RESUMO
BACKGROUND: IL-27 has dual roles in the immune response either stimulating Th1 or inhibiting Th17 cells. Because there is a particular link of IL-23/Th17 axis in the development of cancer and IL-27 has been considered a potential treatment for cancer, we evaluated the gastric and serum concentrations of IL-27 in two mutually exclusive Helicobacter pylori-associated diseases, gastric cancer (GC) and duodenal ulcer (DU). MATERIAL AND METHODS: We prospectively studied 110 H pylori-positive patients and 40 healthy blood donors. Serum and gastric concentrations of IL-27 and cytokines of the Th1/Th17 cells were assessed by ELISA. RESULTS: IL-27 was not detected in GC patients, but the cytokine concentration was very high in the patients with DU. IL-27 was also detected in the gastritis patients and in the H pylori-positive blood donors. IL27RA mRNA expression in peripheral blood mononuclear cells, evaluated by rt-PCR, was stimulated by H pylori strains. The cytokine concentration positively correlated with the Th1 and negatively with Th17 cell representative cytokine levels. Gastric IL-27 concentrations were positively correlated with increased degree of mononuclear and polymorphonuclear cells on the antral gastric mucosa of DU patients in consonance with the DU gastritis pattern. IL-12p70 and IFN-γ gastric concentrations were significantly higher in DU than in GC. Conversely, gastric concentrations of Th17 cell-associated cytokines (IL-1ß, IL-6, IL-17A, IL-23, and TGF-ß) were significantly higher in GC than in DU patients. CONCLUSION: Although H pylori infection is able to elicit IL-27 and IL-27Rα secretion, DU and GC have diametrically opposed cytokine patterns.
Assuntos
Infecções por Helicobacter/genética , Helicobacter pylori/fisiologia , Interleucina-27/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Úlcera Duodenal/genética , Úlcera Duodenal/imunologia , Úlcera Duodenal/microbiologia , Feminino , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Interleucina-17/genética , Interleucina-17/imunologia , Interleucina-27/imunologia , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/microbiologia , Células Th1/imunologia , Células Th17/imunologia , Adulto JovemRESUMO
BACKGROUND: The association between infection with Helicobacter pylori and different gastroduodenal diseases is related to bacterial, host and environmental factors. Studies have demonstrated an association between the genetic diversity of H. pylori, especially in the vacA and cagA genes, and the development of digestive diseases such as peptic ulcer and gastric cancer. In addition, the nature of the host inflammatory response may explain these different manifestations of infection caused by this microorganism. In this respect, host factors that regulate the immune and inflammatory responses involving the functional interaction of H. pylori infection with different components of the immune system, particularly T cells, in gastroduodenal diseases still need further investigation. OBJECTIVE: To characterize the immune response, including immunity induced by infection with H. pylori, especially virulent strains (vacA alleles and cagA gene), by analyzing the cytokine profile and T-cell population present in gastroduodenal diseases in a Brazilian population. METHODS: In a prospective study, gastric biopsies were collected from 554 patients with different gastroduodenal diseases for histological analysis and for the determination of bacterial genotype and cytokine production (IL-4, IL-10, IFN-γ and IL-12) by ELISA. RESULTS: The predominant genotype of the H. pylori strains isolated from the patients studied was s1m1cagA+, which was more common among patients with gastric ulcer, duodenal ulcer and gastric cancer. A significant association was observed between the s1m1cagA+ genotype and a higher degree of inflammation, higher neutrophil activity and the development of intestinal metaplasia. The gastric concentrations of IFN-γ and IL-12 were significantly higher in patients infected with H. pylori than in uninfected individuals. Higher levels of these cytokines were detected in patients with gastric ulcer and cancer, while the levels of IL-4 and IL-10 in the gastric mucosa were lower in these patients. In addition, IFN-γ and IL-12 concentrations in gastric biopsies were higher in patients infected with the virulent s1m1cagA+ genotype. In contrast, IL-4 and IL-10 levels were higher in tissue infected with s2m2cagA in gastric biopsies. CONCLUSION: Our study shows that the interaction between the type of infectious strain and the Th1 immune response can influence and perpetuate gastric inflammation, and thus contributes to the development of the different clinical manifestations of H. pylori infection.
