Relación entre la integridad del CagPAI y los polimorfismos en el gen CagA con la severidad de la gastritis en pacientes infectados con H. pylori CagA positivo
Palabras clave:
Helicobacter pylori, gastritis, factores de virulencia, polimorfismo genéticoResumen
Objetivos: Evaluar la histopatología gástrica en pacientes colombianos con gastritis infectados con Helicobacter pylori CagA-positivo y su asociación a la integridad del islote de patogenicidad Cag (CagPAI) y el número de motivos EPIYA-C presentes en la proteína CagA.
Métodos: Se incluyó a 31 individuos con diagnóstico de gastritis. A partir de biopsias gástricas se aisló H. pylori CagA-positivo y se caracterizó, mediante secuencia, la composición de motivos EPIYA. La histopatología fue evaluada según el sistema Sidney actualizado. Los genes CagA, CagT, CagE y Cag10 fueron genotipificados mediante PCR y electroforesis en agarosa.
Resultados: En total, 24 aislamientos (el 77% de los casos) portaban CagPAI íntegro. De los aislamientos negativos para uno o más genes del CagPAI, 7 de ellos (22%) fueron considerados como portadores de un CagPAI defectuoso. No se observaron diferencias significativas en los promedios de densidad de H. pylori, el grado de inflamación crónica ni la presencia de atrofia glandular o de metaplasia intestinal entre aislamientos con el CagPAI íntegro, en comparación con aislamientos con el CagPAI defectuoso. Tampoco se observaron diferencias significativas en los parámetros histopatológicos entre los aislamientos con un motivo EPIYA-C o más de un motivo EPIYA-C, ni en antro ni en cuerpo, excepto para la infiltración por neutrófilos, que fue significativamente mayor en cuerpo en aislamientos con más de un motivo EPIYA-C (p=0,018).
Conclusiones: No se halló asociación entre la diversidad en los factores de virulencia CagPAI y CagA de aislamientos colombianos, y los hallazgos histopatológicos en la gastritis, otros factores del hospedero o ambientales podrían afectar las características histopatológicas de la gastritis.
Biografía del autor/a
María M. Bravo, Instituto Nacional de Cancerología
Grupo de Investigación en Cáncer y Agentes Infecciosos, Instituto Nacional de Cancerología, Bogotá, D. C., Colombia
Teresa Martínez, Instituto Nacional de Cancerología
Grupo Investigación Epidemiológica, Instituto Nacional de Cancerología, Bogotá, D. C., Colombia
Juan C. Bravo, Fundación Valle del Lili
Departamento de Patología, Fundación Valle del Lili, Santiago de Cali, Valle, Colombia
Referencias bibliográficas
Blaser MJ. Ecology of Helicobacter pylori in the human stomach. J Clin Invest. 1997;100:759-62.
https://doi.org/10.1172/JCI119588
IARC working Group on the evaluation of Carcinogenic Risks to Humans. Schistosomes, liver flukes and Helicobacter pylori. Lyon: International Agency for Research on Cancer; 1994.
McGee DJ, Mobley HL. Pathogenesis of Helicobacter pylori infection. Curr Opin Gastroenterol. 2000;16:24-31.
https://doi.org/10.1097/00001574-200001000-00005
Blaser MJ, Perez-Perez GI, Kleanthous H, et al. Infection with Helicobacter pylori strains possessing CagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res. 1995;55:2111-5.
Quiroga AJ, Cittelly DM, Bravo MM. [BabA2, oipA and CagE Helicobacter pylori genotypes in Colombian patients with gastroduodenal diseases]. Biomédica. 2005;25:325-34.
https://doi.org/10.7705/biomedica.v25i3.1357
Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P, Borodovsky M, et al. Cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci U S A. 1996;93(25):14648-53.
https://doi.org/10.1073/pnas.93.25.14648
Akopyants NS, Clifton SW, Kersulyte D, et al. Analyses of the Cag pathogenicity island of Helicobacter pylori. Mol Microbiol. 1998;28:37-53.
https://doi.org/10.1046/j.1365-2958.1998.00770.x
Tummuru MK, Cover TL, Blaser MJ. Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production. Infect Immun. 1993;61:1799-809.
https://doi.org/10.1128/IAI.61.5.1799-1809.1993
Stein M, Rappuoli R, Covacci A. Tyrosine phosphorylation of the Helicobacter pylori CagA antigen after Cagdriven host cell translocation. Proc Natl Acad Sci U S A. 2000;97:1263-8.
https://doi.org/10.1073/pnas.97.3.1263
Higashi H, Tsutsumi R, Muto S, et al. SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science. 2002;295:683-6.
https://doi.org/10.1126/science.1067147
Hatakeyama M. Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nat Rev Cancer. 2004;4:688-94.
https://doi.org/10.1038/nrc1433
Higashi H, Tsutsumi R, Fujita A, et al. Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci U S A. 2002;99:14428-33.
https://doi.org/10.1073/pnas.222375399
Argent RH, Kidd M, Owen RJ, et al. Determinants and consequences of different levels of CagA phosphorylation for clinical isolates of Helicobacter pylori. Gastroenterology. 2004;127:514-23.
https://doi.org/10.1053/j.gastro.2004.06.006
Argent RH, Hale JL, El-Omar EM, et al. Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns between western and East Asian strains, and influences on interleukin-8 secretion. J Med Microbiol. 2008;57:1062-7.
https://doi.org/10.1099/jmm.0.2008/001818-0
Acosta N, Quiroga A, Delgado P, et al. Helicobacter pylori CagA protein polymorphisms and their lack of association with pathogenesis. World J Gastroenterol. 2010;16:3936-43.
