Regulation of inflammatory immune responses leading to the development of bone destructive autoimmune disease rheumatoid arthritis by IL-27

Hyperactivation of immune responses resulting in excessive release of pro-inflammatory mediators in alveoli/lung structures is the principal pathological feature of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The cytokine hyperactivation in COVID-19 appears to be similar to those seen in rheumatoid arthritis (RA), an autoimmune disease. Emerging evidence conferred the severity and risk of COVID-19 to RA patients. Amid the evidence of musculoskeletal manifestations involving immune-inflammation-dependent mechanisms and cases of arthralgia and/or myalgia in COVID-19, crosstalk between COVID-19 and RA is often debated. The present article sheds light on the pathological crosstalk between COVID-19 and RA, the risk of RA patients in acquiring SARS-CoV-2 infection, and the aspects of SARS-CoV-2 infection in RA development. We also conferred whether RA can exacerbate COVID-19 outcomes based on available clinical readouts. The mechanistic overlapping in immune-inflammatory features in both COVID-19 and RA was discussed. We showed the emerging links of angiotensin-converting enzyme (ACE)-dependent and macrophage-mediated pathways in both diseases. Moreover, a detailed review of immediate challenges and key recommendations for anti-rheumatic drugs in the COVID-19 setting was presented for better clinical monitoring and management of RA patients. Taken together, the present article summarizes available knowledge on the emerging COVID-19 and RA crosstalk and their mechanistic overlaps, challenges, and therapeutic options.

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Novel Nano Carriers for the Treatment of Progressive Auto Immune Disease Rheumatoid Arthritis

Current Pharmaceutical Design ◽

10.2174/1381612826666201021130146 ◽

2020 ◽

Vol 26 ◽

Author(s):

Ritu Mishra ◽

Swati Gupta

Keyword(s):

Rheumatoid Arthritis ◽

Drug Delivery ◽

Autoimmune Disease ◽

Drug Delivery Systems ◽

Clinical Manifestations ◽

Adaptive Immune Response ◽

Delivery Systems ◽

Current Therapy ◽

Genetic And Environmental Factors ◽

Novel Drug

Background: Rheumatoid arthritis (RA) is the most common occurring progressive, autoimmune disease, affecting 1% of the population and the ratio of affected women is three times as compared to men in most developing countries. Clinical manifestations of RA are the presence of anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) in blood, tendered joints and soreness of the muscles. Some other factors which may lead to chronic inflammation are genetic and environmental factors as well as adaptive immune response. Several conventional drugs are available for the treatment of RA but have their own drawbacks which can be overcome by the use of novel drug delivery systems. : The objective of the present review is to focus on the molecular pathogenesis of the disease and its current conventional treatment with special reference to the role of novel drug delivery systems encapsulating anti rheumatic drugs and herbal drugs in passive and receptor mediated active targeting against RA. On reviewing the conventional and current therapeutics agains RA, we conclude that, although the current therapy for the treatment of RA is capable enough, yet more advances in the field of targeted drug delivery will sanguinely result in effective and appropriate treatment of this autoimmune disease.

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Solar Radiation and Vitamin D: Mitigating Environmental Factors in Autoimmune Disease

Journal of Environmental and Public Health ◽

10.1155/2012/619381 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 18

Author(s):

Gerry K. Schwalfenberg

Keyword(s):

Rheumatoid Arthritis ◽

Multiple Sclerosis ◽

Inflammatory Bowel Disease ◽

Vitamin D ◽

Type 1 Diabetes ◽

Autoimmune Disease ◽

Solar Radiation ◽

Inflammatory Bowel

This paper looks at the environmental role of vitamin D and solar radiation as risk reduction factors in autoimmune disease. Five diseases are considered: multiple sclerosis, type 1 diabetes, rheumatoid arthritis, autoimmune disease of the thyroid, and inflammatory bowel disease. Clinical relevant studies and factors that may indicate evidence that autoimmune disease is a vitamin D-sensitive disease are presented. Studies that have resulted in prevention or amelioration of some autoimmune disease are discussed. An example of the utility of supplementing vitamin D in an unusual autoimmune disease, idiopathic thrombocytic purpura, is presented.

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FRI0550 CAN CYTOKINE GENE POLYMORPHISMS BE USEFUL FOR THE THERAPEUTIC CHOICE IN JAPANESE PATIENTS WITH RHEUMATOID ARTHRITIS?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2067 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 876.2-877

Author(s):

