scholarly journals The Role of Cell Organelles in Rheumatoid Arthritis with Focus on Exosomes

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Zahra Payandeh ◽  
Abbas Pirpour Tazehkand ◽  
Ali Azargoonjahromi ◽  
Faezeh Almasi ◽  
Armina Alagheband Bahrami
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Cell Organelle ◽  
T And B Cells ◽  
Cell Organelles ◽  
Joint Injury ◽  
External Stimulation ◽  
Proinflammatory Mediators

AbstractAuto-immune diseases involved at least 25% of the population in wealthy countries. Several factors including genetic, epigenetic, and environmental elements are implicated in development of Rheumatoid Arthritis as an autoimmune disease. Autoantibodies cause synovial inflammation and arthritis, if left untreated or being under continual external stimulation, could result in chronic inflammation, joint injury, and disability. T- and B-cells, signaling molecules, proinflammatory mediators, and synovium-specific targets are among the new therapeutic targets. Exosomes could be employed as therapeutic vectors in the treatment of autoimmune diseases. Herein, the role of cell organelle particularly exosomes in Rheumatoid Arthritis had discussed and some therapeutic applications of exosome highlighted.

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

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
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.

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

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

scholarly journals A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Mie Oki ◽  
Norihiko Watanabe ◽  
Takayoshi Owada ◽  
Yoshihiro Oya ◽  
Kei Ikeda ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
T Lymphocyte ◽  
Lupus Erythematosus ◽  
Susceptibility Gene ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Immunological Homeostasis ◽  
Deficient Mice

Inhibitory coreceptors are thought to play important roles in maintaining immunological homeostasis, and a defect in the negative signals from inhibitory coreceptors may lead to the development of autoimmune diseases. We have recently identified B and T lymphocyte attenuator (BTLA), a new inhibitory coreceptor expressed on immune cells, and we suggest that BTLA may be involved in the development of autoimmune diseases using BTLA-deficient mice. However, the role of BTLA in the pathogenesis of autoimmune diseases in humans remains unknown. We, therefore, examined the possible association between BTLA and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) by conducting a case-control genetic association study. We found that 590C single-nucleotide polymorphism (SNP) of BTLA gene was significantly associated with susceptibility to RA, but not to SLE or SS. Furthermore, RA patients bearing this 590C SNP developed the disease significantly earlier than the patients without this allele. We also found that BTLA with 590C allele lacked the inhibitory activity on concanavalin A- and anti-CD3 Ab-induced IL-2 production in Jurkat T cells. These results suggest that BTLA is an RA-susceptibility gene and is involved in the protection from autoimmunity in humans.

scholarly journals Function and Role of Regulatory T Cells in Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Qi Jiang ◽  
Guocan Yang ◽  
Qi Liu ◽  
Shengjun Wang ◽  
Dawei Cui
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Tissue Injury ◽  
Treg Cells ◽  
Self Tolerance ◽  
Progression Of Disease ◽  
Loss Of Tolerance ◽  
Vital Component ◽  
The Ideal

Rheumatoid arthritis (RA) is a systemic and heterogeneous autoimmune disease with symmetrical polyarthritis as its critical clinical manifestation. The basic cause of autoimmune diseases is the loss of tolerance to self or harmless antigens. The loss or functional deficiency of key immune cells, regulatory T (Treg) cells, has been confirmed in human autoimmune diseases. The pathogenesis of RA is complex, and the dysfunction of Tregs is one of the proposed mechanisms underlying the breakdown of self-tolerance leading to the progression of RA. Treg cells are a vital component of peripheral immune tolerance, and the transcription factor Foxp3 plays a major immunosuppressive role. Clinical treatment for RA mainly utilizes drugs to alleviate the progression of disease and relieve disease activity, and the ideal treatment strategy should be to re-induce self-tolerance before obvious tissue injury. Treg cells are one of the ideal options. This review will introduce the classification, mechanism of action, and characteristics of Treg cells in RA, which provides insights into clinical RA treatment.

scholarly journals Extracellular and Intracellular Factors in Brain Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Kouminin Kanwore ◽  
Piniel Alphayo Kambey ◽  
Xiao-Xiao Guo ◽  
Ayanlaja Abdulrahman Abiola ◽  
Ying Xia ◽  
...  
Keyword(s):  
Brain Cancer ◽  
Chromosome Breakage ◽  
Cell Organelle ◽  
Cell Organelles ◽  
Internal Factors ◽  
Sequence Of Events ◽  
Cell Genome ◽  
Genome Modifications ◽  
Fundamental Requirement

The external and internal factors of the cell are critical to glioma initiation. Several factors and molecules have been reported to be implicated in the initiation and progression of brain cancer. However, the exact sequence of events responsible for glioma initiation is still unknown. Existing reports indicate that glioma stem cells are the cell of glioma origin. During cell division, chromosome breakage, DNA alteration increases the chance of cell genome modifications and oncogene overexpression. Although there is a high risk of gene alteration and oncogene overexpression, not everyone develops cancer. During embryogenesis, the same oncogenes that promote cancers have also been reported to be highly expressed, but this high expression which does not lead to carcinogenesis raises questions about the role of oncogenes in carcinogenesis. The resistance of cancer cells to drugs, apoptosis, and immune cells does not rely solely on oncogene overexpression but also on the defect in cell organelle machinery (mitochondria, endoplasmic reticulum, and cytoskeleton). This review discusses factors contributing to cancer; we report the dysfunction of the cell organelles and their contribution to carcinogenesis, while oncogene overexpression promotes tumorigenesis, maintenance, and progression through cell adhesion. All these factors together represent a fundamental requirement for cancer and its development.

