladies des chiens , Toxocara canis , Toxocarose , Animaux , Chats , Modèles animaux de maladie humaine , Chiens , Femelle , Souris , Souris de lignée C57BL , Protéines recombinantes/génétique , Toxocarose/prévention et contrôle
11.
Clin Exp Allergy ; 50(7): 835-847, 2020 07.
Article de Anglais | MEDLINE | ID: mdl-32314444

RÉSUMÉ

INTRODUCTION: Allergen-specific immunotherapy (AIT) represents a curative approach for treating allergies. In the tropical and subtropical regions of the world, Blomia tropicalis (Blo t 5 and Blo t 21) is the likely dominant source of indoor allergens. AIM: To generate a hypoallergenic Blo t 5/Blo t 21 hybrid molecule that can treat allergies caused by B tropicalis. METHODS: Using in silico design of B tropicalis hybrid proteins, we chose two hybrid proteins for heterologous expression. Wild-type Blo t 5/Blo t 21 hybrid molecule and a hypoallergenic version, termed BTH1 and BTH2, respectively, were purified by ion exchange and size exclusion chromatography and characterized by physicochemical, as well as in vitro and in vivo immunological, experiments. RESULTS: BTH1, BTH2 and the parental allergens were purified to homogeneity and characterized in detail. BTH2 displayed the lowest IgE reactivity that induced basophil degranulation using sera from allergic rhinitis and asthmatic patients. BTH2 essentially presented the same endolysosomal degradation pattern as the shortened rBlo t 5 and showed a higher resistance towards degradation than the full-length Blo t 5. In vivo immunization of mice with BTH2 led to the production of IgG antibodies that competed with human IgE for allergen binding. Stimulation of splenocytes from BTH2-immunized mice produced higher levels of IL-10 and decreased secretion of IL-4 and IL-5. In addition, BTH2 stimulated T-cell proliferation in PBMCs isolated from allergic patients, with secretion of higher levels of IL-10 and lower levels of IL-5 and IL-13, when compared to parental allergens. CONCLUSIONS AND CLINICAL RELEVANCE: BTH2 is a promising hybrid vaccine candidate for immunotherapy of Blomia allergy. However, further pre-clinical studies addressing its efficacy and safety are needed.


Sujet(s)
Allergènes , Protéines d'arthropode , Hypersensibilité , Mites (acariens) , Vaccins , Allergènes/génétique , Allergènes/immunologie , Allergènes/pharmacologie , Animaux , Protéines d'arthropode/génétique , Protéines d'arthropode/immunologie , Protéines d'arthropode/pharmacologie , Cytokines , Femelle , Humains , Hypersensibilité/immunologie , Hypersensibilité/thérapie , Mâle , Souris de lignée BALB C , Mites (acariens)/génétique , Mites (acariens)/immunologie , Vaccins/génétique , Vaccins/immunologie , Vaccins/pharmacologie
13.
Expert Opin Ther Pat ; 30(3): 163-177, 2020 Mar.
Article de Anglais | MEDLINE | ID: mdl-31913726

RÉSUMÉ

Introduction: Allergic illnesses are one of the most prevalent immunological disorders worldwide and house dust mites are important triggers of these diseases. Allergen-specific immunotherapy (AIT) is an alternative treatment to pharmacotherapy and among its technologies, recombinant hypoallergenic derivatives have shown promising features, turn them into safer and more efficient allergy vaccines.Areas covered: Patents and scientific publications referring to advances in the design of Dermatophagoides spp. hypoallergenic molecules. Data were obtained from the Espacenet® and PubMed websites, using different key terms, advanced tools and Boolean operators for searches. The retrieved data were then descriptively analyzed, taking into consideration clinical targets, geographical, temporal, collaborative, and different classification aspects of the productions.Expert opinion: Joint advances of molecular biology, genetic engineering, and bioinformatics technologies led to progresses in the design of Dermatophagoides spp. hypoallergenic derivatives. Collaborative networks seem to be an interesting way not only to improve technologies in AIT but also to boost the number of patents, publications, and grants for researchers. The observed trend for the use of hypoallergenic hybrid molecules was a fundamental AIT advance and this type of molecule appears to be a more attractive product for companies and more convenient, efficient, and safer allergy immunotherapy for patients.


