Enhanced systemic matrix metalloproteinase response in Helicobacter pylori gastritis.

BACKGROUND: Helicobacter pylori causes chronic gastritis, peptic ulcer disease, and is the most important risk factor for non-cardia gastric cancer, and has been shown to upregulate matrix metalloproteinases (MMPs) in infected gastric mucosa. MMPs are proteolytic enzymes regulated by tissue inhibitors of metalloproteinases (TIMPs). AIMS: We set up this study to find out whether H. pylori gastritis induces systemic MMP response. METHODS: Serum samples were collected from patients undergoing gastroscopy; 26 patients had H. pylori gastritis and 18 were H. pylori-negative controls with normal gastric mucosa. Serum MMP levels were analysed by enzyme-linked immunosorbent assay. RESULTS: Significantly elevated serum levels of collagenase-2 (MMP-8), gelatinase B (MMP-9), neutrophil elastase (NE), and myeloperoxidase (MPO), and reduced serum levels of gelatinase A (MMP-2) and TIMP-1 were demonstrated in patients with H. pylori gastritis as compared to H. pylori-negative controls. No significant differences were shown in serum matrilysin-1 (MMP-7) levels. CONCLUSIONS: For the first time, we show enhanced MMP-8 response in H. pylori infection together with other neutrophil degranulation products (MMP-9, MPO, NE). Elevated circulating neutrophil degranulation product levels in serum of H. pylori-positive patients reflect accelerated proteolysis and oxidative stress, and may contribute to extraintestinal sequelae, such as cardiovascular diseases.

Sequence analysis of the genes encoding for H+/K+-ATPase in autoimmune gastritis.

BACKGROUND: H+/K+-ATPase is the target autoantigen in autoimmune gastritis (AIG), an organ-specific autoimmune disease with a strong hereditary component. AIM: To detect possible polymorphisms in H+/K+-ATPase alpha- and beta-subunits in AIG patients. METHODS: Blood samples from 12 Finnish AIG patients were sequenced for the coding regions of genes encoding for H+/K+-ATPase alpha- and beta-subunits; 50-52 Finnish anonymous blood donors served as controls. Additionally, parietal cell and Helicobacter pylori antibodies and serum pepsinogen I levels (PG I) were analysed. RESULTS: In the alpha-subunit, all patients and controls had C-allele at the non-synonymous c.824T>C single nucleotide polymorphism (SNP) resulting in valine substitution for alanine (Val265Ala). In the beta-subunit, a previously unknown non-synonymous SNP resulting in a substitution of alanine residue for valine (Ala248Val) was found in exon 7 in a single patient and none of the controls. All patients had low serum PG I levels and elevated parietal cell antibodies; three had positive H. pylori serology. CONCLUSIONS: At the non-synonymous SNP c.824T>C in the alpha-subunit of H+/K+-ATPase most Finnish individuals with or without AIG have C allele. Genetic variants of the coding regions of genes for H+/K+-ATPase alpha- and beta-subunits are not associated with AIG in Finnish patients.