scholarly journals Longevity, clonal relationship, and transcriptional program of celiac disease–specific plasma cells

2020 ◽  
Vol 218 (2) ◽  
Author(s):  
Ida Lindeman ◽  
Chunyan Zhou ◽  
Linn M. Eggesbø ◽  
Zhichao Miao ◽  
Justyna Polak ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Gene Selection ◽  
Plasma Cells ◽  
Transglutaminase 2 ◽  
Immunoglobulin Gene ◽  
Short Term ◽  
Specific Antigens ◽  
Massive Accumulation ◽  
Disease Specific

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.

scholarly journals Longevity, clonal relationship and transcriptional program of celiac disease-specific plasma cells

2020 ◽  
Author(s):  
Ida Lindeman ◽  
Chunyan Zhou ◽  
Linn M. Eggesbø ◽  
Zhichao Miao ◽  
Justyna Polak ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Gene Selection ◽  
Plasma Cells ◽  
Transglutaminase 2 ◽  
Immunoglobulin Gene ◽  
Short Term ◽  
Specific Antigens ◽  
Massive Accumulation ◽  
Disease Specific

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.

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 ◽  
...  
Keyword(s):  
Population Dynamics ◽  
Celiac Disease ◽  
Lamina Propria ◽  
Plasma Cells ◽  
Transglutaminase 2

T1267 Celiac Disease-Specific Autoantibodies Targeted Against Transglutaminase 2 Increase Endothelial Permeability In Vitro

2008 ◽  
Vol 134 (4) ◽  
pp. A-519
Author(s):  
Essi Myrsky ◽  
Tiina Rauhavirta ◽  
Ilma Korponay-Szabo ◽  
Katri Kaukinen ◽  
Markku Mäki ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Endothelial Permeability ◽  
Transglutaminase 2 ◽  
Disease Specific

scholarly journals High abundance of plasma cells secreting transglutaminase 2–specific IgA autoantibodies with limited somatic hypermutation in celiac disease intestinal lesions

2012 ◽  
Vol 18 (3) ◽  
pp. 441-445 ◽  
Author(s):  
Roberto Di Niro ◽  
Luka Mesin ◽  
Nai-Ying Zheng ◽  
Jorunn Stamnaes ◽  
Michael Morrissey ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Plasma Cells ◽  
Somatic Hypermutation ◽  
Transglutaminase 2 ◽  
High Abundance ◽  
Intestinal Lesions

scholarly journals Autoantibodies in the Extraintestinal Manifestations of Celiac Disease

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1123 ◽  
Author(s):  
Xuechen Yu ◽  
Melanie Uhde ◽  
Peter Green ◽  
Armin Alaedini
Keyword(s):  
Celiac Disease ◽  
Gastrointestinal Symptoms ◽  
Transglutaminase 2 ◽  
The Body ◽  
Extraintestinal Manifestations ◽  
Cell Reactivity ◽  
Pathogenic Potential ◽  
Transglutaminase 3 ◽  
Diagnostic And Prognostic Value

Increased antibody reactivity towards self-antigens is often indicative of a disruption of homeostatic immune pathways in the body. In celiac disease, an autoimmune enteropathy triggered by the ingestion of gluten from wheat and related cereals in genetically predisposed individuals, autoantibody reactivity to transglutaminase 2 is reflective of the pathogenic role of the enzyme in driving the associated inflammatory immune response. Autoantibody reactivity to transglutaminase 2 closely corresponds with the gluten intake and clinical presentation in affected patients, serving as a highly useful biomarker in the diagnosis of celiac disease. In addition to gastrointestinal symptoms, celiac disease is associated with a number of extraintestinal manifestations, including those affecting skin, bones, and the nervous system. Investigations of these manifestations in celiac disease have identified a number of associated immune abnormalities, including B cell reactivity towards various autoantigens, such as transglutaminase 3, transglutaminase 6, synapsin I, gangliosides, and collagen. Clinical relevance, pathogenic potential, mechanism of development, and diagnostic and prognostic value of the various identified autoantibody reactivities continue to be subjects of investigation and will be reviewed here.

