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1.
Arch Pathol Lab Med ; 145(2): 191-200, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33501492

RESUMO

CONTEXT.­: Immune checkpoint inhibitor (CPI) therapies are associated with multi-organ immune-related adverse events. Although colonic mucosal changes have been described, inflammatory changes incited by CPIs in the upper gastrointestinal tract have not been well characterized. OBJECTIVE.­: To investigate morphologic and immunologic changes incited by CPI therapy in the upper gastrointestinal tract. DESIGN.­: We compared the morphology and immune cell phenotype of gastric and duodenal biopsies from patients treated with anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) or anti-programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) antibodies with biopsies from patients with Helicobacter pylori gastritis, patients with celiac disease, and normal controls. RESULTS.­: Gastric biopsies from patients on CPIs showed chronic gastritis mimicking H pylori gastritis. However, CPI gastritis demonstrated greater numbers of CD8+ intraepithelial lymphocytes, less lamina propria inflammation, fewer plasma cells and CD20+ B cells, fewer lymphoid aggregates, and reduced CD4:CD8 ratio in both the lamina propria and the epithelial layer. There were no differences between anti-CTLA-4 and anti-PD-1/PD-L1 gastritis, except for more lymphoid aggregates in anti-PD-1/PD-L1 gastritis. Duodenal biopsies from patients on CPIs revealed chronic duodenitis with villous blunting, mimicking celiac disease. Compared with celiac disease, CPI duodenitis demonstrated higher prevalence of neutrophilic infiltrates and erosions, increased lamina propria CD3 and CD8 T cells, and reduced CD4:CD8 ratio. Upper gastrointestinal biopsies were more inflamed than concomitant colonic biopsies in the majority of patients. CONCLUSIONS.­: The morphologic and immunophenotypic distinctions between CPI-associated upper gastrointestinal injuries and common infectious and autoimmune diseases may provide useful discriminators when clinicians are confronted with gastric and duodenal inflammatory changes in patients receiving CPI therapy.


Assuntos
Doença Celíaca/patologia , Gastrite/patologia , Gastroenteropatias/patologia , Infecções por Helicobacter/patologia , Helicobacter pylori/imunologia , Inflamação/patologia , Antígeno B7-H1/antagonistas & inibidores , Biópsia , Antígeno CTLA-4/antagonistas & inibidores , Doença Celíaca/imunologia , Colo/imunologia , Colo/patologia , Duodeno/imunologia , Duodeno/patologia , Mucosa Gástrica/patologia , Gastrite/imunologia , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/imunologia , Infecções por Helicobacter/imunologia , Imunofenotipagem , Inflamação/induzido quimicamente , Inflamação/imunologia , Fenótipo , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estômago/imunologia , Estômago/patologia , Trato Gastrointestinal Superior/imunologia , Trato Gastrointestinal Superior/patologia
2.
3.
PLoS One ; 15(10): e0240040, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33002056

RESUMO

INTRODUCTION: To prevent gastric cancer, it is important to accurately determine the presence of Helicobacter pylori (HP) infection. However, correctly identifying HP-uninfected individuals is difficult when using the combination of HP antibody and pepsinogen (PG). OBJECTIVE: The aim of this study was to discriminate true HP-uninfected individuals from others without the need for endoscopic examination. METHODS: A total of 684 subjects with no history of HP eradication who underwent a medical checkup at our hospital were enrolled. The "true uninfected individuals" were determined by a negative stool antigen test and no endoscopic findings of HP-associated gastritis. HP antibody was measured by the latex immunoassay method. Logistic regression analysis using a combination of noninvasive parameters was performed to develop a formula for predicting true uninfected individuals. RESULTS: A total of 528 subjects were classified as true uninfected individuals. Logistic regression analysis showed that statistically significant factors for true uninfected individuals were age (p < 0.001), HP antibody (p <0.001), PGI (p <0.001), and PGII (p = 0.012). The areas under the curve (AUCs) for true uninfected individuals were the highest (0.944) upon applying the prediction formula including four parameters: age, HP antibody, PGI, and PGII. Both the sensitivity and the specificity of the four-parameter prediction formula were higher than those of the traditional three-parameter model using HP antibody, PGI, and PGI/II ratio (sensitivity: 93.2% vs. 86.6% and specificity: 88.5% vs. 82.7%). CONCLUSIONS: Our findings suggest that a model with a combination of four noninvasive parameters is useful for predicting true HP-uninfected individuals without the need for endoscopic examination.


