scholarly journals The Helicobacter pylori CagY Protein Drives Gastric Th1 and Th17 Inflammation and B Cell Proliferation in Gastric MALT Lymphoma

2021 ◽  
Vol 22 (17) ◽  
pp. 9459
Author(s):  
Chiara Della Bella ◽  
Maria Felicia Soluri ◽  
Simone Puccio ◽  
Marisa Benagiano ◽  
Alessia Grassi ◽  
...  

Background: the neoplastic B cells of the Helicobacter pylori-related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma proliferate in response to H. pylori, however, the nature of the H. pylori antigen responsible for proliferation is still unknown. The purpose of the study was to dissect whether CagY might be the H. pylori antigen able to drive B cell proliferation. Methods: the B cells and the clonal progeny of T cells from the gastric mucosa of five patients with MALT lymphoma were compared with those of T cell clones obtained from five H. pylori–infected patients with chronic gastritis. The T cell clones were assessed for their specificity to H. pylori CagY, cytokine profile and helper function for B cell proliferation. Results: 22 of 158 CD4+ (13.9%) gastric clones from MALT lymphoma and three of 179 CD4+ (1.7%) clones from chronic gastritis recognized CagY. CagY predominantly drives Interferon-gamma (IFN-γ) and Interleukin-17 (IL-17) secretion by gastric CD4+ T cells from H. pylori-infected patients with low-grade gastric MALT lymphoma. All MALT lymphoma-derived clones dose dependently increased their B cell help, whereas clones from chronic gastritis lost helper activity at T-to-B-cell ratios greater than 1. Conclusion: the results obtained indicate that CagY drives both B cell proliferation and T cell activation in gastric MALT lymphomas.

2018 ◽  
Vol 11 (3) ◽  
pp. 187-193 ◽  
Author(s):  
Petruta Violeta Filip ◽  
◽  
Denisa Cuciureanu ◽  
Laura Sorina Diaconu ◽  
Ana Maria Vladareanu ◽  
...  

Primary gastric lymphoma (PGL) represents a rare pathology, which can be easily misdiagnosed because of unspecific symptoms of the digestive tract. Histologically, PGL can vary from indolent marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) to aggressive diffuse large B-cell lymphoma (DLBCL). During the years, clinical trials revealed the important role of Helicobacter pylori (H. pylori) in the pathogenesis of gastric MALT lymphoma. Infection with Helicobacter pylori is an influential promoter of gastric lymphomagenesis initiation. Long-term studies revealed that eradication therapy could regress gastric lymphomas.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 353-353
Author(s):  
Hyun Ik Shim ◽  
Dong Ho Lee ◽  
Jae Ho Cho ◽  
Cheol Min Shin ◽  
Hyuk Yoon ◽  
...  

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.


1999 ◽  
Vol 117 (5) ◽  
pp. 1105-1112 ◽  
Author(s):  
Mario M. D'Elios ◽  
Amedeo Amedei ◽  
Marta Manghetti ◽  
Francesco Costa ◽  
Cosima T. Baldari ◽  
...  

2014 ◽  
Vol 51 (2) ◽  
pp. 84-89 ◽  
Author(s):  
Karine Sampaio LIMA ◽  
Walton ALBUQUERQUE ◽  
Vitor Nunes ARANTES ◽  
Ana Paula DRUMMOND-LAGE ◽  
Luiz Gonzaga Vaz COELHO

