scholarly journals Responsive population dynamics and wide seeding into the duodenal lamina propria of transglutaminase-2-specific plasma cells in celiac disease

2015 ◽  
Vol 9 (1) ◽  
pp. 254-264 ◽  
Author(s):  
R Di Niro ◽  
O Snir ◽  
K Kaukinen ◽  
G Yaari ◽  
K E A Lundin ◽  
...  
2012 ◽  
Vol 18 (3) ◽  
pp. 441-445 ◽  
Author(s):  
Roberto Di Niro ◽  
Luka Mesin ◽  
Nai-Ying Zheng ◽  
Jorunn Stamnaes ◽  
Michael Morrissey ◽  
...  

2020 ◽  
Vol 218 (2) ◽  
Author(s):  
Ida Lindeman ◽  
Chunyan Zhou ◽  
Linn M. Eggesbø ◽  
Zhichao Miao ◽  
Justyna Polak ◽  
...  

Disease-specific plasma cells (PCs) reactive with transglutaminase 2 (TG2) or deamidated gluten peptides (DGPs) are abundant in celiac disease (CeD) gut lesions. Their contribution toward CeD pathogenesis is unclear. We assessed expression of markers associated with PC longevity in 15 untreated and 26 treated CeD patients in addition to 13 non-CeD controls and performed RNA sequencing with clonal inference and transcriptomic analysis of 3,251 single PCs. We observed antigen-dependent V-gene selection and stereotypic antibodies. Generation of recombinant DGP-specific antibodies revealed a key role of a heavy chain residue that displays polymorphism, suggesting that immunoglobulin gene polymorphisms may influence CeD-specific antibody responses. We identified transcriptional differences between CeD-specific and non–disease-specific PCs and between short-lived and long-lived PCs. The short-lived CD19+CD45+ phenotype dominated in untreated and short-term–treated CeD, in particular among disease-specific PCs but also in the general PC population. Thus, the disease lesion of untreated CeD is characterized by massive accumulation of short-lived PCs that are not only directed against disease-specific antigens.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259082
Author(s):  
Christian B. Lindstad ◽  
Alisa E. Dewan ◽  
Jorunn Stamnaes ◽  
Ludvig M. Sollid ◽  
M. Fleur du Pré

A hallmark of celiac disease is the gluten-dependent production of antibodies specific for deamidated gluten peptides (DGP) and the enzyme transglutaminase 2 (TG2). Both types of antibodies are believed to result from B cells receiving help from gluten-specific CD4+ T cells and differentiating into antibody-producing plasma cells. We have here studied the collaboration between DGP- and TG2-specific B cells with gluten-specific CD4+ T cells using transgenic mice expressing celiac patient-derived T-cell and B-cell receptors, as well as between B-cell transfectants and patient-derived gluten-specific T-cell clones. We show that multivalent TG2-gluten complexes are efficient antigens for both TG2-specific and DGP-specific B cells and allow both types of B cells to receive help from gluten-specific T cells of many different specificities.


Author(s):  
Ida Lindeman ◽  
Chunyan Zhou ◽  
Linn M. Eggesbø ◽  
Zhichao Miao ◽  
Justyna Polak ◽  
...  

ABSTRACTDisease-specific plasma cells (PCs) reactive with transglutaminase 2 (TG2) or deamidated gluten peptides (DGP) are abundant in celiac disease (CeD) gut lesions. Their contribution toward CeD pathogenesis is unclear. We assessed expression of markers associated with PC longevity in 15 untreated and 26 treated CeD patients in addition to 13 non-CeD controls, and performed RNA-sequencing with clonal inference and transcriptomic analysis of 3251 single PCs. We observed antigen-dependent V-gene selection and stereotypic antibodies. Generation of recombinant DGP-specific antibodies revealed a key role of a heavy-chain residue that displays polymorphism, suggesting that immunoglobulin gene polymorphisms may influence CeD-specific antibody responses. We identified transcriptional differences between CeD-specific vs non-disease-specific PCs and between short-lived vs long-lived PCs. The short-lived CD19+CD45+ phenotype dominated in untreated and short-term-treated CeD, in particular among disease-specific PCs but also in the general PC population. Thus, the disease lesion of untreated CeD is characterized by massive accumulation of short-lived PCs that are not only directed against disease-specific antigens.


Author(s):  
UK Mohanta ◽  
A Anisuzzaman ◽  
T Farjana ◽  
PM Das ◽  
S Majumder ◽  
...  

