scholarly journals SAT0047 PRIMARY LYMPHOID TISSUE FROM RHEUMATOID ARTHRITIS PATIENTS HARBOUR CITRULLINE SPECIFIC PLASMA CELLS

2019 ◽  
Author(s):  
Radha Thyagarajan ◽  
Aase Hensvold ◽  
Lena Israelsson ◽  
Johanna Steen ◽  
Heidi Wähämaa ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lymphoid Tissue ◽  
Plasma Cells

THU0103 Synovial plasma cells predict relapse after rituximab therapy in rheumatoid arthritis

2013 ◽  
Vol 71 (Suppl 3) ◽  
pp. 189.1-189
Author(s):  
E. Vital ◽  
Y.M. El-Sherbiny ◽  
K. Henshaw ◽  
S. Dass ◽  
S. Das ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Plasma Cells

scholarly journals POS1223 RAS GUANYL RELEASING PROTEIN 1 (RASGRP1) IN PERIPHERAL B CELLS LINKS RA TO COVID-19

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 895.2-895
Author(s):  
S. Hannawi ◽  
F. Alqutami ◽  
M. Y. Hachim
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Plasma Cells ◽  
Immune Cell ◽  
In Silico Analysis ◽  
Differentially Expressed ◽  
Transcriptional Enhancer ◽  
Activated T Cells

Background:Changes in the B cell subpopulations is a hallmark of the antiviral response against SARS-CoV-2 and is associated with COVID-19 severity (1). Recently our group showed common derangement observed in rheumatoid arthritis (RA) and COVID-19 (2). In RA, synovium attracts potentially autoreactive—B cells and plasma cells that play a central role in RA pathogenesis (3). We were interested to know the similarity in B cell’s transcriptomic changes specific to RA and COVID-19.Objectives:Identify similar upregulated genes in synovium and B cells in RA and at the same time are differentially expressed in B cells infected with SARS-CoV-2 or from COVID-19 patients.Methods:RNAseq dataset (GSE89408) of (218) samples isolated from joint synovial biopsies from subjects with and without rheumatoid arthritis were retrieved from GEO online database. Differentially expressed genes (DRGs) specific to RA were identified after exclusion of those upregulated in Osteoarthritis or other joint condition samples in the same dataset. The RA specific genes were intersected with DEGs between B cells from healthy versus RA as extracted from (GSE110999) dataset. The shortlisted genes specifically upregulated in B cells of RA were identified and were explored in B cells COVID-19 transcriptome datasets using (https://metascape.org/COVID).Results:60 genes were found to be specifically upregulated in RA synovium and B cells and are changed in B cells infected with SARS-CoV-2 or from COVID-19 patients, Figure (1-A). Those genes were involved in interferon signaling, antiviral and immune cell activation. RASGRP1 was common between B cells of RA and COVID-19 and might play a role in the pathogenesis of both, Figure (1-B). RASGRP1 controls ERK/MAPK kinase cascade needed in B-/T-cell differentiation and development. It is vital to protect against viral infection and the autoimmune associated proliferation of activated T-cells like RA (4). We checked its level in another dataset (GSE152641) of the whole blood RNASeq of 62 COVID-19 patients and 24 healthy controls. RASGRP1 was significantly down in COVID-19 compared to healthy control, Figure (1-C).Conclusion:SARS-CoV-2 impair B and T’s cells’ immune response through its action on RASGRP1 and that can be a novel mechanistic explanation of how the virus decreases immune cells and impair the B cell’s humoral immunity.References:[1]Sosa-Hernández VA, Torres-Ruíz J, Cervantes-Díaz R, Romero-Ramírez S, Páez-Franco JC, Meza-Sánchez DE, et al. B Cell Subsets as Severity-Associated Signatures in COVID-19 Patients. Frontiers in Immunology. 2020;11(3244).[2]Hachim MY, Hachim IY, Naeem KB, Hannawi H, Al Salmi I, Hannawi S. C-C chemokine receptor type 5 links COVID-19, rheumatoid arthritis, and Hydroxychloroquine: in silico analysis. Translational Medicine Communications. 2020;5(1):14.[3]Doorenspleet ME, Klarenbeek PL, de Hair MJ, van Schaik BD, Esveldt RE, van Kampen AH, et al. Rheumatoid arthritis synovial tissue harbours dominant B-cell and plasma-cell clones associated with autoreactivity. Ann Rheum Dis. 2014;73(4):756-62.[4]Molineros JE, Singh B, Terao C, Okada Y, Kaplan J, McDaniel B, et al. Mechanistic Characterization of RASGRP1 Variants Identifies an hnRNP-K-Regulated Transcriptional Enhancer Contributing to SLE Susceptibility. Frontiers in Immunology. 2019;10(1066).Disclosure of Interests:None declared

