CagApositive

cagApositive refers to strains of Helicobacter pylori that carry the cagA gene. The cagA gene is part of the cag pathogenicity island (cag PAI) and encodes the CagA protein, which is delivered into gastric epithelial cells through a Type IV secretion system encoded by the same island.

Once inside host cells, CagA is subjected to phosphorylation at conserved EPIYA motifs by host kinases. Phosphorylated CagA can interact with signaling proteins such as SHP-2 phosphatase, leading to altered cell morphology, cytoskeletal rearrangements, disruption of tight junctions, and activation of inflammatory pathways. These cellular changes contribute to increased inflammation and can promote longer-term gastric mucosal damage.

Clinically, cagApositive strains are associated with more severe gastritis, higher risk of peptic ulcers, and an increased association with gastric cancer and MALT lymphoma compared with cagA-negative strains. The virulence of cagA varies by the type of CagA present; East Asian CagA alleles (often containing the EPIYA-D motif) are generally considered more strongly associated with oncogenic potential than the Western types (commonly with EPIYA-C). However, disease outcome depends on multiple factors, including host genetics, environment, and other bacterial virulence determinants such as vacA genotype.

Detection of cagA positivity is typically achieved by PCR testing for the cagA gene, sequencing of the cagA region to determine EPIYA type, or serological methods. Prevalence of cagApositive strains varies geographically and by population, with higher frequencies reported in many regions outside Western Europe and North America. Overall, cagApositivity is a useful marker of virulence in H. pylori but does not by itself predict disease outcome.