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Role of AIM: To establish the relationship of protein tyrosine phosphatase non-receptor type 2 and 22 (PTPN2/22) polymorphisms and mycobacterial infections in Crohn's disease (CD). METHODS: All 133 subjects' blood samples were genotyped for nine single nucleotide polymorphisms (SNPs) in PTPN2/22 using TaqMan™ genotyping, while the effect of the SNPs on PTPN2/22 and IFN-γ gene expression was determined using RT-PCR. Detection of Mycobacterium avium subspecies paratuberculosis (MAP) IS900 gene was done by nPCR after DNA extraction from the isolated leukocytes of each subjects' blood samples. T-cells isolated from the patient samples were tested for response to phytohematoagglutonin (PHA) mitogen or mycobacterial antigens by BrdU proliferation assays for T-cell activity. RESULTS: Out of the nine SNPs examined, subjects with either heterozygous (TC)/minor (CC) alleles in PTPN2:rs478582 occurred in 83% of CD subjects compared to 61% healthy controls (P-values < 0.05; OR = 3.03). Subjects with either heterozygous (GA)/minor (AA) alleles in PTPN22:rs2476601 occurred in 16% of CD compared to 6% healthy controls (OR = 2.7). Gene expression in PTPN2/22 in CD subjects was significantly decreased by 2 folds compared to healthy controls (P-values < 0.05). IFN-γ expression levels were found to be significantly increased by approxiately 2 folds in subjects when either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 were found (P-values < 0.05). MAP DNA was detected in 61% of CD compared to only 8% of healthy controls (P-values < 0.05, OR = 17.52), where subjects with either heterozygous or minor alleles in PTPN2:rs478582 and/or PTPN22:rs2476601 had more MAPbacteremia presence than subjects without SNPs did. The average T-cell proliferation in CD treated with PHA or mycobacteria antigens was, respectively, 1.3 folds and 1.5 folds higher than healthy controls without any significant SNP. CONCLUSION: The data suggests that SNPs in PTPN2/22 affect the negative regulation of the immune response in CD patients, thus leading to an increase in inflammation/apoptosis and susceptibility of mycobacteria.

Role of Helicobacter pylori (H. pylori) is a gastric human pathogen associated with acute and chronic gastritis, 70% of all gastric ulcers, 85% of all duodenal ulcers, and both forms of stomach cancer, mucosal-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Recently, attention has focused on possible relationship between presence of certain virulence factor and H. pylori-associated diseases. Some contradictory data between this bacterium and related disorders has been observed since not all the colonized individuals develop to severe disease. The reported diseases plausibility related to H. pylori specific virulence factors became an interesting story about this organism. Although a number of putative virulence factors have been identified including cytotoxin-associated gene a (cagA) and vacA, there are conflicting data about their actual participation as specific risk factor for H. pylori-related diseases. Duodenal ulcer promoting gene a (dupA) is a virulence factor of H. pylori that is highly associated with duodenal ulcer development and reduced risk of gastric cancer. The prevalence of dupA in H. pylori strains isolated from western countries is relatively higher than in H. pylori strains from Asian countries. Current confusing epidemiological reports will continue unless future sophisticated and molecular studies provide data on functional and complete dupA cluster in H. pylori infected individuals. This paper elucidates available knowledge concerning role of dupA in virulence of H. pylori after a decade of its discovery.