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2.
Nat Commun ; 10(1): 880, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30787307

RESUMO

Asthma is a complex disease with striking disparities across racial and ethnic groups. Despite its relatively high burden, representation of individuals of African ancestry in asthma genome-wide association studies (GWAS) has been inadequate, and true associations in these underrepresented minority groups have been inconclusive. We report the results of a genome-wide meta-analysis from the Consortium on Asthma among African Ancestry Populations (CAAPA; 7009 asthma cases, 7645 controls). We find strong evidence for association at four previously reported asthma loci whose discovery was driven largely by non-African populations, including the chromosome 17q12-q21 locus and the chr12q13 region, a novel (and not previously replicated) asthma locus recently identified by the Trans-National Asthma Genetic Consortium (TAGC). An additional seven loci reported by TAGC show marginal evidence for association in CAAPA. We also identify two novel loci (8p23 and 8q24) that may be specific to asthma risk in African ancestry populations.


Assuntos
Afro-Americanos/genética , Asma/genética , Predisposição Genética para Doença/genética , Asma/epidemiologia , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 8/genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Hispano-Americanos/genética , Humanos , Polimorfismo de Nucleotídeo Único/genética , Estados Unidos/epidemiologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-29033897

RESUMO

BACKGROUND: Combined oral contraceptive (COC) use has been associated with an unfavorable impact on carbohydrate and lipid metabolism in diverse populations of normal weight and obese women. The present study aimed to evaluate the cardiometabolic and inflammatory profiles of women in northeastern Brazil with respect to COC use and obesity. METHODS: We performed a cross-sectional study to verify cardiovascular parameters, including blood pressure (BP), fasting serum glucose, lipid, and inflammatory profile, in a population of women aged 15-45 years, considering obesity and COC use. Our sample consisted of 591 women, 481 women who were COC users, and 110 age-matched women who were COC non-users, classified as obese and non-obese according to BMI. RESULTS: COC use and obesity were associated with increased systolic (p ≤ 0.001) and diastolic BP (p = 0.001), blood glucose (p ≤ 0.001), total cholesterol (p = 0.008), low-density lipoprotein cholesterol (p ≤ 0.001), very low-density lipoprotein cholesterol (p ≤ 0.001), triglycerides (p ≤ 0.001), ferritin (p = 0.006), C-reactive protein (CRP) (p ≤ 0.001), and nitric oxide metabolites (p ≤ 0.001), as well as decreased high-density lipoprotein cholesterol (HDL-c) (p ≤ 0.001) in comparison to controls. CRP and HDL-c levels in obese COC users were determined to be outside reference range values. The odds of having lower levels of HDL-c and elevated CRP increased among obese COC users. COC use was independently associated with low levels of HDL-c, especially second-generation progestins (p < 0.001; OR = 8.976; 95% CI 2.786-28.914). CONCLUSION: Obesity and COC use were associated with alterations in lipid and inflammatory cardiometabolic parameters, particularly increased CRP levels and decreased HDL-c, which are considered markers of cardiovascular disease (CVD) risk. Given the need to prevent unintended pregnancy among obese women, together with weight loss counseling, it is important to evaluate the most effective and safest contraceptive methods to avoid the potential risk of developing CVD.

