Development Of Mucosa-associated Lymphoid Tissue Research Articles

Determination of Autoantibodies to Salivary Gland Antigens.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease marked by dry mouth/dry eye symptoms as a result of the destruction of the salivary and lacrimal glands. Patients with pSS may be at risk for the development of mucosa-associated lymphoid tissue (MALT) lymphoma. Testing of autoantibodies in the oral fluid of patients with pSS or MALT lymphoma using immunoassays may lead to a simple and noninvasive clinical tool for diagnostic or prognostic applications. In this chapter, we describe the procedures and protocols for determining autoantibodies to salivary gland antigens with proteomics-related methods, including 2D gel electrophoresis, liquid chromatography-tandem mass spectrometry (LC-MS/MS), Western blotting, protein microarray, and enzyme-linked immunosorbent assay (ELISA).

Significant association between TNFAIP3 inactivation and biased immunoglobulin heavy chain variable region 4-34 usage in mucosa-associated lymphoid tissue lymphoma.

Both antigenic drive and genetic change play critical roles in the development of mucosa-associated lymphoid tissue (MALT) lymphoma, but neither alone is sufficient for malignant transformation, and lymphoma development critically depends on their cooperation. However, which of these different events concur and how they cooperate in MALT lymphomagenesis is totally unknown. To explore this, we investigated somatic mutations of 17 genes and immunoglobulin heavy chain variable region (IGHV) usage in 179 MALT lymphomas from various sites. We showed that: (1) there was a significant association between the biased usage of IGHV4-34 (binds to the carbohydrate I/i antigens) and inactivating mutation of TNFAIP3 [encoding a global negative regulator of the canonical nuclear factor-κB (NF-κB) pathway] in ocular adnexal MALT lymphoma; (2) IGHV1-69 was significantly overrepresented (54%) in MALT lymphoma of the salivary gland, but was not associated with mutation in any of the 17 genes investigated; and (3) MALT lymphoma lacked mutations that are frequently seen in other B-cell lymphomas characterized by constitutive NF-κB activities, including mutations in CD79B, CARD11, MYD88, TNFRSF11A, and TRAF3. Our findings show, for the first time, a significant association between biased usage of autoreactive IGHV and somatic mutation of NF-κB regulators in MALT lymphoma, arguing for their cooperation in sustaining chronic B-cell receptor signalling and driving oncogenesis in lymphoma development. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Helicobacter suis Causes Severe Gastric Pathology in Mouse and Mongolian Gerbil Models of Human Gastric Disease

Background“Helicobacter (H.) heilmannii” type 1 is the most prevalent gastric non-H. pylori Helicobacter species in humans suffering from gastric disease. It has been shown to be identical to H. suis, a bacterium which is mainly associated with pigs. To obtain better insights into the long-term pathogenesis of infections with this micro-organism, experimental infections were carried out in different rodent models.Methodology/Principal FindingsMongolian gerbils and mice of two strains (BALB/c and C57BL/6) were infected with H. suis and sacrificed at 3 weeks, 9 weeks and 8 months after infection. Gastric tissue samples were collected for PCR analysis, histological and ultrastructural examination. In gerbils, bacteria mainly colonized the antrum and a narrow zone in the fundus near the forestomach/stomach transition zone. In both mice strains, bacteria colonized the entire glandular stomach. Colonization with H. suis was associated with necrosis of parietal cells in all three animal strains. From 9 weeks after infection onwards, an increased proliferation rate of mucosal epithelial cells was detected in the stomach regions colonized with H. suis. Most gerbils showed a marked lymphocytic infiltration in the antrum and in the forestomach/stomach transition zone, becoming more pronounced in the course of time. At 8 months post infection, severe destruction of the normal antral architecture at the inflamed sites and development of mucosa-associated lymphoid tissue (MALT) lymphoma-like lesions were observed in some gerbils. In mice, the inflammatory response was less pronounced than in gerbils, consisting mainly of mononuclear cell infiltration and being most severe in the fundus.Conclusions/Significance H. suis causes death of parietal cells, epithelial cell hyperproliferation and severe inflammation in mice and Mongolian gerbil models of human gastric disease. Moreover, MALT lymphoma-like lesions were induced in H. suis-infected Mongolian gerbils. Therefore, the possible involvement of this micro-organism in human gastric disease should not be neglected.