Assuntos
Anticorpos Antibacterianos/sangue , Infecções por Helicobacter/sangue , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/fisiologia , Pepsinogênio A/sangue , Adulto , Fatores Etários , Idoso , Anticorpos Antibacterianos/imunologia , Área Sob a Curva , Feminino , Gastrite/complicações , Infecções por Helicobacter/complicações , Helicobacter pylori/imunologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade
4.
Aliment Pharmacol Ther ; 51(12): 1222-1232, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32372471

RESUMO

BACKGROUND: The initiating events of chronic gastrointestinal (GI) inflammation in Crohn's disease (CD) and ulcerative colitis (UC) are not well-defined, but GI infections are implicated. AIMS: To define the role of GI infections in risk of incident inflammatory bowel disease (IBD) and synthesise the current body of relevant translational data to provide biological context for associations between GI infections and IBD risk. METHODS: We systematically reviewed electronic databases through February 2020. Clinical studies that provided risk estimates of the association between GI infections and incident IBD were included. Inclusion criteria were broader for translational studies aiming to define mechanisms of GI infections and predisposition to or protection from IBD. RESULTS: Of the studies identified, 63 met full inclusion criteria. Among studies of clinical gastroenteritis, bacteria-specifically, Salmonella species, Campylobacter species and Clostridioides difficile-demonstrated consistent positive associations with risk of incident IBD. Of viruses, norovirus was associated with increased risk of incident CD. Regarding inverse associations with incident IBD, Helicobacter pylori and helminth infections were associated with a generally consistent reduced risk of IBD. Based on a qualitative analysis of the translational data, putative mechanisms involve multiple microbial and immunologic pathways. CONCLUSIONS: Based on this systematic review, certain enteric pathogens are associated with an increased risk of incident IBD, while others are potentially protective. Prospective studies are required to clarify the clinical implications of these enteric pathogens on the risk and course of IBD, and possible therapeutic or preventative benefit.


Assuntos
Doenças Transmissíveis/epidemiologia , Gastroenteropatias/epidemiologia , Doenças Inflamatórias Intestinais/epidemiologia , Colite Ulcerativa/epidemiologia , Doenças Transmissíveis/complicações , Doença de Crohn/complicações , Doença de Crohn/epidemiologia , Gastroenteropatias/complicações , Helicobacter pylori/imunologia , Humanos , Incidência , Doenças Inflamatórias Intestinais/etiologia , Estudos Prospectivos , Fatores de Risco
5.
APMIS ; 128(2): 150-161, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32352605

RESUMO

Infection with Helicobacter pylori is associated with the development of gastric cancer. Although the prevalence of gastric cancer has declined throughout years due to improvement in early screening strategy, mortality due to gastric cancer has not changed. Incidence and mortality due to gastric cancer are higher in developing countries as compared to developed countries. Diagnosis and prognosis of gastric cancer are still poor with patients usually diagnosed with cancer at an advanced stage. Eradication of H. pylori is pertinent for the prevention of gastric cancer. However, the rise in antimicrobial resistance among H. pylori isolates has complicated the prevention strategy. H. pylori express multiple virulence factors for survival in the hostile acid gastric environment. The expression of oncogenic protein cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA), and outer inflammatory protein is essential for H. pylori to exert pathogenesis towards the host. Interestingly, <3% of H. pylori-infected subjects develop gastric cancer, suggesting a unique way of interaction between the host's immune response and H. pylori virulence factors. This article is aimed to review the epidemiology and role of H. pylori in gastric carcinogenesis. A better understanding of the interaction between H. pylori virulence factors and host is required for better gastric cancer prevention.


Assuntos
Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/imunologia , Fatores de Virulência/imunologia , Virulência/imunologia , Carcinogênese/imunologia , Humanos , Prognóstico , Neoplasias Gástricas/microbiologia
6.
Immunity ; 52(4): 573-575, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32294401

RESUMO

Little is known about host-microbiota interactions regulating anti-microbial immunity in the stomach. In this issue, Satoh-Takayama et al. describe an additional immune mechanism involving innate lymphoid cells type 2 (ILC2), which controls infection with Helicobacter pylori, a bacterium associated with inflammation and cancer.


Assuntos
Helicobacter pylori , Linfócitos , Helicobacter pylori/imunologia , Imunidade Inata , Imunoglobulina A , Estômago
7.
Am J Trop Med Hyg ; 103(1): 260-265, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32314688

