RESUMO
OBJECTIVES: Helicobacter pylori (H. pylori)-a gastric bacteria affecting almost 50% of the global population and leading to ulcers and cancer in severe cases-is a growing health concern among Indigenous populations who report a high burden of reported poor general health and gastrointestinal distress. We test hypothesized associations between H. pylori exposure patterns and environmental, social, and biological conditions among a sample of 212 Indigenous Awajún adults (112 males, 100 females, ages 18-65 years) living in the northern Peruvian Amazon. MATERIALS AND METHODS: Dried blood spots were analyzed for H. pylori-specific IgG using a recently developed enzyme-linked immunosorbent assay. Resulting seropositivity rates and antibody concentrations, proxying past exposures to H. pylori were analyzed in relation to relevant environmental (toilet type, floor material, reported water quality), social (household size and education level), and biological (age, sex, BMI, blood pressure, immune and metabolic biomarkers) factors using multivariable regression analyses. RESULTS: We found near ubiquitous seropositivity for H. pylori exposure in our sample (99.1% seropositive). In the regression analyses, elevations in H. pylori antibody concentrations were significantly higher among males compared to females (ß = 0.36, p = 0.01). No associations were found with any other factors. DISCUSSION: Anthropological research in the study communities suggests that the male bias in elevations of H. pylori antibody concentrations is related to cultural and biological factors. Future research is needed to further unravel these biocultural dynamics and determine whether elevations in H. pylori antibody concentrations have clinical relevance for gastrointestinal health outcomes in this population.
Assuntos
Infecções por Helicobacter , Helicobacter pylori , Indígenas Sul-Americanos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Anticorpos Antibacterianos/sangue , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Helicobacter pylori/isolamento & purificação , Imunoglobulina G/sangue , Indígenas Sul-Americanos/estatística & dados numéricos , Peru/epidemiologia , PrevalênciaRESUMO
Helicobacter pylori (H. pylori) infection is highly prevalent, affecting 4.4 billion people globally. This pathogen is a risk factor in the pathogenesis of more than 75% of worldwide cases of gastric cancer. Pattern recognition receptors are essential in the innate immune response to H. pylori infection. They recognize conserved pathogen structures and myriad alarmins released by host cells in response to microbial components, cytokines or cellular stress, thus triggering a robust proinflammatory response, which is crucial in H. pylori-induced gastric carcinogenesis. In this review, we intend to highlight the main pattern recognition receptors involved in the recognition and host response to H. pylori, as well as the main structures recognized and the subsequent inflammatory response.
Assuntos
Infecções por Helicobacter , Receptores de Reconhecimento de Padrão , Infecções por Helicobacter/imunologia , Helicobacter pylori , Humanos , Receptores de Reconhecimento de Padrão/imunologiaRESUMO
Helicobacter pylori is a Gram-negative bacterium found on the luminal surface of the gastric mucosa in at least 50% of the world's human population. The protective effect of breastfeeding against H. pylori infection has been extensively reported; however, the mechanisms behind this protection remain poorly understood. Human IgA from colostrum has reactivity against H. pylori antigens. Despite that IgA1 and IgA2 display structural and functional differences, their reactivity against H. pylori had not been previously determined. We attested titers and reactivity of human colostrum-IgA subclasses by ELISA, immunoblot, and flow cytometry. Colostrum samples from healthy mothers had higher titers of IgA; and IgA1 mostly recognized H. pylori antigens. Moreover, we found a correlation between IgA1 reactivity and their neutralizing effect determined by inhibition of cytoskeletal changes in AGS cells infected with H. pylori. In conclusion, colostrum-IgA reduces H. pylori infection of epithelial gastric cells, suggesting an important role in preventing the bacteria establishment during the first months of life. As a whole, these results suggest that IgA1 from human colostrum provides protection that may help in the development of the mucosal immune system of newborn children.
Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Colostro/imunologia , Helicobacter pylori/imunologia , Imunoglobulina A Secretora/imunologia , Citoesqueleto , Células Epiteliais , Feminino , Mucosa Gástrica/imunologia , Infecções por Helicobacter/imunologia , Humanos , GravidezRESUMO
INTRODUCTION: Inflammation associated with Helicobacter pylori (H. pylori) infection is linked to the development of a gastric precancerous lesion. Helminth infections could influence the pro-inflam matory response to such infection from LTCD4+ Th1 to a less harmful LTCD4+ Th2 response. Ob jective: To characterize the polarization of the LTCD4+ Th2 immune response in co-infected pa tients with H. pylori and helminths from low-risk areas for developing gastric cancer. PATIENTS AND METHOD: We analyzed 63 patients infected by H. pylori (40 adults and 23 children). Through the Multiplex Analysis technology (xMAP), we determined the serum profiles of the interleukins asso ciated with the polarization of the immune response of LTCD4+ Th1 (IL-1Β, INF-γ, TNF-α) as well as the LTCD4+ Th2 (IL-4, IL-10, and IL-13). The ratio between helminths co-infection status in H. pylori-infected patients and the polarization of the immune response mediated by LTCD4+ Th1 and LTCD4+ Th2 was assessed using a Mixed Effects Logistic Regression Model. RESULTS: The frequency of helminths was similar between adults (15%) and children (17%). The polarization of the immu ne response was more prevalent in LTCD4+ Th1. Serum values of interleukins associated with the immune response polarization of LTCD4+ Th1 (IL-1Β, INF-γ, and TNF-α) and LTCD4+ Th2 (IL-4, IL-10, and IL-13) were independent of helminths infection status. CONCLUSION: The prevalence of in testinal parasitic infection was high and the immune response polarization was mainly LTCD4 + Th1.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Coinfecção/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Helmintíase/imunologia , Equilíbrio Th1-Th2 , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Linfócitos T CD4-Positivos/metabolismo , Criança , Pré-Escolar , Coinfecção/sangue , Coinfecção/diagnóstico , Coinfecção/patologia , Feminino , Infecções por Helicobacter/sangue , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/patologia , Helmintíase/sangue , Helmintíase/diagnóstico , Helmintíase/patologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-IdadeRESUMO
Resumen: Introducción: La inflamación asociada con la infección por Helicobacter pylori (H. pylori) se relaciona con la pro gresión de las lesiones precancerosas gástricas. Las infecciones por helmintos podrían modular la respuesta proinflamatoria a la infección por H. pylori desde un perfil tipo LTCD4+ Th1 hacia una respuesta menos perjudicial tipo LTCD4+ Th2. Objetivo: Caracterizar la polarización de la respuesta inmune tipo LTCD4+ Th1/Th2 de pacientes coinfectados por H. pylori y helmintiasis procedentes de áreas de bajo riego para el desarrollo de cáncer gástrico. Pacientes y Método: Se analizaron 63 pacientes, 40 adultos y 23 niños infectados con H. pylori. La determinación de los perfiles séricos de las interleucinas asociadas con la polarización de la respuesta inmune tipo LTCD4+ Th1 (IL-1Β, INF-γ y TNF-α) y tipo LTCD4+ Th2 (IL-4, IL-10 e IL-13) se realizó con Análisis Multiplex (xMAP). La relación entre el estado de coinfección por helmintos en pacientes infectados con H. pylori y la polarización de la respuesta inmune mediada por LTCD4+ Th1 y LTCD4+ Th2, se estudió con un modelo de regresión logístico de efectos mixtos. Resultados: La frecuencia de helmintos fue similar en adultos (15%) y niños (17%). La polarización de la respuesta inmune fue más prevalente hacia el tipo LTCD4+ Th1. Los valores séricos de las interleucinas asociadas con la polarización de la respuesta inmune tipo LTCD4+ Th1 (IL-1 Β, INF-γ y TNF-α) y tipo LTCD4+ Th2 (IL-4, IL-10 e IL-13) fueron independientes del estado de infestación por helmintos. Conclusión: La prevalencia de infección por parasitismo intestinal fue alta y la polarización de la respuesta inmune fue predominantemente hacia un perfil tipo LTCD4 + Th1.