4.
Acta Trop ; 167: 157-162, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28040482

RESUMO

HTLV-1 is the causal agent of Adult T cell Leukemia/lymphoma (ATLL) and HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). The immune response to HTLV-1-infection is polarized to the Th1-type, and the presence of CXCL9/CXCL10 chemokines may lead to an increase in the recruitment of pro-inflammatory molecules in spinal cord tissue, contributing to the damage observed in the development of HAM/TSP. It has been observed that in chronic helminth-infections, such as schistosomiasis, there is a deviation toward the Th2/regulatory immune response. OBJECTIVE: To evaluate the ability of Schistosoma spp. proteins to decrease the in vitro CXCL9 and CXCL10 production by PBMC of HTLV-1-infected individuals. METHODS: The Schistosoma proteins rSm29, rSh-TSP-2 and PIII were added to PBMC cultures of HTLV-1-infected individuals and the levels of chemokines in the supernatants were measured using a sandwich ELISA method. RESULTS: The addition of rSm29 to the cultures resulted in decreased production of CXCL9 in all the analyzed individuals and HAM/TSP group (18167±9727pg/mL, p=0.044; 20237±6023pg/mL, p=0.028, respectively) compared to the levels in unstimulated cultures (19745±9729pg/mL; 25078±2392pg/mL, respectively). The addition of rSh-TSP-2 decreased the production of CXCL9 in all studied individuals and carriers group (16136±9233pg/mL, p=0.031; 13977±8857pg/mL, p=0.026) vs unstimulated cultures (19745±9729pg/mL; 18121±10508pg/mL, respectively). Addition of PIII did not alter the results. There was no significant change in the levels of CXCL10 by the addition of the studied proteins. CONCLUSION: The Schistosoma proteins used in this study were able to down modulate the production of CXCL9, a chemokine associated with the inflammatory process in HTLV-1-infection.


Assuntos
Quimiocina CXCL10/imunologia , Infecções por HTLV-I/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Leucócitos Mononucleares/imunologia , Schistosoma/imunologia , Adulto , Animais , Portador Sadio , Técnicas de Cultura de Células , Feminino , Genes Supressores de Tumor , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares
5.
Rev Inst Med Trop Sao Paulo ; 58: 53, 2016 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-27410913

RESUMO

OBJECTIVE: To identify the main bacterial species associated with community-acquired urinary tract infection (UTI) and to assess the pattern of ciprofloxacin susceptibility among bacteria isolated from urine cultures. METHODS: We conducted a retrospective study in all the patients with community-acquired UTI seen in Santa Helena Laboratory, Camaçari, Bahia, Brazil during five years (2010-2014). All individuals who had a positive urine culture result were included in this study. RESULTS: A total of 1,641 individuals met the inclusion criteria. Despite the fact that participants were female, we observed a higher rate of resistance to ciprofloxacin in males. The most frequent pathogens identified in urine samples were Escherichia coli, Klebsiella pneumoniae and Staphylococcus saprophyticus. Antimicrobial resistance has been observed mainly for ampicillin, sulfamethoxazole + trimethoprim and ciprofloxacin. Moreover, E. coli has shown the highest rate of ciprofloxacin resistance, reaching 36% of ciprofloxacin resistant strains in 2014. CONCLUSION: The rate of bacterial resistance to ciprofloxacin observed in the studied population is much higher than expected, prompting the need for rational use of this antibiotic, especially in infections caused by E. coli. Prevention of bacterial resistance can be performed through control measures to limit the spread of resistant microorganisms and a rational use of antimicrobial policy.


Assuntos
Antibacterianos/farmacologia , Ciprofloxacino/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Infecções Urinárias/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/microbiologia , Farmacorresistência Bacteriana Múltipla , Feminino , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/classificação , Bactérias Gram-Positivas/isolamento & purificação , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
6.
Clin Dev Immunol ; 2013: 710647, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24348679

RESUMO

The Th2 immune response in chronic schistosomiasis is associated with the development of periportal fibrosis. However, little is known about the phenotype and activation status of T cells in the process. Objective. To evaluate the profile of T cells in schistosomiasis patients with periportal fibrosis. Methods. It was a cross-sectional study, conducted in the village of Agua Preta, Bahia, Brazil, which included 37 subjects with periportal fibrosis determined by ultrasound. Peripheral blood mononuclear cells were obtained by the Ficcol-hypaque gradient and the frequency of T cells expressing the surface markers CD28, CD69, CD25, and CTLA-4 was determined by flow cytometry. Results. The frequency of CD4(+)CD28(+) T lymphocytes was higher in individuals with moderate to severe fibrosis compared to patients with incipient fibrosis. We did not observe any significant difference in the frequency of CD4(+) T cells expressing CD69 among groups of individuals. There was also no significant difference in the frequency of CD8(+) T cells expressing CD28 or CD69 among the studied groups. Individuals with moderate to severe fibrosis presented a lower frequency of CD8(+) T cells, CD4(+)CD25(high) T cells, and CD4(+)CTLA-4(+) T cells when compared to patients without fibrosis or incipient fibrosis. The frequency of CD4(+)CD25(low) cells did not differ between groups. Conclusion. The high frequency of activated T cells coinciding with a low frequency of putative Treg cells may account for the development of periportal fibrosis in human schistosomiasis.


