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INTRODUCTION AND AIMS: Celiac disease (CD) is an autoimmune enteropathy that develops in genetically susceptible individuals. The typical gastrointestinal manifestation is diarrhea but symptoms of dyspepsia, such as epigastric pain, nausea, or satiety, can sometimes appear. Previous studies have reported that the prevalence of CD in patients with dyspepsia can be as high as 7%. The aim of the present study was to evaluate CD seroprevalence in subjects with dyspeptic symptoms and a control group in a Mexican population. MATERIAL AND METHODS: A case-control study was conducted on blood donors that answered the PAGI-SYM questionnaire for dyspepsia and in whom IgA antibodies to tissue transglutaminase 2 (IgA anti-tTG2) and IgG antibodies to deamidated gliadin peptide (IgG anti-DGP) were determined. CD seroprevalence in subjects with dyspeptic symptoms and in asymptomatic subjects was compared. RESULTS: A total of 427 subjects (76.3% men), with a mean patient age of 34 years (range of 18-65 years) were included. Of those participants, 87 (20.3%) had symptoms of dyspepsia (group A) and 340 (79.6%) were asymptomatic (group B). Antibodies were positive in one (1.15%) of the group A subjects (1/87, 95% CI 0.2-6 %), whereas they were positive in 4 (1.18%) of the group B subjects (4/340, 95% CI 0.4-2.9%, pâ¯=â¯0.59). CONCLUSIONS: CD seroprevalence in the study population with dyspeptic symptoms (1%) was not different from that of the control population. Thus, CD screening in Mexican patients with dyspepsia is not justified.
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INTRODUCTION AND AIM: Cancer is the result of the interaction of genetic and environmental factors. It has recently been related to viral infections, one of which is human papillomavirus. The aim of the present study was to describe the frequency of human papillomavirus infection in patients with digestive system cancers. MATERIALS AND METHODS: A prospective, multicenter, observational study was conducted on patients with gastrointestinal cancer at 2public healthcare institutes in Veracruz. Two tumor samples were taken, one for histologic study and the other for DNA determination of human papillomavirus and its genotypes. Anthropometric variables, risk factors, sexual habits, tumor location, and histologic type of the cancer were analyzed. Absolute and relative frequencies were determined using the SPSS version 24.0 program. RESULTS: Fifty-three patients were studied. They had gastrointestinal cancer located in: the colon (62.26%), stomach (18.87%), esophagus (7.55%), rectum (7.55%), and small bowel (3.77%). Human papillomavirus was identified in 11.32% of the patients, 66.7% of which corresponded to squamous cell carcinoma and 33.3% to adenocarcinoma. Only genotype 18 was identified. Mean patient age was 61.8±15.2 years, 56.60% of the patients were men, and 43.40% were women. A total of 15.8% of the patients had a family history of cancer and 31.6% had a personal history of the disease, 38.6% were tobacco smokers, and 61.4% consumed alcohol. Regarding sex, 5.3% of the patients said they were homosexual, 3.5% were bisexual, 29.8% engaged in oral sex, and 24.6% in anal sex. CONCLUSIONS: Our study showed that human papillomavirus infection was a risk factor for the development of gastrointestinal cancer, especially of squamous cell origin.