ContextGastric mucosa-associated lymphoid tissue (MALT) lymphoma is clearly associated with Helicobacter pylori gastritis and can be cured with anti- H pylori therapy alone. The presence of t(11;18)(q21;q21) translocation is thought to predict a lower response rate to anti- H pylori treatment.ObjectivesTo study the presence of t(11;18)(q21;q21) genetic translocation and its clinical impact in low-grade gastric MALT lymphoma Brazilian patients.MethodsA consecutive series of eight patients with gastric MALT lymphoma were submitted to gastroscopy, endoscopic ultrasound, histopathological examination, H pylori search and RT-PCR-based methodology. All patients received anti-H pylori treatment. Eradicated patients were followed-up every 3-6 months for 2 years.ResultsEight patients were studied. All patients had tumor involvement restricted to the mucosa or submucosa and seven patients had low-grade gastric MALT lymphoma. All infected patients achieved H pylori eradication. Histological tumor regression was observed in 5/7 (71%) of the low-grade gastric MALT lymphoma patients. The presence of t(11;18)(q21;q21) translocation was found in 4 (57%) of these patients; among them only two had histological tumor regression following H pylori eradication.ConclusionsRT-PCR is a feasible and efficient method to detect t(11;18)(q21;q21) translocation, being carried out in routine molecular biology laboratories. The early detection of such translocation can be very helpful for better targeting the therapy to be applied to gastric MALT lymphoma patients.


2015 ◽  
Vol 72 (5) ◽  
pp. 431-436 ◽  
Author(s):  
Sasa Grgov ◽  
Vuka Katic ◽  
Miljan Krstic ◽  
Aleksandar Nagorni ◽  
Biljana Radovanovic-Dinic ◽  
...  

Background/Aim. Lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) of the stomach usually occurs as a consequence of Helicobacter pylori (H. pylori) infection. The aim of this study was to investigate the long-term effect of treatment of low-grade gastric MALT lymphoma with the H. pylori eradication method. Methods. In the period 2002-2012 in 20 patients with dyspepsia, mean age 55.1 years, the endoscopic and histologic diagnosis of gastric MALT lymphoma in the early stages were made. Histological preparations of endoscopic biopsy specimens were stained with hematoxyllineosin (HE), histochemical and immunohistochemical methods. Results. Endoscopic findings of gastritis were documented in 25% of the patients, and 75% of the patients had hypertrophic folds, severe mucosal hyperemia, fragility, nodularity, exulcerations and rigidity. Histopathologically, pathognomonic diagnostic criterion were infiltration and destruction of glandular epithelium with neoplastic lymphoid cells, the so-called lymphoepithelial lesions. In all 20 patients H. pylori was verified by rapid urease test and Giemsa stain. After the triple eradication therapy complete remission of MALT lymphoma was achieved in 85% of the patients, with no recurrence of lymphoma and H. pylori infection in the average follow-up period of 48 months. In 3 (15%) of the patients, there was no remission of MALT lymphoma 12 months after the eradication therapy. Of these 3 patients 2 had progression of MALT lymphoma to diffuse large-cell lymphoma. Conclusion. Durable complete re-mission of low-grade gastric MALT lymphoma is achieved in a high percentage after eradication of H. pylori infection, thus preventing the formation of diffuse large-cell lymphoma and gastric adenocarcinoma.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5010-5010
Author(s):  
Takakazu Kawase ◽  
Keitaro Matsuo ◽  
Tsuneya Nakamura ◽  
Junya Kanda ◽  
Hidemi Ito ◽  
...  