Assuntos
Úlcera Duodenal/imunologia , Mucosa Gástrica/imunologia , Gastrite/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/genética , Neoplasias Gástricas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Citocinas/biossíntese , DNA Bacteriano , Úlcera Duodenal/microbiologia , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/microbiologia , Genes Bacterianos/imunologia , Genótipo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Prospectivos , Neoplasias Gástricas/microbiologia , Adulto JovemRESUMO
ABSTRACT BACKGROUND: The association between infection with Helicobacter pylori and different gastroduodenal diseases is related to bacterial, host and environmental factors. Studies have demonstrated an association between the genetic diversity of H. pylori, especially in the vacA and cagA genes, and the development of digestive diseases such as peptic ulcer and gastric cancer. In addition, the nature of the host inflammatory response may explain these different manifestations of infection caused by this microorganism. In this respect, host factors that regulate the immune and inflammatory responses involving the functional interaction of H. pylori infection with different components of the immune system, particularly T cells, in gastroduodenal diseases still need further investigation. OBJECTIVE: To characterize the immune response, including immunity induced by infection with H. pylori, especially virulent strains (vacA alleles and cagA gene), by analyzing the cytokine profile and T-cell population present in gastroduodenal diseases in a Brazilian population. METHODS: In a prospective study, gastric biopsies were collected from 554 patients with different gastroduodenal diseases for histological analysis and for the determination of bacterial genotype and cytokine production (IL-4, IL-10, IFN-γ and IL-12) by ELISA. RESULTS: The predominant genotype of the H. pylori strains isolated from the patients studied was s1m1cagA+, which was more common among patients with gastric ulcer, duodenal ulcer and gastric cancer. A significant association was observed between the s1m1cagA+ genotype and a higher degree of inflammation, higher neutrophil activity and the development of intestinal metaplasia. The gastric concentrations of IFN-γ and IL-12 were significantly higher in patients infected with H. pylori than in uninfected individuals. Higher levels of these cytokines were detected in patients with gastric ulcer and cancer, while the levels of IL-4 and IL-10 in the gastric mucosa were lower in these patients. In addition, IFN-γ and IL-12 concentrations in gastric biopsies were higher in patients infected with the virulent s1m1cagA+ genotype. In contrast, IL-4 and IL-10 levels were higher in tissue infected with s2m2cagA in gastric biopsies. CONCLUSION: Our study shows that the interaction between the type of infectious strain and the Th1 immune response can influence and perpetuate gastric inflammation, and thus contributes to the development of the different clinical manifestations of H. pylori infection.
RESUMO CONTEXTO: A associação da infecção por Helicobacter pylori com diferentes doenças gastroduodenais pode estar associada a fatores bacterianos, do hospedeiro e do ambiente. Nesse contexto, estudos têm demonstrado que a diversidade genética do H. pylori, sobretudo nos genes vacA e cagA, está associada ao desenvolvimento de doenças gastroduodenais como a úlcera péptica e o câncer gástrico. Além disso, a natureza da resposta inflamatória do hospedeiro pode explicar essas diferentes manifestações da infecção por esse microrganismo. Portanto, fatores do hospedeiro que regulam as respostas imunológica e inflamatória, envolvendo a interação funcional da infecção por H. pylori com diferentes membros do compartimento imunológico, especialmente respostas imunes de células T nas doenças gastroduodenais, ainda precisam ser melhor estudados. OBJETIVO: Caracterizar a resposta imune, incluindo imunidade induzida por infecção pelo H. pylori, especialmente com cepas virulentas de H. pylori (alelos vacA e gene cagA), através da análise do perfil de citocinas e da caracterização da população de células T presentes em doenças gastroduodenais em nossa população. MÉTODOS: Em um estudo prospectivo, foram coletadas biópsias gástricas de 554 pacientes portadores das diferentes doenças gastroduodenais. Nas amostras biológicas destes pacientes foi realizada a determinação do genótipo bacteriano e a detecção das citocinas IL-4, IL-10, INF-γ e IL-12 através do método Elisa. Foram obtidas biópsias gástricas para avaliação histológica. RESULTADOS: Observamos que o genótipo predominante nas cepas de H. pylori isoladas dos pacientes estudados foi s1m1cagA positivo, sendo mais frequentes entre os pacientes com úlcera gástrica, úlcera duodenal e câncer gástrico. Houve associação significativa das cepas com o genótipo s1m1cagA positivo com maior grau de inflamação, atividade neutrofílica e desenvolvimento de metaplasia intestinal. As concentrações gástricas de INF-γ e IL-12 foram significativamente mais elevadas em pacientes infectados pelo H. pylori do que nos não infectados. Foram detectados níveis mais elevados dessas citocinas nos portadores de úlcera e câncer gástrico, sendo que nesses pacientes foram observados níveis mais baixos de IL-4 e IL-10 na mucosa gástrica. Além disso, as concentrações de INF-γ e IL-12 em biópsias gástricas, foram mais elevadas nos pacientes portadores das cepas bacterianas virulentas s1m1cagA+. Contrariamente, os níveis de IL-4 e IL-10 foram maiores em tecido infectado por cepas s2m2cagA. Pacientes com maior grau de inflamação, de atividade neutrofílica e presença de metaplasia intestinal, apresentaram níveis mais elevados de INF-γ e IL-12 e uma concentração mais baixa de IL-4 e IL-10 nas biópsias gástricas. CONCLUSÃO: Nosso estudo demonstra que a interação entre o tipo de cepa infectante e resposta imunológica com perfil Th1, podem influenciar e perpetuar a inflamação gástrica contribuindo para o desenvolvimento de diferentes manifestações clínicas na infecção pelo H. pylori.