Gastric Autoantigenic Proteins inHelicobacter PyloriInfection

Abstract

PurposeThis study tried to identify novel gastric autoimmune antigens that might be involved in aggravating the atrophic gastritis among patients with Helicobacter pylori infection using two-dimensional immunoblotting analysis.Materials and MethodsProteins from gastric mucosal antrectomy specimens and AGS cells (gastric adenocarcinoma cell lines derived from a Caucasian patient who had received no prior therapy) were 2-dimensionally immunoblotted separately with a pool of 300 sera from H. pylroi-infected patients at Gyeongsang National University Hospital.ResultsThirty-eight autoantigenic proteins including alcohol dehydrogenase [NADP+], alpha enolase, gastrokine-1, gastric triacylglycerol lipase, heat shock 70 kDa protein 1, and peroxiredoxin-2 were identified in the gastric mucosal tissue. Fourteen autoantigenic proteins including programmed cell death 6-interacting protein, serum albumin and T-complex protein 1 subunit gamma were identified in the AGS cells. Albumin, alpha-enolase, annexin A3, cytoplasmic actin 1, heat shock cognate 71 kDa protein and leukocyte elastase inhibitor were commonly observed autoantigenic proteins in both gastric mucosal tissue and AGS cells. Alpha-enolase, glutathione S-transferase P, heat shock cognate 71 kDa protein, heat shock 70 kDa protein 1, human mitochondrial adenosine triphosphate synthase (ATP) subunit beta, mitochondrial 60 kDa heat shock protein, peroxiredoxin-2, 78 kDa glucose-regulated protein precursor, tyrosine-protein phosphatase non-receptor type 11 and Tryptophan-Aspartic acid (WD) repeat-containing protein 1 showed 60% or higher amino acid positivity.ConclusionThese newly identified gastric autoimmune antigens might be useful in the control and prevention of gastroduodenal disorders, and might be valuable in breaking the vicious circle that exists in gastroduodenal disorders if their pathophysiological roles could be understood in the progress of chronic atrophic gastritis, gastroduodenal ulcers, intestinal metaplasia, and gastric carcinogenesis.

Autoantibodies to a specific peptide epitope of human Hsp60 (ATVLA) with homology to Helicobacter pylori HspB in H. pylori‐infected patients

“…Among infectious agents, Chlamydophila pneumoniae , H. pylori and also viruses are often typed as a source of cross‐reacting exogenous antigens, whereas oxLDL, phospholipids and Hsp60 as human autoantigens potentially involved in atherogenesis . Hsp60 of bacterial origin induces host immune responses to fight infection, whereas autologous Hsp60 should remain tolerated.…”

“…Helicobacter pylori which are Gram‐negative rods, colonize the gastric epithelium of humans and if not eradicated, can persist for the whole life constituting a risk factor of excessive inflammatory response potentially leading to gastric or duodenal ulcers, chronic gastritis and even mucosa‐associated lymphoid tissue (MALT) lymphoma or gastric cancer . The role of H. pylori in extragastric diseases including immune thrombocytopenic purpura (ITP), iron deficiency anemia (IDA), vitamin B12 deficiency, cardiovascular diseases, diabetes mellitus, dermatological and neurologic disorders as well as lung cancer was suggested . One concept links these extragastric diseases with molecular mimicry between human and H. pylori compounds released from lysed bacteria , which destroy the gastric barrier and induce humoral and cellular immune responses deleterious to the host .…”

“…The role of H. pylori in extragastric diseases including immune thrombocytopenic purpura (ITP), iron deficiency anemia (IDA), vitamin B12 deficiency, cardiovascular diseases, diabetes mellitus, dermatological and neurologic disorders as well as lung cancer was suggested . One concept links these extragastric diseases with molecular mimicry between human and H. pylori compounds released from lysed bacteria , which destroy the gastric barrier and induce humoral and cellular immune responses deleterious to the host . A well‐documented example of cross‐reactivity caused by antigenic mimicry is Guillan‐Barre Syndrome, a neurodegenerative disease linked to Campylobacter jejuni infection .…”

Molecular mimicry inHelicobacter pyloriinfections

“…A proteomics investigation of anti-gastric autoantibody profiles in the sera of 300 Korean adults infected with H. pylori , revealed nearly forty autoantigenic proteins, including nicotinamide adenine dinucleotide phosphate (NADP+) alcohol dehydrogenase, alpha enolase, gastrokine-1, gastric triacylglycerol lipase, Hsp70 kDa protein 1, and peroxiredoxin-2. These proteins were detected in the gastric mucosal tissue[ 59 ]. The programmed cell death 6 - interacting protein, serum albumin and T-complex protein 1 subunit gamma were identified in the AGS cells.…”

“…Many previous studies have stated that chronic infection with H. pylori has a significant influence on the immune system. Therefore, the possible mechanisms of H. pylori infections in the pathogenesis of the majority of extragastric diseases include chronic local or systemic inflammation and the initiation of autoimmune responses[ 59 ].…”