Helicobacter pylori and autoimmune disease: cause or bystander

Abstract

Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research.

Keywords: Autoimmunity; Gastritis; Helicobacter pylori; Infection; Mimicry; Rheumatology.

Figure 1

A “multiple hit” molecular mimicry mechanism involving microbial mimics originated from Helicobacter pylori and other microbes linked with primary biliary cirrhosis. The major autoepitope of primary biliary cirrhosis-specific anti-mitochondrial antibodies (PDC-E2, pyruvate dehydrogenase complex) shares amino acid similarities with 4 microbial mimics from Helicobacter pylori (H. pylori)[142], N. aromaticivorans[154], L. delbrueckii[155,156], and E. coli[140,157,158]. The working hypothesis is that exposure of susceptible individuals to infections caused by these microbial agents will initiate humoral and cellular immune responses against microbial epitopes (in our case, these will be those sharing similarity with the self-epitope). Antibodies or T-cells against the microbial mimics may then cross-react with the human autoepitope initiating an autoreactive immune response which could lead to the induction of cellular damage and the perpetuation of autoimmunity (and can cause autoimmune disease). Experimental data so far provided demonstrate the existence of cross-reactive responses between self and microbial peptides from E. coli, N. amoraticivorans, and L. delbrueckii. However, experimental testing has shown that the H. pylori mimic (from urease beta) is not a target of cross-reactive responses specifically present in primary biliary cirrhosis[159]. The prevailing notion is that the mimic from H. pylori does not share amino acid similarity to an extent that could initiate cross-reactive response. On the contrary, the other microbial mimics have sufficient homologies with the human autoepitope and can promote molecular mimicry-based immune responses against self.