RESUMO

Infection by Helicobacter pylori is a major risk factor for gastric cancer (GC), the second leading cause of cancer-related death worldwide. Although biomarkers such as pepsinogens (PGs) and soluble urokinase plasminogen activator receptor (suPAR) may have diagnostic and/or prognostic value in patients with GC, their levels may be affected by H. pylori infection. The aim of this study was to investigate the association of the presence of antibodies to H. pylori and cytotoxin-associated gene A (CagA) with plasma levels of PGs and suPAR in a cohort of Guatemalan GC patients and controls. To this end, levels of suPAR, Pepsinogens I and II (PGI and PGII), and antibodies to H. pylori and CagA toxin were determined by ELISA in plasma samples from 67 GC patients and 136 matched healthy controls. Seropositivity for CagA was significantly higher in patients with GC than in controls. Pepsinogens II and suPAR levels were higher and PGI/PGII ratios were lower in GC patients than in controls. There was a significant association of H. pylori seropositivity status with increased levels of PGII and lower PGI/PGII ratios, particularly in the control (non-GC) population. The levels of suPAR were not significantly affected by H. pylori or CagA seropositivity status. These results suggest that the seropositivity status for H. pylori and CagA need to be taken into account during the GC diagnostic process.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/imunologia , Pepsinogênio A/sangue , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Neoplasias Gástricas/microbiologia , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Guatemala/epidemiologia , Infecções por Helicobacter/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Neoplasias Gástricas/sangue
8.
BMC Infect Dis ; 20(1): 310, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32334539

RESUMO

BACKGROUND: Investigating distinct individual- and household-level risk factors for acquiring Helicobacter pylori (H. pylori) infection can inform disease prevention efforts and implicate possible routes of transmission. This study determined the magnitude of H. pylori infection among schoolchildren in Ziway, central Ethiopia and identified personal and household correlates of H. pylori infection in young Ethiopian children. METHODS: A total of 434 schoolchildren participated in this cross-sectional study. Infection status was assessed using antigen and antibody rapid tests. Demographic and lifestyle information was obtained from parents via an interviewer-led questionnaire. Univariate and multivariate logistic regressions were performed to assess the relationships between potential individual- and household-level risk factors and H. pylori infection. RESULTS: The prevalence of H. pylori infection was 65.7% (285/434). Of the personal variables assessed, the age group 10-14 years was found to be significantly associated with higher odds of H. pylori infection in univariate analysis (COR = 2.22, 95% CI: 1.06-4.66, p = 0.03) and remained positively correlated after adjusting for confounding factors. Of the household-level factors explored, having a traditional pit or no toilet was found to be significantly associated with 3.93-fold higher odds of H. pylori infection (AOR = 3.93, 95% CI: 1.51-10.3, p = 0.01), while the presence of smokers in the household was associated with 68% lower odds of infection (AOR = 0.32, 95% CI: 0.11-0.89, p = 0.03). CONCLUSION: This study from a developing country provides additional evidence for older age as a personal risk factor for H. pylori infection and identifies correlations between socioeconomic and sanitation household factors and positive childhood infection status. The associations reported here support the hypothesized fecal-oralroute of transmission for H. pylori.


Assuntos
Infecções por Helicobacter/epidemiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Etiópia/epidemiologia , Características da Família , Fezes/microbiologia , Feminino , Infecções por Helicobacter/transmissão , Helicobacter pylori/imunologia , Humanos , Modelos Logísticos , Masculino , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e Questionários
9.
Immunity ; 52(4): 635-649.e4, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32240600

RESUMO

The intestinal microbiota shapes and directs immune development locally and systemically, but little is known about whether commensal microbes in the stomach can impact their immunological microenvironment. Here, we report that group 2 innate lymphoid cells (ILC2s) were the predominant ILC subset in the stomach and show that their homeostasis and effector functions were regulated by local commensal communities. Microbes elicited interleukin-7 (IL-7) and IL-33 production in the stomach, which in turn triggered the propagation and activation of ILC2. Stomach ILC2s were also rapidly induced following infection with Helicobacter pylori. ILC2-derived IL-5 resulted in the production of IgA, which coated stomach bacteria in both specific pathogen-free (SPF) and H. pylori-infected mice. Our study thus identifies ILC2-dependent IgA response that is regulated by the commensal microbiota, which is implicated in stomach protection by eliminating IgA-coated bacteria including pathogenic H. pylori.


Assuntos
Microbioma Gastrointestinal/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/patogenicidade , Imunoglobulina A/biossíntese , Interleucina-5/imunologia , Estômago/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Linhagem da Célula/genética , Linhagem da Célula/imunologia , Feminino , Regulação da Expressão Gênica , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/imunologia , Imunidade Humoral , Imunidade Inata , Interleucina-33/genética , Interleucina-33/imunologia , Interleucina-5/genética , Interleucina-7/genética , Interleucina-7/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Cultura Primária de Células , Transdução de Sinais , Estômago/microbiologia , Simbiose/imunologia , Subpopulações de Linfócitos T/classificação
10.
Intern Med ; 59(12): 1473-1480, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32188803

