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A B M Da Silveira - One of the best experts on this subject based on the ideXlab platform.

  • relation between mast cells concentration and serotonin expression in chagasic Megacolon development
    Parasite Immunology, 2017
    Co-Authors: Michelle A R Freitas, N Segatto, N Tischler, E C De Oliveira, Axel Brehmer, A B M Da Silveira
    Abstract:

    Chagas′ disease still reaching about 10 million people in the world. In South America, one of the most severe forms of this disease is the Megacolon, characterized by severe constipation, dilated sigmoid colon and rectum and severe malnutrition. Previous data suggested that mast cells and serotonin (5-HT) expression could be involved in intestinal homeostasis control, avoiding the chagasic Megacolon development. The aim at this study was to characterize the presence of mast cells and expression of serotonin in chagasic patients with and without Megacolon and evaluate the relation between mast cells, serotonin and Megacolon development. Our results demonstrated that patients without Megacolon feature a large amount of serotonin and few mast cells, while patients with Megacolon feature low serotonin expression and a lot of mast cells. We believe that serotonin may be involved in the inflammatory process control, triggered by mast cells, and the presence of this substance in large quantities of the intestine could represent a mechanism of Megacolon prevention. This article is protected by copyright. All rights reserved.

  • interstitial cells of cajal crucial for the development of Megacolon in human chagas disease
    Colorectal Disease, 2013
    Co-Authors: Samir Jabari, E C De Oliveira, A B M Da Silveira, Karl Quint, Andre Wirries, Winfried Neuhuber, Axel Brehmer
    Abstract:

    Aim Megacolon, chronic dilation of a colonic segment,is accompanied by extensive myenteric neuron loss. However, this fails to explain unequivocally the formation of Megacolon. We aimed to study further enteric structures that are directly or indirectly involved in colonic motility. Method From surgically removed Megacolon segments of seven Chagasic patients, three sets of cryosections from oral, Megacolonic and anal zones were immunohistochemically quadruple-stained for smooth-muscle actin (SMA), synaptophysin (SYN, for nerve fibres), S100 (glia) and c-Kit (interstitial cells of Cajal, ICCs). Values of area measurements were related to the appropriate muscle layer areas and these proportions were compared with those of seven non-Chagasic control patients. Results Whereas nerve and glia profile proportions did not mirror unequivocally the changes of Chagasic colon calibre (nondilation/dilation/nondilation), the proportions of SMA (i.e. muscle tissue density) and c-Kit (i.e. ICC density) did so: they decreased from the oral to the Megacolonic segment but increased to the anal zones (muscle tissue density: control 68.3%, oral 54.3%, mega 42.1%, anal 47.6%; ICC-density: control 1.8%, oral 1.1%, mega 0.4, anal 0.8%). Conclusion Of the parameters evaluated, muscle tissue and ICC densities may be involved in the formation of Chagasic Megacolon, although the mechanism of destruction cannot be deduced.

  • Characterization of the presence and distribution of Foxp3+ cells in chagasic patients with and without Megacolon
    Human immunology, 2008
    Co-Authors: A B M Da Silveira, Michelle A R Freitas, E C De Oliveira, Fernanda Fortes De Araújo, Juliana A. S. Gomes, Ana Thereza Chaves, Salustiano Gabriel Neto, Alejandro O. Luquetti, Gilmar Da Cunha Souza, Roberto Bernardino Júnior
    Abstract:

    Patients with Chagas's disease in the chronic phase regularly present with the chagasic Megacolon. This form is characterized by inflammation, neuronal destruction, and organ dilatation. Chagasic patients with Megacolon always present with inflammatory process near the enteric plexuses of the colon, as previously demonstrated. The aim of this study is to characterize the presence and distribution of Foxp3(+) cells in the muscle layers and neuronal plexuses area of the colon from chagasic patients with and without Megacolon. Our results demonstrated that chagasic patients without Megacolon presented with an increased concentration of Foxp3(+) cells in all colon layers compared with chagasic patients with Megacolon and noninfected individuals. These cells were situated mainly near the blood vessels and rarely were associated with the inflammatory foci. We believe that the presence of Foxp3(+) cells may help to control the inflammatory process through the management of lymphocyte migration and, consequently, prevent neuronal destruction and chagasic Megacolon development.

