Abstract
The
iceA
locus of
Helicobacter pylori
includes one of two mutually exclusive gene families,
iceA1
and
iceA2
. Colonization with
iceA1
strains is associated with enhanced acute mucosal inflammation, and adherence to gastric epithelial cells in vitro induces expression of
iceA1
but not
iceA2
mRNA; however, both transcripts can be detected in vivo. The aim of this study was to determine whether differing levels of
iceA
transcription in vivo may contribute to disease pathogenesis. RNA from 41
H. pylori-positive gastric biopsy specimens was reverse transcribed to cDNA. Quantitative PCR was performed using biotinylated iceA1
,
iceA2
, and 16S rRNA primers, and binding of biotinylated products to streptavidin-coated plates was detected by hybridization with a fluorescein-labeled probe.
iceA
genotypes were determined by PCR and sequence analysis. All 41 samples contained detectable
H. pylori
16S rRNA, with similar levels in
iceA1
- (
n
= 10) and
iceA2
(
n
= 31)-colonized patients (
P
= 0.34). Biopsy specimens from four (40%) and 19 (61%) persons colonized with
iceA1
or
iceA2
strains, respectively, had detectable
iceA
RNA. Acute inflammatory scores were significantly higher in
iceA1
RNA-positive patients than in
iceA1
RNA-negative,
iceA2
RNA-positive, or
iceA2
RNA-negative subjects (
P
≤ 0.05 for each). Within the
iceA2
RNA-positive group,
H. pylori
strains with a single 35-amino-acid cassette were associated with significantly higher mucosal
iceA2
transcript levels (
P
= 0.014 versus strains with two cassettes). These results indicate that the levels of transcription of
H. pylori iceA1
and
iceA2
and of 16S rRNA are independent and that particular
iceA2
gene structures are associated with enhanced transcription. The finding that
iceA1
transcription levels are significantly associated with the intensity of neutrophilic infiltration suggests that heterogeneity in inflammatory scores among persons colonized with
H. pylori iceA1
strains reflects levels of
iceA1
transcription in vivo.