Immune disorders of the gastrointestinal tract

2010 ◽  
pp. 2244-2256
Author(s):  
D.J. Unsworth
Keyword(s):  
Small Intestine ◽  
Gastrointestinal Tract ◽  
B Lymphocytes ◽  
Lamina Propria ◽  
Thoracic Duct ◽  
Lymphoid Tissue ◽  
Plasma Cells ◽  
Immunoglobulin A ◽  
Systemic Circulation ◽  
Lymphoid Follicles

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....

Rheumatoid arthritis: basic mechanisms in joints

ESC CardioMed ◽  
2018 ◽  
pp. 1109-1112
Author(s):  
Oliver Distler ◽  
Caroline Ospelt
Keyword(s):  
Rheumatoid Arthritis ◽  
Plasma Cells ◽  
Cell Formation ◽  
Synovial Fibroblasts ◽  
Inflammatory Cell Infiltrate ◽  
Cytokines And Chemokines ◽  
Mitogen Activated Protein ◽  
Sublining Layer ◽  
Destructive Processes ◽  
Hands And Feet

Rheumatoid arthritis (RA) is a destructive polyarthritis which mostly starts in the small joints of the hands and feet. In the course of the disease, more proximal joints also become involved. The progressive destruction of joint structures is mediated by the chronically inflamed, hyperplasic synovial tissue, which attaches to and degrades the adjacent joint cartilage. Typical changes of the RA synovium are increased cellularity in the synovial lining and sublining layer, including vascularization, giant cell formation, and immigration of immune cells. The inflammatory cell infiltrate comprises macrophages, monocytes, dendritic cells, T cells, B cells, plasma cells, innate lymphoid cells, and mast cells. These cells together with resident stromal cells (synovial fibroblasts) form a complex network and maintain inflammatory and destructive processes via the secretion of various cytokines and chemokines. Intracellularly, cytokine-activated receptor signalling is mediated via protein kinase-dependent signalling pathways, such as mitogen-activated protein kinases and Janus kinase, which leads to the activation of transcription factors and thus changes in the transcriptional programme. Gene transcription is additionally modified by epigenetic mechanisms and post-transcriptionally by microRNA.

Mucosa-associated lymphoid tissue lymphoma of the thyroid with abundant IgG4-positive plasma cells

2013 ◽  
Vol 40 (6) ◽  
pp. 587-590 ◽  
Author(s):  
Kentaro Miki ◽  
Yorihisa Orita ◽  
Yasuharu Sato ◽  
Iwao Sugitani ◽  
Misato Noyama ◽  
...  
Keyword(s):  
Lymphoid Tissue ◽  
Plasma Cells

Steady-state generation of mucosal IgA+ plasmablasts is not abrogated by B-cell depletion therapy with rituximab

Blood ◽  
2010 ◽  
Vol 116 (24) ◽  
pp. 5181-5190 ◽  
Author(s):  
Henrik E. Mei ◽  
Daniela Frölich ◽  
Claudia Giesecke ◽  
Christoph Loddenkemper ◽  
Karin Reiter ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Steady State ◽  
B Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Ki 67

AbstractThe anti-CD20 antibody rituximab depletes human B cells from peripheral blood, but it remains controversial to what extent tissue-resident B cells are affected. In representative patients with rheumatoid arthritis, we here demonstrate that recently activated presumably short-lived plasmablasts expressing HLA-DRhigh and Ki-67 continuously circulate in peripheral blood after B-cell depletion by rituximab at 26%-119% of their initial numbers. They circulate independent of splenectomy, express immunoglobulin A (IgA), β7 integrin, and C-C motif receptor 10 (CCR10) and migrate along CCL28 gradients in vitro, suggesting their mucosal origin. These plasmablasts express somatically hypermutated VH gene rearrangements and spontaneously secrete IgA, exhibiting binding to microbial antigens. Notably, IgA+ plasmablasts and plasma cells were identified in the lamina propria of patients treated with rituximab during peripheral B-cell depletion. Although a relation of these “steady state”–like plasmablasts with rheumatoid arthritis activity could not be found, their persistence during B-cell depletion indicates that their precursors, that is, B cells resident in the mucosa are not deleted by this treatment. These data suggest that a population of mucosal B cells is self-sufficient in adult humans and not replenished by CD20+ B cells immigrating from blood, lymphoid tissue, or bone marrow, that is, B cells depleted by rituximab.