  • neuronal plasticity of the enteric nervous system is correlated with chagasic Megacolon development
    Parasitology, 2008
    Co-Authors: A B M Da Silveira, Michelle A R Freitas, E C De Oliveira, Salustiano Gabriel Neto, Alejandro O. Luquetti, Rodrigo Correaoliveira, J B Furness, Davila D Reis
    Abstract:

    Chagas' disease is one of the few functional gastrointestinal disorders for which a causative agent has been identified. However, some pathological aspects of the chagasic megasyndromes are still incompletely understood. Chagasic Megacolon is characterized by an inflammatory process, organ dilatation and neuronal reduction in both plexuses of the enteric nervous system (ENS). Although some studies on the ENS in Chagas' disease have been performed, the process of neuronal destruction and neuronal regeneration still remains unclear. Our hypothesis is that the regeneration process of the ENS may be involved with the mechanisms that prevent or retard organ dilatation and chagasic Megacolon development. For that reason, we evaluated the neuronal regeneration with the marker GAP-43 in the colon's neuronal plexuses from chagasic patients with Megacolon, and from non-infected individuals. Visual examination and quantitative analysis revealed an increased neuronal regeneration process in the dilated portion from chagasic patients when compared with the non-dilated portion and with non-infected individuals. We believe that this increased regeneration can be interpreted as an accentuated neuronal plasticity that may be a response of the ENS to avoid Megacolon propagation to the entire organ and maintain the colon functional innervation.

  • Megacolon in chagas disease a study of inflammatory cells enteric nerves and glial cells
    Human Pathology, 2007
    Co-Authors: A B M Da Silveira, Sheila Jorge Adad, Elenice M Lemos, Rodrigo Correaoliveira, J B Furness, Debora Davila Reis
    Abstract:

    After acute infestation with the Chagas disease parasite, Trypanosoma cruzi, some patients who are serologically positive develop chronic Megacolon and megaesophagus, whereas others are symptom-free. Chagas disease with gastrointestinal involvement involves an inflammatory invasion of the enteric plexuses and degeneration of enteric neurons. It is known that glial cells can be involved in enteric inflammatory responses. The aims were to determine the nature of any difference in lymphocytic invasion, enteric neurons, and enteric glial cells in seropositive individuals with and without Megacolon. We have compared colonic tissue from serologically positive individuals with and without symptoms and from seronegative controls. Subjects with Megacolon had significantly more CD-57 natural killer cells and TIA-1 cytotoxic lymphocytes within enteric ganglia, but numbers of CD-3 and CD-20 immunoreactive cells were not significantly elevated. The innervation of the muscle was substantially reduced to about 20% in Megacolon, but asymptomatic seropositive subjects were not different to seronegative controls. Glial cell loss occurred equally in symptomatic and unaffected seropositive subjects, although the proportion with glial fibrillary acidic protein was greater in seropositive, nonsymptomatic subjects. Development of Megacolon after acute infection with T cruzi is associated with maintained invasion of enteric ganglia with cytotoxic T cells and loss of muscle innervation, but changes in glial cell numbers are not associated with progression of enteric neuropathy.

E C De Oliveira - One of the best experts on this subject based on the ideXlab platform.

  • The distribution and chemical coding of enteroendocrine cells in Trypanosoma cruzi-infected individuals with chagasic Megacolon
    Histochemistry and Cell Biology, 2021
    Co-Authors: Patrícia Rocha Martins, E C De Oliveira, Josiane Fakhry, Adriana Jacaúna De Oliveira, Thayse Batista Moreira, Linda J. Fothergill, Débora D’Ávila Reis, John B. Furness
    Abstract:

    Chagas disease is caused by the parasite , Trypanosoma cruzi that causes chronic cardiac and digestive dysfunction. Megacolon, an irreversible dilation of the left colon, is the main feature of the gastrointestinal form of Chagas disease. Patients have severe constipation, a consequence of enteric neuron degeneration associated with chronic inflammation. Dysmotility, infection, neuronal loss and a chronic exacerbated inflammation, all observed in Chagas disease, can affect enteroendocrine cells (EEC) expression, which in turn, could influence the inflammatory process. In this study, we investigated the distribution and chemical coding of EEC in the dilated and non-dilated portion of T. cruzi -induced Megacolon and in non-infected individuals (control colon). Using immunohistochemistry, EECs were identified by applying antibodies to chromogranin A (CgA), glucagon-like peptide 1 (GLP-1), 5-hydroxytryptamine (5-HT), peptide YY (PYY) and somatostatin (SST). Greater numbers of EEC expressing GLP-1 and SST occurred in the dilated portion compared to the non-dilated portion of the same patients with Chagas disease and in control colon, but numbers of 5-HT and PYY EEC were not significantly different. However, it was noticeable that EEC in which 5-HT and PYY were co-expressed were common in control colon, but were rare in the non-dilated and absent in the dilated portion of chagasic Megacolon. An increase in the number of CgA immunoreactive EEC in chagasic patients reflected the increases in EEC numbers summarised above. Our data suggests that the denervation and associated chronic inflammation are accompanied by changes in the number and coding of EEC that could contribute to disorders of motility and defence in the chagasic Megacolon.