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Neoplasias Gástricas/imunologia , Helicobacter pylori/genética , Infecções por Helicobacter/imunologia , Úlcera Duodenal/imunologia , Mucosa Gástrica/imunologia , Gastrite/imunologia , Neoplasias Gástricas/microbiologia , Proteínas de Bactérias/genética , DNA Bacteriano , Reação em Cadeia da Polimerase , Estudos Prospectivos , Citocinas/biossíntese , Helicobacter pylori/isolamento & purificação , Infecções por Helicobacter/microbiologia , Úlcera Duodenal/microbiologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastrite/microbiologia , Genes Bacterianos/imunologia , Genótipo , Pessoa de Meia-Idade , Antígenos de Bactérias/genéticaRESUMO
ABSTRACT BACKGROUND: As being the first bacteria determined to be carcinogenic, Helicobacter pylori (H. pylori) is a pathogen localized in the stomach in more than half of the world population. Some earlier studies have found a relation between tissue histocompatibility antigens and gastric cancers depending on the regions. OBJECTIVE: The present study aimed to determine the distribution of human leukocyte antigen (HLA) class I and class II antigens in H. pylori-positive pediatric patients with active gastritis and duodenal ulcer, excluding cancer cases, in our center. METHODS: The study included 40 patients diagnosed with H. pylori-positive active gastritis and duodenal ulcer and 100 controls consisting of healthy donor candidates. The HLA class I and class II antigens were studied in the isolated DNA samples using the polymerase chain reaction sequence-specific oligonucleotide probes. RESULTS: The frequency of HLA-B*51 antigen was significantly higher in the patient group than in the control group (40% vs 17%; P=0.003). There was no difference between the two groups in terms of the frequencies of HLA-A, HLA-C, HLA-DR, and HLA-DQ antigens. CONCLUSION: It was determined that HLA-B*51 plays a critical role in H. pylori infection.
RESUMO CONTEXTO: Determinada como sendo a primeira bactéria cancerígena, o Helicobacter pylori (H. pylori) é um patógeno localizado no estômago em mais da metade da população mundial. Alguns estudos anteriores têm encontrado uma relação entre câncer gástrico e antígenos de histocompatibilidade de tecido dependendo das regiões. OBJETIVO: O presente estudo teve como objetivo determinar a distribuição em nosso centro do antígeno leucocitário humano (HLA) de classe I e antígenos classe II em pacientes pediátricos H. pylori-positivos com gastrite e úlcera duodenal ativas, excluindo casos de câncer. MÉTODOS: O estudo incluiu 40 pacientes H. pylori-positivos diagnosticados com gastrite e úlcera duodenal ativas e 100 controles consistindo de candidatos doadores saudáveis. Foram estudadas nas amostras de DNA isoladas o antígeno leucocitário humano classe I e antígenos classe II, utilizando-se as cadeias de sequência específica de polimerase do oligonucleotideo. RESULTADOS: A frequência do antígeno HLA - B * 51 foi significativamente maior no grupo de pacientes do que no grupo controle (40% vs 17%; P=0,003). Não houve diferença entre os dois grupos em termos das frequências dos antígenos HLA-A, HLA-DR, HLA-DQ e HLA-C. CONCLUSÃO: Determinou-se que o HLA - B * 51 desempenha um papel crítico na infecção pelo H. pylori.
Assuntos
Humanos , Masculino , Feminino , Criança , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Helicobacter pylori , Infecções por Helicobacter/imunologia , Úlcera Duodenal/imunologia , Gastrite/imunologia , Estudos de Casos e Controles , Infecções por Helicobacter/complicações , Gastrite/microbiologiaRESUMO
BACKGROUND: As being the first bacteria determined to be carcinogenic, Helicobacter pylori (H. pylori) is a pathogen localized in the stomach in more than half of the world population. Some earlier studies have found a relation between tissue histocompatibility antigens and gastric cancers depending on the regions. OBJECTIVE: The present study aimed to determine the distribution of human leukocyte antigen (HLA) class I and class II antigens in H. pylori-positive pediatric patients with active gastritis and duodenal ulcer, excluding cancer cases, in our center. METHODS: The study included 40 patients diagnosed with H. pylori-positive active gastritis and duodenal ulcer and 100 controls consisting of healthy donor candidates. The HLA class I and class II antigens were studied in the isolated DNA samples using the polymerase chain reaction sequence-specific oligonucleotide probes. RESULTS: The frequency of HLA-B*51 antigen was significantly higher in the patient group than in the control group (40% vs 17%; P=0.003). There was no difference between the two groups in terms of the frequencies of HLA-A, HLA-C, HLA-DR, and HLA-DQ antigens. CONCLUSION: It was determined that HLA-B*51 plays a critical role in H. pylori infection.