Sujet(s)
Désensibilisation immunologique/méthodes , Hypersensibilité/thérapie , Pyroglyphidae/immunologie , Allergènes/immunologie , Animaux , Humains , Hypersensibilité/immunologie , Brevets comme sujet
14.
Parasite Immunol ; 42(3): e12694, 2020 03.
Article de Anglais | MEDLINE | ID: mdl-31884701

RÉSUMÉ

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.


Sujet(s)
Anticorps antiprotozoaires/analyse , Hypersensibilité/immunologie , Immunité cellulaire , Immunoglobuline E/immunologie , Toxoplasmose/immunologie , Adulte , Animaux , Antigènes de protozoaire/immunologie , Asthme/immunologie , Brésil , Cytokines/analyse , Femelle , Humains , Immunoglobuline G/sang , Interleukine-10/immunologie , Adulte d'âge moyen , Pyroglyphidae/immunologie , Toxoplasma/immunologie
15.
Helicobacter ; 24(6): e12662, 2019 Dec.
Article de Anglais | MEDLINE | ID: mdl-31571359

RÉSUMÉ

BACKGROUND AND AIM: The relationship between race/ethnicity and H pylori infection has been extensively reported, with a higher prevalence of infection observed in black individuals. Whether such differences are due to genetic factors underlying African ancestry remains to be clarified. In the present study, we evaluated the association between the proportion of individual African ancestry and H pylori infection in a sample of 1046 children living in a large Latin American urban center. MATERIALS AND METHODS: Estimation of individual biogeographical ancestry was based on 370,539 SNPs and performed using the ADMIXTURE software. Multivariate logistic regression models and mediation analysis considering the influence of previously recognized socioenvironmental risk factors to H pylori infection were performed. All analyses were conducted using the statistical package STATA v.14.0. RESULTS: Each 10% increase in the proportion of individual African ancestry was positively and independently associated with H pylori infection in our population (adjusted OR = 1.22, 95% CI = 1.10-1.36, P < .001). Mediation analysis demonstrated that only 9.23% of the effect of the individual African ancestry on H pylori infection was explained by factors such as household income, the absence of street paving and crowding. CONCLUSIONS: The results suggest that genetic variants that covariate with African ancestry may explain an important part of the racial differences observed for the prevalence of H pylori infection.


Sujet(s)
1766/génétique , Infections à Helicobacter/ethnologie , Infections à Helicobacter/génétique , 1766/statistiques et données numériques , Anticorps antibactériens/sang , Enfant , Enfant d'âge préscolaire , Études de cohortes , Femelle , Prédisposition génétique à une maladie , Infections à Helicobacter/épidémiologie , Infections à Helicobacter/microbiologie , Helicobacter pylori/immunologie , Helicobacter pylori/isolement et purification , Helicobacter pylori/physiologie , Humains , Amérique latine/épidémiologie , Amérique latine/ethnologie , Mâle , Polymorphisme de nucléotide simple , Population urbaine/statistiques et données numériques
16.
Int Arch Allergy Immunol ; 180(3): 159-172, 2019.
Article de Anglais | MEDLINE | ID: mdl-31563904

RÉSUMÉ

BACKGROUND: The dawn of the "omics" technologies has changed allergy research, increasing the knowledge and identification of new allergens. However, these studies have been almost restricted to Dermatophagoides spp. Although Blomia tropicalis has long been established as a clinically important source of allergens, a thorough proteomic characterization is still lacking for this dust mite. OBJECTIVE: To increase knowledge of B. tropicalis allergens through proteomic analysis. METHODS: Eleven in-bred lineages of B. tropicalis were obtained from 11 unique different pregnant females. Their somatic extracts were analyzed and compared with a commercially available extract by liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: Considerable differences in the protein expression profiles were found among the breeds, and most of them displayed higher expression levels of major allergens than the commercially available extract. Blo t 2 was the most prominent allergenic protein in the analyzed extracts. Six identified allergens and 14 isoforms have not yet been recognized by IUIS. Conversely, 3 previously recognized B. tropicalis allergens were not found. CONCLUSIONS: The clear impact of inbreeding on allergen content shown by our study leads us to conclude that the quantification and/or identification of allergens from in-bred lines should be routinely considered for mite cultivation in order to select breeds with higher amounts of major allergens. In this sense, LC-MS/MS may be a useful method to achieve this quality control for research and commercial purposes.