  • relation between mast cells concentration and serotonin expression in chagasic Megacolon development
    Parasite Immunology, 2017
    Co-Authors: Michelle A R Freitas, N Segatto, N Tischler, E C De Oliveira, Axel Brehmer, A B M Da Silveira
    Abstract:

    Chagas′ disease still reaching about 10 million people in the world. In South America, one of the most severe forms of this disease is the Megacolon, characterized by severe constipation, dilated sigmoid colon and rectum and severe malnutrition. Previous data suggested that mast cells and serotonin (5-HT) expression could be involved in intestinal homeostasis control, avoiding the chagasic Megacolon development. The aim at this study was to characterize the presence of mast cells and expression of serotonin in chagasic patients with and without Megacolon and evaluate the relation between mast cells, serotonin and Megacolon development. Our results demonstrated that patients without Megacolon feature a large amount of serotonin and few mast cells, while patients with Megacolon feature low serotonin expression and a lot of mast cells. We believe that serotonin may be involved in the inflammatory process control, triggered by mast cells, and the presence of this substance in large quantities of the intestine could represent a mechanism of Megacolon prevention. This article is protected by copyright. All rights reserved.

  • trypanosomiasis induced Megacolon illustrates how myenteric neurons modulate the risk for colon cancer in rats and humans
    PLOS Neglected Tropical Diseases, 2015
    Co-Authors: E C De Oliveira, Mariângela Ottoboni Brunaldi, Sergio Britto Garcia, Bruno Zene Motta, Annuar Jose Chaguri, Vinicius Kannen
    Abstract:

    Background Trypanosomiasis induces a remarkable myenteric neuronal degeneration leading to Megacolon. Very little is known about the risk for colon cancer in chagasic Megacolon patients. To clarify whether chagasic Megacolon impacts on colon carcinogenesis, we investigated the risk for colon cancer in Trypanosoma cruzi (T. cruzi) infected patients and rats. Methods Colon samples from T. cruzi-infected and uninfected patients and rats were histopathologically investigated with colon cancer biomarkers. An experimental model for chemical myenteric denervation was also performed to verify the myenteric neuronal effects on colon carcinogenesis. All experiments complied the guidelines and approval of ethical institutional review boards. Results No colon tumors were found in chagasic Megacolon samples. A significant myenteric neuronal denervation was observed. Epithelial cell proliferation and hyperplasia were found increased in chagasic Megacolon. Analyzing the argyrophilic nucleolar organiser regions within the cryptal bottom revealed reduced risk for colon cancer in Chagas’ Megacolon patients. T. cruzi-infected rats showed a significant myenteric neuronal denervation and decreased numbers of colon preneoplastic lesions. In chemical myenteric denervated rats preneoplastic lesions were reduced from the 2nd wk onward, which ensued having the colon myenteric denervation significantly induced. Conclusion/Significance Our data suggest that the trypanosomiasis-related myenteric neuronal degeneration protects the colon tissue from carcinogenic events. Current findings highlight potential mechanisms in tropical diseases and cancer research.

  • interstitial cells of cajal crucial for the development of Megacolon in human chagas disease
    Colorectal Disease, 2013
    Co-Authors: Samir Jabari, E C De Oliveira, A B M Da Silveira, Karl Quint, Andre Wirries, Winfried Neuhuber, Axel Brehmer
    Abstract:

    Aim Megacolon, chronic dilation of a colonic segment,is accompanied by extensive myenteric neuron loss. However, this fails to explain unequivocally the formation of Megacolon. We aimed to study further enteric structures that are directly or indirectly involved in colonic motility. Method From surgically removed Megacolon segments of seven Chagasic patients, three sets of cryosections from oral, Megacolonic and anal zones were immunohistochemically quadruple-stained for smooth-muscle actin (SMA), synaptophysin (SYN, for nerve fibres), S100 (glia) and c-Kit (interstitial cells of Cajal, ICCs). Values of area measurements were related to the appropriate muscle layer areas and these proportions were compared with those of seven non-Chagasic control patients. Results Whereas nerve and glia profile proportions did not mirror unequivocally the changes of Chagasic colon calibre (nondilation/dilation/nondilation), the proportions of SMA (i.e. muscle tissue density) and c-Kit (i.e. ICC density) did so: they decreased from the oral to the Megacolonic segment but increased to the anal zones (muscle tissue density: control 68.3%, oral 54.3%, mega 42.1%, anal 47.6%; ICC-density: control 1.8%, oral 1.1%, mega 0.4, anal 0.8%). Conclusion Of the parameters evaluated, muscle tissue and ICC densities may be involved in the formation of Chagasic Megacolon, although the mechanism of destruction cannot be deduced.

