scholarly journals The Expression of Non-Coding RNAs and Their Target Molecules in Rheumatoid Arthritis: A Molecular Basis for Rheumatoid Pathogenesis and Its Potential Clinical Applications

2021 ◽  
Vol 22 (11) ◽  
pp. 5689
Author(s):  
Chang-Youh Tsai ◽  
Song-Chou Hsieh ◽  
Chih-Wei Liu ◽  
Cheng-Hsun Lu ◽  
Hsien-Tzung Liao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Growth Factors ◽  
Plasma Cells ◽  
Gene Mutations ◽  
Cardiovascular Complications ◽  
Adaptive Immune Cells ◽  
Nuclear Antigens ◽  
Chronic Synovitis ◽  
Target Molecules ◽  
Non Coding Rnas

Rheumatoid arthritis (RA) is a typical autoimmune-mediated rheumatic disease presenting as a chronic synovitis in the joint. The chronic synovial inflammation is characterized by hyper-vascularity and extravasation of various immune-related cells to form lymphoid aggregates where an intimate cross-talk among innate and adaptive immune cells takes place. These interactions facilitate production of abundant proinflammatory cytokines, chemokines and growth factors for the proliferation/maturation/differentiation of B lymphocytes to become plasma cells. Finally, the autoantibodies against denatured immunoglobulin G (rheumatoid factors), EB virus nuclear antigens (EBNAs) and citrullinated protein (ACPAs) are produced to trigger the development of RA. Furthermore, it is documented that gene mutations, abnormal epigenetic regulation of peptidylarginine deiminase genes 2 and 4 (PADI2 and PADI4), and thereby the induced autoantibodies against PAD2 and PAD4 are implicated in ACPA production in RA patients. The aberrant expressions of non-coding RNAs (ncRNAs) including microRNAs (miRs) and long non-coding RNAs (lncRNAs) in the immune system undoubtedly derange the mRNA expressions of cytokines/chemokines/growth factors. In the present review, we will discuss in detail the expression of these ncRNAs and their target molecules participating in developing RA, and the potential biomarkers for the disease, its diagnosis, cardiovascular complications and therapeutic response. Finally, we propose some prospective investigations for unraveling the conundrums of rheumatoid pathogenesis.

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

Autoantibodies to extractable nuclear antigens (ENAs) pattern in rheumatoid arthritis patients: Relevance and clinical implications

2021 ◽  
Vol 17 (5) ◽  
pp. 250-257
Author(s):  
Yasser Emad ◽  
Yasser Ragab ◽  
Nevin Hammam ◽  
Nashwa El-Shaarawy ◽  
Ossama Ibrahim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Implications ◽  
Nuclear Antigens

scholarly journals AB0163 ELECTROCARDIOGRAPHIC MANIFESTATIONS IN PATIENTS WITH SEROPOSITIVE RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1108.2-1108
Author(s):  
S. Spitsina ◽  
E. Mozgovaya ◽  
A. Trofimenko ◽  
S. Bedina ◽  
M. Mamus
Keyword(s):  
Rheumatoid Arthritis ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Heart Defects ◽  
Clinical Manifestations ◽  
Blood Chemistry ◽  
Cardiovascular Complications ◽  
Silent Myocardial Ischemia ◽  
Conduction Disorders ◽  
Artery Disease