Sujet(s)
Allergènes/immunologie , Extrait cellulaire/immunologie , Hypersensibilité/immunologie , Phéromones/immunologie , Sarcoptidae/immunologie , Allergènes/isolement et purification , Animaux , Lignées consanguines d'animaux , Variation intra-population , Extrait cellulaire/composition chimique , Chromatographie en phase liquide , Femelle , Humains , Phéromones/isolement et purification , Grossesse , Spécificité d'espèce , Spectrométrie de masse en tandem , Transcriptome
17.
Gene ; 715: 143991, 2019 Oct 05.
Article de Anglais | MEDLINE | ID: mdl-31357023

RÉSUMÉ

BACKGROUND: Asthma is a complex disease with worldwide public health relevance, is related to environmental causes and a genetic predisposition. The chromosomal 17q12-21 locus has been consistently demonstrated to be associated with asthma risk. The effects of variants in the 17q12-21 locus on childhood asthma were first identified in a genome wide- association study. Since that time, those findings have been replicated in different populations but not in South American populations. OBJECTIVE: This study aimed to investigate the role of variants in the 17q12-21 locus on asthma in a sample of Brazilian children. METHODS: This was a cross-sectional study conducted on a cohort of 1247 children. These analyses used 50 Single Nucleotide Variants (SNVs) in the 17q12-21 locus were genotyped as part of a genome wide association study (GWAS). RESULTS: Four SNVs (rs4065275, rs12603332, rs73985228 and rs77777702) were associated with childhood asthma. The rs73985228 exhibited the strongest association across the different genetic models (OR, 95%CI 2.8, 1.44-3.21, p < 0.01). In an analysis that was stratified by atopy, two SNVs (rs73985228 and rs2715555) were found to be associated with atopic and non-atopic asthma. For the first time, we observed a significant interaction with seropositivity for the Varicella zoster virus (for rs4065275, p = 0.02, and for rs12603332, p = 0.04); i.e., the association was found in those who were seropositive but not in those who were seronegative for this virus. CONCLUSIONS: We confirmed the associations of variants in the 17q12-21 locus with atopic and non-atopic asthma and identified an interaction with seropositivity for the Varicella zoster virus.


Sujet(s)
Asthme/génétique , Chromosomes humains de la paire 17/génétique , Prédisposition génétique à une maladie , Herpèsvirus humain de type 3 , Polymorphisme de nucléotide simple , Infection à virus varicelle-zona/génétique , Asthme/virologie , Enfant , Enfant d'âge préscolaire , Études transversales , Femelle , Locus génétiques , Étude d'association pangénomique , Humains , Mâle
18.
Article de Anglais | MEDLINE | ID: mdl-31126515

