scholarly journals Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells

2022 ◽  
Vol 23 (2) ◽  
pp. 905
Author(s):  
Sunhee Jang ◽  
Eui-Jong Kwon ◽  
Jennifer Jooha Lee
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Autoimmune Disease ◽  
Immune Cells ◽  
Cartilage Destruction ◽  
Systemic Autoimmune Disease ◽  
Pannus Formation ◽  
Systemic Complications ◽  
Tissue Proliferation ◽  
Novel Therapeutic

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic complications. Currently, advanced understandings of the pathologic mechanisms of autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies that cause RA have been achieved, despite the fact that much remains to be elucidated. This review provides an updated pathogenesis of RA which will unveil novel therapeutic targets.

scholarly journals Mast Cells in Early Rheumatoid Arthritis

2019 ◽  
Vol 20 (8) ◽  
pp. 2040 ◽  
Author(s):  
Felice Rivellese ◽  
Francesca Wanda Rossi ◽  
Maria Rosaria Galdiero ◽  
Costantino Pitzalis ◽  
Amato de Paulis
Keyword(s):  
Rheumatoid Arthritis ◽  
Innate Immunity ◽  
Mast Cells ◽  
Autoimmune Disease ◽  
Animal Models ◽  
Immune Cells ◽  
Systemic Autoimmune Disease ◽  
Disease Development ◽  
Early Ra ◽  
Contradictory Data

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation of the synovial membrane, with thickening of the synovial layer, cellular hyperplasia, and infiltration of immune cells. Mast cells (MCs) are cells of the innate immunity present in healthy synovia and part of the cellular hyperplasia characterizing RA synovitis. Although their presence in synovia has been well described, the exact functions and the correlation of MCs with disease development and progression have been debated, particularly because of contradictory data obtained in animal models and from patients with longstanding disease. Here, we present a revision of the literature on MCs in RA, including the most recent observations obtained from patients with early RA, indicating MCs as relevant markers of disease severity in early RA.

scholarly journals Chromatin accessibility landscapes of immune cells in rheumatoid arthritis nominate monocytes in disease pathogenesis

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dandan Zong ◽  
Beibei Huang ◽  
Young Li ◽  
Yichen Lu ◽  
Nan Xiang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Immune Cells ◽  
Cell Types ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Systemic Autoimmune Disease ◽  
Healthy Donors ◽  
Dna Regulatory Elements

Abstract Background Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease that involves a variety of cell types. However, how the epigenetic dysregulations of peripheral immune cells contribute to the pathogenesis of RA still remains largely unclear. Results Here, we analysed the genome-wide active DNA regulatory elements of four major immune cells, namely monocytes, B cells, CD4+ T cells and CD8+ T cells, in peripheral blood of RA patients, osteoarthritis (OA) patients and healthy donors using Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq). We found a strong RA-associated chromatin dysregulation signature in monocytes, but no other examined cell types. Moreover, we found that serum C-reactive protein (CRP) can induce the RA-associated chromatin dysregulation in monocytes via in vitro experiments. And the extent of this dysregulation was regulated through the transcription factor FRA2. Conclusions Together, our study revealed a CRP-induced pathogenic chromatin dysregulation signature in monocytes from RA patients and predicted the responsible signalling pathway as potential therapeutic targets for the disease.

scholarly journals Regulatory Role of the RNA N6-Methyladenosine Modification in Immunoregulatory Cells and Immune-Related Bone Homeostasis Associated With Rheumatoid Arthritis

2021 ◽  
Vol 8 ◽  
Author(s):  
Danping Fan ◽  
Ya Xia ◽  
Cheng Lu ◽  
Qinbin Ye ◽  
Xiaoyu Xi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
Immune Cells ◽  
Systemic Autoimmune Disease ◽  
Bone Homeostasis ◽  
Rna Modifications ◽  
Cellular Processes ◽  
Immunoregulatory Cells ◽  
The Relationship

Rheumatoid arthritis (RA) is a systemic autoimmune disease for which the etiology has not been fully elucidated. Previous studies have shown that the development of RA has genetic and epigenetic components. As one of the most highly abundant RNA modifications, the N6-methyladenosine (m6A) modification is necessary for the biogenesis and functioning of RNA, and modification aberrancies are associated with various diseases. However, the specific functions of m6A in the cellular processes of RA remain unclear. Recent studies have revealed the relationship between m6A modification and immune cells associated with RA. Therefore, in this review, we focused on discussing the functions of m6A modification in the regulation of immune cells and immune-related bone homeostasis associated with RA. In addition, to gain a better understanding of the progress in this field of study and provide the proper direction and suggestions for further study, clinical application studies of m6A modification were also summarized.