Assuntos
Fibrose/etiologia , Subpopulações de Linfócitos/imunologia , Sistema Porta/patologia , Esquistossomose/complicações , Esquistossomose/imunologia , Adolescente , Adulto , Idoso , Brasil , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Criança , Estudos Transversais , Feminino , Humanos , Imunofenotipagem , Ativação Linfocitária/imunologia , Subpopulações de Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Esquistossomose/diagnóstico , Esquistossomose mansoni/imunologia , Adulto Jovem
7.
Neuroimmunomodulation ; 20(4): 233-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23752304

RESUMO

UNLABELLED: Human T cell lymphotropic virus type 1 (HTLV-1) is the causal agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). While the immune response to HTLV-1 infection is polarized to the Th1-type, chronic helminth infections drive the Th2- and T regulatory-type, and are able to downregulate the inflammatory response in some autoimmune diseases. OBJECTIVE: To evaluate whether Schistosoma spp. antigens alter the in vitro cytokine response in HTLV-1 infection. METHODS: The recombinant Schistosoma antigens Sm29 and ShTSP2 (tetraspanin) and PIII, a fraction of the Schistosoma mansoni adult worm antigen were added to peripheral blood mononuclear cell (PBMC) cultures of HTLV-1-infected individuals and the levels of interferon (IFN)-γ and interleukin (IL)-10 in the supernatants were measured using the ELISA sandwich technique. RESULTS: Compared to the levels of cytokine in nonstimulated cultures, the levels of IFN-γ were reduced in 50, 47 and 50% of patients by the presence of Sm29, ShTsp2 and PIII, respectively. The downregulation of IFN-γ production in the presence of Sm29 antigen was observed mainly in subjects who had lower basal levels of this cytokine. The levels of IL-10, however, increased by the addition of the three antigens in the cultures in 74, 62 and 44% of individuals, respectively. In addition, there was a decrease in the ratio of IFN-γ/IL-10 levels in cultures stimulated with Sm29 and ShTSP2 when compared to nonstimulated ones. CONCLUSIONS: The Schistosoma spp. antigens used in this study were able to downmodulate IFN-γ production in vitro in HTLV-1 infection. This may be associated with the increased levels of IL-10 induced by the antigens.


Assuntos
Antígenos de Helmintos/imunologia , Infecções por Deltaretrovirus/imunologia , Regulação para Baixo/imunologia , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Schistosoma mansoni/imunologia , Linfócitos T Reguladores/imunologia , Células Th2/imunologia , Adulto , Animais , Antígenos de Helmintos/sangue , Células Cultivadas , Infecções por Deltaretrovirus/sangue , Feminino , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Inflamação/sangue , Inflamação/imunologia , Inflamação/parasitologia , Interferon gama/antagonistas & inibidores , Interferon gama/biossíntese , Interleucina-10/biossíntese , Masculino , Pessoa de Meia-Idade , Neuroesquistossomose , Schistosoma mansoni/isolamento & purificação , Linfócitos T Reguladores/parasitologia , Células Th2/parasitologia , Adulto Jovem
8.
Genet Epidemiol ; 37(4): 393-401, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23554133