Assuntos
Úlcera Duodenal/imunologia , Gastrite/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Estudos de Casos e Controles , Criança , Feminino , Gastrite/microbiologia , Infecções por Helicobacter/complicações , Humanos , MasculinoRESUMO
Colonization of the gastric mucosa by Helicobacter pylori can lead to peptic ulcer and gastric adenocarcinoma. TLRs are signaling receptors involved in the recognition of microorganisms, and polymorphisms in their genes may influence the innate and adaptive immune response to H. pylori, affecting the clinical outcomes of the infection. We assessed the association between single nucleotide polymorphisms in TLR9 and TLR5 and gastroduodenal diseases. All patients were genotyped by allelic discrimination in regions 1174C>T and 1775A>G of TLR5 and -1237T>C and 2848G>A of TLR9. The 2848A allele of TLR9 was more frequent in duodenal ulcer and showed an association of risk with this pathology. Polymorphisms in TLR5 were not found to be associated with disease. Patients with polymorphisms in TLR9 and TLR5 expressed significantly lower levels of IL-1ß and TNF-α, whereas polymorphisms in TLR5 also decreased the expression of IL-6 and IL-10. Our findings suggest that 2848G>A polymorphism in TLR9 increases the risk for the development of duodenal ulcer probably by modifying the inflammatory response to H. pylori infection. This is the first study to show an association of 2848A allele of TLR9 with duodenal ulcer and with altered expression of inflammatory cytokines in the gastric mucosa.
Assuntos
Úlcera Duodenal/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Receptor 5 Toll-Like/genética , Receptor Toll-Like 9/genética , Adulto , Idoso , Citocinas/metabolismo , Úlcera Duodenal/genética , Feminino , Mucosa Gástrica/imunologia , Regulação da Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Infecções por Helicobacter/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
OBJECTIVES: Peptic ulcer disease (PUD) is highly prevalent among adults but less common in children. Helicobacter pylori infection, the main cause of PUD, is, however, acquired extremely early in life. The aim of the study was to analyze clinical characteristics of children with PUD in a country with a high prevalence of the disease and to evaluate which host factors could determine this clinical outcome. METHODS: Children referred for upper gastrointestinal (GI) endoscopy with suspicion of peptic diseases were included prospectively during an 8-year period. Antral biopsies were performed to determine H pylori presence and mucosal cytokines profile. RESULTS: A total of 307 children between 3 and 18 years old were enrolled. Of the total, 237 children (46% boys) with complete data were included. H pylori infection was confirmed in 133 (56.1%) participants. Duodenal ulcer (DU) was diagnosed in 32 patients (13.5%); among them 29 were infected with H pylori (90.6%). Infected children had a nodular appearance of the gastric mucosa more often than noninfected children. Noninfected children had fewer lymphoid follicles and less inflammatory infiltrate than infected children. Only mucosal polymorphonuclear cell infiltration was more intense in DU-infected children as compared with non-DU-infected children. DU-infected children had higher levels of mucosal interferon-γ than noninfected and non-DU-infected patients. Non-DU-infected children had also higher levels of mucosal interleukin-10 than noninfected patients (P < 0.05). CONCLUSIONS: PUD in children, especially DU, is strongly associated with H pylori infection in developing countries. There is no distinctive clinical presentation of children with PUD. T-helper cytokine balance may influence clinical outcomes in children.