RESUMO

Objective The aim of the present study was to evaluate the effectiveness and limitations of a serum screening system for predicting the risk of gastric cancer. Methods Serum pepsinogen I (PG I)/pepsinogen II (PG II) and Helicobacter pylori (HP) antibody levels were measured. Subjects were classified into four groupsaccording to their serological status (the ABC classification system). The grade of atrophic gastritis was assessed endoscopically. We evaluated gastric cancer detection rates according to the ABC classification system and the endoscopic grade of atrophy. Patients Individuals who underwent esophagogastroduodenoscopy (EGD) in a health check were prospectively enrolled in the present study. Results According to the ABC classification system, the gastric cancer detection rates in groups A, B, C, and D were 0.07% (4/6,105), 0.5% (8/1,739), 0.8% (16/2,010), and 1.1% (3/281), respectively. The gastric cancer detection rates in subjects with no atrophy, closed type (C-type) atrophy, and open type (O-type) atrophy were 0% (0/4,567), 0.2% (4/2,581), and 0.9% (27/2,987), respectively. In group A (HP(-)/PG(-)), the proportions of subjects with no atrophy, C-type atrophy, and O-type atrophy were 71.2%, 22.8%, and 6.0%, respectively. In group A, the gastric cancer detection rates in subjects with no atrophy, C-type atrophy, and O-type atrophy were 0%, 0.07%, and 0.8%, respectively. Conclusion The ABC classification system is useful for predicting the risk of gastric cancer. However, this system was limited in group A, which included individuals with a high risk of developing gastric cancer. An endoscopic diagnosis of atrophy may be more effective than the ABC classification system for predicting the risk of gastric cancer.


Assuntos
Helicobacter pylori/imunologia , Pepsinogênio A/sangue , Pepsinogênio C/sangue , Neoplasias Gástricas/sangue , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Biomarcadores Tumorais , Detecção Precoce de Câncer , Endoscopia do Sistema Digestório , Feminino , Gastrite Atrófica/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Pepsinogênio A/imunologia , Pepsinogênio C/imunologia , Estudos Prospectivos , Risco Ajustado , Neoplasias Gástricas/patologia , Adulto Jovem
11.
Comp Immunol Microbiol Infect Dis ; 70: 101449, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32126431

RESUMO

Abdominal aortic aneurysm (AAA) is a degenerative inflammatory disease with unknown etiology. AAA is characterized by abdominal aortic dilatation more than 3 cm and is often asymptomatic, but the rupture of aneurysm can lead to death. Age, smoking and male sex are major predisposing factors of AAA. This study compares the effect of Helicobacter (H.) pylori and Lactobacillus (L.) acidophilus on the cytokine profile of PBMCs of 5 men with abdominal aortic aneurysm (AAA) and 5 men with normal/insignificant angiography, CT-Scan and ultrasonography results in the single-culture and in the co-culture with HUVECs. IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17 F, IL-21, IL-22, IFN-γ and TNF-α were measured in culture supernatants using a commercial fluorescent-labeled-bead assay. In general, CagA+ H. pylori-extract induced higher production of IFN-γ, IL-13 and IL-21 by PBMCs. Treatment of patients' PBMCs with CagA+H. pylori-extract induced Th2 cytokines while treatment of controls' PBMCs with CagA+H. pylori-extract increased Th1 cytokines. In the co-culture, however, patients' PBMCs produced Th1 cytokines irrespective of extract treatment, while controls' PBMCs produced Th2 cytokines and decreased IL-10. CagA+ H. pylori- as well as L. acidophilus-extract induced higher levels of IL-9 by controls' PBMCs in co-culture with HUVECs than patients (P = 0.05 and P = 0.01). The cytokine pattern of PBMCs induced by CagA+ H. pylori- and L. acidophilus-extracts in the co-culture with HUVECs shows differences in AAA patients and in comparison to controls. Decreased secretion of IL-9, IL-21 and IL-22 by PBMCs of patients treated with CagA+ H. pylori extract in co-culture, as opposed to non-AAA controls may indicate the active role ECs play in AAA. Simultaneous production of IL-10 and Th1 cytokines in patients and pronounced Th2 cytokines in controls in response to both bacteria may point to the inherent differences between patients and controls, which need further investigation.