  • glial fibrillary acidic protein and s 100 colocalization in the enteroglial cells in dilated and nondilated portions of colon from chagasic patients
    Human Pathology, 2009
    Co-Authors: Alexandre B M Da Silveira, Michelle A R Freitas, E C De Oliveira, Salustiano Gabriel Neto, Alejandro O. Luquetti, Rodrigo Correaoliveira, J B Furness, Debora Davila Reis
    Abstract:

    After acute immunoreactive infestation with the Chagas' disease parasite, Trypanosoma cruzi, some patients develop chronic Megacolon, whereas others remain asymptomatic. Chronic chagasic patients with gastrointestinal involvement exhibit inflammation and degeneration of enteric neurons. Our hypothesis is that enteric glial cells may be involved in the modulation of enteric inflammatory responses or even control the colon's dilatation. The aims of this study were to characterize the phenotype of enteric glial cells according to the expression of S-100 and glial fibrillary acidic protein and to look for correlation between these data and the neuronal loss in the colon of chagasic patients. We studied both dilated and nondilated portions of chagasic Megacolon. We used a pan-enteric glial cell marker (anti-S-100), a subpopulation enteric glial cell marker (anti-glial fibrillary acidic protein), and a pan-neuronal marker (anti-Human protein C and protein D) with double-labeled sheets using a confocal microscope. Our results demonstrate that neuronal loss is similar in dilated and nondilated portions of chagasic Megacolon. Moreover, the results indicate that neuronal destruction present in chagasic Megacolon is preceded by glial component loss. The nondilated portion of chagasic Megacolon exhibited increased expression of glial fibrillary acidic protein comparable with the dilated portion and also to the noninfected group. Our results suggest that glial fibrillary acidic protein enteric glial cells prevent dilatation of the organ and protect the enteric nervous system against the inflammatory process and neuronal destruction, preventing the destruction from expanding to unaffected areas of the colon.

Norihiro Komiya - One of the best experts on this subject based on the ideXlab platform.

  • Protective Human Leucocyte Antigen Haplotype, HLA- DRB1*01-B*14, against Chronic Chagas Disease in Bolivia
    2016
    Co-Authors: Florencia Del Puerto, Juan Eiki Nishizawa, Mihoko Kikuchi, Yelin Roca, Cinthia Avilas, Javier Lora, Freddy Udalrico, Gutierrez Velarde, Sachio Miura, Norihiro Komiya
    Abstract:

    Background: Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8–10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA) regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. Methodology: Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG), and Barium enema colon X-ray. 31.4 % of the examinees showed ECG alterations, 15.7 % Megacolon and 58.1 % showed neither of them. A further 62 seropositive Megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region) mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. Principal Findings: The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from Megacolon as well as in those with ECG alteration and/or Megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD), and the HLA-DRB1*01

  • protective human leucocyte antigen haplotype hla drb1 01 b 14 against chronic chagas disease in bolivia
    PLOS Neglected Tropical Diseases, 2012
    Co-Authors: Florencia Del Puerto, Juan Eiki Nishizawa, Mihoko Kikuchi, Yelin Roca, Cinthia Avilas, Javier Lora, Sachio Miura, Alberto Gianella, Freddy Udalrico Gutierrez Velarde, Norihiro Komiya
    Abstract:

    Background Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8–10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA) regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. Methodology Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG), and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% Megacolon and 58.1% showed neither of them. A further 62 seropositive Megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region) mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. Principal Findings The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from Megacolon as well as in those with ECG alteration and/or Megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD), and the HLA-DRB1*01-B*14-MICA*011haplotype was associated with resistance against chronic Chagas disease. Conclusions This is the first report of HLA haplotype association with resistance to chronic Chagas disease.

Florencia Del Puerto - One of the best experts on this subject based on the ideXlab platform.

