Immunoglobulin G1 Antibody Response toHelicobacter pyloriHeat Shock Protein 60 Is Closely Associated with Low-Grade Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Abstract

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is related to Helicobacter pylori infection. Specifically, it has been pointed out that pathogenesis of MALT lymphoma involves the 60-kDa heat shock protein (hsp60). To investigate humoral immune responses to the H. pylori hsp60 in patients with gastroduodenal diseases and patients with MALT lymphoma, the hsp60 of H. pylori was expressed with a glutathione S-transferase fusion protein and was purified (recombinant hsp60). Sera were obtained from H. pylori-positive patients with gastroduodenal diseases (MALT lymphoma, n ‫؍‬ 13; gastric ulcer, n ‫؍‬ 20; duodenal ulcer, n ‫؍‬ 20; gastritis, n ‫؍‬ 20) and from H. pylori-negative healthy volunteers (n ‫؍‬ 9). Sera from patients with MALT lymphoma were also obtained at two times: before and after eradication therapy. Antibodies to hsp60 and H. pylori were assessed by enzyme-linked immunosorbent assay. The levels of immunoglobulin G (IgG) antibodies to the hsp60 of H. pylori-positive patients with gastroduodenal diseases were significantly elevated compared to those in the controls. The levels of IgG1 antibodies to hsp60 were elevated and correlated with the levels of anti-H. pylori antibodies in patients with MALT lymphoma. Humarol immunity against hsp60 may be important and relevant to gastroduodenal diseases induced by H. pylori infection.Helicobacter pylori is now recognized as a cause of gastritis, peptic ulcer, gastric cancer, and gastric mucosa-associated lymphoid tissue (MALT) lymphoma (9, 19). Several H. pylori pathogenic factors, including CagA and VacA, may contribute to the gastric mucosal damage (6, 7). In recent years, it has also been accepted that host immune reactions play an important role in the pathogenesis of H. pylori infection. Although H. pylori is a noninvasive bacterium and is restricted to gastric epithelial cells, infection with H. pylori induces humoral and cellular immune responses in the gastric mucosa (16,22). Bacterial attachment causes induction of interleukin-8 (IL-8) release, and Cag proteins evoke activation of nuclear factor-B and release of IL-8 that may support leukocyte attachment during inflammation (8,17,21). However, the bacterial antigens associated with inflammation are still not clear.Heat shock proteins (hsp's) are immunodominant antigens in various diseases including H. pylori infection (4, 26). Our previous studies have shown that the 60-kDa hsp (hsp60) is expressed in the follicular dendritic cells of the gastric mucosa in patients with gastric MALT lymphoma (15) and that antibodies to human hsp60 can be detected in MALT lymphoma patients (14). These results indicate that hsp60 may be associated with the host immune reaction in H. pylori infection, specifically, the pathogensis of gastric MALT lymphoma.In the present study, H. pylori hsp60 recombinant protein was expressed, and the levels of immunoglobulin G (IgG), IgG1, IgG2, IgM, and IgA antibodies to hsp60 in sera were measured in patients with gastric ulcer, duodenal ulcer, gastritis, and gastric MALT lympho...

Treatment of low-grade gastric MALT-lymphoma unresponsive to Helicobacter pylori therapy

“…Regrettably, we identified 12 studies in which data regarding oncologic treatments eventually used in 152 patients following H. pylori therapy were not provided [38][39][40][41][42][43][44][45][46][47][48][49]. While waiting for a prospective, randomized study, future series on lymphoma remission following H. pylori eradication should provide data on the oncologic therapeutic success in those patients who failed to respond to antibiotic therapy.…”

“…Of these, 29 trials were finally included , whilst the remaining 12 studies were excluded due to lack of either treatment option chosen or treatment efficacy following H. pylori eradication therapy failure [38][39][40][41][42][43][44][45][46][47][48][49]. Among the 29 trials included in this pooled-data analysis, the study design was prospective in 21 series and retrospective in the remaining eight series.…”

Helicobacter pylori—An Infectious Risk Factor for Atherosclerosis?

“…For example, H. pylori-derived HSP60 (Hp-HSP60) is an important antigen that is abundantly expressed under various environmental stressors 113) . Hp-HSP60 has been found to appear on antigen-presenting cells in the germinal center in the gastric lymphoid tissues of patients infected with H. pylori 114) , and antibodies cross-reactive to both endogenous HSP60 and Hp-HSP60 have been found in the sera of H. pyloriinfected patients 115,116) . Notably, IgG antibodies against a particular amino acid sequence of Hp-HSP60 are able to recognize full-sequenced human HSP60, indicating that immune responses against HSP60 of pathogenic origin are misdirected to a human counterpart 117) .…”

Antibodies against heat shock protein 60 derived from Helicobacter pylori: Diagnostic implications in cardiovascular disease

“…We obtained the full sequence of Hp-HSP60 (Hp-HSP60 w ; Met 1 eMet 545 ) and two soluble peptides in Hp-HSP60 (which have about 90% identical amino acids). They were Hp-HSP60 II (referred to as Hp-HSP60 2 in a previous paper [28]); Glu 101 eSer 200 , and Hp-HSP60 IVeV (referred to as Hp-HSP60 4e5 in a previous paper [28]); Ile 300 eGly 435 . The homology of the amino acid sequence between human and Hp derived HSP60s is shown in Fig.…”

“…1. These recombinant proteins were expressed as described previously [28]. PCR primers were designed based on sequences published in GenBank.…”