Abstract: Introduction: Inflammation associated with Helicobacter pylori (H. pylori) infection is linked to the development of a gastric precancerous lesion. Helminth infections could influence the pro-inflam matory response to such infection from LTCD4+ Th1 to a less harmful LTCD4+ Th2 response. Ob jective: To characterize the polarization of the LTCD4+ Th2 immune response in co-infected pa tients with H. pylori and helminths from low-risk areas for developing gastric cancer. Patients and Method: We analyzed 63 patients infected by H. pylori (40 adults and 23 children). Through the Multiplex Analysis technology (xMAP), we determined the serum profiles of the interleukins asso ciated with the polarization of the immune response of LTCD4+ Th1 (IL-1Β, INF-γ, TNF-α) as well as the LTCD4+ Th2 (IL-4, IL-10, and IL-13). The ratio between helminths co-infection status in H. pylori-infected patients and the polarization of the immune response mediated by LTCD4+ Th1 and LTCD4+ Th2 was assessed using a Mixed Effects Logistic Regression Model. Results: The frequency of helminths was similar between adults (15%) and children (17%). The polarization of the immu ne response was more prevalent in LTCD4+ Th1. Serum values of interleukins associated with the immune response polarization of LTCD4+ Th1 (IL-1Β, INF-γ, and TNF-α) and LTCD4+ Th2 (IL-4, IL-10, and IL-13) were independent of helminths infection status. Conclusion: The prevalence of in testinal parasitic infection was high and the immune response polarization was mainly LTCD4 + Th1.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Linfócitos T CD4-Positivos/imunologia , Helicobacter pylori/imunologia , Infecções por Helicobacter/imunologia , Equilíbrio Th1-Th2 , Coinfecção/imunologia , Helmintíase/imunologia , Biomarcadores/sangue , Linfócitos T CD4-Positivos/metabolismo , Modelos Logísticos , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/patologia , Infecções por Helicobacter/sangue , Coinfecção/diagnóstico , Coinfecção/patologia , Coinfecção/sangue , Helmintíase/diagnóstico , Helmintíase/patologia , Helmintíase/sangueRESUMO
INTRODUCTION: HP causes local inflammation in the stomach and a systemic humoral immune response. No relationship was found in adult studies investigating the association between HP infection and neutrophil/lymphocyte ratio (NLR) and mean platelet volume (MPV). To our knowledge, there is no study in children. We aimed to evaluate the association between NLR and MPV values with HP infection, severity classification, and pre- and post-treatment status. POPULATION AND METHODS: Patients with dyspepsia aged between 2-18 years and without any chronic diseases undergoing gastroduodenoscopy were included in the study. Endoscopic mucosal biopsy was performed, HP presence and infection severity were determined according to Sydney Classification. RESULTS: 153 patients with HP positivity and 211 patients with HP negativity were included in the study, the mean age of them was 13.3 ± 3.4 years and 13.1 ± 3.5 years, respectively. No statistically significant difference was found between patients with HP positive and negative patients and also between severity subgroups of HP positive patients in terms of NLR and MPV (p > 0.05). CONCLUSIONS: There was no association between NLR and MPV values with HP infection, severity classification, or pre- and post-treatment status.
Introducción: El Helicobacter pylori (HP) causa inflamación local en el estómago y una respuesta inmunitaria humoral sistémica. En los estudios que investigaron la asociación entre la infección por HP y el índice de neutrófilos/linfocitos (INL) y el volumen plaquetario medio (VPM) en adultos, no se observó ninguna relación. Hasta donde sabemos, no se hicieron estudios en niños. Nuestro objetivo fue evaluar la asociación entre los valores de INL y VPM y la infección por HP, la clasificación de la gravedad y el estado antes y después del tratamiento. Población y métodos: En el estudio se incluyeron pacientes de 2 a 18 años de edad con dispepsia y sin enfermedades crónicas sometidos a una endoscopía alta. Se hizo una biopsia endoscópica de la mucosa y se determinaron la presencia de HP y la gravedad de la infección según la clasificación de Sídney. Resultados: Se incluyeron en el estudio 153 pacientes con HP y 211 sin HP; la media de edad fue de 13,3 ± 3,4 años y 13,1 ± 3,5 años, respectivamente. No se observaron diferencias estadísticamente significativas entre los pacientes con y sin HP ni tampoco entre los subgrupos de pacientes con HP según la gravedad en relación con el INL y el VPM (p > 0,05). Conclusiones: No se observó una asociación entre los valores de INL y VPM y la infección por HP, la clasificación de la gravedad ni el estado antes y después del tratamiento.