RESUMO

Characterization of genetic admixture of populations in the Americas and the Caribbean is of interest for anthropological, epidemiological, and historical reasons. Asthma has a higher prevalence and is more severe in populations with a high African component. Association of African ancestry with asthma has been demonstrated. We estimated admixture proportions of samples from six trihybrid populations of African descent and determined the relationship between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 237 ancestry informative markers in asthmatics and nonasthmatic controls from Barbados (190/277), Jamaica (177/529), Brazil (40/220), Colombia (508/625), African Americans from New York (207/171), and African Americans from Baltimore/Washington, D.C. (625/757). We estimated individual ancestries and evaluated genetic stratification using Structure and principal component analysis. Association of African ancestry and asthma and tIgE was evaluated by regression analysis. Mean ± SD African ancestry ranged from 0.76 ± 0.10 among Barbadians to 0.33 ± 0.13 in Colombians. The European component varied from 0.14 ± 0.05 among Jamaicans and Barbadians to 0.26 ± 0.08 among Colombians. African ancestry was associated with risk for asthma in Colombians (odds ratio (OR) = 4.5, P = 0.001) Brazilians (OR = 136.5, P = 0.003), and African Americans of New York (OR: 4.7; P = 0.040). African ancestry was also associated with higher tIgE levels among Colombians (ß = 1.3, P = 0.04), Barbadians (ß = 3.8, P = 0.03), and Brazilians (ß = 1.6, P = 0.03). Our findings indicate that African ancestry can account for, at least in part, the association between asthma and its associated trait, tIgE levels.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Asma/etnologia , Asma/genética , Imunoglobulina E/genética , Afro-Americanos/genética , Algoritmos , Asma/epidemiologia , Barbados , Brasil , Estudos de Casos e Controles , Colômbia , District of Columbia , Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença , Humanos , Imunoglobulina E/sangue , Jamaica , Modelos Estatísticos , Epidemiologia Molecular , New York , Fatores de Risco
9.
J Parasitol Res ; 2012: 520308, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23209879

RESUMO

High levels of proinflammatory cytokines such as IFN-γ and TNF are associated with tissue lesions in cutaneous leishmaniasis (CL). We previously demonstrated that Schistosoma mansoni antigens downmodulate the in vitro cytokine response in CL. In the current study we evaluated whether S. mansoni antigens alter monocyte and T-lymphocyte phenotypes in leishmaniasis. Peripheral blood mononuclear cells of CL patients were cultured with L. braziliensis antigen in the presence or absence of the S. mansoni antigens rSm29, rSmTSP-2- and PIII. Cells were stained with fluorochrome conjugated antibodies and analyzed by flow cytometry. The addition of rSm29 to the cultures decreased the expression of HLA-DR in nonclassical (CD14(+)CD16(++)) monocytes, while the addition of PIII diminished the expression of this molecule in classical (CD14(++)CD16(-)) and intermediate (CD14(++)CD16(+)) monocytes. The addition of PIII and rSmTSP-2 resulted in downmodulation of CD80 expression in nonclassical and CD86 expression in intermediate monocytes, respectively. These two antigens increased the expression of CTLA-4 in CD4(+) T cells and they also expanded the frequency of CD4(+)CD25(high)Foxp3(+) T cells. Taken together, we show that S. mansoni antigens, mainly rSmTSP-2 and PIII, are able to decrease the activation status of monocytes and also to upregulate the expression of modulatory molecules in T lymphocytes.