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Neoplasias Gastrointestinais/epidemiologia , Infecções por Papillomavirus/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/epidemiologia , Feminino , Neoplasias Gastrointestinais/complicações , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Papillomaviridae , Infecções por Papillomavirus/complicações , Estudos Prospectivos , Fatores de Risco , Comportamento SexualRESUMO
Listeriolysin O (LLO) has been proposed as a potential carrier or adjuvant molecule in the vaccination field. However, the cytotoxic and pro-apoptotic effects of LLO are the major limitations for this purpose. Here, we have performed a preclinical safety evaluation and characterized a new potential adjuvant application for a non-cytolytic LLO mutant (dtLLO) to enhance and modulate the immune response against the envelope (E) protein from dengue virus. In addition, we have studied the adjuvant effects of dtLLO on human immune cells and the role of membrane cholesterol for the binding and proinflammatory property of the toxoid. Our in-vivo results in the murine model confirmed that dtLLO is a safer molecule than wild-type LLO (wtLLO), with a significantly increased survival rate for mice challenged with dtLLO compared with mice challenged with wtLLO (P < 0·001). Histopathological analysis showed non-toxic effects in key target organs such as brain, heart, liver, spleen, kidney and lung after challenge with dtLLO. In vitro, dtLLO retained the capacity of binding to plasma membrane cholesterol on the surface of murine and human immune cells. Immunization of 6-8-week-old female BALB/c mice with a combination of dtLLO mixed with E protein elicited a robust specific humoral response with isotype diversification of immunoglobulin (Ig)G antibodies (IgG1 and IgG2a). Finally, we demonstrated that cholesterol and lipid raft integrity are required to induce a proinflammatory response by human cells. Taken together, these findings support a potential use of the dtLLO mutant as a safe and effective adjuvant molecule in vaccination.
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Adjuvantes Imunológicos , Antígenos Virais/imunologia , Toxinas Bacterianas/imunologia , Vírus da Dengue/imunologia , Proteínas de Choque Térmico/imunologia , Proteínas Hemolisinas/imunologia , Imunidade Humoral , Proteínas Mutantes/imunologia , Animais , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos/imunologia , Toxinas Bacterianas/genética , Colesterol/metabolismo , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Dengue/imunologia , Dengue/patologia , Dengue/prevenção & controle , Modelos Animais de Doenças , Feminino , Proteínas de Choque Térmico/genética , Proteínas Hemolisinas/genética , Hemólise/imunologia , Imunização , Mediadores da Inflamação/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Lipídeos de Membrana/metabolismo , Camundongos , Proteínas Mutantes/genética , Ligação Proteica/imunologiaRESUMO
Biodegradables Chitosan-based Nanoparticles (CS NPs) have been extensively studied as delivery system for therapeutic molecules and as efficient carriers or adjuvants in experimental vaccination. Physicochemical association between CS NPs and antigens is a key step for the biological function as carrier devices. However, for the adjuvant CS NPs property, it is not well known if coupling with vaccine antigens is required or not to potentiate the immune response. To address this issue, in this work, we evaluated the potential adjuvant effect of CS NPs by simply mixing with two different antigens such as Bovine Serum Albumin (BSA) or E protein from Dengue Virus serotype 2 (E protein DENV2). Thus the CS NPs were prepared by ionic gelation with sodium tripolyphosphate, resulting particles among 68 and 188 nm of size. Immunization of 68 week old female BALB/c mice, were carried out by intraperitoneal route with a simple combination of CS NPs either with BSA (CS NPs-BSA) at 10 µg or with E protein DENV2 (CS NPs-Protein E) at 5 µg. Combinations with the above antigens with CS NPs elicited robust specific primary and secondary humoral responses comparable to alum, a well-known adjuvant. BSA-specific IgG titers were detectable by day 14 after priming with the CS NPs-BSA formulation, with titers that ranged from 102 to 103 EU ml-. After a second immunization, the anti-BSA titers ranged around 104 EU ml-. In contrast, in the group of mice immunized with the protein alone, BSA-specific serum IgG titers were undetectable at day 14 and 28. For the immunizations with the CS NPs-E protein formulation, we observed also a remarkable specific-antibody production in the primary response, with titers reaching 103 EU ml-. After the booster immunization the anti-E protein DENV2 antibodies titers reached peak values around 104 EU ml-. Interestingly, for both antigens, the combination with CS NPs polarized the immune response to a Th2-like profile, which is characterized mainly by the production of the IgG1 Isotype, confirming that CS NPs can enhance and modulate the humoral immune responses against different antigens independently of physicochemical conjugation. This could represent a simplification in the use of CS NPs as adjuvants in vaccination.
