Rheumatoid Arthritis: Pathophysiology

1999 ◽  
Vol 12 (4) ◽  
pp. 282-292 ◽  
Author(s):  
Walter F. Stanaszek ◽  
Bruce C. Carlstedt
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Cells ◽  
Environmental Factors ◽  
Immune Complexes ◽  
Disease Process ◽  
Signs And Symptoms ◽  
Diagnostic Parameters

This article reviews the incidence, etiology, and pathophysiology of rheumatoid arthritis (RA), along with signs and symptoms, laboratory, and other diagnostic parameters of the disease. Criteria utilized for defining RA are discussed. While the primary cause is unknown, theories implicate genetic, hormonal, viral, bacterial, autoimmune, atmospheric, and environmental factors. Recent studies focus on the role of immune complexes, endothelial cells, and antibodies in the disease process.

Role of Leukocytes and Endothelial Cells in the Development of Angiogenesis in Inflammation and Wound Healing

2001 ◽  
Vol 125 (1) ◽  
pp. 67-71 ◽  
Author(s):  
Mark W. Lingen
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Blood Vessels ◽  
Peripheral Blood ◽  
Inflammatory Process ◽  
Signs And Symptoms ◽  
Critical Component ◽  
Complex Environment ◽  
Seminal Article

Abstract The basic signs and symptoms of inflammation and wound healing have been appreciated for thousands of years. However, the specific cells involved and their roles in this complex environment are still being elucidated today. In 1926, the origin of the phagocytic mononuclear ameboid wandering cell (macrophage) had not been determined. One popular theory was that the cells were differentiated from the endothelial cells of the nearby blood vessels, whereas others believed that the cells came from the peripheral blood or resting wandering cells. The purpose of this article is to review the seminal article published by Lang regarding this topic nearly 75 years ago. In addition, this article will review what is now known with regard to the role of the macrophage and endothelial cells in the development of angiogenesis, which is arguably the most critical component of successful inflammatory process or wound healing.

scholarly journals Number of individual ACPA reactivities in synovial fluid immune complexes, but not serum anti-CCP2 levels, associate with inflammation and joint destruction in rheumatoid arthritis

2018 ◽  
Vol 77 (9) ◽  
pp. 1345-1353 ◽  
Author(s):  
Azita Sohrabian ◽  
Linda Mathsson-Alm ◽  
Monika Hansson ◽  
Ann Knight ◽  
Jörgen Lysholm ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Disease Activity ◽  
Immune Complexes ◽  
Magnetic Beads ◽  
Joint Destruction ◽  
Joint Pathology ◽  
A New Technique ◽  
Laboratory Measures

IntroductionIndividual patients with rheumatoid arthritis (RA) show divergent specific anti-citrullinated protein/peptide antibodies (ACPA) patterns, but hitherto no individual ACPA specificity has consistently been linked to RA pathogenesis. ACPA are also implicated in immune complexes (IC)-associated joint pathology, but until now, there has been no method to investigate the role of individual ACPA in RA IC formation and IC-associated pathogenesis.MethodsWe have developed a new technique based on IC binding to C1q-coated magnetic beads to purify and solubilise circulating IC in sera and synovial fluids (SF) from 77 patients with RA. This was combined with measurement of 19 individual ACPA in serum, SF and in the IC fractions from serum and SF. We investigated whether occurrence of individual ACPA as well as number of ACPA in these compartments was related to clinical and laboratory measures of disease activity and inflammation.ResultsThe majority of individual ACPA reactivities were enriched in SF as compared with in serum, and levels of ACPA in IC were regulated independently of levels in serum and SF. No individual ACPA reactivity in any compartment showed a dominating association to clinical and laboratory measures of disease activity and severity. Instead, the number of individual ACPA reactivities in the IC fraction from SF associated with a number of markers of joint destruction and inflammation.ConclusionsOur data highlight the polyclonality of ACPA in joint IC and the possibility that a broad ACPA repertoire in synovial fluid IC might drive the local inflammatory and matrix-degrading processes in joints, in analogy with antibody-induced rodent arthritis models.

