Introduction
For autoimmune atrophic gastritis (AAG) two pathogenetic models are proposed: a pure autoimmune disorder or gastric autoimmunity triggered by Helicobacter pylori (Hp) infection. In AAG, the diagnosis of Hp infection with conventional methods is challenging due to oxyntic mucosa atrophy, hypochlorhydria, and gradual Hp clearance. Formerly, Hp seropositivity in AAG with negative Hp histology was shown by Western blotting. A Hp multiplex serology assay allowing simultaneous detection of antibodies to several Hp proteins and virulence factors has not been used so far in sera of AAG pts to test for Hp exposure.
Aims & Methods
The aim was to assess seroreactivity against Hp proteins in AAG pts, Hp negative at histological evaluation of gastric biopsies and without history of Hp infection.
Single centre case-control study on 75 adults with histological AAG diagnosis, age 63 (18-88) yrs, F:M 2.4:1, parietal cell (PCA)-intrinsic factor autoantibodies (IFA) positivity in 81.3%-41.3%. AAG pts were compared with 2 control groups: 62 healthy stomach subjects (HS), age 65.5 (23-90) yrs, F:M 1.1:1, and 16 controls with Hp-positive antral non-atrophic gastritis (NAHp), age 59.5 (31-78) yrs, F:M 1.7:1. All 153 subjects had gastroscopy with biopsies, according to the updated Sydney system, for clinical suspicion of AAG (anaemia or dyspepsia) or AAG follow-up. Frozen sera (-20°C) were analysed by Hp multiplex serology assay. This assay is based on a glutathione-S-transferase (GST) capture immunosorbent assay combined with fluorescent bead technology measuring antibody responses to 13 Hp proteins (CagA, VacA, UreA, HP0875, NapA, HpaA, HyuA, HcpC, Cad, GroEl, HP0231, HP0305, HP1564). Median fluorescent intensity (MFI) values for each antigen were determined in a 1:1000 serum dilution. Seropositivity to individual antigens was defined as MFI above cut-off. Hp seropositivity was defined as being positive for >3 or more antigens.
Results
AAG pts showed a higher, but not significantly, Hp seropositivity than HS (n=16/21.3% vs n=6/9.7%, p=0.06), but a significantly lower seropositivity than NAHp (12/75%, p<0.0001). The number of participants positive to none of the Hp antigens was similar in AAG and HS (n=22/29.3% vs n=24/38.7%,p=0.25), and significantly higher than in NAHp (n=1/6.2%,p=0.05). The number of seroreactive antigens was significantly higher in AAG than in HS (mean±SEM 2.2±0.3 vs 1.4±0.2, p=0.04), and lower than in NAHp (5.4 ± 0.7, p<0.0001). Hp antigens seroreactive in >50% of the 16 Hp seropositive AAG pts included GroEL, NapA, CagA, HyuA, Catalase, HcpC, and HP1564; UreA and VacA were seropositive in 37.5%/16 seropositive AAG pts.
Severe corpus atrophy was significantly more frequent in the 22 AAG pts without any seroreactivity (0 Hp antigens) than in seropositives (p=0.019) suggesting more severe disease in pts never exposed to Hp. IFA positivity was nearly 2x in Hp seronegatives compared to seropositives (45.8% vs 25%, p=0.137) albeit not significant. An inverse relationship between anti-UreA and IFA titers was shown (Spearman’s rho -0.25 (95%CI -0.46 to -0.03), p=0.03), suggesting an opposite trend of Hp immunoreactivity and gastric autoimmunity.
Conclusion
By Hp multiplex serology, 30% of histologically Hp negative AAG pts had complete absence of seroreactivity, likely belonging to the pure AAG type. In contrast, 20% of AAG pts showed exposure to Hp, indicating that infection might have played a role in triggering gastric autoimmunity. The remaining 50% of AAG pts showed a weak seropositivity, probably belonging to a grey zone, not definitively categorizable by this approach.
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