https://doi.org/10.3748/wjg.v16.i31.3936
Dixon MF, Genta RM, Yardley JH, et al. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20:1161-81.
https://doi.org/10.1097/00000478-199610000-00001
Tummuru MK, Sharma SA, Blaser MJ. Helicobacter pylori picB, a homologue of the Bordetella pertussis toxin secretion protein, is required for induction of IL-8 in gastric epithelial cells. Mol Microbiol. 1995;18:867-76.
https://doi.org/10.1111/j.1365-2958.1995.18050867.x
Maeda S, Yoshida H, Ikenoue T, et al. Structure of Cag pathogenicity island in Japanese Helicobacter pylori isolates. Gut. 1999;44:336-41.
https://doi.org/10.1136/gut.44.3.336
Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med. 2002;347:1175-86.
https://doi.org/10.1056/NEJMra020542
Peek RM Jr, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer. 2002;2:28-37. 21. Blaser MJ, Berg DE. Helicobacter pylori genetic diversity and risk of human disease. J Clin Invest. 2001;107:767-73.
https://doi.org/10.1172/JCI12672
Israel DA, Peek RM. Pathogenesis of Helicobacter pyloriinduced gastric inflammation. Aliment Pharmacol Ther. 2001;15:1271-90.
https://doi.org/10.1046/j.1365-2036.2001.01052.x
Helicobacter and Cancer Collaborative Group. Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts3. Gut. 2001;49:347-53.
https://doi.org/10.1136/gut.49.3.347
Honda S, Fujioka T, Tokieda M, et al. Development of Helicobacter pylori-induced gastric carcinoma in Mongolian gerbils. Cancer Res. 1998;58:4255-9.
Kuipers EJ, Pérez-Pérez GI, Meuwissen SG, et al. Helicobacter pylori and atrophic gastritis: importance of the CagA status. J Natl Cancer Inst. 1995;87:1777-80.
https://doi.org/10.1093/jnci/87.23.1777
Weel JF, van der Hulst RW, Gerrits Y, et al. The interrelationship between cytotoxin-associated gene A, vacuolating cytotoxin, and Helicobacter pylori-related diseases. J Infect Dis. 1996;173:1171-5.
Bravo LE, van Doom LJ, Realpe JL, et al. Virulence-associated genotypes of Helicobacter pylori: do they explain the African enigma? Am J Gastroenterol. 2002;97:2839-42.
https://doi.org/10.1111/j.1572-0241.2002.07031.x
Quiroga AJ, Huertas A, Cómbita AL, et al. Variation in the number of EPIYA-C repeats in CagA protein from Co- lombian Helicobacter pylori strains and its ability middle to induce hummingbird phenotype in gastric epithelial cells. Biomédica. 2010;30:251-8.
https://doi.org/10.7705/biomedica.v30i2.188
Hsu PI, Hwang IR, Cittelly D, et al. Clinical presentation in relation to diversity within the Helicobacter pylori Cag pathogenicity island5. Am J Gastroenterol. 2002;97:2231-8.
https://doi.org/10.1111/j.1572-0241.2002.05977.x
Kauser F, Khan AA, Hussain MA, et al. The Cag pathogenicity island of Helicobacter pylori is disrupted in the majority of patient isolates from different human popu- lations. J Clin Microbiol. 2004;42:5302-8.
https://doi.org/10.1128/JCM.42.11.5302-5308.2004
Nguyen LT, Uchida T, Tsukamoto Y, et al. Clinical relevance of CagPAI intactness in Helicobacter pylori isolates from Vietnam. Eur J Clin Microbiol Infect Dis. 2010;29:651-60.
https://doi.org/10.1007/s10096-010-0909-z
Shimoyama T, Crabtree JE. Mucosal chemokines in Helicobacter pylori infection. J Physiol Pharmacol. 1997;48:315-23.
Umit H, Tezel A, Bukavaz S, et al. The relationship between virulence factors of Helicobacter pylori and severity of gastritis in infected patients. Dig Dis Sci. 2009;54:103-10.
Schneider N, Krishna U, Romero-Gallo J, et al. Role of Helicobacter pylori CagA molecular variations in induction of host phenotypes with carcinogenic potential. J Infect Dis. 2009;199:1218-21.
https://doi.org/10.1086/597416
Sicinschi LA, Correa P, Peek RM, et al. CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions. Clin Microbiol Infect. 2010;16:369-78.
https://doi.org/10.1111/j.1469-0691.2009.02811.x
Yamaoka Y, El-Zimaity HM, Gutiérrez O, et al. Relation- ship between the CagA 3' repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH. Gastroenterology. 1999;117:342-9.
https://doi.org/10.1053/gast.1999.0029900342
Rizzato C, Torres J, Plummer M, et al. Variations in helicobacter pylori cytotoxin-associated genes and their influence in progression to gastric cancer: implications for prevention. PLoS One. 2012;7:e29605.
https://doi.org/10.1371/journal.pone.0029605
Reyes-León A, Atherton JC, Argent RH, et al. Heteroge- neity in the activity of Mexican Helicobacter pylori strains in gastric epithelial cells and its association with diversity in the CagA gene. Infect Immun. 2007;75:3445-54.
https://doi.org/10.1128/IAI.01951-06
Sgouras DN, Panayotopoulou EG, Papadakos K, et al. CagA and VacA polymorphisms do not correlate with severity of histopathological lesions in Helicobacter pylori-infected Greek children. J Clin Microbiol. 2009;47:2426-34.
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