Prevalence, population dynamics and pathological effects of intestinal helminths in Black Bengal goats were studied by examining 150 viscera collecting from different slaughter houses of Mymensingh district from the period of November 2005 to May 2006 in the Department of Parasitology and Pathology, Bangladesh Agricultural University, Mymensingh,  of which 94.67% goats were infected with one or more species of helminths. A total of 5 species of helminth parasites were identified such as Oesophagostomum columbianum (92%), Trchuris ovis (56.66%), Schistosoma indicum (38%), Moniezia expansa (10.66%) and Moniezia benedeni (2.66%). Single infection was observed in case of O. columbianum (16%) and S. indicum (2.66%). Single sex infection was established by S. indicum male (5.33%). Overall mean parasitic burden was 34.02±2.20. Mean parasitic burden was the highest in case of O. columbianum (29.91±2.00) followed by that of T. ovis (5.70±0.47), S. indicum (4.66±0.42), M. expansa (2.59±0.54) and M. benedeni (1.00±00). Prevalence of intestinal helminth was significantly (P < 0.05) higher in winter (100%) than that in summer (89.33%). Calculated odds ratio in between winter and summer was 18, which indicated that Black Bengal goats were 18 times more susceptible to helminth infection in winter. Parasitic burden was also higher in winter (41.53±3.15) than that in summer (25.52±2.57) season. Pathological lesions were observed in case of O. columbianum, T. ovis and S. indicum infection. In O. columbianum infection, hard, raised, slightly yellowish to greenish colored nodules measuring 0.25×0.50 cm were observed. Microscopically, it was characterized by catarrhal inflammation associated with destruction and desquamation of epithelial cells. Affected tissues were infiltrated chiefly with lymphocytes, macrophages, a few eosinophils and occasionally with plasma cells and neutrophils. Caseation and fibrous tissue proliferation were also noticed. But moderate infection with T. ovis was characterized by catarrhal inflammation along with the petechial haemorrhages on the intestinal mucosa where parasites were firmly attached. Histopathologically, it was characterized by destruction of lining epithelium of villi of caecum and colon along with the cellular infiltration predominantly with lymphocytes, few eosinophils and occasionally by macrophages. Lymph nodes of the lamina propria were enlarged. In case of S. indicum infection, haemorrhages were observed particularly on the rectal mucosa. Numerous eggs were found in the mucosal scraping from intestinal surface. Microscopically, lamina propria was thick and inflammed. Granulomatous response was observed which was characterized by the infiltration of epitheloid cells and proliferation of fibroblasts. The present study clearly suggests that Black Bengal goats are susceptible to intestinal helminths in both winter and summer seasons and most of the parasites recovered were associated with the production of variable degree of pathological lesions. That is why proper attempts should be made to control all these parasites. Key words: Prevalence, population dynamics, pathological effects, intestinal helminths, goat DOI = 10.3329/bjvm.v5i1.1313 Bangl. J. Vet. Med. (2007). 5 (1 & 2): 63-69


Author(s):  
D.J. Unsworth

The gastrointestinal tract is protected by gut-associated lymphoid tissue that provides an environment where interaction occurs between luminal antigen and specially adapted immune tissue in Peyer’s patches (small intestine only) or lymphoid follicles. T and B lymphocytes primed in the gut migrate into the systemic circulation via the thoracic duct but home preferentially to the lamina propria of the intestine. Plasma cells of the lamina propria secrete immunoglobulin A as a dimer linked by a joining peptide....


Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2736
Author(s):  
Venla Ylönen ◽  
Katri Lindfors ◽  
Marleena Repo ◽  
Heini Huhtala ◽  
Valma Fuchs ◽  
...  

Non-biopsy diagnosis of celiac disease is possible in children with anti-transglutaminase 2 antibodies (TGA) > 10× the upper limit of normal (ULN) and positive anti-endomysial antibodies (EMA). Similar criteria have been suggested for adults, but evidence with different TGA assays is scarce. We compared the performance of four TGA tests in the diagnosis of celiac disease in cohorts with diverse pre-test probabilities. Serum samples from 836 adults with either clinical suspicion or family risk of celiac disease were tested with four commercial TGA assays, EmA and celiac disease-associated genetics. The diagnosis was set based on duodenal lesion or, in some cases, using special methods. 137 (57%) patients with clinical suspicion and 85 (14%) of those with family risk had celiac disease. Positive predictive value (PPV) for 10×ULN was 100% in each TGA test. The first non-diagnostic investigations were encountered with ULN 1.0×–5.1× in the clinical cohort and 1.3×–4.9× in the family cohort, respectively. Using the assays’ own cut-offs (1×ULN) the PPVs ranged 84–100%. Serology-based diagnosis of celiac disease was accurate in adults using different commercial kits and pre-test probabilities using 10×ULN. The results also suggest that the ULN threshold for biopsy-omitting approach could be lower.


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