10.
PLoS One ; 7(5): e35863, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22574126

RESUMO

BACKGROUND: IL-13 is a signature cytokine of the helper T cell type 2 (TH2) pathway which underlies host defense to helminthic infection and activates production of IgE in both parasitized populations and in urban settings after allergen exposure. METHODOLOGY/PRINCIPAL FINDINGS: Two functional polymorphisms in IL13, rs1800925 (or c.1-1111C>T) and rs20541 (or R130Q) were previously found to be associated with Schistosoma hematobium infection intensity. They have not been thoroughly explored in S. mansoni-endemic populations, however, and were selected along with 5 tagging SNPs for genotyping in 812 individuals in 318 nuclear families from a schistosomiasis-endemic area of Conde, Bahia, in Brazil. Regression models using GEE to account for family membership and family-based quantitative transmission disequilibrium tests (QTDT) were used to evaluate associations with total serum IgE (tIgE) levels and S. mansoni fecal egg counts adjusted for non-genetic covariates. We identified a protective effect for the T allele at rs20541 (P = 0.005) against high S. mansoni egg counts, corroborated by QTDT (P = 0.014). Our findings also suggested evidence for protective effects for the T allele at rs1800925 and A allele at rs2066960 after GEE analysis only (P = 0.050, 0.0002). CONCLUSIONS/SIGNIFICANCE: The two functional variants in IL13 are protective against high S. mansoni egg counts. These markers showed no evidence of association with tIgE levels, unlike tIgE levels previously studied in non-parasitized or atopic study populations.


Assuntos
Interleucina-13/genética , Polimorfismo de Nucleotídeo Único , Schistosoma mansoni/patogenicidade , Esquistossomose mansoni/genética , Esquistossomose mansoni/prevenção & controle , Adulto , Animais , Brasil/epidemiologia , Doenças Endêmicas/prevenção & controle , Feminino , Humanos , Imunoglobulina E/sangue , Desequilíbrio de Ligação , Masculino , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/imunologia , Células Th2/imunologia
11.
J Parasitol Res ; 2012: 394981, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23320145

RESUMO

Periportal fibrosis in schistosomiasis has been associated to the host immune response to parasite antigens. We evaluated the immune response in S. mansoni infected individuals with different degrees of periportal fibrosis. Cytokine and chemokines were measured in serum and in supernatants of PBMC cultures stimulated with the soluble adult worm (SWAP) or egg (SEA) antigens, using a sandwich ELISA. The levels of IL-5 in response to SEA were higher in individuals with moderate to severe fibrosis (310.9 pg/mL) compared to individuals without fibrosis (36.8 pg/mL; P = 0.0418). There was also a higher production of TNF-α in cultures stimulated with SWAP in patients with insipient fibrosis (1446 pg/mL) compared to those without fibrosis (756.1 pg/mL; P = 0.0319). The serum levels of IL-13 and MIP-1α were higher in subjects without fibrosis than in those with moderate to severe fibrosis. However a positive association between serum levels of IL-13, TNF-α, MIP-1α, and RANTES and S. mansoni parasite burden was found. From these data we conclude that IL-5 and TNF-α may participate in liver pathology in schistosomiasis. The positive association between IL-13, TNF-α, MIP-1α, and RANTES with parasite burden, however, might predict the development of liver pathology.

12.
Mem Inst Oswaldo Cruz ; 106(7): 856-63, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22124559

RESUMO

Schistosoma mansoni infection or associated products are able to down-modulate the type 1 CD4+ T cell inflammatory response characteristic of autoimmune diseases. In this study, we evaluated how S. mansoni antigens altered the immune response that was induced by the soluble Leishmania antigen (SLA) from cutaneous leishmaniasis (CL) patients. Cytokines were measured from the supernatants of peripheral blood mononuclear cell cultures stimulated with SLA. This was performed using the sandwich enzyme linked immunosorbent assay technique in the presence or absence of S. mansoni recombinant antigens Sm29, SmTSP-2 and PIII. The addition of S. mansoni antigens to the cultures resulted in the reduction of interferon gamma (IFN-γ) levels in 37-50% of patients. Although to a lesser extent, the antigens were also able to decrease the production of tumour necrosis factor-alpha (TNF-α). We compared patients that either had or did not have reduction in IFN-γ and TNF-α production in cultures stimulated with SLA in the presence of S. mansoni antigens. We found that there was no significant difference in the levels of interleukin (IL)-10 and IL-5 in response to S. mansoni antigens between the groups. The antigens used in this study down-modulated the in vitro proinflammatory response induced by SLA in a group of CL patients through a currently undefined mechanism.