scholarly journals Role of transglutaminase 2 in celiac disease pathogenesis

2012 ◽  
Vol 34 (4) ◽  
pp. 513-522 ◽  
Author(s):  
Cornelius Klöck ◽  
Thomas R. DiRaimondo ◽  
Chaitan Khosla
Keyword(s):  
Celiac Disease ◽  
Transglutaminase 2 ◽  
Disease Pathogenesis

scholarly journals Identification of wheat proteins involved in active stage of celiac disease: are gamma gliadins the major disease-specific antigens?

2011 ◽  
Vol 1 (S1) ◽  
Author(s):  
Bharani Srinivasan ◽  
Claudia Constantin ◽  
Margit Focke Tejkl ◽  
Innes Swoboda ◽  
Irene Mittermann ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Active Stage ◽  
Wheat Proteins ◽  
Major Disease ◽  
Specific Antigens ◽  
Disease Specific

Saphenopopliteal ligation and stripping of small saphenous vein: does extended stripping provide better results?

2012 ◽  
Vol 27 (8) ◽  
pp. 390-397 ◽  
Author(s):  
N Samuel ◽  
D Carradice ◽  
T Wallace ◽  
G E Smith ◽  
F A K Mazari ◽  
...  
Keyword(s):  
Saphenous Vein ◽  
Small Sample ◽  
Clinical Severity ◽  
Complication Rates ◽  
Short Term ◽  
Clinical Recurrence ◽  
Severity Scores ◽  
One Year ◽  
Disease Specific

Objective Saphenopopliteal ligation (SPL) for venous insufficiency is a challenging procedure, with mixed results being reported. The role of stripping of the small saphenous vein (SSV) is contentious. This prospective observational study aimed to assess the risks and benefits of this procedure. Methods Fifty patients underwent SPL under general anaesthesia by a single surgeon in a tertiary referral vascular centre. The aim was to perform inversion stripping in each case, but in a proportion this was not possible. Patients were grouped into SPL with short segment excision ≤5 cm ( n = 23) and SPL with extended stripping >5 cm ( n = 27). Outcome measures included venous clinical severity scores (VCSS), quality of life (QoL), Aberdeen varicose vein questionnaire (AVVQ), patient satisfaction, recurrence and complication rates. Results Intragroup analysis demonstrated statistically significant improvements in VCSS ( P < 0.001), and QoL measures (generic and disease-specific AVVQ) ( P < 0.050) with both treatments. Intergroup analysis demonstrated statistically significant superior VCSS scores at one year ( P = 0.001), AVVQ at three months and one year ( P < 0.05), and cosmetic satisfaction at one year ( P = 0.011) in the SPL extended stripping group. There was no difference in clinical recurrence 1/23 (4.3%) versus 1/27 (3.7%) ( P = 0.900) or complication rates ( P > 0.050). Conclusions SPL with or without stripping is an effective procedure improving clinical severity and QoL in the short term. Early outcomes favour SPL with extended stripping to offer greater improvement in disease-specific QoL, venous severity and cosmesis. With this small sample, there is no evidence of increased complications following stripping, or increased short-term recurrence without it. Greater numbers and follow-up are required to make firm conclusions.

scholarly journals TG2-gluten complexes as antigens for gluten-specific and transglutaminase-2 specific B cells in celiac disease

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
Keyword(s):  
T Cells ◽  
Celiac Disease ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Plasma Cells ◽  
Transglutaminase 2 ◽  
Celiac Patient ◽  
Cell Clones ◽  
To Receive

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.

Role of affect in short-term memory for paired associates.

1968 ◽  
Vol 78 (3, Pt.1) ◽  
pp. 494-501 ◽  
Author(s):  
Calvin F. Nodine ◽  
James H. Korn
Keyword(s):  
Short Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Paired Associates
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