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 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

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 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.

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 Signatures of B Cell Receptor Repertoire Following Pneumocystis Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Han Sun ◽  
Hu-Qin Yang ◽  
Kan Zhai ◽  
Zhao-Hui Tong
Keyword(s):  
B Cells ◽  
B Cell ◽  
Single Cell ◽  
Plasma Cells ◽  
Somatic Hypermutation ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Repertoire ◽  
Elevated Expression ◽  
Pneumocystis Infection

B cells play vital roles in host defense against Pneumocystis infection. However, the features of the B cell receptor (BCR) repertoire in disease progression remain unclear. Here, we integrated single-cell RNA sequencing and single-cell BCR sequencing of immune cells from mouse lungs in an uninfected state and 1–4 weeks post-infection in order to illustrate the dynamic nature of B cell responses during Pneumocystis infection. We identified continuously increased plasma cells and an elevated ratio of (IgA + IgG) to (IgD + IgM) after infection. Moreover, Pneumocystis infection was associated with an increasing naïve B subset characterized by elevated expression of the transcription factor ATF3. The proportion of clonal expanded cells progressively increased, while BCR diversity decreased. Plasma cells exhibited higher levels of somatic hypermutation than naïve B cells. Biased usage of V(D)J genes was observed, and the usage frequency of IGHV9-3 rose. Overall, these results present a detailed atlas of B cell transcriptional changes and BCR repertoire features in the context of Pneumocystis infection, which provides valuable information for finding diagnostic biomarkers and developing potential immunotherapeutic targets.

scholarly journals Non-Biopsy Serology-Based Diagnosis of Celiac Disease in Adults Is Accurate with Different Commercial Kits and Pre-Test Probabilities

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2736
Author(s):  
Venla Ylönen ◽  
Katri Lindfors ◽  
Marleena Repo ◽  
Heini Huhtala ◽  
Valma Fuchs ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Transglutaminase 2 ◽  
Clinical Suspicion ◽  
Family Risk ◽  
Serum Samples ◽  
Clinical Cohort ◽  
The Family ◽  
Endomysial Antibodies ◽  
Commercial Kits ◽  
Diagnostic Investigations

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.

scholarly journals Plasma Cells Are the Most Abundant Gluten Peptide MHC-expressing Cells in Inflamed Intestinal Tissues From Patients With Celiac Disease

2019 ◽  
Vol 156 (5) ◽  
pp. 1428-1439.e10 ◽  
Author(s):  
Lene Støkken Høydahl ◽  
Lisa Richter ◽  
Rahel Frick ◽  
Omri Snir ◽  
Kristin Støen Gunnarsen ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Plasma Cells ◽  
Gluten Peptide
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