Digestive Diseases and Sciences, Vol. 50, No. 2 (February 2005), pp. 375–380 ( C  2005) DOI: 10.1007/s10620-005-1613-1 Genotypic and Phenotypic Stability of Helicobacter pylori Markers in a Nine-Year Follow-up Study of Patients with Noneradicated Infection ANDERS GUSTAVSSON, MD,* MAGNUS UNEMO, PhD,† BJ ¨ ORN BLOMBERG, MD, PhD,* and DAN DANIELSSON, MD, PhD† The cagA gene, alleles of the vacA gene,random amplified polymorphic DNA (RAPD), and neutrophil activating capacity (HpNAC) were used to examine paired H. pylori isolates from 10 noneradicated individuals 9 years apart. Paired isolates from each patient were indistinguishable with regard to vacA alleles, RAPD, and HpNAC. Isolates from nine patients showed concordance for the cagA gene, which was not detected in the recent isolate of the tenth patient. Antibodies to CagA were, however, demonstrated in the serum specimens 9 years apart and were also present in two other patients whose paired isolates were cagA-, indicating the existence of both cagA+ and cagA- organisms, with the latter predominating in some patients. The present study suggests a greater stability of phenotypic and genotypic markers of H. pylori than previously regarded. This might be true for a community with low infection and transmission rates. Complementary techniques like microarrays might, however, disclose evolutionary changes not identified here. KEY WORDS: Helicobacter pylori; vacA; cagA; neutrophil activation; genetic diversity; serology. Helicobacter pylori infection, one of the most common bacterial infections in the world, is frequently acquired in early childhood, and in developing countries as many as 70–90% of the population are colonized before the age of 15–19 years. In industrial countries, the infection is ac- quired at a fairly constant rate of 0.5–2% per year, reach- ing prevalences of 20–30% in adults <50 years of age. However, in age cohorts 50 years and older, as many as 50–70% may be infected as a consequence of childhood acquisition (1, 2). Manuscript received July 18, 2004; accepted August 12, 2004. From the *Department of Medicine, Division of Gastroenterology, and †Department of Clinical Microbiology, ¨ Orebro University Hospital, ¨ Orebro, Sweden. Address for reprint requests: Magnus Unemo, Department of Clinical Microbiology, ¨ Orebro University Hospital, SE-701 85 ¨ Orebro, Sweden; magnus.unemo@orebroll.se. Practically all individuals infected with H. pylori will develop chronic gastritis but numerous studies have demonstrated that only a minority of them will develop clinical disease; 10–15% may develop peptic ulcer dis- ease (PUD) and 0.5–2% gastric cancer (GCA) or mucosa- associated lymphoid tissue (MALT) lymphoma (3–6). The reasons for this are unclear. Besides heavy urease produc- tion and flagellae, common to all clinical isolates and nec- essary for the colonization of the stomach for survival in this hostile environment, there is increasing evidence that some strains are more virulent than others. The expres- sion of two major phenotypic markers and/or their gene alleles has attracted the most attention: vacuolating cyto- toxin A (VacA), a protein with a molecular weight of ap- proximately 87 kDa, and cytotoxin-associated antigen A (CagA), a protein with a molecular weight of 114–129 kDa (7, 8). VacA is encoded by the particular alleles s1/m1 or Digestive Diseases and Sciences, Vol. 50, No. 2 (February 2005) 375 0163-2116/05/0200-0375/0 C  2005 Springer Science+Business Media, Inc.