MALT und Epithel der Mittelohrschleimhaut. Morphologische Untersuchung

The mucosa of the middle ear and the Eustachian Tube changes in different ways when faced with recurrent episodes of inflammation. It thereby adapts to these new stimuli and insults from the environment. One of these changes is the development of MALT (mucosa associated lymphoid tissue). Another adaptation is an alteration of the epithelium. It was therefore the purpose of this study to look for a connection between the occurrence of these changes. 90 sections of temporal bones were examined under the light microscope and the incidence of MALT and nature of the epithelium found were compared. Particularly in the middle ear, we demonstrated that in cases where MALT was found within the mucosa, columnar epithelium was frequently found in locations where it is typically rare. Squamous epithelium was in many cases replaced by cuboidal epithelium. We demonstrated that the mucosa of the middle ear changed its morphology towards the characteristics typically found in the upper respiratory tract in cases where MALT had developed as subepithelial lymphoid follicles. It can therefore be concluded that both changes represent the mucosa's reaction to recurrent or chronic inflammation.

Histological and immunohistochemical study of the lymphoid tissue in the normal stomach of the gnotobiotic pig.

Animal models have been developed in which the role of Helicobacter pylori in the pathogenesis of different gastroduodenal diseases can be investigated. The gnotobiotic pig was one of the first animal models used. In this model, Helicobacter pylori infection causes gastritis, which shows some similarities to that in humans, such as the development of mucosa-associated lymphoid tissue (MALT). Hence, this animal model can be used to study the development of MALT in the normal stomach. The aim of our study is to see if lymphoid tissue is present or absent in the normal stomach of gnotobiotic pigs before birth and if so, to investigate its development and composition as a function of gestational age and location in the stomach. Therefore, we studied 82 foetal piglets using routine histology and immunohistochemistry. Our findings show that lymphoid tissue is present at birth. It is composed of lymphoid nodules, a diffuse mononuclear infiltrate and intra-epithelial lymphocytes. The development is a sequential process. The lymphoid tissue in the stomach at birth is composed of the immunohistochemically different immunocompetent cells normally present. In conclusion, MALT is present in normal foetal gnotobiotic pig gastric mucosa, and in this model the stomach is no exception to the rest of the gastrointestinal tract.

Accurate Diagnosis of Helicobacter pylori: Serologic Testing

Serologic testing is a useful noninvasive testing strategy for H. pylori. It is particularly useful in areas where the prevalence of H. pylori is high and inexpensive point-of-contact fingerprick tests are used. Sensitive tests are valuable ways of excluding H. pylori infection and can be used in conjunction with a direct test (urease histology culture or breath test) to confirm absence of H. pylori if the two methods are concordant. Serologic testing is more definitive and differentiating if the antigenic epitopes of H. pylori can be differentiated based on the antigenic epitopes that specifically associate with gastric cancer, peptic ulcer, and nonulcer dyspepsia. A study by Kawahara's group reported that Hsp 60 may be involved in the development of mucosa-associated lymphoid tissue based on ELISA. The idea of differentiating antigens for H. pylori may open a new area for use of serologic testing in the diagnostic approach of H. pylori infections.

Eradication of Helicobacter pylori and regression of B-cell lymphoma

There is an increasing body of evidence implicating a causal association between Helicobacter pylori and the development of mucosa-associated lymphoid tissue (MALT) associated B-cell gastric lymphoma. Investigators have noted that almost all patients with H pylori-associated chronic gastritis develop lymphoid follicles. Some of these patients demonstrate infiltration of B cells and lymphoepithelial lesions typical of MALT lymphoma. When gastric tissue from patients with gastric B-cell lymphoma is analyzed for H pylori infection, the overwhelming majority of patients demonstrate this condition. Epidemiologic nested case-control studies have shown that patients with gastric non-Hodgkin's lymphoma are substantially more likely that matched controls to have H pylori infection. This situation may be analogous to the linkage between chronic Epstein-Barr virus and lymphoma. The mechanisms inducing the development of lymphoma are not clear, but it has been suggested that chronic infection with H pylori results in the stimulation of H pylori-responsive T cells which in turn activate B cells with the subsequent development of a mutation to a monoclonal B-cell population. Recent evidence indicates that cure of H pylori infection produces regression of MALT lymphoma within 3 to 12 months in approximately 75% of antibiotic-treated patients. Individual responsiveness remains unpredictable, however, and careful and prolonged endoscopic and histologic follow-up is needed. Large, well-controlled studies are necessary, however, to determine the duration of 'cure' and the appropriate setting for treatment.

Helicobacter pyloriand the Evolution of Gastritis

Following the isolation of Helicobacter pylori from the stomachs of patients with peptic ulcer in 1982, intensive research has examined the relationship between this organism and gastritis. H. pylori affects the grade and activity of gastritis, the quality of surface epithelial cells, and the nature of mucus production. Gastritis results from a direct action, involving bacterial cytotoxins and enzymes, and also in an indirect way through the effect of monocyte and granulocyte infiltration. Eradication of H. pylori leads to the long-term healing of gastritis. H. pylori is also associated with intestinal metaplasia and the development of mucosa-associated lymphoid tissue (MALT). Regression of MALT lymphomas has been reported after H. pylori eradication treatment.