Assuntos
Aneurisma da Aorta Abdominal/imunologia , Proteínas de Bactérias/farmacologia , Citocinas/imunologia , Helicobacter pylori/imunologia , Lactobacillus acidophilus/imunologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Idoso , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/farmacologia , Proteínas de Bactérias/imunologia , Técnicas de Cocultura , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Pessoa de Meia-Idade , Células Th1/imunologia , Células Th2/imunologia
12.
Helicobacter ; 25(3): e12687, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32147867

RESUMO

BACKGROUND: Helicobacter pylori prevalence varies greatly worldwide. We explored the prevalence of H. pylori and CagA seropositivity among adults aged 18-44 years living in the Netherlands by ethnicity and migration status (first vs second generation). MATERIALS AND METHODS: Participants from six different ethnic groups were selected from the population-based multi-ethnic HELIUS study in Amsterdam, the Netherlands. Serum samples were tested for H. pylori antigens using a validated Luminex-based multiplex serology assay. Prevalence ratios were estimated using Poisson regression analysis. RESULTS: A total of 4683 participants aged 18-44 years were randomly selected based on sex, ethnicity, and age. H. pylori seroprevalence was highest in the Ghanaian group (84%), followed by Moroccan (81%), Turkish (66%), African Surinamese (51%), South-Asian Surinamese (48%), and Dutch (17%) participants. All ethnic minority groups had a significantly higher risk of being H. pylori seropositive compared to the Dutch group. This association was strongest among participants born outside the Netherlands (first generation), but was still significant and apparent among second-generation participants. Among first-generation participants, all groups, except the Moroccans, had a significantly higher proportion of individuals with a cagA + H. pylori strain compared to the Dutch participants. CONCLUSION: Helicobacter pylori seroprevalence among first-generation migrants is high in the Netherlands and remains elevated among second-generation migrants (ie, those born in the Netherlands). High exposure to H. pylori, and especially to the more virulent cagA+ strain, highlights the need for tailored prevention of gastric diseases (notably peptic ulcers and cancers) among migrants.


Assuntos
Grupos Étnicos/estatística & dados numéricos , Infecções por Helicobacter/epidemiologia , Estudos Soroepidemiológicos , Adolescente , Adulto , Antígenos de Bactérias/sangue , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/sangue , Proteínas de Bactérias/imunologia , Feminino , Helicobacter pylori/imunologia , Humanos , Masculino , Países Baixos/epidemiologia , Prevalência , Adulto Jovem
13.
Am J Clin Pathol ; 153(5): 686-694, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32145011

RESUMO

OBJECTIVES: Helicobacter pylori stool antigen test (HpSAT) appropriateness was investigated by assessing its testing and positivity rates in Calgary, Canada. METHODS: The laboratory information system was accessed for all patients who received an HpSAT in 2018. Testing volume, test results, age, and sex of patients were collected. Sociodemographic risk factors and geospatial analysis were performed by matching laboratory data to the 2016 census data. Testing appropriateness was defined as a concordance between testing and positivity rates for each sociodemographic variable. RESULTS: In 2018, 25,518 H pylori stool antigen tests were performed in Calgary, with an overall positivity rate of 14.7%. Geospatial mapping demonstrated significant distribution variations of testing and positivity rates of HpSAT in the city. Certain sociodemographic groups studied (eg, recent immigrants) appeared to be appropriately tested (testing rate relative risk [RR] = 2.26, positivity rate RR = 4.32; P < .0001), while other groups (eg, male) may have been undertested (testing rate RR = 0.85, positivity rate RR = 1.14; P < .0001). CONCLUSIONS: Determining concordance of testing and positivity rate of a laboratory test can be used for assessing testing appropriateness for other diseases in other jurisdictions. This study demonstrated some at-risk patients may be missed for H pylori testing.


Assuntos
Antígenos de Bactérias/análise , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/imunologia , Adolescente , Adulto , Idoso , Canadá , Criança , Pré-Escolar , Feminino , Infecções por Helicobacter/imunologia , Humanos , Técnicas Imunoenzimáticas , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
14.
Cancer Causes Control ; 31(6): 601-606, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32222845

RESUMO

PURPOSE: Helicobacter pylori (H. pylori) is the leading cause of gastric cancer. High antibody levels to H. pylori virulence factors Vacuolating cytotoxin A (VacA) and Cytotoxin-associated gene A (CagA) have been suggested as gastric cancer risk markers. In the USA, H. pylori sero-prevalence is twofold higher in African Americans compared to whites. We sought to assess whether African Americans also exhibit higher antibody levels to VacA and CagA. METHODS: Antibody responses to H. pylori proteins were measured by multiplex serology in 686 African Americans and whites of the Southern Community Cohort Study. Among VacA- and CagA-seropositives, we analyzed the association of race with antibody level using logistic regression models to produce odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Sero-positive African Americans had significantly higher mean antibody levels to both VacA and CagA, which resulted in increased odds for the highest quartile of antibody levels compared to sero-positive whites (VacA, OR: 6.08; 95% CI 3.41, 10.86; CagA, OR: 3.77; 95% CI 1.61, 8.84). CONCLUSION: Our findings support future studies to assess the association of differential antibody responses by race with risk of gastric cancer in the USA, which could then aid in developing targeted H. pylori eradication strategies.