RÉSUMÉ

BACKGROUND: Asthma is a chronic disease of the airways and its most common phenotype is characterized by a T2 type response with IgE production and inflammatory mediators in response to common allergens. Cysteinyl leukotrienes (CysLTs), LTC4, LTD4 and LTE4, are mediators known to possess important proinflammatory action. CysLTs can bind to the Cysteinyl leukotriene receptor type 2 (CysLTR2) and activate an inflammatory. Polymorphisms in CysLTR2 have been associated with asthma and atopy, although the mechanism is not clear. OBJECTIVE: To evaluate the association between genetic polymorphisms in CYSLTR2 with asthma phenotypes, atopy markers and helminth infection. METHODS: Genotyping was performed using a panel Illumina and carried out in 1245 participants of SCAALA program (Social Change, Asthma, Allergy in Latin American). Logistic regressions for asthma, helminth infections (Trichuris trichiura and Ascaris lumbricoides) and allergy markers (skin tests and IgE production) were performed using PLINK 1.9 software adjusted for sex, age, helminth infection and ancestry markers. RESULTS: The G allele of rs1323556 was negatively associated with asthma in the additive model (OR 0.74, 95% CI 0.59-0.93) and in the dominant model (OR 0.71, 95% CI 0.53-0.74). The G allele of rs1575464 was also negatively associated with asthma in two genetic models, additive (OR 0.77, 95% CI 0.62-0.96) and dominant (OR 0.73, 95% CI 0.55-0.97). The G allele of rs61735175 was positively associated with asthma severity in the additive model (OR 1.72, 95% CI 1.07-2.77) and in the dominant model (OR 1.77, 95% CI 1.09-2.85). Five SNVs were associated with atopy markers and four SNVs were associated with helminth infections. CONCLUSION: Polymorphisms in the CYSLTR2 gene are associated with asthma, atopy markers and helminth infection in Brazilian individuals, which may lead to protection or risk for such conditions, however, more studies are needed to evaluate the functional of this variants here in described.


Sujet(s)
Asthme/génétique , Prédisposition génétique à une maladie , Hypersensibilité immédiate/génétique , Récepteurs aux leucotriènes/génétique , Allergènes/génétique , Allergènes/immunologie , Animaux , Asthme/épidémiologie , Asthme/parasitologie , Enfant , Enfant d'âge préscolaire , Femelle , Études d'associations génétiques , Génotype , Helminthiase/épidémiologie , Helminthiase/génétique , Helminthiase/parasitologie , Helminthes/génétique , Helminthes/pathogénicité , Humains , Hypersensibilité , Hypersensibilité immédiate/parasitologie , Inflammation/épidémiologie , Inflammation/génétique , Inflammation/parasitologie , Mâle , Phénotype , Polymorphisme de nucléotide simple/génétique
19.
Cytokine ; 113: 177-184, 2019 01.
Article de Anglais | MEDLINE | ID: mdl-30539779

RÉSUMÉ

Asthma and allergy affect hundreds of millions of people from childhood to old age. In most of them, the inflammatory process of respiratory allergies involves the participation of type 2 cytokines, derived from T helper-2 (Th2)-cell, and Group 2 Innate Lymphoid (ILC2) Cells. An efficient memory Th2 cell response is dependent on IL-13 produced by ILC2s, causing allergic lung inflammation and elevated serum levels of immunoglobulin E. ILC2 cells are derived from common lymphoid progenitors and their growing depends on the transcription factor RORA. The aim of this work was to identify genetic variants in RORA associated with asthma phenotypes and allergy markers. Genomic DNA samples of 1246 individuals participating from Social Changes Asthma and Allergy in Latin America Program (SCAALA) have been genotyped using Illumina Human 2.5 Omni Beadchip. Logistics regressions have been performed to analyze the association among RORA variants and asthma, skin prick tests (SPT), specific IgE and type 2 cytokine production. Twelve single nucleotide variants (SNVs) were significantly associated with atopy (P < 0.01), in which four of them, rs10162630, rs17191519, rs17270243, and rs55796775 and their haplotypes were strongly and positively associated (P < 0.001). Furthermore, these variants increased the RORA gene expression in silico analysis. Other SNVs in RORA were associated with allergy markers, atopic and non-atopic asthma. Therefore, it is believed that variants in RORA gene may influence immunologic features of asthma and allergies and could be possible targets for future treatment of allergic diseases.


Sujet(s)
Asthme/génétique , Prédisposition génétique à une maladie/génétique , Hypersensibilité/génétique , Membre-1 du groupe F de la sous-famille-1 de récepteurs nucléaires/génétique , Polymorphisme de nucléotide simple/génétique , Marqueurs biologiques/métabolisme , Enfant , Enfant d'âge préscolaire , Études de cohortes , Cytokines/génétique , Femelle , Génotype , Humains , Immunité innée/génétique , Immunoglobuline E/sang , Immunoglobuline E/génétique , Inflammation/génétique , Interleukine-13/génétique , Poumon/métabolisme , Mâle , Lymphocytes auxiliaires Th2/métabolisme
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