Roles of leptin on the key effector cells of rheumatoid arthritis

2021 ◽  
Vol 233 ◽  
pp. 92-96
Author(s):  
Zhen Wang ◽  
Xinxin Huang ◽  
Xiaokang Ye ◽  
Xia Li ◽  
Jing Wei
Author(s):  
Ranjeny Thomas ◽  
Andrew P. Cope

In depth molecular and cellular analysis of synovial tissue and fluid from patients with rheumatoid arthritis has provided important insights into understanding disease pathogenesis. Advances in the 1980s and 1990s included modern cloning strategies, sensitive and specific assays for inflammatory mediators, production of high-affinity neutralizing monoclonal antibodies, advances in flow cytometry, and gene targeting and transgenic strategies in rodents. In the 21st century, technological platforms offer unparalleled opportunities for systematic and unbiased interrogation of the disease process at a whole-genome level. Here we describe the key molecular and cellular characteristics of the inflamed synovium and how infiltrating cells get there. With this background, we outline current concepts of the different phases of disease, how the first phase of genetic susceptibility evolves into autoimmunity, triggered by the exposome, prior to the onset of clinically apparent inflammatory disease. We then describe the pathways that actively contribute to this early inflammatory phase and document the key effector cells and molecules of the innate and adaptive immune systems that orchestrate and maintain chronic synovial inflammatory responses. We summarize how this inflammatory milieu translates to cartilage destruction and bone resorption in synovial joints, and conclude by reviewing those factors in inflamed synovium that promote immune homeostasis.


1991 ◽  
Vol 34 (4) ◽  
pp. 423-431 ◽  
Author(s):  
Christian Hendrich ◽  
Jens G. Kuipers ◽  
Waldemar Kolanus ◽  
Reinhold E. Schmidt ◽  
Michael Hammer

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Li Zhu ◽  
Huaizhou Wang ◽  
Yu Wu ◽  
Zhengwen He ◽  
Yanghua Qin ◽  
...  

Rheumatoid arthritis (RA) is a complex and not fully understood autoimmune disease associated with multijoint damage. The main effector cells, the synovial fibroblasts, are apoptosis resistant and hyperplastic which indicate that autophagy level is high in synovial tissue. Real-time PCR, immunocytochemistry, and western blotting were used in this paper to study the autophagy status of the synovial tissues obtained from RA and OA patients at the time of joint replacement surgery. We further evaluated the correlation between autophagy levels with RA activity-associated serum markers with SPSS. The results showed that the expression levels (both in mRNA and in protein level) of autophagy-related proteins (belcin1, Atg5, and LC3) in the synovial tissue of patients with active rheumatoid arthritis (n=20) were significantly higher than those in OA patients (n=16). We further showed that the LC3-II/β-actin relative gray value was strongly correlated with the serum levels of several RA activity-related markers: CRP, ESR, CCP, and RF. Our results indicate that evaluating the autophagy level of synovial biopsies might be a useful way to diagnose RA and to estimate the disease activity. Reducing the expression level of autophagy-related genes might become a new therapeutic target for active rheumatoid arthritis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuqian Wang ◽  
Jie Huang ◽  
Duoli Xie ◽  
Dongyi He ◽  
Aiping Lu ◽  
...  

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation and bone erosion. The exact mechanism of RA is still unknown, but various immune cytokines, signaling pathways and effector cells are involved. Disease-modifying antirheumatic drugs (DMARDs) are commonly used in RA treatment and classified into different categories. Nevertheless, RA treatment is based on a “trial-and-error” approach, and a substantial proportion of patients show failed therapy for each DMARD. Over the past decades, great efforts have been made to overcome treatment failure, including identification of biomarkers, exploration of the reasons for loss of efficacy, development of sequential or combinational DMARDs strategies and approval of new DMARDs. Here, we summarize these efforts, which would provide valuable insights for accurate RA clinical medication. While gratifying, researchers realize that these efforts are still far from enough to recommend specific DMARDs for individual patients. Precision medicine is an emerging medical model that proposes a highly individualized and tailored approach for disease management. In this review, we also discuss the potential of precision medicine for overcoming RA treatment failure, with the introduction of various cutting-edge technologies and big data.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 196 ◽  
Author(s):  
William D. Shipman ◽  
Dragos C. Dasoveanu ◽  
Theresa T. Lu

Tertiary lymphoid organs are found at sites of chronic inflammation in autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. These organized accumulations of T and B cells resemble secondary lymphoid organs and generate autoreactive effector cells. However, whether they contribute to disease pathogenesis or have protective functions is unclear. Here, we discuss how tertiary lymphoid organs can generate potentially pathogenic cells but may also limit the extent of the response and damage in autoimmune disease.


2010 ◽  
Vol 62 (10) ◽  
pp. 2886-2899 ◽  
Author(s):  
Klaus W. Frommer ◽  
Birgit Zimmermann ◽  
Florian M. P. Meier ◽  
Dirk Schröder ◽  
Matthias Heil ◽  
...  

Autoimmunity ◽  
2012 ◽  
Vol 45 (5) ◽  
pp. 353-363 ◽  
Author(s):  
Alison Finnegan ◽  
Susan Ashaye ◽  
Keith M. Hamel

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