Assuntos
Afro-Americanos/estatística & dados numéricos , Anticorpos Antibacterianos , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Helicobacter pylori , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Helicobacter pylori/patogenicidade , Humanos , Estudos Soroepidemiológicos , Sudeste dos Estados Unidos , Fatores de Virulência/imunologia
15.
J Immunol ; 204(6): 1421-1428, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32152211

RESUMO

The goal of this Brief Review is to highlight literature that demonstrates how cytokines made by T lymphocytes impact the gastric epithelium, especially during Helicobacter pylori infection. These cytokines effect many of the diverse functions of the epithelium and the epithelium's interactions with H. pylori The focal point of this Brief Review will be on how T cell cytokines impact antimicrobial function and barrier function and how T cell cytokines influence the development and progression of cancer. Furthermore, the modulation of epithelial-derived chemokines by H. pylori infection will be discussed.


Assuntos
Citocinas/metabolismo , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Neoplasias Gástricas/imunologia , Linfócitos T/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Antígenos de Bactérias/imunologia , Modelos Animais de Doenças , Progressão da Doença , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Mucosa Gástrica/citologia , Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Humanos , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia , Linfócitos T/metabolismo
16.
Gastroenterol. hepatol. (Ed. impr.) ; 43(3): 117-125, mar. 2020. tab
Artigo em Inglês | IBECS | ID: ibc-190784

RESUMO

BACKGROUND: At present only monoclonal EIA (enzyme-immunoassay) stool antigen-tests have obtained optimal accuracy in the diagnosis of Helicobacter pylori. Our aim was to evaluate the accuracy of two stool antigen-tests, the validated Premier Platinum HpSA PLUS (EIA test) and the newly available ImmunoCard STAT! HpSA HD (rapid test) for the initial diagnosis and the confirmation of eradication of H. pylori infection. PATIENTS AND METHODS: Patients with indication of H. pylori diagnosis, or confirmation after treatment were included. Data were coded to protect personal data and ensure blindness between tests. Accuracy was considered as coincident diagnosis with the gold standard (13C-urea breath test, UBT). The EIA was used as a bench standard. All stool tests were performed in duplicate. RESULTS: 264 patients completed the protocol (100 naïve, 164 post-eradication). Average age was 52 years, 61% women, 11% ulcer. Positive diagnoses by UBT were 41% for naïve and 17% for post-eradication. Overall ImmunoCard and EIA accuracies were respectively 91% (95%C. I. =88-94%) and 89% (86-93%), sensitivities 72% (67-78%) and 72% (67-78%), and specificities 98% (96-100%), and 95% (92-97%). Concordance between ImmunoCard and EIA was 95% (93-98%). DISCUSSION: Our results indicate that the newly available ImmunoCard rapid stool antigen-test achieves 90% accuracy, with high specificity but suboptimal sensitivity. The ImmunoCard attained equivalent accuracies as the EIA bench standard, with 95% concordance


ANTECEDENTES: En la actualidad, únicamente los métodos de detección de antígenos en heces monoclonales basados en enzimoinmunoanálisis (ELISA) han obtenido una adecuada precisión para el diagnóstico de la infección por Helicobacter pylori. Nuestro objetivo fue evaluar la exactitud (sensibilidad y especificidad) de 2 métodos de antígenos en las heces, el previamente validado Premier Platinum HpSA® PLUS (ELISA) y el nuevo ImmunoCard® STAT! HpSA® HD (test rápido), para el diagnóstico inicial y la confirmación de la erradicación de la infección por H. pylori. PACIENTES Y MÉTODOS: Se incluyeron pacientes en los que estaba indicado el diagnóstico inicial de la infección por H. pylori o su confirmación tras el tratamiento. Los datos fueron codificados y los evaluadores de ambos test fueron ciegos para los resultados de las pruebas diagnósticas. El resultado principal fue la coincidencia con el resultado del patrón oro (prueba del aliento con 13C-urea). Los test en heces se realizaron por duplicado. RESULTADOS: Doscientos sesenta y cuatro pacientes completaron el protocolo (100 naïve, 164 posterradicación). La edad media fue de 52 años, el 61% fueron mujeres y el 11% tenían úlcera péptica. La prueba del aliento fue positiva en el 41% de los pacientes naïve y en el 17% posterradicación. La exactitud global del método rápido y del ELISA fue, respectivamente, 91% (IC 95%: 88-94%) y 89% (86-93%), la sensibilidad 72% (67-78%) y 72% (67-78%), y la especificidad 98% (96-100%) y 95% (92-97%). La concordancia entre el método ImmunoCard® y ELISA fue del 95% (93-98%). DISCUSIÓN: El nuevo método rápido de antígenos en heces (ImmunoCard® STAT! HpSA® HD) tiene una exactitud diagnóstica del 90%, con una elevada especificidad, pero una sensibilidad insuficiente. El método ImmunoCard® tiene una exactitud equivalente al método ELISA estándar, con una concordancia del 95%