  • Protective Human Leucocyte Antigen Haplotype, HLA- DRB1*01-B*14, against Chronic Chagas Disease in Bolivia
    2016
    Co-Authors: Florencia Del Puerto, Juan Eiki Nishizawa, Mihoko Kikuchi, Yelin Roca, Cinthia Avilas, Javier Lora, Freddy Udalrico, Gutierrez Velarde, Sachio Miura, Norihiro Komiya
    Abstract:

    Background: Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8–10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA) regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. Methodology: Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG), and Barium enema colon X-ray. 31.4 % of the examinees showed ECG alterations, 15.7 % Megacolon and 58.1 % showed neither of them. A further 62 seropositive Megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region) mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. Principal Findings: The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from Megacolon as well as in those with ECG alteration and/or Megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD), and the HLA-DRB1*01

  • protective human leucocyte antigen haplotype hla drb1 01 b 14 against chronic chagas disease in bolivia
    PLOS Neglected Tropical Diseases, 2012
    Co-Authors: Florencia Del Puerto, Juan Eiki Nishizawa, Mihoko Kikuchi, Yelin Roca, Cinthia Avilas, Javier Lora, Sachio Miura, Alberto Gianella, Freddy Udalrico Gutierrez Velarde, Norihiro Komiya
    Abstract:

    Background Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8–10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA) regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. Methodology Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG), and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% Megacolon and 58.1% showed neither of them. A further 62 seropositive Megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region) mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. Principal Findings The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from Megacolon as well as in those with ECG alteration and/or Megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD), and the HLA-DRB1*01-B*14-MICA*011haplotype was associated with resistance against chronic Chagas disease. Conclusions This is the first report of HLA haplotype association with resistance to chronic Chagas disease.

Sachio Miura - One of the best experts on this subject based on the ideXlab platform.

  • Protective Human Leucocyte Antigen Haplotype, HLA- DRB1*01-B*14, against Chronic Chagas Disease in Bolivia
    2016
    Co-Authors: Florencia Del Puerto, Juan Eiki Nishizawa, Mihoko Kikuchi, Yelin Roca, Cinthia Avilas, Javier Lora, Freddy Udalrico, Gutierrez Velarde, Sachio Miura, Norihiro Komiya
    Abstract:

    Background: Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8–10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA) regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. Methodology: Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG), and Barium enema colon X-ray. 31.4 % of the examinees showed ECG alterations, 15.7 % Megacolon and 58.1 % showed neither of them. A further 62 seropositive Megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region) mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. Principal Findings: The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from Megacolon as well as in those with ECG alteration and/or Megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD), and the HLA-DRB1*01

  • protective human leucocyte antigen haplotype hla drb1 01 b 14 against chronic chagas disease in bolivia
    PLOS Neglected Tropical Diseases, 2012
    Co-Authors: Florencia Del Puerto, Juan Eiki Nishizawa, Mihoko Kikuchi, Yelin Roca, Cinthia Avilas, Javier Lora, Sachio Miura, Alberto Gianella, Freddy Udalrico Gutierrez Velarde, Norihiro Komiya
    Abstract:

    Background Chagas disease, caused by the flagellate parasite Trypanosoma cruzi affects 8–10 million people in Latin America. The mechanisms that underlie the development of complications of chronic Chagas disease, characterized primarily by pathology of the heart and digestive system, are not currently understood. To identify possible host genetic factors that may influence the clinical course of Chagas disease, Human Leucocyte Antigen (HLA) regional gene polymorphism was analyzed in patients presenting with differing clinical symptoms. Methodology Two hundred and twenty nine chronic Chagas disease patients in Santa Cruz, Bolivia, were examined by serological tests, electrocardiogram (ECG), and Barium enema colon X-ray. 31.4% of the examinees showed ECG alterations, 15.7% Megacolon and 58.1% showed neither of them. A further 62 seropositive Megacolon patients who had undergone colonectomy due to acute abdomen were recruited. We analyzed their HLA genetic polymorphisms (HLA-A, HLA-B, MICA, MICB, DRB1 and TNF-alpha promoter region) mainly through Sequence based and LABType SSO typing test using LUMINEX Technology. Principal Findings The frequencies of HLA-DRB1*01 and HLA-B*14:02 were significantly lower in patients suffering from Megacolon as well as in those with ECG alteration and/or Megacolon compared with a group of patients with indeterminate symptoms. The DRB1*0102, B*1402 and MICA*011 alleles were in strong Linkage Disequilibrium (LD), and the HLA-DRB1*01-B*14-MICA*011haplotype was associated with resistance against chronic Chagas disease. Conclusions This is the first report of HLA haplotype association with resistance to chronic Chagas disease.