S. Tsujimoto ◽

M. Shigesaka ◽

A. Tanaka ◽

Y. Ozaki ◽

T. Ito ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Autoimmune Disease ◽

Gene Polymorphisms ◽

Therapeutic Response ◽

Bone Erosion ◽

Japanese Patients ◽

Cartilage Degradation ◽

Cytokine Gene ◽

Biological Dmards ◽

Cytokine Gene Polymorphisms

Background:Rheumatoid arthritis (RA) is a common autoimmune disease. It is characterized by systemic synovitis with bone erosion and joint cartilage degradation(1). Production of autoantibody is important for autoimmune disease. Cytokines play crucial roles in its pathogenesis(2). SNP distribution varies between races. Few studies have examined SNP targeted at Japanese patients. The analysis of cytokine gene polymorphisms is important factor of pathophysiology and treatment.Objectives:This analysis was aimed to investigate the association between cytokine gene polymorphisms and autoantibody and therapeutic response in Japanese RA patients.Methods:This study subjects consisted of 100 RA patients and 50 healthy controls. We extracted data on patient sex, age, disease duration, rheumatoid factor (RF), anti cyclic citrullinated peptide (anti-CCP) antibody and therapeutic response including methotrexate (MTX) and biological DMARDs. Genomic DNA was isolated from peripheral blood, these were genotyped for TNFα, TGFβ1, IL-6, IL-10 and IFNγ polymorphisms. We analyzed these data using a chi-square test.Results:IL-10 (-819 C/T and -592 C/A) revealed that there were significant decrease in the frequency of IL-10 (-819) CC genotype and (-592) CC genotype as compared to controls in RA patients. Genotyping of IL-10 showed that there was significant decrease ACC/ACC genotype (Table 1).IFNγ (+874 A/T) revealed that there was significant decrease in the frequency of TT genotype as compared to controls (Table 1).No significant differences in TNFα, TGFβ1and IL-6 genotypes and alleles frequency were observed between RA patients and control.TGFβ1(+869 A/T) in patients with anti-CCP antibody positive revealed that there was significant decrease in the frequency of TT genotype as compared to patients with anti-CCP antibody negative (Table 2).No significant association between RF and any cytokine gene polymorphism.Analyzing cytokine gene polymorphisms could be useful for treatment with MTX and biological DMARDs.Table 1.Table 2.Conclusion:IL-10 (-819 C/T, -592 C/A) and IFNγ (+874 A/T) polymorphism might be related to RA in Japanese population. In addition, TGFβ1(+869 A/T) polymorphism might be associated with the production of anti-CCP antibody. These results suggest that the analyzing cytokine gene polymorphisms may offer promise as useful factors in the choice of treatment for Japanese RA patients.References:[1] Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010; 376: 1094–108.[2] McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007 Jun;7(6):429-42.Disclosure of Interests:None declared

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AB0925-PARE A NARRATIVE REVIEW ASSESSING THE ROLE OF DIETARY SALT AS AN ENVIRONMENTAL RISK FACTOR FOR THE ONSET AND SEVERITY OF RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2972 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1484.1-1484

Author(s):

S. Ahmed ◽

E. Nikiphorou ◽

J. Bayliss

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factor ◽

Autoimmune Disease ◽

Environmental Risk ◽

Narrative Review ◽

Environmental Risk Factor ◽

T Helper ◽

Dietary Salt ◽

Salt Consumption

Background:The role of dietary salt consumption in the etiopathogenesis of Rheumatoid Arthritis (RA), and autoimmune disease in general, has received renewed interest. This has been fueled by the increased prevalence of autoimmune disease worldwide correlating with western diets and heightened consumption of salt rich foods and also studies at the cellular level demonstrating induction of IL 17 producing T helper cells (Th17) by dietary salt.Objectives:To conduct a narrative review of observational studies and clinical trials on the role of dietary salt as an environmental risk factor for the onset and development of RA.Methods:A comprehensive search was done of the literature from 2010 to 2021, using the search terms dietary salt and RA; the native interfaces EBSCO and Ovid were used. Databases searched included Pubmed, Embase, EMCare, Medline and CINAHL using a Population, Exposure and Outcome framework; the MESH terms RA, risk factors, nutrition and salt were used. Data was extracted by an independent reviewer.Results:Out of the 72 studies initially identified, 50 were included in this review. Studies in murine models have demonstrated that high concentrations of sodium chloride promote the differentiation of T helper lymphocytes, via the serum- and glucocorticoid- inducible kinase 1 (SGK1) mediator towards the proinflammatory Th17 driven immune response. Six studies were carried out in human subjects. Study design ranged from cross sectional observational to nested case control studies. Sodium intake amongst participants characterized as having high intake, or being placed in the higher quartiles, ranged from 4.5-5grams per day. 5 out of 6 studies demonstrated that increased dietary salt consumption is associated with earlier onset RA. One study suggested an association between high salt intake and erosive disease at diagnosis and the development of anti-citrullinated protein antibodies (ACPA), although evidence was weak and from a single study only. Another study found that increased consumption of salt was only associated with risk of RA in smokers, highlighting the need to explore confounding variables further.Conclusion:This narrative review of the literature provides some evidence that supports a role of excess dietary salt consumption as a risk factor for the onset and severity of RA.Disclosure of Interests:None declared

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The Role of Src Kinase in Macrophage-Mediated Inflammatory Responses

Mediators of Inflammation ◽

10.1155/2012/512926 ◽

2012 ◽

Vol 2012 ◽

pp. 1-18 ◽

Cited By ~ 115

Author(s):

