Introduction
Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder characterized by corpus-restricted atrophy and pseudopyloric or intestinal metaplasia, associated with reduced hydrochloric acid and intrinsic factor production and heterogeneous clinical consequences. The aetiology of AAG is autoimmune, but the role of Helicobacter pylori (Hp) has been proposed, although not definitively proven. A possible antigenic crossreactivity with H+,K+-ATPase, the main autoantigen in AAG, has been reported and Hp seropositivity has been described in histologically Hp negative AAG. One study employed molecular biology techniques to characterize a cohort of AAG patients as definitively Hp naïve.
Aims & Methods
The aim was to assess the presence of Hp-related genes in corpus mucosa biopsies of pts with AAG and Hp-positive and negative ctr by using real-time PCR.
Single-centre, experimental molecular biology study on 55 pts with histologically diagnosed AAG, of whom at histology 52 were Hp negative (age 61.5, range 28-88 yrs, 75% F, 96.2% parietal cell (PCA) and 44.2% intrinsic factor antibodies (IFA) positive), while 3 were Hp positive (age 74,69,33 yrs; 1 F; all 3 PCA and 1 IFA positive). Ctr were 4 pts who underwent gastroscopy for non-ulcer dyspepsia, 2 with Hp-positive superficial antral gastritis (positive ctr), and 2 with a healthy stomach (negative ctr). Hp serology (ELISA or multiplex) was available from all pts. DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue sections of corpus mucosa biopsies and real-time PCR was performed using specific probes for UreA, UreC, and CagA Hp related genes; 16sRNA and Beta2 microglobulin (B2M) specific probes were used as amplification ctr of bacterial and human DNA (real-time PCR cycle threshold (CT) >28<38).
Results
In 4(7.7%) of the 52 histologically Hp negative AAG pts, Hp-related genes were detected, in 4(7.7%) UreC, in 3(5.8%) UreA, and in 1(1.9%) CagA. All of them (3 F, aged 88,85,58,56 yrs) had positive Hp serology and PCA, only one was IFA-positive. The detectability of B2M and bacterial 16sRNA genes did not differ in UreC-positive or UreC-negative pts (B2M CT mean 29.6±1.2 for Ure-C positives vs 29.7±1.4 for Ure-C negatives, p=0.99; 16SrRNA gene CT mean 29.9±1.2 vs 29.4±1.2, p=0.27) indicating that the not-detectability of Hp-related genes was unrelated to reduced amounts of gastric bacterial or human DNA. Hp serology was positive in all 4 histologically Hp-negative AAG pts positive for UreC compared to 5/48(10.4%) UreC negative pts (p<0.0001) indicating previous exposure. PCA were present in all 4 UreC positive AAG pts compared to 46/48(95.8%) of UreC negatives (p=0.68). IFA positivity in UreC negatives was nearly 2x higher than that of UreC positives (45.8% vs 25%, p=0.42) without reaching significance. In 2/3 pts with histologically Hp-positive AAG, Hp-related genes could be detected; in the remaining patient, nor UreA, UreC neither CagA gene could be found (M, 69 yrs, no anemia, PCA-IFA-Hp serology positive).
Conclusion
In >90% of histologically Hp-negative and PCA or IFA positive AAG pts, Hp-related genes cannot be retrieved in the gastric mucosa. In 10% of these Hp-genes negative AAG pts, previous exposure to Hp can be testified by positive serology.
Hp-related genes can be detected in gastric biopsies in <10% of histologically Hp-negative AAG patients and positive Hp serology further confirms the role of Hp in this group.
These findings show that primary, Hp naive AAG is the more common type, but in a subset of pts, AAG seems to be secondary to Hp infection.
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