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Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Compostos de Alúmen/química , Antígenos/química , Quitosana/química , Imunidade Humoral/efeitos dos fármacos , Nanopartículas/química , Animais , Antígenos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Soroalbumina Bovina/química , Soroalbumina Bovina/imunologia , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/imunologiaRESUMO
BACKGROUND: The cost-effectiveness for screening for celiac disease (CD) in patients with irritable bowel syndrome (IBS), specifically in the diarrhea (IBS-D) subtype, is beneficial if the prevalence is >1%. However, recent studies have shown controversial results. In this large case-control study, our aim was to determine the prevalence of CD and a panel of related antibodies in patients diagnosed with IBS. MATERIALS AND METHODS: Four hundred IBS patients (Rome III) and 400 asymptomatic healthy controls were prospectively evaluated using antihuman tissue transglutaminase (h-tTG IgA) and deamidated gliadin peptide antibodies (DGP II IgA and DGP II IgG). Duodenal biopsy was performed on the patients that were positive for the h-tTG IgA and/or DGP II IgG antibodies. RESULTS: The mean age of the population was 44.47 ± 18.01 years and 335 (82%) of the subjects were women. Twenty-one patients and six controls had at least one positive test for CD (5.25% VS 1.5%, p = 0.003, OR 3.63 [95% CI 1.4-9.11]). Eighteen patients were positive for h-tTG and/or DGP-II IgG. Histologic confirmation of CD was 2.5% in the IBS patients vs 0.5% in the controls (p = 0.04, OR 5.21). The IBS-D subtype had the highest prevalence for serological positivity (12.7%). CONCLUSIONS: Up to 5.2% of the patients with IBS according to the Rome III criteria were positive for at least one of the CD-related antibodies and 2.5% had biopsy-confirmed CD. Therefore, in our population, screening for CD in subjects with IBS appears to be a reasonable strategy, especially in the IBS-D subgroup.
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Autoanticorpos/sangue , Doença Celíaca/sangue , Doença Celíaca/epidemiologia , Síndrome do Intestino Irritável/sangue , Síndrome do Intestino Irritável/epidemiologia , Adulto , Estudos de Casos e Controles , Doença Celíaca/classificação , Feminino , Humanos , Imunoglobulina A/sangue , Síndrome do Intestino Irritável/classificação , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos ProspectivosRESUMO
Listeriolysin O (LLO) is a thiol-activated cholesterol-dependent pore-forming toxin and the major virulence factor of Listeria monocytogenes (LM). Extensive research in recent years has revealed that LLO exerts a wide array of biological activities, during the infection by LM or by itself as recombinant antigen. The spectrum of biological activities induced by LLO includes cytotoxicity, apoptosis induction, endoplasmic reticulum stress response, modulation of gene expression, intracellular calcium oscillations, and proinflammatory activity. In addition, LLO is a highly immunogenic toxin and the major target for innate and adaptive immune responses in different animal models and humans. Recently, the crystal structure of LLO has been published in detail. Here, we review the structure-function relationship for this fascinating microbial molecule, highlighting the potential uses of LLO in the fields of biomedicine and biotechnology, particularly in vaccination.
