Immunoglobulin G1 Antibody Response toHelicobacter pylori Heat 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 ofH. pylori was expressed with a glutathioneS-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.

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Serum Antibodies to Helicobacter pylori and its Heat-Shock Protein 60 Correlate with the Response of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma to Eradication of H. pylori

Helicobacter ◽

10.1111/j.1083-4389.2004.00225.x ◽

2004 ◽

Vol 9 (3) ◽

pp. 194-200 ◽

Cited By ~ 12

Author(s):

Ryuta Takenaka ◽

Kenji Yokota ◽

Motowo Mizuno ◽

Hiroyuki Okada ◽

Tatsuya Toyokawa ◽

...

Keyword(s):

Helicobacter Pylori ◽

Heat Shock ◽

Gastric Mucosa ◽

Heat Shock Protein ◽

Lymphoid Tissue ◽

Heat Shock Protein 60 ◽

Serum Antibodies ◽

H Pylori

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Low-grade gastric mucosa-associated lymphoid tissue lymphoma: Clinicopathological factors associated with Helicobacter pylori eradication and tumor regression.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.353 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 353-353

Author(s):

Hyun Ik Shim ◽

Dong Ho Lee ◽

Jae Ho Cho ◽

Cheol Min Shin ◽

Hyuk Yoon ◽

...

Keyword(s):

Helicobacter Pylori ◽

Gastric Mucosa ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Tumor Regression ◽

Neutrophil Infiltration ◽

Tumor Location ◽

Gastric Malt Lymphoma ◽

Low Grade ◽

H Pylori

353 Background: Eradication of Helicobacter pylori is widely accepted as the initial therapy for low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The aim of this study was to assess the remission and relapse rates of low-grade gastric MALT lymphoma after H. pylori eradication and to identify the clinical factors affecting remission. Methods: We retrospectively analyzed 151 patients diagnosed with gastric MALT lymphoma from May 2003 to December 2018. Results: Of the 151 patients, 112 (74.2%) had an H. pylori infection. Total regression rates with eradication was 90.2% (101/112) in H. pylori-positive patients and 55% (11/20) in H. pylori-negative patients. Age, sex, tumor location, endoscopic findings, and the severity of mononuclear lymphocytes were not related to achieving successful initial H. pylori eradication and remission. However, patients with a smaller H. pylori burden ( p=0.030) and less neutrophil infiltration ( p=0.003) were more likely to achieve a successful initial H. pylori eradication. H. pylori ( p<0.001) and the burden ( p=0.020) were significantly related to remission of MALT lymphoma. Conclusions: The results show that H. pylori burden and neutrophil infiltration were inversely related to the success of the initial H. pylori eradication procedure and that the H. pylori burden was inversely related to the remission of MALT lymphoma.

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Immune Response against a Cross-Reactive Epitope on the Heat Shock Protein 60 Homologue of Helicobacter pylori

Infection and Immunity ◽

10.1128/iai.68.6.3448-3454.2000 ◽

2000 ◽

Vol 68 (6) ◽

pp. 3448-3454 ◽

Cited By ~ 39

Author(s):

Hiroyuki Yamaguchi ◽

Takako Osaki ◽

Masanori Kai ◽

Haruhiko Taguchi ◽

Shigeru Kamiya

Keyword(s):