Se Eun Byeon ◽

Young-Su Yi ◽

Jueun Oh ◽

Byong Chul Yoo ◽

Sungyoul Hong ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Immune Responses ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Src Kinase ◽

Multiple Roles ◽

Cellular Migration ◽

Pharmaceutical Drugs ◽

Tyrosine Protein Kinase

Src kinase (Src) is a tyrosine protein kinase that regulates cellular metabolism, survival, and proliferation. Many studies have shown that Src plays multiple roles in macrophage-mediated innate immunity, such as phagocytosis, the production of inflammatory cytokines/mediators, and the induction of cellular migration, which strongly implies that Src plays a pivotal role in the functional activation of macrophages. Macrophages are involved in a variety of immune responses and in inflammatory diseases including rheumatoid arthritis, atherosclerosis, diabetes, obesity, cancer, and osteoporosis. Previous studies have suggested roles for Src in macrophage-mediated inflammatory responses; however, recently, new functions for Src have been reported, implying that Src functions in macrophage-mediated inflammatory responses that have not been described. In this paper, we discuss recent studies regarding a number of these newly defined functions of Src in macrophage-mediated inflammatory responses. Moreover, we discuss the feasibility of Src as a target for the development of new pharmaceutical drugs to treat macrophage-mediated inflammatory diseases. We provide insights into recent reports regarding new functions for Src that are related to macrophage-related inflammatory responses and the development of novel Src inhibitors with strong immunosuppressive and anti-inflammatory properties, which could be applied to various macrophage-mediated inflammatory diseases.

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Antigen mimicry in autoimmune disease. Can immune responses to microbial antigens that mimic acetylcholine receptor act as initial triggers of myasthenia gravis?

Human Immunology ◽

10.1016/s0198-8859(99)00117-2 ◽

2000 ◽

Vol 61 (3) ◽

pp. 255-265 ◽

Cited By ~ 19

Author(s):

Philip Deitiker ◽

Tetsuo Ashizawa ◽

M.Zouhair Atassi

Keyword(s):

Autoimmune Disease ◽

Immune Responses ◽

Myasthenia Gravis ◽

Acetylcholine Receptor ◽

Antigen Mimicry

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Minicircles for Investigating and Treating Arthritic Diseases

Pharmaceutics ◽

10.3390/pharmaceutics13050736 ◽

2021 ◽

Vol 13 (5) ◽

pp. 736

Author(s):

Yeri Alice Rim ◽

Yoojun Nam ◽

Narae Park ◽

Ji Hyeon Ju

Keyword(s):

Rheumatoid Arthritis ◽

Autoimmune Disease ◽

Gene Transfer ◽

Gene Delivery ◽

Viral Vectors ◽

Cartilage Tissue ◽

Minimal Size ◽

Gene Delivery System ◽

Related Disease ◽

Efficient Delivery

Gene delivery systems have become an essential component of research and the development of therapeutics for various diseases. Minicircles are non-viral vectors with promising characteristics for application in a variety of fields. With their minimal size, minicircles exhibit relatively high safety and efficient delivery of genes of interest into cells. Cartilage tissue lacks the natural ability to heal, making it difficult to treat osteoarthritis (OA) and rheumatoid arthritis (RA), which are the two main types of joint-related disease. Although both OA and RA affect the joint, RA is an autoimmune disease, while OA is a degenerative joint condition. Gene transfer using minicircles has also been used in many studies regarding cartilage and its diseased conditions. In this review, we summarize the cartilage-, OA-, and RA-based studies that have used minicircles as the gene delivery system.

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Vitamin D as a Principal Factor in Mediating Rheumatoid Arthritis-Derived Immune Response

BioMed Research International ◽

10.1155/2019/3494937 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 13

Author(s):

Muhammad M. Aslam ◽

Peter John ◽

Attya Bhatti ◽

Sidrah Jahangir ◽

M. I. Kamboh

Keyword(s):

Rheumatoid Arthritis ◽

Vitamin D ◽

Immune Responses ◽

Molecular Mechanisms ◽

Genetic Factors ◽

Autoimmune Disorder ◽

Serum Levels ◽

Principal Factor ◽

Phosphate Homeostasis ◽

Low Serum

Rheumatoid arthritis (RA) is a systemic multifactorial autoimmune disorder. The interactions between diverse environmental and genetic factors lead to the onset of this complex autoimmune disorder. Serum levels of vitamin D (VD) are involved in the regulation of various immune responses. Vitamin D is a key signaling molecule in the human body that maintains calcium as well as phosphate homeostasis. It also regulates the functions of the immune system and, thus, can play a substantial role in the etiology of various autoimmune disorders, including RA. Low serum VD levels have been found to be associated with a higher risk of RA, although this finding has not been replicated consistently. The molecular mechanisms by which VD influences autoimmunity need to be further explored to understand how variation in plasma VD levels could affect the pathogenesis of RA. This mini-review focuses on the influence of VD and its serum levels on RA susceptibility, RA-associated complexities, treatment, and transcriptome products of key proinflammatory cytokines, along with other cytokines that are key regulators of inflammation in rheumatoid joints.

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