Abstract Abstract 5010 Extranodal marginal zone B-cell lymphoma of mucosaassociated lymphoid tissue (MALT Lymphoma) is low-grade extranodal lymphoma, and it comprises 7-8% of all B cell lymphomas, and up to 50% of primary gastric lymphoma. It is known that a preexisting chronic inflammation such as Helicobactoer pylori (H. pylori) gastritis can influence its development, however, some MALT lymphomas with no evidence of such inflammation are found. Protracted remissions may be induced by H. pylori eradication therapy, but cases with t(11;18)(q21;q21) appear to be resistant to the therapy. t(11;18)(q21;q21) has been observed in 25-50% of the cases and API2 at 11q21 and MALT1 at 18q21 are fused as a result of this translocation. Thus, API2-MALT1 fusion positive and negative MALT lymphoma may have different etiology, although histological features of both MALT lymphomas have not been clearly delineated. To clarify differences of epidemiological features between API2-MALT1 fusion positive and negative gastric MALT lymphoma, we conducted a case-control study of 61 newly and histologically diagnosed gastric MALT lymphoma cases (14 of API2-MALT1 fusion positive cases and 47 of negative cases) and 610 age and sex frequency-matched non-cancer controls. API2-MALT1 fusion was evaluated by a multiplex reverse transcription-polymerase chain reaction using formalin-fixed, paraffinembedded sections. We evaluated the association with alcohol intake (never drinkers, occasional drinkers, and frequent but moderate (<50 g/day of alcohol) and frequent and heavy drinkers (≥50 g/day of alcohol)), smoking (<5, 5-19, 20-39, ≥40 pack-years), past history of gastroduodenal ulcer, height, and risk of API2-MALT1 fusion positive and negative gastric MALT lymphoma. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using multinomial logistic models adjusted for potential confounders. A significant association was observed between past history of gastroduodenal ulcer and the risk only among fusion negative cases, with ORs of subjects with past history of gastroduodenal ulcer of 2.86 (95% CI, 1.31-6.14; p = 0.008) compared to subjects without past history of gastroduodenal ulcer. No clear associations were observed between alcohol intake, smoking, height and the risk irrespective of positivity of API2-MALT1 fusion. These findings suggest that past history of gastroduodenal ulcer, which may be due to H.pylori infection, does not associated with the carcinogenic mechanism of API2-MALT1 fusion positive gastric MALT lymphoma, and fusion positive and negative tumors have different etiology. Further investigations using large data sets are needed. Disclosures No relevant conflicts of interest to declare.


2004 ◽  
Vol 72 (2) ◽  
pp. 880-888 ◽  
Author(s):  
Philippe Lehours ◽  
Armelle Ménard ◽  
Sandrine Dupouy ◽  
Bernard Bergey ◽  
Fréderique Richy ◽  
...  

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.


2001 ◽  
Vol 19 (6) ◽  
pp. 1600-1609 ◽  
Author(s):  
Christian Thiede ◽  
Thomas Wündisch ◽  
Birgit Alpen ◽  
Beatrix Neubauer ◽  
Andrea Morgner ◽  
...  

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.


2013 ◽  
pp. 154-158
Author(s):  
Angelo Zullo ◽  
Cesare Hassan ◽  
Francesca Cristofari ◽  
Claudia Iegri ◽  
Nicoletta Villiva ◽  
...  

The incidence of primary gastric lymphoma in Italy is considerably higher than that observed in the rest of Europe. It is widely accepted that gastric B-cell, low-grade mucosalassociated lymphoid tissue (MALT) lymphoma is caused by specific host-bacterial interactions that occur during Helicobacter pylori infection. This review examines recent findings on the origins, diagnosis, treatment, and follow-up of gastric MALT lymphomas. Clinical and endoscopic findings at diagnosis vary widely. In a substantial number of cases, the patient presents only vague dyspeptic symptoms or poorly defined abdominal pain with no macroscopic lesions on the gastric mucosa. Review of data from 32 trials in which a total of 1,387 MALT-lymphoma patients of the stomach were treated solely with H. pylori eradication revealed high remission rates when the disease is treated early (stage I-II1). Neoplasia confined to the submucosa, antral localization of tumors, and negativity for the API2-MALT1 translocation were associated with a high probability of remission following H. pylori eradication. When the latter approach is not sufficient, radiotherapy, chemotherapy and, in selected cases, surgery are associated with high success rates; data on the efficacy of monoclonal antibody therapy (rituximab) are still limited. Five-year survival rates are higher than 90%. Patients whose tumors have been eliminated require close, long-term endoscopic follow-up since recurrence has been reported in some cases. Broader clinical follow-up is also advisable because the incidence of other solid tumors and of cardiovascular events is reportedly increased in these patients.


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