Assuntos
Mucosa Gástrica/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori , Úlcera Péptica/imunologia , Úlcera Péptica/microbiologia , Adolescente , Biópsia , Criança , Pré-Escolar , Citocinas/análise , Úlcera Duodenal/imunologia , Úlcera Duodenal/microbiologia , Feminino , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Imunidade nas Mucosas , Masculino , Neutrófilos/patologiaRESUMO
OBJECTIVE: To study the association between anti-VacA antibodies and pre-neoplastic lesions (IM), gastric cancer (GC), and duodenal ulcer (DU). METHODS: A case-control study that included 347 patients, 90 with IM, 60 with GC, 52 with DU, and 145 with non-atrophic gastritis was conducted. For the analysis, a polytomous logistic regression models were used. Anti-VacA antibodies were identified in sera from these patients, either by Western blot assay (WB), using antigens produced by H. pylori s1m1 strain, or by neutralization assay challenging HeLa cells with H. pylori VacA s1m1 cytotoxin. RESULTS: Results of the WB assay showed no association between WB-anti-VacA antibodies and gastroduodenal diseases. In contrast, when antibodies that neutralize VacA cytotoxic activity were studied, a significant association was found with IM (OR 2.7, 95% CI 1.4-5.1) and DU (OR 2.3, 95% CI 1.1-4.9) and an even stronger association with GC (OR 3.9, 95% CI 1.8-8.5). A significant association with histological subtypes of GC (diffuse and intestinal) and of IM (complete and incomplete) was also found. In addition, the association showed a significant dose-response effect in the case of GC, but not of DU or IM. These associations did not change substantially after adjustment for confounding factors. MAIN CONCLUSION: This study showed that VacA-neutralizing antibodies are significantly associated with gastroduodenal diseases, especially GC, and that they might be used as risk markers of GC and DU.
Assuntos
Anticorpos Antibacterianos/sangue , Anticorpos Neutralizantes/sangue , Proteínas de Bactérias/imunologia , Úlcera Duodenal/imunologia , Úlcera Duodenal/microbiologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Bactérias/imunologia , Estudos de Casos e Controles , Feminino , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de RiscoRESUMO
Helicobacter pylori infection is mainly acquired in childhood, and polymorphisms in the host genes coding for Toll-like receptors (TLRs) may influence the innate and adaptive immune response to the infection, affecting the susceptibility to H. pylori or the disease outcomes. Our aim was to investigate whether TLR4, TLR2, and TLR5 polymorphisms were associated with H. pylori susceptibility and risk for duodenal ulcer in children. Gastric biopsy specimens were obtained at endoscopy for evaluation of H. pylori status, TLR4, TLR2 and TLR5 polymorphisms from 486 children (254 H. pylori-negative and 232 H. pylori-positive: 72 with and 160 without duodenal ulcer). cagA status of H. pylori infection was investigated by PCR. The levels of gastric cytokines were detected by ELISA. H. pylori-positivity or duodenal ulcer were not associated with TLR2, TLR4 or TLR5 polymorphisms. Otherwise, the presence of TLR4 polymorphic allele was associated with infection by cagA-positive strains and with increased gastric levels of interleukin-8 and interleukin-10. TLR4 polymorphism might ultimately contribute to more severe consequences of the infection in adulthood since it was associated with susceptibility to cagA-positive H. pylori infection early in life.
Assuntos
Úlcera Duodenal/genética , Úlcera Duodenal/microbiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Helicobacter pylori/imunologia , Polimorfismo Genético , Receptores Toll-Like/genética , Adolescente , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Criança , Pré-Escolar , Citocinas/análise , Suscetibilidade a Doenças , Úlcera Duodenal/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Mucosa Gástrica/química , Mucosa Gástrica/imunologia , Infecções por Helicobacter/imunologia , Humanos , Lactente , Masculino , Reação em Cadeia da Polimerase , Fatores de Risco , Fatores de Virulência/genéticaRESUMO
Helicobacter pylori is associated with peptic ulcer and gastric adenocarcinoma. Toll-like receptors (TLRs) participate in H. pylori recognition, and single-nucleotide polymorphisms (SNPs) in TLRs are associated with impaired immune response. We aimed to evaluate the association of TLR2/R753Q and TLR4/D299G/T399I SNPs with gastroduodenal diseases; and study the effect of SNPs on cytokine and chemokine expression in the gastric mucosa. Study included 450 Mexican patients with gastroduodenal diseases. SNPs in TLRs 2 and 4 genes were analyzed by allele-specific PCR. Cytokines and chemokines were assessed by qRT-PCR and immunoassay. TLR4/D299G/T399I polymorphisms were more frequent in duodenal ulcer and showed a trend in gastric cancer, when compared with non-atrophic gastritis. Patients with TLR4 polymorphisms expressed significantly lower levels of IL-1beta, IL-6, IL-8 and GRO-alpha; and higher levels of TNF-alpha, IL-10, MCP-1 and MIP-1alpha . SNPs in TLR4 gene had an association with severe H. pylori-associated disease and with modified pattern of inflammatory cytokines and chemokines in the gastric mucosa. These results suggest that TLR4 SNPs contributes importantly to the clinical outcome of H. pylori infection.