Background:Cardiovascular disease in rheumatoid arthritis (RA) is more common than in general population. Particular attention should be paid to cardiac dysfunction, as their timely diagnosis strongly affects the general outcome.Objectives:To assess the prevalence of arrhythmias and conduction disorders in patients with seropositive RA without clinical manifestations of coronary artery disease, as well as to determine their relationship with activity and duration of RA.Methods:The research was carried out in agreement with the WMA Declaration of Helsinki principles. 48 patients with seropositive RA were included in the study. The exclusion criteria were: age over 60 years; obesity; congenital heart defects; coronary artery disease; peripheral atherosclerosis; thyroid disease; diabetes mellitus. All patients were assessed using general physical, laboratory and instrumental survey including CBC, blood chemistry panel, as well as ECG. RA diagnosis was verified using the 2010 ACR / EULAR classification criteria. Central tendencies were expressed as mean ±SD.Results:All the included persons were women. Their average age was 50.50 ± 7.22 years, and average duration of the disease was 8.13 ± 2.34 years. All patients had articular form (without systemic manifestations) of moderate and high activity. The patients were treated with basic and NSAIDs therapy; no glucocorticoids were applied at the time of the examination. Using 12-lead ECG arrhythmias and conduction disorders were revealed in 27 (56.25%) of RA patients. Sinus rhythm deviations had the highest (31.25%) prevalence for all arrhythmias, comprising sinus tachycardias (18.75%), sinus bradycardias (6.25%), and sinus arrhythmias (6.25%). Premature beats were registered in 12.5% cases, being supraventricular and ventricular ones in equal proportions. We have found left anterior bundle branch block in 6 (12.5%) of patients. Despite absence of any angina symptoms, 9 (18.75%) of patients had myocardial repolarization disturbances, either as ST depression deeper than 0.1 mV or as negative T wave appearance, which were quite similar to silent myocardial ischemia manifestations. All the patients with these two features had RA history of more than 10 years. There was no relationship between the prevalence of the manifestations and radiographic stage of RA.Conclusion:Arrhythmias and conduction disorders are quite frequent finding in seropositive RA (56.25% and 18.75%, respectively). Their incidence and severity do not coincide exactly with the radiographic progression in joints, while their prevalence generally increases with disease duration.These data highlight the importance of additional Holter ECG monitoring in RA for revelation and treatment of silent life-threatening cardiovascular complications.Disclosure of Interests:None declared

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

scholarly journals Rheumatoid arthritis synovial fluid neutrophils drive inflammation through production of chemokines, reactive oxygen species and neutrophil extracellular traps

2020 ◽  
Author(s):  
Helen L Wright ◽  
Max Lyon ◽  
Elinor A Chapman ◽  
Robert J Moots ◽  
Steven W Edwards
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Neutrophil Migration ◽  
Joint Damage ◽  
Inflammatory Disorder ◽  
Ros Production ◽  
Chronic Inflammatory Disorder ◽  
Adaptive Immune Cells ◽  
Activated Neutrophils ◽  
Healthy Control

Rheumatoid arthritis (RA) is a chronic inflammatory disorder affecting synovial joints. Neutrophils are believed to play an important role in both the initiation and progression of RA, and large numbers of activated neutrophils are found within both synovial fluid (SF) and synovial tissue from RA joints. In this study we analysed paired blood and SF neutrophils from patients with severe, active RA (DAS28>5.1, n=3) using RNA-seq. 772 genes were significantly different between blood and SF neutrophils. IPA analysis predicted that SF neutrophils had increased expression of chemokines and ROS production, delayed apoptosis, and activation of signalling cascades regulating the production of NETs. This activated phenotype was confirmed experimentally by incubating healthy control neutrophils in cell-free RA SF, which was able to delay apoptosis and induce ROS production in both unprimed and TNFα primed neutrophils (p<0.05). RA SF significantly increased neutrophil migration through 3μM transwell chambers (p<0.05) and also increased production of NETs by healthy control neutrophils, including exposure of myeloperoxidase (MPO) and citrullinated histone-H3-positive DNA NETs. IPA analysis predicted NET production was mediated by signalling networks including AKT, RAF1, SRC and NF-κB. Our results expand the understanding of the molecular changes that take place in the neutrophil transcriptome during migration into inflamed joints in RA, and the altered phenotype in RA SF neutrophils. Specifically, RA SF neutrophils lose their migratory properties, residing within the joint to generate signals that promote joint damage, as well as inflammation via recruitment and activation of both innate and adaptive immune cells. We propose that this activated SF neutrophil phenotype contributes to the chronic inflammation and progressive damage to cartilage and bone observed in patients with RA.

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