Background: Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder affecting the gastric oxyntic mucosa. Two pathogenetic models are proposed: a pure autoimmune disorder or gastric autoimmunity triggered by Helicobacter pylori (Hp)-infection. In AAG, histological diagnosis of Hp may be challenging and serology can help assess exposure to Hp-infection. This study aimed to determine seroreactivity to Hp-antigens in AAG patients by using Hp-multiplex serology assay. Methods: A single-centre case-control study on 178 adults: 75 patients with serological and histological AAG diagnosis, 25 controls with histologically Hp-positive-non-atrophic gastritis (Ctr-NAG-Hp+) and 78 subjects with a healthy stomach (Ctr-HS). Sera were analysed using Hp-multiplex serology assay allowing simultaneous detection of antibodies to 13 Hp-proteins. Overall positivity cutoff: seroreactivity to more than 3 Hp-antigens. Results: The number of seroreactive Hp-antigens was higher in AAG than in Ctr-HS(mean +/- SEM 2.2 +/- 0.3 vs 1.4 +/- 0.22,p=0.02) and lower than in Ctr-NAG-Hp+ patients (mean +/- SEM 5.4 +/- 0.5,p<0.001).Overall Hp-seropositivity in AAG was two-fold higher than in Ctr-HS but not statistically significant (21.1% vs 10.3%,p=0.06) and lower than in Ctr-NAG-Hp+(80%,p<0.0001). Complete absence of seroreactivity was similar in AAG and Ctr-HS (29.3% vs 38.5%, p=0.23) and significantly higher than in Ctr-NAG-Hp+ (4%, p=0.009). Main immunogenic Hp-proteins were HP0010(GroEL),HP1098(HcpC),HP0695(HyuA),HP0875(Catalase),HP1564,HP0547(CagA) and HP0243(NapA) with seroreactivity in >50% of AAG patients. Conclusions: By Hp-multiplex serology, 30% of histologically Hp-negative AAG pts had no seroreactivity, likely belonging to the pure AAG type. Conversely, 20% of AAG pts showed Hp exposure, indicating that infection might have triggered gastric autoimmunity. The remaining AAG patients showed seroreactivity below cut-off for seropositivity and thus not definitively categorisable by this approach. (c) 2025 The Authors. Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Helicobacter pylori multiplex serology in patients with autoimmune atrophic gastritis negative for Helicobacter pylori at histology: A case-control study / Vavallo, M., Butt, J., Cingolani, S., Cozza, G., Schiavone, F.P., Dilaghi, E., Belloni, L., Franchitto, M., Annibale, B., Waterboer, T., Lahner, E.. - In: DIGESTIVE AND LIVER DISEASE. - ISSN 1878-3562. - 58:2(2026), pp. 212-219. [10.1016/j.dld.2025.12.002]
Helicobacter pylori multiplex serology in patients with autoimmune atrophic gastritis negative for Helicobacter pylori at histology: A case-control study
Vavallo M.;Butt J.;Schiavone F. P.;Dilaghi E.;Franchitto M.;Annibale B.;Lahner E.
2026
Abstract
Background: Autoimmune atrophic gastritis (AAG) is an immune-mediated disorder affecting the gastric oxyntic mucosa. Two pathogenetic models are proposed: a pure autoimmune disorder or gastric autoimmunity triggered by Helicobacter pylori (Hp)-infection. In AAG, histological diagnosis of Hp may be challenging and serology can help assess exposure to Hp-infection. This study aimed to determine seroreactivity to Hp-antigens in AAG patients by using Hp-multiplex serology assay. Methods: A single-centre case-control study on 178 adults: 75 patients with serological and histological AAG diagnosis, 25 controls with histologically Hp-positive-non-atrophic gastritis (Ctr-NAG-Hp+) and 78 subjects with a healthy stomach (Ctr-HS). Sera were analysed using Hp-multiplex serology assay allowing simultaneous detection of antibodies to 13 Hp-proteins. Overall positivity cutoff: seroreactivity to more than 3 Hp-antigens. Results: The number of seroreactive Hp-antigens was higher in AAG than in Ctr-HS(mean +/- SEM 2.2 +/- 0.3 vs 1.4 +/- 0.22,p=0.02) and lower than in Ctr-NAG-Hp+ patients (mean +/- SEM 5.4 +/- 0.5,p<0.001).Overall Hp-seropositivity in AAG was two-fold higher than in Ctr-HS but not statistically significant (21.1% vs 10.3%,p=0.06) and lower than in Ctr-NAG-Hp+(80%,p<0.0001). Complete absence of seroreactivity was similar in AAG and Ctr-HS (29.3% vs 38.5%, p=0.23) and significantly higher than in Ctr-NAG-Hp+ (4%, p=0.009). Main immunogenic Hp-proteins were HP0010(GroEL),HP1098(HcpC),HP0695(HyuA),HP0875(Catalase),HP1564,HP0547(CagA) and HP0243(NapA) with seroreactivity in >50% of AAG patients. Conclusions: By Hp-multiplex serology, 30% of histologically Hp-negative AAG pts had no seroreactivity, likely belonging to the pure AAG type. Conversely, 20% of AAG pts showed Hp exposure, indicating that infection might have triggered gastric autoimmunity. The remaining AAG patients showed seroreactivity below cut-off for seropositivity and thus not definitively categorisable by this approach. (c) 2025 The Authors. Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