scholarly journals Managing Osteoporosis and Joint Damage in Patients with Rheumatoid Arthritis: An Overview

2021 ◽  
Vol 10 (6) ◽  
pp. 1241
Author(s):  
Yoshiya Tanaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Structural Damage ◽  
Kinase Inhibitors ◽  
Joint Destruction ◽  
Joint Damage ◽  
Nuclear Factor Κb ◽  
Cartilage Destruction ◽  
Janus Kinase ◽  
Systemic Autoimmune Disease ◽  
And Cartilage

In rheumatoid arthritis, a representative systemic autoimmune disease, immune abnormality and accompanying persistent synovitis cause bone and cartilage destruction and systemic osteoporosis. Biologics targeting tumor necrosis factor, which plays a central role in the inflammatory process, and Janus kinase inhibitors have been introduced in the treatment of rheumatoid arthritis, making clinical remission a realistic treatment goal. These drugs can prevent structural damage to bone and cartilage. In addition, osteoporosis, caused by factors such as menopause, aging, immobility, and glucocorticoid use, can be treated with bisphosphonates and the anti-receptor activator of the nuclear factor-κB ligand antibody. An imbalance in the immune system in rheumatoid arthritis induces an imbalance in bone metabolism. However, osteoporosis and bone and cartilage destruction occur through totally different mechanisms. Understanding the mechanisms underlying osteoporosis and joint destruction in rheumatoid arthritis leads to improved care and the development of new treatments.

Antibody modified gold nanoparticles for fast colorimetric screening of rheumatoid arthritis

The Analyst ◽  
2019 ◽  
Vol 144 (11) ◽  
pp. 3613-3619 ◽  
Author(s):  
Bruno Veigas ◽  
Ana Matias ◽  
Tomás Calmeiro ◽  
Elvira Fortunato ◽  
Alexandra R. Fernandes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gold Nanoparticles ◽  
Autoimmune Disease ◽  
Joint Inflammation ◽  
Systemic Autoimmune Disease ◽  
Ageing Population ◽  
Chronic Disability ◽  
High Prevalence

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation and one of the main causes of chronic disability worldwide with high prevalence in the ageing population.

Murine systemic autoimmune disease induced by mercuric chloride (HgCl2): Hg-specific helper T-cells react to antigen stored in macrophages

1993 ◽  
Vol 15 (2) ◽  
pp. 151-161 ◽  
Author(s):  
Malgorzata Kubicka-Muranyi ◽  
Olaf Behmer ◽  
Markus Uhrberg ◽  
Hanne Klonowski ◽  
Joachim Bister ◽  
...  
Keyword(s):  
T Cells ◽  
Autoimmune Disease ◽  
Mercuric Chloride ◽  
Helper T Cells ◽  
Systemic Autoimmune Disease

scholarly journals TCR repertoire analysis reveals effector memory T cells differentiation into Th17 cells in rheumatoid arthritis

2019 ◽  
Author(s):  
Xu Jiang ◽  
Shi-yu Wang ◽  
Chen Zhou ◽  
Jing-hua Wu ◽  
Yu-hao Jiao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Th17 Cells ◽  
Cell Receptor ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Systemic Autoimmune Disease ◽  
Autoreactive T Cell

AbstractThe pathogenesis of rheumatoid arthritis (RA), a systemic autoimmune disease characterized by autoreactive T-cell accumulation and pro-inflammatory cytokine overproduction, is unclear. Systematically addressing T-cell receptor (TCR) repertoires of different CD4+ T-cell subsets could help understand RA pathogenesis. Here, peripheral CD4+ T cells from treatment-naïve RA patients and healthy controls were sorted into seven subsets including naïve, effector, central memory, effector memory (EMT), Th1, Th17, and regulatory T cells. T-cell receptor β chain repertoires were then analyzed by next-generation sequencing. We identified T-cell clonal expansion in EMT and Th17 cells, with highly similar TCR repertoires between them. Ex vivo experiments demonstrated the preferred differentiation from EMT to Th17 cells in RA. Moreover, TCR diversity in subsets including Th17 was negatively correlated with RA disease activity indices such as C-reactive protein and erythrocyte sedimentation rate. Thus, shared and abnormally expanded EMT and Th17 TCR repertoires might be pivotal for RA pathogenesis.