Assuntos
Plaquetas/metabolismo , Infecções por Helicobacter/diagnóstico , Helicobacter pylori , Linfócitos/metabolismo , Neutrófilos/metabolismo , Índice de Gravidade de Doença , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Estudos Transversais , Duodenoscopia , Feminino , Gastroscopia , Infecções por Helicobacter/sangue , Infecções por Helicobacter/imunologia , Helicobacter pylori/isolamento & purificação , Humanos , MasculinoRESUMO
O objetivo deste trabalho foi relacionar os achados anatomopatológicos das lesões gástricas subclínicas de ocorrência natural em leitões com a presença, ou não, de Helicobacter spp. por meio da imuno-histoquímica. Foram utilizados 48 leitões de linhagem genética comercial. Os animais foram adquiridos em uma granja comercial, com peso médio de 34 Kg e idade média de 79 dias; após o abate, seus estômagos foram coletados e avaliados. Avaliações histopatológicas e imuno-histoquímicas foram realizadas em amostras das regiões anatômicas aglandular e glandular. Macroscopicamente, 34 (70,83%) leitões apresentaram lesões na região aglandular, enquanto que em 14 animais (29,17%) não foram encontradas alterações nesta região. Dos estômagos com lesão, 14 foram classificados como grau 1, seis como grau 2 e 14 como grau 3. Microscopicamente, 44 amostras (91,66%) apresentaram paraqueratose. Deste total, 22 apresentaram a forma discreta, 20 a moderada e dois a acentuada. Na avaliação macroscópica da porção glandular, 41 (85,4%) animais apresentaram alteração em pelo menos uma das três regiões, e em somente sete (14,6%) não foram encontradas lesões em nenhuma delas. Em 14 deles, houve aumento da atividade mucípara, em dois, houve erosão e, em cinco, hiperemia. As lesões na região glandular do estômago foram mais extensas no antro e no cárdia, seguidas do fundo. Em relação à análise imuno
The aim of this study was to relate the anatomopathological findings of naturally occurring subclinical gastric lesions in piglets, with or without Helicobacter spp. through immunohistochemistry. Forty-eight piglets of commercial genetic lineage were used. The animals were acquired in a commercial farm, with an average weight of 34 kg and an average age of 79 days, and after slaughter, their stomachs were collected and evaluated. Samples from the glandular and aglandular anatomical regions were evaluated. Macroscopically, 34 (70.83%) samples had lesions on aglandular region, while 14 (29.17%) nothing had. Of the injured stomachs, 14 were classified as grade 1, six as grade 2 and 14 as grade 3. Microscopically, 44 samples (91.66%) showed parakeratosis. Of these, 22 showed a discreet manner, 20 moderate and two severe. In the glandular region, in 41 (85.4%) samples there was a change in at least one of the three regions, and only seven animals (14.6%) showed no change in any of the three. Fourteen samples showed increased muciparous activity, two showed erosion and five hyperemia. The lesions were higher in antral regions and cardic, followed the fundus. In relation to immunohistochemistry, 21(43.8%) samples were negative in all areas, 24 (50%) were positive in at least one, and none were positive in all. The anatomopathological findings showed a statistical relationship with the bacteria, and its immunostaining, not associated with gastric lesions in certain regions, demonstrates its saprophytic and opportunistic character.