Assuntos
Antígenos de Protozoários/farmacologia , Citocinas/biossíntese , Leishmaniose Cutânea/imunologia , Leucócitos Mononucleares/imunologia , Schistosoma mansoni/imunologia , Adolescente , Adulto , Animais , Antígenos de Protozoários/imunologia , Criança , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Interferon gama/biossíntese , Interleucina-10/biossíntese , Interleucina-5/biossíntese , Leishmaniose Cutânea/sangue , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/biossíntese , Adulto Jovem
13.
Mem. Inst. Oswaldo Cruz ; 106(7): 856-863, Nov. 2011. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-606650

RESUMO

Schistosoma mansoni infection or associated products are able to down-modulate the type 1 CD4+ T cell inflammatory response characteristic of autoimmune diseases. In this study, we evaluated how S. mansoni antigens altered the immune response that was induced by the soluble Leishmania antigen (SLA) from cutaneous leishmaniasis (CL) patients. Cytokines were measured from the supernatants of peripheral blood mononuclear cell cultures stimulated with SLA. This was performed using the sandwich enzyme linked immunosorbent assay technique in the presence or absence of S. mansoni recombinant antigens Sm29, SmTSP-2 and PIII. The addition of S. mansoni antigens to the cultures resulted in the reduction of interferon gamma (IFN-γ) levels in 37-50 percent of patients. Although to a lesser extent, the antigens were also able to decrease the production of tumour necrosis factor-alpha (TNF-α). We compared patients that either had or did not have reduction in IFN-γ and TNF-α production in cultures stimulated with SLA in the presence of S. mansoni antigens. We found that there was no significant difference in the levels of interleukin (IL)-10 and IL-5 in response to S. mansoni antigens between the groups. The antigens used in this study down-modulated the in vitro proinflammatory response induced by SLA in a group of CL patients through a currently undefined mechanism.


Assuntos
Adolescente , Adulto , Animais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antígenos de Protozoários/farmacologia , Citocinas/biossíntese , Leishmaniose Cutânea/imunologia , Leucócitos Mononucleares/imunologia , Schistosoma mansoni/imunologia , Antígenos de Protozoários/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Interferon gama/biossíntese , /biossíntese , /biossíntese , Leishmaniose Cutânea/sangue , Fator de Necrose Tumoral alfa/biossíntese
14.
Am J Respir Crit Care Med ; 178(10): 1017-22, 2008 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-18827265

RESUMO

RATIONALE: Asthma prevalence and severity are high among underserved minorities, including those of African descent. The Duffy antigen/receptor for chemokines is the receptor for Plasmodium vivax on erythrocytes and functions as a chemokine-clearing receptor. Unlike European populations, decreased expression of the receptor on erythrocytes is common among populations of African descent, and results from a functional T-46C polymorphism (rs2814778) in the promoter. This variant provides an evolutionary advantage in malaria-endemic regions, because Duffy antigen/receptor for chemokines-negative erythrocytes are more resistant to infection by P. vivax. OBJECTIVES: To determine the role of the rs2814778 polymorphism in asthma and atopy as measured by total serum IgE levels among four populations of African descent (African Caribbean, African American, Brazilian, and Colombian) and a European American population. METHODS: Family-based association tests were performed in each of the five populations to test for association between the rs2814778 polymorphism and asthma or total IgE concentration. MEASUREMENTS AND MAIN RESULTS: Asthma was significantly associated with the rs2814778 polymorphism in the African Caribbean, Colombian, and Brazilian families (P < 0.05). High total IgE levels were associated with this variant in African Caribbean and Colombian families (P < 0.05). The variant allele was not polymorphic among European Americans. CONCLUSIONS: Susceptibility to asthma and atopy among certain populations of African descent is influenced by a functional polymorphism in the gene encoding Duffy antigen/receptor for chemokines. This genetic variant, which confers resistance to malarial parasitic infection, may also partially explain ethnic differences in morbidity of asthma.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Asma/genética , Sistema do Grupo Sanguíneo Duffy/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de Superfície Celular/genética , Adolescente , Adulto , Barbados , Brasil , Estudos de Casos e Controles , Colômbia , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Estados Unidos
15.
J Infect Dis ; 198(8): 1227-36, 2008 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-18717640