Rheumatoid Arthritis: Etiology and Pathogenesis

2014 ◽  
Author(s):  
Gary S. Firestein ◽  
Anna-Karin H. Ekwall
Keyword(s):  
Rheumatoid Arthritis ◽  
Intracellular Signaling ◽  
Cartilage Damage ◽  
Signs And Symptoms ◽  
American College Of Rheumatology ◽  
European League Against Rheumatism ◽  
Citrullinated Proteins ◽  
Definition Of

Rheumatoid arthritis (RA) is among the most common forms of chronic inflammatory arthritis. It affects approximately 1% of adults and is two to three times more prevalent in women than in men. There are no specific laboratory tests for RA; diagnosis depends on a constellation of signs and symptoms that can be supported by serology and radiographs. The disease evolves over many years as a consequence of repeated environmental stress causing inflammation and immune activation followed by a breakdown of tolerance in individuals with a specific genetic background. This review describes the definition of RA; its etiology, including genetics, infections, the role of smoking and citrullination of proteins, and epigenetic mechanisms; and its pathogenesis, including synovial histopathology, bone and cartilage damage, adaptive and innate immunity, and the role of cytokines and intracellular signaling. Tables include the 1987 American Rheumatism Association criteria for the classification of RA and the 2010 American College of Rheumatology/European League Against Rheumatism classification for RA. Figures show citrullinated proteins in airway cells, a section of a proliferative synovium from a patient with a classic RA, and scalloped regions of erosion at the junction between a proliferative inflamed rheumatoid synovium and the bone. This review contains 3 highly rendered figures, 2 tables, and 71 references.

scholarly journals Cross-linking of IgGs bound on circulating neutrophils leads to an activation of endothelial cells: possible role of rheumatoid factors in rheumatoid arthritis-associated vascular dysfunction

2013 ◽  
Vol 10 (1) ◽  
pp. 27 ◽  
Author(s):  
Emmanuelle Rollet-Labelle ◽  
Myriam Vaillancourt ◽  
Louis Marois ◽  
Marianna M Newkirk ◽  
Patrice E Poubelle ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Cells ◽  
Vascular Dysfunction ◽  
Cross Linking ◽  
Rheumatoid Factors

scholarly journals A Disintegrin and Metalloprotease 15 is Expressed on Rheumatoid Arthritis Synovial Tissue Endothelial Cells and may Mediate Angiogenesis

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 32 ◽  
Author(s):  
Shinichiro Nishimi ◽  
Takeo Isozaki ◽  
Kuninobu Wakabayashi ◽  
Hiroko Takeuchi ◽  
Tsuyoshi Kasama
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Cells ◽  
Conditioned Medium ◽  
Inflammatory Diseases ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Tnf Α ◽  
Adhesion Index

A disintegrin and metalloprotease 15 (ADAM15) is involved in several malignancies. In this study, we investigated the role of ADAM15 in rheumatoid arthritis (RA) angiogenesis. Soluble ADAM15 (s-ADAM15) in serum from RA and normal (NL) subjects was measured using ELISA. To determine membrane-anchored ADAM15 (ADAM15) expression in RA synovial tissues, immunohistochemistry was performed. To examine the role of ADAM15 in angiogenesis, we performed in vitro Matrigel assays and monocyte adhesion assays using human umbilical vein endothelial cells (HUVECs) transfected with ADAM15 siRNA. Finally, to investigate whether angiogenic mediators were affected by ADAM15, cytokines in ADAM15 siRNA-transfected HUVEC-conditioned medium were measured. ADAM15 was significantly higher in RA serum than in NL serum. ADAM15 was also expressed on RAST endothelial cells. ADAM15 siRNA-treated HUVECs had decreased EC tube formation in response to RA synovial fluids compared with non-treated HUVECs. The adhesion index of ADAM15 siRNA-transfected HUVECs was significantly lower than the adhesion index of control siRNA-transfected HUVECs. ENA-78/CXCL5 and ICAM-1 were decreased in tumor necrosis factor (TNF)-α-stimulated ADAM15 siRNA-transfected HUVEC-conditioned medium compared with TNF-α-stimulated control siRNA-transfected HUVEC-conditioned medium. These data show that ADAM15 plays a role in RA angiogenesis, suggesting that ADAM15 might be a potential target in inflammatory diseases such as RA.

scholarly journals The role of imaging in rheumatoid arthritis

2018 ◽  
Vol 22 (1) ◽  
Author(s):  
Kgomotso Kgoebane ◽  
Mahmood M.T.M. Ally ◽  
Martha C. Duim-Beytell ◽  
Farhana E. Suleman
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Process ◽  
Classification Criteria ◽  
Reactive Protein ◽  
American College Of Rheumatology ◽  
European League Against Rheumatism ◽  
Soft Tissue Involvement ◽  
Imaging Detection ◽  
Hands And Feet

Conventional radiographs of the hands and feet have traditionally been used in the diagnosis, management and monitoring of patients with rheumatoid arthritis (RA). However, they are not sensitive enough to detect changes early in the disease process. Erosions may only be visible up to two years after the onset of disease, and soft tissue involvement may not be detected at all. Early diagnosis can also be made challenging as markers such as erythrocyte sedimentation rate and C-reactive protein may be normal in up to 20% – 25% of cases. The latest classification criteria (American College of Rheumatology/European League Against Rheumatism [ACR/EULAR] Rheumatoid Arthritis Classification criteria 2010), often used to diagnose RA, incorporate the role of ultrasound and magnetic resonance imaging detection of synovitis, enabling earlier diagnosis and correct classification of patients. This article looks at the role of the various imaging modalities used in the diagnosis and management of RA.