Escherichia Coli ◽

Immune Response ◽

Helicobacter Pylori ◽

Heat Shock ◽

Heat Shock Protein ◽

Enzyme Linked Immunosorbent Assay ◽

Heat Shock Protein 60 ◽

Epitope Region ◽

H Pylori ◽

Human Hsp60

ABSTRACT We previously established a monoclonal antibody (MAb), designated H9, which reacts with the heat shock protein 60 (HSP60) homologue ofHelicobacter pylori as well as with other bacterial and human HSP60s. To determine the importance of a cross-reactive epitope on H. pylori HSP60 in H. pyloriimmunopathogenesis, we performed (i) mapping of an epitope on H. pylori HSP60 recognized by the H9 MAb, (ii) analysis of immunoglobulin G responses of patients with or without H. pylori infection to its epitope region, and (iii) studies of the protective effect of immunization with its epitope region onH. pylori infection in mice. The epitope recognized by the H9 MAb was mapped to the sequence of amino acids 189 to 203 (VEGMQFDRGYLSPYF) on the H. pylori HSP60 molecule. It was confirmed that the synthesized peptide designated pH9 was recognized by the H9 MAb. Enzyme-linked immunosorbent assay analysis showed that patients with H. pylori infection (n = 349) had significantly lower titers of pH9 antibody than did uninfected patients (n = 200) (P < 0.001), but this was not the case with purified H. pylori HSP60 recombinant Escherichia coli GroEL, or recombinant human HSP60. In C57BL/6 mice immunized with the pH9 peptide with Freund's complete adjuvant (FCA), the number of H. pylori organisms colonizing the stomach was significantly lower than that in mice immunized with pCont plus FCA (P < 0.0001) or FCA only (P < 0.005). The results suggest that the immune response to the cross-reactive epitope (pH9 region) on H. pylori HSP60 is unique and might be associated with protection against H. pylori infection.

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Evaluation of the Association of Nine Helicobacter pylori Virulence Factors with Strains Involved in Low-Grade Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Infection and Immunity ◽

10.1128/iai.72.2.880-888.2004 ◽

2004 ◽

Vol 72 (2) ◽

pp. 880-888 ◽

Cited By ~ 75

Author(s):

Philippe Lehours ◽

Armelle Ménard ◽

Sandrine Dupouy ◽

Bernard Bergey ◽

Fréderique Richy ◽

...

Keyword(s):

Helicobacter Pylori ◽

Gastric Mucosa ◽

Virulence Factors ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Gastric Lymphoma ◽

Gastric Malt Lymphoma ◽

Low Grade ◽

H Pylori ◽

Few Data

ABSTRACT Helicobacter pylori has been associated with the development of two malignant diseases: gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Although the cag pathogenicity island, especially the cagA gene, has been linked with adenocarcinoma, few data concerning H. pylori pathogenic factors involved in low-grade gastric MALT lymphoma are available. The goal of this study was to analyze the prevalence of and correlation between genes coding for seven H. pylori virulence factors (cagA, cagE, vacA, iceA, babA, hopQ, and oipA) and two novel adhesins (sabA and hopZ) by comparing a collection of 43 H. pylori strains isolated from patients with low-grade gastric MALT lymphoma to 39 strains isolated from age-matched patients with gastritis only. Our results show that taken individually, none of the nine genes tested can be considered associated with MALT strains and allow us to conclude that MALT pathogenesis is not linked with more proinflammatory H. pylori strains. We demonstrated that in patients infected with strains harboring the iceA1 allele, sabA functional status, and hopZ “off” status, the odds of developing a MALT lymphoma were 10 times higher. However, the low prevalence of such strains (10 of 43 MALT strains) renders this triple association a low-sensitivity marker for MALT strains. Our data confirmed that H. pylori virulence factors are correlated with one another. If the involvement of H. pylori in MALT lymphoma is well established, the pathomechanism by which gastric lymphoma occurs remains to be identified.

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Long-Term Persistence of Monoclonal B Cells After Cure of Helicobacter pylori Infection and Complete Histologic Remission in Gastric Mucosa–Associated Lymphoid Tissue B-Cell Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.6.1600 ◽

2001 ◽

Vol 19 (6) ◽

pp. 1600-1609 ◽

Cited By ~ 83

Author(s):

Christian Thiede ◽

Thomas Wündisch ◽

Birgit Alpen ◽

Beatrix Neubauer ◽

Andrea Morgner ◽

...

Keyword(s):

Helicobacter Pylori ◽

B Cells ◽

Sequence Analysis ◽

Gastric Mucosa ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Gastric Malt Lymphoma ◽