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Toxinas Bacterianas , Proteínas de Choque Térmico , Proteínas Hemolisinas , Listeria monocytogenes , Vacinação , Animais , Toxinas Bacterianas/química , Toxinas Bacterianas/imunologia , Proteínas de Choque Térmico/química , Proteínas de Choque Térmico/imunologia , Proteínas Hemolisinas/química , Proteínas Hemolisinas/imunologia , Humanos , Listeria monocytogenes/química , Listeria monocytogenes/imunologia , Estrutura Terciária de Proteína , Relação Estrutura-AtividadeRESUMO
Previous studies have revealed the clinical relevance of pro-inflammatory cytokine production during dengue virus (DENV) infections. In this study, we evaluated the production of interleukin-21 (IL-21), a key soluble mediator mainly produced by CD4+ T cells. The aim of this study was to investigate the role of IL-21 production during the clinical course of primary and secondary DENV infections and the potential association of IL-21 serum levels with the disease pathogenesis. Blood samples from DENV-infected patients were collected on different days after the onset of symptoms. Patients were classified according to their phase of disease (acute vs. convalescent phases), the type of infection (primary vs. secondary), and the clinical severity of their disease (dengue fever (DF) vs. dengue hemorrhagic fever (DHF)). IL-21 levels were measured using a quantitative capture ELISA assay. The levels of IL-21 were significantly elevated in the disease group compared with the control group. IL-21 was detected in primary and secondary DENV infections, with a significantly higher concentration in the convalescent phase of primary infections. IL-21 levels were significantly higher in patients with secondary acute DHF infections when compared with those with secondary acute DF infection. There was a relationship between the elevated serum levels of IL-21 and the production of DENV-specific IgM and IgG antibodies. Taking together, our results show for the first time the involvement of IL-21 during the clinical course of DENV infections. We speculate that IL-21 may play a protective role in the context of the convalescent phase of primary infections and the acute phase of secondary infections.
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Vírus da Dengue , Dengue/metabolismo , Interleucinas/biossíntese , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Dengue/diagnóstico , Dengue/imunologia , Vírus da Dengue/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Interleucinas/sangue , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto JovemRESUMO
Uncontrolled and intricate production of inflammatory factors is the characteristic feature of dengue infection. The triggering receptor expressed in myeloid cells-1 (TREM-1), expressed on the surface of monocytes and neutrophils, is capable of enhancing and regulating the inflammatory response via the production of different mediators in bacterial and viral infections. Here, both the expression of TREM-1 on human monocytes and neutrophils from peripheral blood of dengue infected individuals, as well as the levels of the soluble form of TREM-1 (sTREM-1) in the sera of these patients were compared against healthy controls. A significant reduction of TREM-1 expression was observed in neutrophils during the first days of infection, followed by a gradual recovery throughout the course of infection. Also, sera from DENV-infected patients exhibited significantly higher sTREM-1 levels than healthy individuals. The difference was more pronounced during the first 5 days after the onset of symptoms. These findings highlight the dynamic process of TREM-1 expression during DENV infection. We hypothesized that increment of free sTREM-1 could be a compensatory mechanism aiming to counteract the inflammatory process elicited during DENV infection.
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Vírus da Dengue/imunologia , Dengue/imunologia , Glicoproteínas de Membrana/biossíntese , Monócitos/imunologia , Neutrófilos/imunologia , Receptores Imunológicos/biossíntese , Adolescente , Adulto , Células Cultivadas , Criança , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Humanos , Imunidade Inata , Imunomodulação , Masculino , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Monócitos/virologia , Neutrófilos/virologia , Receptores Imunológicos/sangue , Receptores Imunológicos/genética , Receptor Gatilho 1 Expresso em Células Mieloides , Adulto JovemRESUMO
Lipopopeptidephosphoglycan (LPPG) is a complex macromolecule from the surface of Entamoeba histolytica trophozoites. We analysed the interaction between LPPG and human macrophages and dendritic cells (DCs) and found that LPPG is internalized by these cells and activates them. The internalization process involves intracellular traffic from the cell membrane to late endosomes, as shown by co-localization of LPPG with late endosomes marked with FITC-dextran and LAMP-1. LPPG-activated DCs have increased expression of co-stimulatory molecules CD80, CD86 and CD40 and produce pro-inflammatory cytokines TNF-alpha, IL-8 and IL-12. Taken together, these results show that LPPG activates antigen-presenting cells and reaches intracellular compartments that are involved in antigen presentation.