Causal associations of circulating Helicobacter pylori antibodies with stroke and the mediating role of inflammation

• Published in: Inflammation research Vol. 72; no. 6; pp. 1193 - 1202
• Main Authors: Guo, Xingzhi, Tang, Peng, Zhang, Xin, Li, Rui
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2023; Springer Nature B.V
• Subjects: Allergology; Antibodies; Antigens, Bacterial - metabolism; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biomedical and Life Sciences; Biomedicine; C-reactive protein; Dermatology; Genome-wide association studies; Genome-Wide Association Study; Genomes; Health risks; Helicobacter Infections - complications; Helicobacter pylori; Helicobacter pylori - genetics; Helicobacter pylori - metabolism; Humans; Immunology; Infections; Inflammation - complications; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; Neurology; Original Research Paper; Peptic ulcers; Pharmacology/Toxicology; Proteins; Rheumatology; Risk; Signal transduction; Stroke; Stroke - complications; Stroke; C-reactive protein; Vacuolating cytotoxin-A; Mendelian randomization; Helicobacter pylori
• ISSN: 1023-3830; 1420-908X; 1420-908X
• DOI: 10.1007/s00011-023-01740-0

Background Observational studies have shown that Helicobacter pylori ( H. pylori ) infection and H. pylori antibodies are associated with an increased risk of stroke. However, which and how H. pylori antibodies serve as the causal determinant of the development of stroke remains largely unknown. Methods Genome-wide association studies (GWAS) on seven different antibodies of H. pylori -specific proteins, stroke, and stroke subtypes were included in this study. Mendelian randomization (MR) and multivariable MR (MVMR) analysis were performed to assess the causal associations between H. pylori antibodies and the development of stroke and to determine the potential mechanisms underlying the associations. Results Genetically predicted serum H. pylori vacuolating cytotoxin-A (VacA) antibody level was associated with an increased risk of all-cause stroke (odds ratio [OR] = 1.04, 95% CI 1.01–1.07, P  = 0.017) and cardioembolic stroke (CES, OR = 1.11, 95% CI 1.04–1.18, P  = 0.001). The results of multivariable MR (MVMR) showed that C-reactive protein (CRP), but not monocyte chemoattractant protein-1 and peptic ulcer, mediated the causal effects of VacA-positive H. pylori infection on all-cause stroke and CES. No strong causal associations were found between other H. pylori antibodies and stroke and its subtypes. Conclusions Our results demonstrate that H. pylori VacA antibody is the only causal determinant associated with the risk of stroke in the spectrum of H. pylori -related antibodies, in which CRP may mediate the association. This study suggests that inhibition of the CRP signaling pathway may reduce the risk of stroke in patients with VacA-positive H. pylori infection.