Low Grade ◽

H Pylori

PURPOSE: Cure of Helicobacter pylori infection is associated with remission induction in the majority of patients with low-grade gastric mucosa associated lymphoid tissue (MALT) lymphoma in localized stages; however, limited data exist as to whether these patients may be cured of their lymphoma. The present study was performed to investigate whether the polymerase chain reaction (PCR) for the rearranged immunoglobulin heavy chain region may be used to define “molecular” remission. PATIENTS AND METHODS: Ninety-seven patients who suffered from low-grade gastric MALT lymphoma stage IE were observed with central pathology and molecular biology after cure of H pylori infection. PCR was performed with the use of consensus primers for the framework regions 1, 2, and 3 and monoclonality was corroborated by sequence analysis. In selected cases, microdissection was performed to study the origin of the monoclonal B cells. RESULTS: Of the 97 patients, 77 obtained complete endoscopic and histologic remission (CR). Twenty of 44 patients with PCR monoclonality at diagnosis and with sufficient molecular follow-up displayed monoclonal bands for a median time of 20.5 months after CR (range, 0 to 50.4 months). These B cells were related to the original lymphoma clone by sequence analysis. Microdissection analysis identified basal lymphoid aggregates as the source of these monoclonal B cells. Local relapse occurred in and was observed by PCR in four patients. All four patients displayed monoclonal PCR before relapse, and three of these four showed ongoing PCR monoclonality throughout their course, indicating the persistence of malignant cells. CONCLUSION: Half of all patients with gastric MALT lymphoma show long-term PCR monoclonality up to several years after cure of H pylori infection and CR. Patients with monoclonal PCR should be observed closely, whereas long-term PCR negativity may indicate cure of the disease.

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Genetic Characterization and Clinical Features of Helicobacter pylori Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Cancers ◽

10.3390/cancers13122993 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2993

Author(s):

Barbara Kiesewetter ◽

Christiane Copie-Bergman ◽

Michael Levy ◽

Fangtian Wu ◽

Jehan Dupuis ◽

...

Keyword(s):

Gastric Mucosa ◽

Signaling Pathways ◽

Clinical Features ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Targeted Sequencing ◽

Clinicopathological Parameters ◽

Gastric Malt Lymphoma ◽

Genetic Changes ◽

H Pylori

Background: In Western countries, the prevalence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma has declined over the last three decades. Contemporaneously, H. pylori negative gastric MALT lymphoma is increasingly encountered, and their genetic basis and clinical features remain elusive. Methods: A total of 57 cases of H. pylori negative gastric MALT lymphoma were reviewed and investigated for chromosome translocation by fluorescence in-situ hybridization and for somatic mutations by the targeted sequencing of 93 genes. Results: MALT1 translocation, most likely t(11;18)(q21;q21)/BIRC3-MALT1, was detected in 39% (22/57) cases, and IGH translocation was further seen in 12 MALT1-negative cases, together accounting for 60% of the cohort. Targeted sequencing was successful in 35 cases, and showed frequent mutations in NF-κB signaling pathways (TNFAIP3 = 23%, CARD11 = 9%, MAP3K14 = 9%), together affecting 14 cases (40%). The NF-κB pathway mutations were mutually exclusive from MALT1, albeit not IGH translocation, altogether occurring in 86% of cases. There was no significant correlation between the genetic changes and clinicopathological parameters. The patients showed a median of progression-free survival (PFS) of 66.3 months, and a significant superior PFS when treated with systemic versus antibiotic therapy (p = 0.004). Conclusion: H. pylori negative gastric MALT lymphoma is characterized by highly frequent genetic changes in the NF-κB signaling pathways.

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T(11;18)(q21;q21) is associated with advanced mucosa-associated lymphoid tissue lymphoma that expresses nuclear BCL10

Blood ◽

10.1182/blood.v98.4.1182 ◽

2001 ◽

Vol 98 (4) ◽

pp. 1182-1187 ◽

Cited By ~ 172

Author(s):

Hongxiang Liu ◽

Hongtao Ye ◽

Ahmet Dogan ◽

Renzo Ranaldi ◽

Rifat A. Hamoudi ◽

...

Keyword(s):