scholarly journals Molecular aspects of rheumatoid arthritis: role of environmental factors

FEBS Journal ◽  
2008 ◽  
Vol 275 (18) ◽  
pp. 4456-4462 ◽  
Author(s):  
Shu Kobayashi ◽  
Shigeki Momohara ◽  
Naoyuki Kamatani ◽  
Hiroshi Okamoto
Keyword(s):  
Rheumatoid Arthritis ◽  
Environmental Factors ◽  
Molecular Aspects

scholarly journals Pathogenesis of IgA Vasculitis: An Up-To-Date Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Song ◽  
Xiaohan Huang ◽  
Guizhen Yu ◽  
Jianjun Qiao ◽  
Jun Cheng ◽  
...  
Keyword(s):  
Abdominal Pain ◽  
Environmental Factors ◽  
Immune Complexes ◽  
Small Vessel Vasculitis ◽  
Acquired Immunity ◽  
Iga Vasculitis ◽  
Immune Reactions ◽  
Diseased Vessel ◽  
Schonlein Purpura

Immunoglobin A (IgA) vasculitis (IgAV), formerly called the Henoch-Schönlein purpura (HSP), is a small vessel vasculitis, characterized by IgA1-dominant immune deposition at diseased vessel walls. IgAV is the most common form of vasculitis in children; typical symptoms include palpable purpura, arthritis or arthralgia, abdominal pain, and hematuria or proteinuria. Galactose-deficient IgA1 is detected in the tissues of the kidney and skin in patients with IgAV; it forms immune complexes leading to subsequent immune reactions and injuries. This report provides the recent advances in the understanding of environmental factors, genetics, abnormal innate and acquired immunity, and the role of galactose-deficient IgA1 immunocomplexes in the pathogenesis of IgAV.

scholarly journals AB0065 HGF/C-MET SIGNALING PROMOTE ANGIOGENESIS THROUGH CXCL16 IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1063.2-1063
Author(s):  
M. Hosonuma ◽  
T. Isozaki ◽  
H. Furuya ◽  
Y. Yamazaki ◽  
Y. Ikari ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cloning And Expression ◽  
Treatment Resistant ◽  
Monocyte Migration ◽  
Factor C ◽  
Hepatocyte Growth

Background:Hepatocyte growth factor (HGF) binds to the receptor tyrosine kinase c-Met and is a multifunctional cytokine that promotes processes such as cell proliferation, survival, differentiation, migration and angiogenesis [1]. We previously reported that HGF is produced by inflammation in the RA synovium, and activates monocyte migration to the synovium and promotes bone destruction through its own chemotactic effect and enhanced chemokine production in the synovium [2].Objectives:Therefore, we next aimed to determine the role of HGF in RA angiogenesis.Methods:The expression of HGF / c-Met in the serum and synovial tissues (STs) of RA patients and controls and human umbilical vein endothelial cells (HUVECs) was evaluated by ELISA and immunostaining. The effect of HGF/c-Met signaling on the promotion of CXCL16 production from HUVECs and RA fibroblast-like synoviocytes (FLSs) was determined by ELISA. To examine the role of HGF in angiogenesis, we performed in vitro Matrigel assays using HUVECs treated with HGF.Results:HGF in serum in treatment-naive RA patients was significantly higher than that in controls and HGF in serum in treatment-resistant RA showed a significant positive correlation with CXCL16. c-Met were expressed on vascular endothelial cells of RA STs and HUVECs. Stimulation of HUVECs with HGF dose-dependently increased CXCL16 production. c-Met signal inhibition by SU11274 suppressed TNF-α stimulation-enhanced CXCL16 production by RA FLSs in a dose-dependent manner. Furthermore, HGF induced HUVEC tube formation by 1.8-fold.Conclusion:HGF is produced by inflammation in the RA synovium, and activates angiogenesis through its own potent angiogenic effect and enhanced production of CXCL16 in the synovium. These results indicate that a strategy targeting c-Met signalling may be important for resolving treatment-resistant RA.References:[1]Nakamura T, Nishizawa T, Hagiya M, et al. Molecular cloning and expression of human hepatocyte growth factor. Nature. 1989 Nov 23;342(6248):440-3.[2]Hosonuma M, Sakai N, Furuya H, et al. Inhibition of hepatocyte growth factor/c-Met signalling abrogates joint destruction by suppressing monocyte migration in rheumatoid arthritis. Rheumatology (Oxford). 2021 Jan 5;60(1):408-419.Disclosure of Interests:None declared

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