Assuntos
Quimiocinas/análise , Citocinas/análise , Úlcera Duodenal/genética , Gastrite/genética , Infecções por Helicobacter/complicações , Helicobacter pylori , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Adulto , Idoso , Estudos de Casos e Controles , Úlcera Duodenal/imunologia , Feminino , Gastrite/imunologia , Humanos , Masculino , Metaplasia , Pessoa de Meia-Idade , Neoplasias Gástricas/imunologiaRESUMO
The immunological mechanisms involved in the development of duodenal ulcer, especially in childhood, are unclear. Helicobacter pylori-positive children and adults, with and without duodenal ulcer, were therefore compared with respect to CD4(+) T-cells, and CD8(+) T-cells, B-cells and B1a-cells, as well as cell activation (CD4(+)/HLA-DR(+) and CD8(+)/HLA-DR(+)) and co-stimulatory (CD4(+)/CD28(+) and CD8(+)/CD28(+)) markers, in peripheral blood. Children with and without duodenal ulcer differed significantly. In particular, there was a phenotypic change in CD8(+) T-cells from children with ulcer that involved a 200% increase in the number of CD8(+)/HLA-DR(+) cells/mm(3) and a decrease of 34.2% in the number of CD8(+)/CD28(+) cells/mm(3). This phenotype of chronically activated memory CD8(+) T-cells, which has also been observed in patients with AIDS and tuberculosis, is associated with disease severity and progression. A lower frequency of B1a-cells was also observed in the group of children with ulcer. Conversely, no difference between infected adults with and without ulcer was observed, but the percentage of CD4(+)/HLA-DR(+) cells was lower in adults with ulcer, suggesting that a down-regulated immune response may play a role in the development of duodenal ulcer in adults. Gastric inflammation correlated positively with CD4(+) and chronically activated CD4(+) T-cells in children and adults without duodenal ulcer, respectively. These results suggest that there are differences in the immunophenotyping profile between H. pylori-positive children and adults with duodenal ulcer, indicating the possibility of distinct immune mechanisms in the development of the disease according to age.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Úlcera Duodenal/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Adolescente , Adulto , Fatores Etários , Idoso , Linfócitos B/imunologia , Criança , Úlcera Duodenal/sangue , Feminino , Antígenos HLA-DR/imunologia , Infecções por Helicobacter/microbiologia , Humanos , Imunofenotipagem/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Subpopulações de Linfócitos T/imunologiaRESUMO
Helicobacter pylori infection is highly prevalent in Chile (73%). Usually a minority of infected patients develops complications such as ulcers and gastric cancer that have been associated with the presence of virulence factors (cagA, vacA) and host T helper response (Th1/Th2). Our aim was to evaluate the relationship between strain virulence and host immune response, using a multiple regression approach for the development of a model based on data collected from H. pylori infected patients in Chile. We analyzed levels of selected cytokines determined by ELISA (interleukin (IL)-12, IL-10, interferon (IFN)-gamma and IL-4) and the presence of cagA and vacA alleles polymorphisms determined by PCR in antral biopsies of 41 patients referred to endoscopy. By multiple regression analysis we established a correlation between bacterial and host factors using clinical outcome (gastritis and duodenal ulcer) as dependent variables. The selected model was described by: clinical outcome=0.867491 (cagA)+0.0131847 (IL-12/IL-10)+0.0103503 (IFN-gamma/IL-4) and it was able to explain over 90% of clinical outcomes observations (R(2)=96.4). This model considers that clinical outcomes are better explained by the interaction of host immune factors and strain virulence as a complex and interdependent mechanism.