Malt Lymphoma ◽

Lymphoid Tissue ◽

Fusion Transcript ◽

Low Grade ◽

Chain Reaction ◽

Nuclear Expression ◽

Molecular Events ◽

Multistep Process ◽

Polymerase Chain ◽

H Pylori

The development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a multistep process and can be clinico-pathologically divided into Helicobacter pylori-associated gastritis, low-grade tumors, and high-grade tumors. The molecular events underlying this progression are largely unknown. However, identification of the genes involved in MALT lymphoma-specific t(11;18)(q21;q21) and t(1;14)(p22;q32) has provided fresh insights into the pathogenesis of this disease. T(11;18)(q21;q21) results in a chimeric transcript between the API2 and theMALT1 genes, whereas t(1;14) (p22;q32) causes aberrant nuclear BCL10 expression. Significantly, nuclear BCL10 expression also occurs frequently in MALT lymphomas without t(1;14)(p22;q32), suggesting an important role for BCL10 in lymphoma development. Thirty-three cases of H pylori gastritis, 72 MALT lymphomas, and 11 mucosal diffuse large B-cell lymphomas (DLBCL) were screened for t(11;18)(q21;q21) by reverse transcription–polymerase chain reaction followed by sequencing. BCL10 expression in lymphoma cases was examined by immunohistochemistry. The API2–MALT1 fusion transcript was not detected in H pylorigastritis and mucosal DLBCL but was found in 25 of 72 (35%) MALT lymphomas of various sites. Nuclear BCL10 expression was seen in 28 of 53 (53%) of MALT lymphomas. Of the gastric cases, the largest group studied, the frequency of both t(11;18)(q21;q21) and nuclear BCL10 expression was significantly higher in tumors that showed dissemination to local lymph nodes or distal sites (14 of 18 = 78% and 14 of 15 = 93%, respectively) than those confined to the stomach (3 of 29 = 10% and 10 of 26 = 38%). Furthermore, t(11;18)(q21;q21) closely correlated with BCL10 nuclear expression. These results indicate that both t(11;18)(q21;q21) and BCL10 nuclear expression are associated with advanced MALT lymphoma and that their oncogenic activities may be related to each other.

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An unusual presentation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma following blunt abdominal trauma

BMJ Case Reports ◽

10.1136/bcr-2019-230878 ◽

2019 ◽

Vol 12 (10) ◽

pp. e230878

Author(s):

Karim Nashed ◽

Keith Lai ◽

Tyler Stevens ◽

Gareth Morris-Stiff

Keyword(s):

Gastric Mucosa ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Motor Vehicle ◽

Large Mass ◽

Vehicle Collision ◽

Repeat Endoscopy ◽

Multiple Biopsies ◽

H Pylori

A 79-year-old woman presented to the emergency department following a motor vehicle collision. As part of her workup she underwent a CT scan which identified a large mass containing calcifications centred around the gastric antrum, and while being assessed she produced 500 mL of haematemesis. An endoscopy revealed an area of friable mucosa the nature of which was uncertain, and multiple biopsies revealed amyloid deposition and active Helicobacter pylori gastritis. Following review of imaging and pathology, a diagnosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma was established. She was treated with quadruple therapy for the H. pylori and at 6-month follow-up she is asymptomatic with repeat endoscopy revealing healing of the ulceration and no biopsy evidence of H. pylori or MALT.

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Antibody to Heat Shock Protein Can Be Used for Early Serological Monitoring of Helicobacter pylori Eradication Treatment

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.7.4.574-577.2000 ◽

2000 ◽

Vol 7 (4) ◽

pp. 574-577 ◽

Cited By ~ 12

Author(s):

Naoko Yunoki ◽

Kenji Yokota ◽

Motowo Mizuno ◽

Yoshiro Kawahara ◽

Masayasu Adachi ◽

...

Keyword(s):

Helicobacter Pylori ◽

Heat Shock ◽

Antimicrobial Agents ◽

Eradication Therapy ◽

Enzyme Linked Immunosorbent Assay ◽

Peptic Ulcers ◽

Whole Cell ◽

Humoral Immune ◽

Whole Cell Lysate ◽

H Pylori

ABSTRACT Infection with Helicobacter pylori induces humoral immune responses against various antigens of the bacterium. Heat shock proteins (hsps) are immunodominant antigens in various diseases including H. pylori infection. In the present study, we measured the anti-hsp antibody titers in 42 patients with H. pylori-infected peptic ulcers during a bacterial eradication study. The patients were treated with a proton pump inhibitor and antimicrobial agents to eradicate the organism. Their sera were obtained at pretreatment and at 1 month and 6 months after the eradication therapy. The titers of immunoglobulin G antibodies to theH. pylori hsp, whole-cell lysate, and urease (30-kDa subunit) antigens in serum were measured by a capture enzyme-linked immunosorbent assay. The levels of H. pylori hsp60 antibodies in sera collected 1 month after treatment had declined significantly, even when changes in the titers of antibodies to whole-cell and urease antigens were not apparent. These results suggest that measurement of antibodies to H. pylorihsp60 in serum is useful for the early monitoring of the effectiveness of eradication therapy.

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