RESUMO

BACKGROUND: Evidence of genetic control for total serum IgE (tIgE) level has been reported in multiple populations, although populations with substantial exposure to helminths have yielded lower estimates of heritability, despite evidence suggesting that genes also control a significant portion of the variation in the number of Schistosoma mansoni eggs per gram of fecal matter. METHODS: By use of a whole-population ascertainment scheme, 822 individuals were enrolled from a schistosomiasis-endemic area in Conde, Bahia, in Brazil. Heritability was estimated by using an additive polygenic model, and segregation analysis was performed for 2 quantitative traits, tIgE level and egg count. RESULTS: After adjusting for nongenetic covariates, the heritability of log-transformed tIgE level and log-transformed egg count was estimated at 60% and 31%, respectively. No evidence for a single major gene controlling tIgE level or egg count was observed in segregation analysis for 781 individuals and 403 individuals, respectively, in 318 families, however, which suggests complex biological control. CONCLUSIONS: The high heritability of tIgE level indicates that genetic factors are likely to control tIgE level even in the presence of helminthic infection. Substantial heritability for the burden of S. mansoni infection was confirmed in these Brazilian families. Further genetic studies will be needed to dissect the specific genetic factors that underlie these traits.


Assuntos
Doenças Endêmicas , Imunoglobulina E/sangue , Schistosoma mansoni/imunologia , Schistosoma mansoni/patogenicidade , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/genética , Adolescente , Adulto , Idoso , Animais , Anticorpos Anti-Helmínticos/sangue , Brasil/epidemiologia , Criança , Fezes/parasitologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Ovos de Parasitas , Schistosoma mansoni/crescimento & desenvolvimento , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/parasitologia
16.
Ann Allergy Asthma Immunol ; 96(5): 713-8, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16729785

RESUMO

BACKGROUND: Helminth infections have been associated with reduced reactivity to aeroallergens, which could be related to interleukin 10 (IL-10) production, as reported in schistosomiasis. OBJECTIVE: To compare skin responses to aeroallergens with Der p specific IL-10 production in patients with asthma or rhinitis according to Ascaris infection status. METHODS: Cross-sectional study of 113 patients with asthma or rhinitis from a region endemic for geohelminths. Stool examinations and skin prick tests to aeroallergens were performed in all the patients. Der p specific IL-10 production was measured in the supernatant of peripheral blood mononuclear cell (PBMC) cultures of a subsample of 53 patients. RESULTS: Forty-seven patients had Ascaris in their stool samples. Skin test results were positive in 77% of Ascaris-infected patients and in 71% of uninfected individuals. Median levels of Der p specific IL- 10 in PBMC cultures of infected and uninfected patients were similar (7.8 and 8.4 pg/mL, respectively). The lack of association remained when parasite load was taken into account and when patients with evidence of previous infection were removed from the uninfected group. CONCLUSIONS: In patients with asthma or rhinitis living in an urban area endemic for geohelminths, we found no association between Ascaris infection and skin reactivity to aeroallergens. Furthermore, there was no difference in Der p specific IL-10 production by PBMCs. These negative findings indicate that different from what is observed in Schistosoma infection, Ascaris lumbricoides infection in individuals living in an urban area does not induce strong regulatory responses.


Assuntos
Antígenos de Dermatophagoides/imunologia , Ascaríase/imunologia , Asma/microbiologia , Interleucina-10/metabolismo , Rinite Alérgica Sazonal/microbiologia , Adolescente , Adulto , Alérgenos , Animais , Ascaríase/epidemiologia , Ascaris lumbricoides/imunologia , Asma/imunologia , Estudos Transversais , Poluentes Ambientais , Feminino , Humanos , Interleucina-10/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Rinite Alérgica Sazonal/imunologia , Testes Cutâneos
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