scholarly journals Expression levels of HLA-DRB and HLA-DQ are associated with MHC Class II haplotypes in healthy individuals and rheumatoid arthritis patients

2021 ◽  
Author(s):  
Miranda Houtman ◽  
Anna Dzebisashvili ◽  
Espen Hesselberg ◽  
Anatoly Dubnovitsky ◽  
Genadiy Kozhukh ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Mhc Class Ii ◽  
Immune Cells ◽  
Class Ii ◽  
Differentially Expressed ◽  
Healthy Individuals ◽  
Expression Levels ◽  
Hla Dr ◽  
Hla Dq

AbstractHLA-DRB1 alleles have been associated with several autoimmune diseases. In anti-citrullinated protein antibody positive rheumatoid arthritis (ACPA-positive RA), HLA-DRB1 shared epitope (SE) alleles are the major genetic risk factors. In order to investigate whether expression of different alleles of major histocompatibility complex (MHC) Class II genes influence functions of immune cells, we investigated transcriptomic profiles of a variety of immune cells from healthy individuals carrying different HLA-DRB1 alleles. Sequencing libraries from peripheral blood mononuclear cells, CD4+ T cells, CD8+ T cells, and CD14+ monocytes of 32 genetically pre-selected healthy female individuals were generated, sequenced and reads were aligned to the standard reference. For the MHC region, reads were mapped to available MHC reference haplotypes and AltHapAlignR was used to estimate gene expression. Using this method, HLA-DRB and HLA-DQ were found to be differentially expressed in different immune cells of healthy individuals as well as in whole blood samples of RA patients carrying HLA-DRB1 SE-positive versus SE-negative alleles. In contrast, no genes outside the MHC region were differentially expressed between individuals carrying HLA-DRB1 SE-positive and SE-negative alleles. Existing methods for HLA-DR allele-specific protein expression were evaluated but were not mature enough to provide appropriate complementary information at the protein level. Altogether, our findings suggest that immune effects associated with different allelic forms of HLA-DR and HLA-DQ may be associated not only with differences in the structure of these proteins, but also with differences in their expression levels.

scholarly journals The Therapeutic Landscape of Rheumatoid Arthritis: Current State and Future Directions

2021 ◽  
Vol 12 ◽  
Author(s):  
Shahin Shams ◽  
Joseph M. Martinez ◽  
John R. D. Dawson ◽  
Juan Flores ◽  
Marina Gabriel ◽  
...  
Keyword(s):  
Biological Sciences ◽  
Rheumatoid Arthritis ◽  
Side Effects ◽  
Autoimmune Disease ◽  
Treatment Modalities ◽  
Systemic Autoimmune Disease ◽  
Inadequate Response ◽  
Current State ◽  
Therapeutic Landscape ◽  
Socioeconomic Consequences

Rheumatoid arthritis (RA) is a debilitating autoimmune disease with grave physical, emotional and socioeconomic consequences. Despite advances in targeted biologic and pharmacologic interventions that have recently come to market, many patients with RA continue to have inadequate response to therapies, or intolerable side effects, with resultant progression of their disease. In this review, we detail multiple biomolecular pathways involved in RA disease pathogenesis to elucidate and highlight pathways that have been therapeutic targets in managing this systemic autoimmune disease. Here we present an up-to-date accounting of both emerging and approved pharmacological treatments for RA, detailing their discovery, mechanisms of action, efficacy, and limitations. Finally, we turn to the emerging fields of bioengineering and cell therapy to illuminate possible future targeted therapeutic options that combine material and biological sciences for localized therapeutic action with the potential to greatly reduce side effects seen in systemically applied treatment modalities.

scholarly journals Current Therapeutic Options in the Treatment of Rheumatoid Arthritis

2019 ◽  
Vol 8 (7) ◽  
pp. 938 ◽  
Author(s):  
Köhler ◽  
Günther ◽  
Kaudewitz ◽  
Lorenz
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
Disease Activity ◽  
Physical Function ◽  
Chronic Inflammation ◽  
Early Treatment ◽  
Joint Destruction ◽  
Therapeutic Options ◽  
Systemic Autoimmune Disease ◽  
Control Disease

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints. Untreated RA leads to a destruction of joints through the erosion of cartilage and bone. The loss of physical function is the consequence. Early treatment is important to control disease activity and to prevent joint destruction. Nowadays, different classes of drugs with different modes of action are available to control the inflammation and to achieve remission. In this review, we want to discuss differences and similarities of these different drugs.

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