Assuntos
Animais , Estômago/microbiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/patologia , Infecções por Helicobacter/veterinária , Suínos/anatomia & histologia , Suínos/imunologia , Suínos/lesões , Úlcera Gástrica/microbiologiaRESUMO
The present study aimed to evaluate the influence of the IL1B -31C/T polymorphism on gastric inflammatory response and precancerous lesions development - atrophic gastritis (AG) and intestinal metaplasia (IM) - in patients positive for Helicobacter pylori infection with functional dyspepsia (FD). The diagnosis of FD followed the Rome III criteria, and the H. pylori infection was evaluated by urease test and histological examination of gastric biopsies (corpus, antrum, and incisura). The severity of chronic inflammation and inflammatory activity, as well as the presence of precancerous lesions were evaluated accordingly to the updated Sydney System. Genotyping of the IL1B -31C/T polymorphism (rs1143627) was performed by polymerase chain reaction-restriction fragment length polymorphism. A total of 303 patients positive for H. pylori infection with FD were analyzed (81.8% women; mean age of 46.3 ± 12.3 years). No differences were observed in overall genotype frequencies among outcomes evaluated. However, in the dominant -31C allele model (CC+CT vs. TT), the frequency of the TT genotype was significantly higher among patients with moderate/severe chronic inflammation of the antrum than the frequency of the CC+CT genotypes (80.8% vs. 65.2%; OR = 2.25; 95% CI = 1.23-4.24; P = .005). The presence of AG and IM in the gastric mucosa of patients was of 19.5% and 19.1%, respectively. No significant association was observed concerning the frequencies of the genotypes of IL1B -31C/T polymorphism with development of precancerous lesions. In conclusion, our data suggest that genetic variants of the IL1B -31C/T polymorphism play a role in chronic inflammation of the gastric mucosa in H. pylori-infected FD patients.
Assuntos
Dispepsia/genética , Gastrite/genética , Genótipo , Infecções por Helicobacter/genética , Helicobacter pylori/fisiologia , Inflamação/genética , Interleucina-1beta/genética , Adulto , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Infecções por Helicobacter/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Lesões Pré-CancerosasRESUMO
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
O objetivo deste trabalho foi relacionar os achados anatomopatológicos das lesões gástricas subclínicas de ocorrência natural em leitões com a presença, ou não, de Helicobacter spp. por meio da imuno-histoquímica. Foram utilizados 48 leitões de linhagem genética comercial. Os animais foram adquiridos em uma granja comercial, com peso médio de 34 Kg e idade média de 79 dias; após o abate, seus estômagos foram coletados e avaliados. Avaliações histopatológicas e imuno-histoquímicas foram realizadas em amostras das regiões anatômicas aglandular e glandular. Macroscopicamente, 34 (70,83%) leitões apresentaram lesões na região aglandular, enquanto que em 14 animais (29,17%) não foram encontradas alterações nesta região. Dos estômagos com lesão, 14 foram classificados como grau 1, seis como grau 2 e 14 como grau 3. Microscopicamente, 44 amostras (91,66%) apresentaram paraqueratose. Deste total, 22 apresentaram a forma discreta, 20 a moderada e dois a acentuada. Na avaliação macroscópica da porção glandular, 41 (85,4%) animais apresentaram alteração em pelo menos uma das três regiões, e em somente sete (14,6%) não foram encontradas lesões em nenhuma delas. Em 14 deles, houve aumento da atividade mucípara, em dois, houve erosão e, em cinco, hiperemia. As lesões na região glandular do estômago foram mais extensas no antro e no cárdia, seguidas do fundo. Em relação à análise imuno(AU)
The aim of this study was to relate the anatomopathological findings of naturally occurring subclinical gastric lesions in piglets, with or without Helicobacter spp. through immunohistochemistry. Forty-eight piglets of commercial genetic lineage were used. The animals were acquired in a commercial farm, with an average weight of 34 kg and an average age of 79 days, and after slaughter, their stomachs were collected and evaluated. Samples from the glandular and aglandular anatomical regions were evaluated. Macroscopically, 34 (70.83%) samples had lesions on aglandular region, while 14 (29.17%) nothing had. Of the injured stomachs, 14 were classified as grade 1, six as grade 2 and 14 as grade 3. Microscopically, 44 samples (91.66%) showed parakeratosis. Of these, 22 showed a discreet manner, 20 moderate and two severe. In the glandular region, in 41 (85.4%) samples there was a change in at least one of the three regions, and only seven animals (14.6%) showed no change in any of the three. Fourteen samples showed increased muciparous activity, two showed erosion and five hyperemia. The lesions were higher in antral regions and cardic, followed the fundus. In relation to immunohistochemistry, 21(43.8%) samples were negative in all areas, 24 (50%) were positive in at least one, and none were positive in all. The anatomopathological findings showed a statistical relationship with the bacteria, and its immunostaining, not associated with gastric lesions in certain regions, demonstrates its saprophytic and opportunistic character.(AU)