B-Zell stimulatorische Faktoren der TNF-Familie bei MALT-Lymphomen des Magens

Marginalzonen B-Zell-Lymphome vom MALT-Typ des Magens sind zu ca. 90% mit einer HP-induzierten chronischen Gastritis assoziiert. Die Eradikation von HP kann in frühen Stadien zu einer Remission des Lymphoms führen. Dies und die Tatsache, dass die Proliferation von Lymphomzellen in vitro auf die Anwe...

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Bibliographic Details
Main Author: Sivanathan, Visvakanth
Format: Doctoral Thesis
Language:German
Published: Philipps-Universität Marburg 2010
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Table of Contents: Early gastric MALT (mucosa associated lymphoid tissue) lymphoma is still dependent on antigen presentation as indicated by the remission after Helicobacter pylori (H.p.) eradication. Autocrine and paracrine secretion of B-cell stimulatory factors by inflammatory bystander cells may sustain lymphoma growth and survival. The TNF (tumor necrosis factor) familiy members BAFF (B cell- activating factor of the TNF family) and APRIL (A Proliferation Inducing-ligand) have previously been shown to be expressed in B-cell lymphomas. We assessed the expression levels of BAFF and APRIL, as well as their receptors BAFF-R (BAFF receptor) and TACI (Transmembrane Activator and CAML Interactor) in 24 patients with early gastric MALT lymphomas by real-time quantitative PCR of snap-frozen biopsy samples. Distant biopsies with gastric MALT, but without evidence for lymphoma, from the same patients were used for intra-individual comparison. A second independent cohort of 28 patients with H.p.-associated chronic gastritis was used for inter-individual comparison. BAFF was significantly up-regulated in lymphoma tissue when compared with chronic gastritis in the inter-individual group (chronic gastritis 0,03 [standard deviation (SD)=0,21] < lymphoma tissue 0,07 [SD=0,16], Mann Whitney test (MWT) p=0,03). APRIL (chronic gastritis 24,01 [SD=19,94]) > lymphoma tissue 10,41 [SD= 6,93], unpaired t-test p=0,007) as well as TACI (chronic gastritis 16,82 [SD=6060,83] > lymphoma tissue 5,34 [SD=8,47], MWT p=0,01) were down-regulated in lymphoma tissue in comparison to the chronic gastritis tissue. No differences could be shown for the same genes in the intra-individual comparison group. No differences were found for BAFF-R between all groups. The higher expression of BAFF in both, lymphoma and non-neoplastic gastritis, in gastric MALT lymphoma as compared to lymphoid tissue of chronic gastritis cases suggests an involvement of BAFF in the development of gastric MALT lymphoma. In addition, the lower expression of TACI as a negative regulator of B-cell development may further support the importance of B-cell stimulatory factors and their receptors. However, the absence of significant differences within a given patient with gastric MALT lymphoma indicates the necessity of additional events for full transformation.