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Antígenos Virais/análise , Helicobacter pylori/isolamento & purificação , Infecções por Helicobacter/diagnóstico , Fezes/química , Helicobacter pylori/imunologia , Ensaio de Imunoadsorção Enzimática , Testes Respiratórios , Curva ROC , Sensibilidade e Especificidade , Estudos Prospectivos
17.
World J Gastroenterol ; 26(4): 424-432, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32063691

RESUMO

BACKGROUND: The ABCD stratification [(combination of serum pepsinogen (PG) levels and titers of antibody (immunoglobulin G, IgG) against Helicobacter pylori (H. pylori)] is effective for the classification of individuals at risk of developing gastric cancer (GC). The Kita-Kyushu lung cancer antigen-1 (KK-LC-1) is a Cancer/Testis antigen frequently expressed in GC. AIM: To evaluate the effectiveness of KK-LC-1 and ABCD stratification in the diagnosis of GC. METHODS: We analyzed the gene expression of KK-LC-1 in surgical specimens obtained from GC tumors. The levels of serum PG I/PG II and IgG against H. pylori were measured. According to their serological status, the patients were classified into the four groups of the ABCD stratification. RESULTS: Of the 77 examined patients, 63 (81.8%) expressed KK-LC-1. The IgG titers of H. pylori and PG II were significantly higher in patients expressing KK-LC-1 than those measured in patients not expressing KK-LC-1 (P = 0.0289 and P = 0.0041, respectively). The expression of KK-LC-1 in group C [PG method (+)/H. pylori infection (+)] was as high as 93.9% high. KK-LC-1 was also detected in group A [-/-]. CONCLUSION: The KK-LC-1 expression in GC was associated with H. pylori infection and atrophic status, so that, KK-LC-1 may be a useful marker for the diagnosis of GC.


Assuntos
Anticorpos Antibacterianos/sangue , Antígenos de Neoplasias/sangue , Infecções por Helicobacter/sangue , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/imunologia , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Feminino , Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Humanos , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Pepsinogênio A/sangue , Pepsinogênio C/sangue , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/microbiologia
18.
Epidemiol Infect ; 148: e20, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-32019616

RESUMO

Infectious diseases, such as Helicobacter pylori, which produce systemic inflammation may be one key factor in the onset of autoimmunity. The association between H. pylori and antinuclear antibodies (ANA), a marker of autoimmunity, has been understudied. Data from the 1999-2000 National Health and Nutrition Examination Survey were used to evaluate the cross-sectional association between H. pylori seroprevalence and ANA positivity in US adults aged ≥20 years. ANA was measured in a 1:80 dilution of sera by indirect immunofluorescence using HEp-2 cells (positive ⩾3). H. pylori immunoglobulin G enzyme-linked immunosorbent assays were used to categorise individuals as seropositive or seronegative. H. pylori seropositivity and ANA positivity were common in the adult US population, with estimated prevalences of 33.3% and 9.9%, respectively. Both were associated with increasing age. H. pylori seropositivity was associated with higher odds of ANA (prevalence odds ratio = 1.89, 95% confidence interval = 1.08-3.33), adjusted for age, sex, race/ethnicity, educational attainment and body mass index. H. pylori infection may be one key factor in the loss of self-tolerance, contributing to immune dysfunction.


Assuntos
Anticorpos Antinucleares/sangue , Anticorpos Antibacterianos/sangue , Doenças Autoimunes/epidemiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Estudos Soroepidemiológicos , Estados Unidos/epidemiologia , Adulto Jovem
19.
mBio ; 11(1)2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019805