Assuntos
Citocinas/imunologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/virologia , Helicobacter pylori/imunologia , Helicobacter pylori/patogenicidade , Fatores de Virulência/genética , Adolescente , Adulto , Alelos , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Criança , Pré-Escolar , Úlcera Duodenal/imunologia , Úlcera Duodenal/virologia , Feminino , Gastrite/imunologia , Gastrite/virologia , Helicobacter pylori/genética , Humanos , Masculino , Pessoa de Meia-Idade , Células Th1/imunologia , Células Th2/imunologiaRESUMO
Background: Measurement of changes in serum antibodies is an excellent predictor of Helicobacter pylori eradication after antibiotic treatment. Aim: To measure the changes in serum antibody titers to Helicobacter pylori, before and after treatment. Material and methods: IgG antibodies to H. pylori were prospectively evaluated in 107 duodenal ulcer patients treated either with antibiotics (amoxicillin, metronidazole and bismuth subsalicylate) plus omeprazole or omeprazole alone. IgG antibody levels were determined using an "in house" ELISA in sera from 49 eradicated patients that received quadruple therapy and 58 non-eradicated patients (12 in whom antibiotic therapy failed and 46 that received omeprazole alone). Endoscopy, urease test, microscopy, and culture of gastric biopsies confirmed H. pylori eradication. Results: Patients in whom H. pylori was eradicated, showed a maintained drop in serum antibody titers that ranged from 15 percent, 62 percent, 74 percent to 76 percent at 28 days, 4, 8 and 12 months respectively. Such reduction was not observed in patients treated with omeprazole. Patients, in whom quadruple therapy failed to eradicate H. pylori, showed a discrete and transient decrease in antibody titers. By the fourth month, patients in whom eradication with quadruple therapy was not achieved, irrespective of whether they received quadruple therapy or omeprazole alone. Conclusions: A 45 percent decrease in IgG titer after 4 months is indicative of therapeutic success in H. pylori eradication. Therefore, serology may be useful to monitor the outcome of antibiotic therapy
Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Imunoglobulina G/metabolismo , Helicobacter pylori/efeitos dos fármacos , Úlcera Duodenal/tratamento farmacológico , Imunoglobulina G/sangue , Ensaio de Imunoadsorção Enzimática , Estudos Prospectivos , Helicobacter pylori/imunologia , Resultado do Tratamento , Antibacterianos/uso terapêutico , Úlcera Duodenal/etiologia , Úlcera Duodenal/imunologiaRESUMO
Several studies have demonstrated that enzyme-linked immunosorbent assay is not a sensitive and specific method to diagnose Helicobacter pylori infection in children, especially in the younger ones. Since serum immune response can also be determined by immunoblotting and it permits the detection of antibodies to virulence factors such as CagA and VacA, we evaluated the accuracy of a commercial immunoblotting test to diagnose H. pylori infection and to assess the humoral immune response to different H. pylori antigens in 122 children who underwent upper gastrointestinal endoscopy. The presence of H. pylori was determined in antral biopsy specimens by culture, preformed urease test, and histological analysis. H. pylori was identified by microbiological and histopathological methods in 66 children (including all of the 21 who had duodenal ulcer). Antibodies to H. pylori were detected in 63 infected children and in 8 noninfected ones. The sensitivity, specificity, and positive and negative predictive values of the immunoblotting test were 95.5, 85.7, 88.7, and 94.1%, respectively. The number of immunoreactive bands increased with age (P = 0.003), and the bands of 35 kDa (P = 0.013); 89 kDa, the VacA antigen (P = 0.001); and 116 kDa, the CagA antigen (P = 0.00004) were more frequently observed in older children. The frequency of the bands of 89 kDa (P = 0.001) and 116 kDa (P = 0.03) was higher in children with duodenal ulcer than in H. pylori-positive children without the disease. In conclusion, the immunoblotting test appears to be useful for the diagnosis of H. pylori infection in children, even in the younger ones.
Assuntos
Anticorpos Antibacterianos/sangue , Úlcera Duodenal/imunologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/imunologia , Helicobacter pylori , Adolescente , Formação de Anticorpos , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Criança , Pré-Escolar , Úlcera Duodenal/complicações , Ensaio de Imunoadsorção Enzimática , Feminino , Infecções por Helicobacter/complicações , Helicobacter pylori/imunologia , Helicobacter pylori/patogenicidade , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , VirulênciaRESUMO
We have previously cloned 10 Helicobacter pylori antigen genes from a Chilean strain including: cytotoxin VacA, a truncated region of CagA (called A17), a species-specific protein (Ag26), urease subunits (UreA, UreB), a flagellin, (FlaB), heat shock proteins (HspA and HspB), an adhesin (HpaA) and a lipoprotein (Lpp20). Immunogenicity of these antigens was tested by immunoblot with sera of Chilean infected patients, revealing that HpaA, A17, HspB and VacA were more frequently recognized (86%, 82%, 68% and 68%, respectively). According to the clinical condition, it was determined that Lpp20 was preferentially recognized by sera from non-ulcer dyspepsia patients (80%), A17 and VacA by patients with duodenal ulcer (92% and 83% respectively), and HspB by patients with duodenal ulcer (83%) and gastric cancer (90%). An ELISA was developed with a purified mixture of A17 and VacA antigens to test the different groups of patients. It was found that sera from duodenal ulcer patients showed higher values than those from non-ulcer dyspepsia patients, but this difference was not significant (p<0.2). Moreover, sera from gastric cancer patients showed values lower than those from non-ulcer dyspepsia patients (p<0.019). These results indicate that, in the Chilean population, antibodies raised against VacA and A 7 are not markers either for duodenal ulcer or for gastric cancer.
