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Small-intestinal TG2-specific plasma cells at different stages of coeliac disease.

ABSTRACT: In coeliac disease, ingestion of gluten induces the production of transglutaminase 2 (TG2)-targeted autoantibodies by TG2-specific plasma cells present at high frequency in the small intestinal mucosa in untreated disease. During treatment with a gluten-free diet (GFD), the number of these cells decreases considerably. It has not been previously investigated whether the cells are also present prior to development of villous atrophy, or in non-responsive patients and those with dietary lapses. We aimed to define the frequency of small bowel mucosal TG2-specific plasma cells in coeliac disease patients with varying disease activity, and to investigate whether the frequency correlates with serum and small intestinal TG2-targeting antibodies as well as mucosal morphology and the number of intraepithelial lymphocytes. Mucosal TG2-specific plasma cells were found in 79% of patients prior to development of mucosal damage, in all patients with villous atrophy, and in 63% of the patients after 1 year on GFD. In these disease stages, TG2-specific plasma cells accounted for median of 2.3, 4.3, and 0.7% of all mucosal plasma cells, respectively. After long-term treatment, the cells were present in 20% of the patients in clinical remission (median 0%) and in 60% of the patients with poor dietary adherence (median 5.8%). In patients with non-responsive coeliac disease despite strict GFD, the cells were found in only one (9%) subject; the cells accounted for 2.4% of all plasma cells. A positive correlation between the percentage of TG2-specific plasma cells and serum TG2 antibody levels (rS?=?0.69, P?

SUBMITTER: Hietikko M

PROVIDER: S-EPMC6282384 | biostudies-other | 2018 Dec

REPOSITORIES: biostudies-other

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Small-intestinal TG2-specific plasma cells at different stages of coeliac disease.

Hietikko Minna M Koskinen Outi O Kurppa Kalle K Laurila Kaija K Saavalainen Päivi P Salmi Teea T Ilus Tuire T Huhtala Heini H Kaukinen Katri K Lindfors Katri K

BMC immunology 20181206 1

<h4>Background</h4>In coeliac disease, ingestion of gluten induces the production of transglutaminase 2 (TG2)-targeted autoantibodies by TG2-specific plasma cells present at high frequency in the small intestinal mucosa in untreated disease. During treatment with a gluten-free diet (GFD), the number of these cells decreases considerably. It has not been previously investigated whether the cells are also present prior to development of villous atrophy, or in non-responsive patients and those with ...[more]

PMID: 30522434

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Project description:The biosynthesis of membrane proteins and glycoproteins has been studied in rat intestinal crypt and villus cells by measuring the incorporation of L-[5,6-3H] fucose, D-[2-3H] mannose and L-[3,4,5-3H] leucine, given intraperitoneally, into Golgi, lateral-basal and luminal membranes. Incorporation of leucine and mannose was approximately equal in crypt and villus cells, whereas fucose incorporation was markedly higher (3-4 times) in the differentiated villus cells. As previously reported [Quaroni, Kirsch & Weiser (1979) Biochem J. 182. 203-212] most of the fucosylated glyco-proteins synthesized in the villus cells and initially present in the Golgi and lateral-basal membranes were found re-distributed, within 3-4h of label administration, in the luminal membrane. A similar process appeared to occur in the crypt cells, where, however, only few fucose-labelled glycoproteins were identified. In contrast, most of the leucine-labelled and many mannose-labelled membrane components found in the lateral-basal membrane of both crypt and villus cells did not seen to undergo a similar re-distribution process. The fucosylated glycoproteins of the intestinal epithelial cells represent, therefore, a special class of membrane components, most of which appear with differentiation, that are selectively localized in the luminal portion of the plasmalemma. In contrast with the marked differences in protein and glycoprotein patterns between the luminal membrane of villus and crypt cells, only minor differences were found between their lateral-basal membrane components: their protein patterns on sodium dodecyl sulphate/polyacrylamide slab gels, and the patterns of fucose-, mannose- and leucine-labelled components (analysed 3-4h after label administration) were very similar. Although the minor differences detected may be of importance, it appears that most of the surface-membrane changes accompanying cell differentiation in the intestinal epithelial cells are localized in the luminal portion of their surface membrane.

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Small-intestinal TG2-specific plasma cells at different stages of coeliac disease.

Publications

Small-intestinal TG2-specific plasma cells at different stages of coeliac disease.

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