RESUMO

The cag type IV secretion system (cag-T4SS) of Helicobacter pylori exploits specific cellular carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), such as CEACAM1, -3, -5, and -6, as cellular receptors for CagA translocation into human gastric epithelial cells. We studied the interaction of H. pylori with human CEACAM1, CEACAM3, and CEACAM6 receptors (hCEACAMs) expressed on myeloid cells from CEACAM-humanized mice. Human and CEACAM-humanized mouse polymorphonuclear neutrophils (PMNs) allowed a specific HopQ-dependent interaction strongly enhancing CagA translocation. Translocated CagA was tyrosine phosphorylated, which was not seen in wild-type (wt) murine neutrophils. In contrast, human or murine bone marrow-derived macrophages and dendritic cells (DCs) revealed a low hCEACAM expression and bacterial binding. CagA translocation and tyrosine-phosphorylation was low and independent of the HopQ-CEACAM interaction. Neutrophils, but not macrophages or DCs, from CEACAM-humanized mice, significantly upregulated the proinflammatory chemokine MIP-1α. However, macrophages showed a significantly reduced amount of CXCL1 (KC) and CCL2 (MCP-1) secretion in CEACAM-humanized versus wt cells. Thus, H. pylori, via the HopQ-CEACAM interaction, controls the production and secretion of chemokines differently in PMNs, macrophages, and DCs. We further show that upon H. pylori contact the oxidative burst of neutrophils and phagocytosis of H. pylori was strongly enhanced, but hCEACAM3/6 expression on neutrophils allowed the extended survival of H. pylori within neutrophils in a HopQ-dependent manner. Finally, we demonstrate that during a chronic mouse infection, H. pylori is able to systemically downregulate hCEACAM1 and hCEACAM6 receptor expression on neutrophils, probably to limit CagA translocation efficiency and most likely gastric pathology.IMPORTANCE Helicobacter pylori is highly adapted to humans and evades host immunity to allow its lifelong colonization. However, the H. pylori mouse model is artificial for H. pylori, and few adapted strains allow gastric colonization. Here, we show that human or CEACAM-humanized, but not mouse neutrophils are manipulated by the H. pylori HopQ-CEACAM interaction. Human CEACAMs are responsible for CagA phosphorylation, activation, and processing in neutrophils, whereas CagA translocation and tyrosine phosphorylation in DCs and macrophages is independent of the HopQ-CEACAM interaction. H. pylori affects the secretion of distinct chemokines in CEACAM-humanized neutrophils and macrophages. Most importantly, human CEACAMs on neutrophils enhance binding, oxidative burst, and phagocytosis of H. pylori and enhance bacterial survival in the phagosome. The H. pylori-CEACAM interaction modulates PMNs to reduce the H. pylori CagA translocation efficiency in vivo and to fine-tune the expression of CEACAM receptors on neutrophils to limit translocation of CagA and gastric pathology.


Assuntos
Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Helicobacter pylori/imunologia , Neutrófilos/microbiologia , Fagocitose , Translocação Genética , Animais , Animais Geneticamente Modificados , Antígenos CD/genética , Antígenos CD/metabolismo , Antígeno Carcinoembrionário/genética , Antígeno Carcinoembrionário/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Linhagem Celular , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Humanos , Macrófagos/imunologia , Macrófagos/microbiologia , Masculino , Camundongos , Neutrófilos/imunologia , Fosforilação , Ligação Proteica , Transporte Proteico
20.
J Med Microbiol ; 69(3): 457-464, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32100714

RESUMO

Introduction. Helicobacter pylori is associated with gastrointestinal disease, most notably gastric cancer. Cytotoxin-associated antigen A (CagA), an important virulence factor for H. pylori pathogenicity, induces host cells to release inflammatory factors, especially interleukin-8 (IL-8). The mechanism by which C-terminal CagA induces IL-8 production has been studied extensively, but little is known about the role of the N-terminus.Aim. To investigate the effect of CagA303-456aa (a peptide in the N-terminal CagA) on IL-8 production by gastric epithelial cells.Methodology. CagA303-456aa was produced by a prokaryotic expression system and purified by Strep-tag affinity chromatography. An integrin ß1 (ITGB1)-deficient AGS cell line was constructed using the CRISPR/Cas9 technique, and NCTC 11637 cagA and/or cagL knockout mutants were constructed via homologous recombination. The levels of IL-8 production were determined by enzyme-linked immunosorbent assay (ELISA), and p38 and ERK1/2 phosphorylation were examined by Western blot.Results. CagA303-456aa induced IL-8 expression by AGS cells. IL-8 induction by CagA303-456aawas specifically inhibited by ITGB1 deficiency. Notably, CagA303-456aa activated the phosphorylation of both p38 and ERK1/2, and blocking p38 and ERK1/2 activity significantly reduced IL-8 induction by CagA303-456aa. ITGB1 deficiency also inhibited the activation of p38 phosphorylation by CagA303-456aa. Finally, experiments in CagA and/or CagL knockout bacterial lines demonstrated that extracellular CagA might induce IL-8 production by AGS cells.Conclusion. Residues 303-456 of the N-terminal region of CagA induce IL-8 production via a CagA303-456-ITGB1-p38-IL-8 pathway, and ERK1/2 is also involved in the release of IL-8. Extracellular CagA might induce IL-8 production before translocation into AGS cells.


Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Integrina beta1/metabolismo , Interleucina-8/metabolismo , Peptídeos/metabolismo , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Linhagem Celular Tumoral , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Feminino , Helicobacter pylori/patogenicidade , Humanos , Sistema de Sinalização das MAP Quinases , Peptídeos/genética , Fosforilação , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
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