Assuntos
Anticorpos Antibacterianos/sangue , Antígenos de Bactérias , Úlcera Duodenal/imunologia , Dispepsia/imunologia , Helicobacter pylori/imunologia , Neoplasias Gástricas/imunologia , Adulto , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Biomarcadores , Estudos de Casos e Controles , Chile , Úlcera Duodenal/complicações , Dispepsia/complicações , Ensaio de Imunoadsorção Enzimática , Escherichia coli/genética , Genes Bacterianos , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/imunologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Helicobacter pylori/genética , Humanos , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Neoplasias Gástricas/complicaçõesRESUMO
Duodenal ulcer is a multifactorial entity where a genetic predisposition and extrinsic elements seem to concur in its origin. A series of genetic and extrinsic markers were determined in 50 patients with duodenal ulcer and 50 controls matched by age, sex and socioeconomical status. HLA antigens dit not have significant differences. Blood group O Rh+ was predominant (p < 0.01). Secretor status of antigen HBO in saliva was positive in 70% of patients (p < 0.001). Serum Pepsinogen I was increased in 85% of cases (p < 0.001). Immunoglobulin G anti H. pylori was positive in 62% of ulcerous (p < 0.001). The highest sensibility and negative predictive value was represented by increased serum pepsinogen levels (85%); the highest specificity and positive predictive value was to Ig G anti H. pylori (90 and 86%). These results affirm the polygenic character of the duodenal ulcer disease.
Assuntos
Úlcera Duodenal/genética , Sistema ABO de Grupos Sanguíneos/genética , Sistema ABO de Grupos Sanguíneos/imunologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Úlcera Duodenal/sangue , Úlcera Duodenal/imunologia , Úlcera Duodenal/microbiologia , Feminino , Antígenos HLA/genética , Antígenos HLA/imunologia , Helicobacter pylori/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Pepsinogênios/sangue , Sistema do Grupo Sanguíneo Rh-Hr/genética , Sistema do Grupo Sanguíneo Rh-Hr/imunologia , Sensibilidade e EspecificidadeRESUMO
The objective of this study was to evaluate the accuracy of an indirect immunofluorescence (IIF) test for serodiagnosis of Helicobacter pylori infection in children and to determine how the test is affected by the presence of antibodies against Campylobacter jejuni. We studied 65 consecutive children (two with endoscopically confirmed duodenal ulcer) and a series of 18 children with duodenal ulcer. Thirty children were H. pylori negative, as determined by culture, by the preformed urease test, and by carbolfuchsin-stained smears. The microorganism was identified by microbiological methods in 35 of the 65 (53.85%) consecutive patients studied and in all children with duodenal ulcer. The titer of the IIF test was > or = 1:20 in the sera of all children with duodenal ulcer and in the sera of 30 of 33 H. pylori-positive children without duodenal ulcer. No H. pylori-negative children had titers > 1:10. A serum dilution of 1:20 discriminated between H. pylori-infected and noninfected children. Absorption with C. jejuni did not change the levels of IgG against H. pylori. When five patients who had been successfully treated with metronidazole, amoxycillin, and furazolidone for 7 days were retested, a slight decrease in anti-H. pylori IgG levels was noted from the third month on. The decrease was more significant 9 months after the eradication of the microorganism.
Assuntos
Úlcera Duodenal/microbiologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Adolescente , Antibacterianos/uso terapêutico , Anticorpos Antibacterianos/sangue , Campylobacter jejuni/imunologia , Criança , Pré-Escolar , Úlcera Duodenal/sangue , Úlcera Duodenal/tratamento farmacológico , Úlcera Duodenal/imunologia , Imunofluorescência , Infecções por Helicobacter/sangue , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Humanos , Imunoglobulina G/sangue , Lactente , Masculino , Sensibilidade e EspecificidadeRESUMO
1. The accuracy of an indirect immunofluorescence (IIF) test for the serodiagnosis of Helicobacter pylori infection was evaluated in adult patients and compared with culture, preformed urease test and smears stained with carbolfuchsin. 2. We studied 80 consecutive patients submitted to gastroduodenoscopy (17 of whom were found to have duodenal ulcer) plus 57 patients with duodenal ulcer. 3. H. pylori was identified by microbiological methods in 65 of the 80 consecutive patients and in all 57 patients with duodenal ulcer. 4. Among the 74 patients with duodenal ulcer, 71 presented antibody titers > or = 1:20 and 46 of the 48 H. pylori-positive patients without duodenal ulcer presented antibody titers > or = 1:20. 5. Thirteen of the 15 H. pylori-negative patients presented antibody titers < or = 1:10. 6. The sensitivity, specificity and positive predictive value of the IIF test were 95.9%, 88.8% and 98.4%, respectively. 7. The seroprevalence of H. pylori in 380 asymptomatic Brazilian blood donors was also studied by the IIF test. The presence of IgG antibodies against H. pylori was observed in 62.1% of the individuals. The prevalence of H. pylori infection increased with age and no difference was observed between males (60.3%) and females (66.6%).