scholarly journals Gene expression profiling of pulmonary mucosa-associated lymphoid tissue lymphoma identifies new biologic insights with potential diagnostic and therapeutic applications

Blood ◽  
2009 ◽  
Vol 113 (3) ◽  
pp. 635-645 ◽  
Author(s):  
Wee J. Chng ◽  
Ellen D. Remstein ◽  
Rafael Fonseca ◽  
P. Leif Bergsagel ◽  
Julie A. Vrana ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Lymphoid Tissue ◽  
Plasma Cells ◽  
Nuclear Factor Κb ◽  
Gene Signature ◽  
Chemokine Signaling ◽  
Pathologic Features

Abstract We conducted comprehensive gene expression profiling (GEP) of primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma (n = 33) and compared the results to GEP of other B- and T-cell lymphomas and normal lymphocytes to identify novel markers and deregulated pathways. MALT has a prominent T-cell signature and a marginal zone/memory B-cell profile. Four novel transcripts were specifically overexpressed in MALT, and 2 of these, MMP7 and SIGLEC6, were validated at the protein level. GEP also revealed distinct molecular subsets in MALT. One subset, characterized by MALT1 translocations, showed overexpression of nuclear factor-κB (NF-KB) pathway genes but also was enriched for chemokine signaling pathways. Another subset showed increased plasma cells and a prominent plasma cell gene signature. By analyzing several genes with very high (“spiked”) expression in individual cases, we identified clusters with different biologic characteristics, such as samples with MALT1 translocations having high expression of MALT1 and RARA, samples with plasmacytic differentiation having high FKBP11 expression, and samples with high RGS13 expression tending to have trisomy 3 and reactive follicles. In conclusion, MALT subgroups with distinct pathologic features defined by distinct groups of deregulated genes were identified. These genes could represent novel diagnostic and therapeutic targets.

Antigen-selected, immunoglobulin-secreting cells persist in human spleen and bone marrow

Blood ◽  
2004 ◽  
Vol 103 (10) ◽  
pp. 3805-3812 ◽  
Author(s):  
Julia I. Ellyard ◽  
Danielle T. Avery ◽  
Tri Giang Phan ◽  
Nathan J. Hare ◽  
Philip D. Hodgkin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Humoral Immunity ◽  
Lymphoid Tissue ◽  
Plasma Cells ◽  
Small Population ◽  
Lymphoid Tissues ◽  
B Cell Differentiation ◽  
Human Spleen ◽  
Human Disorders

Abstract Plasma cells (PCs) represent the final stage of B-cell differentiation and are devoted to the production of immunoglobulin (Ig). Perturbations to their development can result in human disorders characterized by PC expansion and hypergammaglobulinemia. Ig-secreting cells (ISCs) have been identified in secondary lymphoid tissues and bone marrow (BM). Most ISCs in lymphoid tissue are short-lived; in contrast, ISCs that migrate to the BM become long-lived PCs and continue to secrete immunoglobulin for extended periods. However, a small population of long-lived PCs has been identified in rodent spleen, suggesting that PCs may persist in secondary lymphoid tissue and that the spleen, as well as the BM, plays an important role in maintaining long-term humoral immunity. For these reasons, we examined ISCs in human spleen and identified a population that appears analogous to long-lived rodent splenic PCs. Human splenic ISCs shared morphologic, cellular, molecular, and functional characteristics with long-lived PCs in BM, demonstrating their commitment to the PC lineage. Furthermore, the detection of highly mutated immunoglobulin V region genes in splenic ISCs suggested they are likely to be antigen-selected and to secrete high-affinity immunoglobulin. Thus, our results suggest that splenic ISCs have an important role in humoral immunity and may represent the affected cell type in some B-cell dyscrasias.

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