The Intact dupA Cluster Is a More Reliable Helicobacter pylori Virulence Marker than dupA Alone

Abstract

The duodenal ulcer promoting (dupA) gene, located in the plasticity region of Helicobacter pylori, is associated with duodenal ulcer development. dupA was predicted to form a type IV secretory system (T4SS) with vir genes around dupA (dupA cluster). We investigated the prevalence of dupA and dupA clusters and clarified associations between the dupA cluster status and clinical outcomes in the U.S. population. In all, 245 H. pylori strains were examined using PCR to evaluate the status of dupA and the adjacent vir genes predicted to form T4SS, in addition to the status of cag pathogenicity island (PAI). The associations between dupA cluster status and interleukin-8 (IL-8) and IL-12 production were also examined. The presence of dupA and all adjacent vir genes were defined as a complete dupA cluster. Many variations related to the status of dupA and dupA cluster genes were identified. Concurrent H. pylori infection and the presence of a complete dupA cluster increases duodenal ulcer risk compared to H. pylori infection with incomplete dupA cluster or without the dupA gene independent on the cag PAI status (adjusted odds ratio, 2.13; 95% confidence interval, 1.13 to 4.03). Gastric mucosal IL-8 levels were also significantly higher in the complete dupA cluster group than in other groups (P ‫؍‬ 0.01). In conclusion, although the causal relationship between the dupA cluster and duodenal ulcer development is not proved, the presence of a complete dupA cluster but not dupA alone, is associated with duodenal ulcer development.

Volume 34 Number 3

“…In this study, the presence of a complete dupA cluster rather than dupA alone was found to be associated with the development of DU and increased IL-8 production, suggesting that the complete dupA cluster is required for full expression of this virulence factor 31 .…”

“…Given this, a recent study by Jung et al 31 investigated if genetic differences in the makeup of the dupA gene may explain this disparity. In this study, the presence of a complete dupA cluster rather than dupA alone was found to be associated with the development of DU and increased IL-8 production, suggesting that the complete dupA cluster is required for full expression of this virulence factor 31 .…”

“…The current chemotherapeutic regimes used to treat HL are also associated with an increased risk of the development of secondary cancers and strategies to reduce the dependence of the current level of chemotherapy are under development, particularly for children 30 . EBV-associated HL, often when refractory to chemotherapy, has also been successfully treated with adoptive cellular therapy 29,[31][32][33][34][35][36] . While initial studies focussed on the LCL-based approach used to treat PTLD, more recent approaches have specifically targeted the induction of T cells specific for EBNA1 and LMP1&2 37 .…”

“…While initial studies focussed on the LCL-based approach used to treat PTLD, more recent approaches have specifically targeted the induction of T cells specific for EBNA1 and LMP1&2 37 . These approaches have proved to be successful in phase 1 clinical studies and are currently being evaluated in phase II studies 31 .…”

“…Has been detected in a small number of asthma exacerbations in young children [29][30][31][32] Parainfluenza viruses Can cause lower respiratory tract infection in young children…”