scholarly journals Citrullination and PAD Enzyme Biology in Type 1 Diabetes – Regulators of Inflammation, Autoimmunity, and Pathology

2021 ◽  
Vol 12 ◽  
Author(s):  
Mei-Ling Yang ◽  
Fernanda M. C. Sodré ◽  
Mark J. Mamula ◽  
Lut Overbergh
Keyword(s):  
Rheumatoid Arthritis ◽  
Type 1 Diabetes ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Nod Mice ◽  
Neutrophil Extracellular Trap ◽  
Comprehensive Overview ◽  
General Role

The generation of post-translational modifications (PTMs) in human proteins is a physiological process leading to structural and immunologic variety in proteins, with potentially altered biological functions. PTMs often arise through normal responses to cellular stress, including general oxidative changes in the tissue microenvironment and intracellular stress to the endoplasmic reticulum or immune-mediated inflammatory stresses. Many studies have now illustrated the presence of ‘neoepitopes’ consisting of PTM self-proteins that induce robust autoimmune responses. These pathways of inflammatory neoepitope generation are commonly observed in many autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and type 1 diabetes (T1D), among others. This review will focus on one specific PTM to self-proteins known as citrullination. Citrullination is mediated by calcium-dependent peptidylarginine deiminase (PAD) enzymes, which catalyze deimination, the conversion of arginine into the non-classical amino acid citrulline. PADs and citrullinated peptides have been associated with different autoimmune diseases, notably with a prominent role in the diagnosis and pathology of rheumatoid arthritis. More recently, an important role for PADs and citrullinated self-proteins has emerged in T1D. In this review we will provide a comprehensive overview on the pathogenic role for PADs and citrullination in inflammation and autoimmunity, with specific focus on evidence for their role in T1D. The general role of PADs in epigenetic and transcriptional processes, as well as their crucial role in histone citrullination, neutrophil biology and neutrophil extracellular trap (NET) formation will be discussed. The latter is important in view of increasing evidence for a role of neutrophils and NETosis in the pathogenesis of T1D. Further, we will discuss the underlying processes leading to citrullination, the genetic susceptibility factors for increased recognition of citrullinated epitopes by T1D HLA-susceptibility types and provide an overview of reported autoreactive responses against citrullinated epitopes, both of T cells and autoantibodies in T1D patients. Finally, we will discuss recent observations obtained in NOD mice, pointing to prevention of diabetes development through PAD inhibition, and the potential role of PAD inhibitors as novel therapeutic strategy in autoimmunity and in T1D in particular.

scholarly journals The role of Th17 lymphocytes in pathogenesis of autoimmune arthritides

2014 ◽  
Vol 124 (1) ◽  
pp. 55-58
Author(s):  
Katarzyna Pogoda ◽  
Maria Pyszniak ◽  
Magdalena Bańka ◽  
Beata Rybojad ◽  
Jacek Tabarkiewicz
Keyword(s):  
Rheumatoid Arthritis ◽  
Juvenile Idiopathic Arthritis ◽  
Autoimmune Diseases ◽  
Inflammatory Disease ◽  
Th17 Cells ◽  
Th17 Lymphocytes ◽  
Inflammatory Phenotype ◽  
Long Time ◽  
Adults And Children

Abstract Th17 cells are newly described population of lymphoctyes, that recruits neutrophils to the site of inflammation and activate inflammatory phenotype of various tissues. They also play a pivotal role in autoimmune diseases and cancers. These cells secrete mainly different isoforms of IL-17, but also IL-21 and IL-22. Rheumatoid arthritis and juvenile idiopathic arthritis are the most common autoimmune joints’ inflammatory disease, affecting respectively adults and children. For a long time the immunopathogenesis of autoimmune diseases has been associated with Th1 lymphocytes. This hypothesis has changed after the discovery of Th17 cells, which are thought to be key mediators of autoimmune arthritides

Treatment of Severe Autoimmune Diseases with Autologous Hematopoietic Stem Cell Transplantation

2017 ◽  
Vol 71 (1) ◽  
pp. 10-14
Author(s):  
Zlate Stojanoski ◽  
Anzelika Karadzova-Stojanoska ◽  
Aleksandra Pivkova-Veljanovska ◽  
Sonja Genadieva-Stavrik ◽  
Lazar Cadievski ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Autoimmune Disease ◽  
Stem Cell Transplantation ◽  
Autoimmune Diseases ◽  
Cell Transplantation ◽  
Lupus Erythematosus ◽  
Systemic Lupus

Abstract Introduction. Autoimmune diseases are a family of more than 100 heterogeneous conditions that affect 5 to 8% of the world’s population. The etiology is still un-known but the disregulation of the regulatory T-lymphocytes play a central role inthe autoimmunity and the success of the long-term remission. Although conventional immunosuppression and new biological agents can provide disease control in severely affected patients, such treatments are rarely curative and alternative strategies are needed. Indeed, severe forms of systemic autoimmune diseases, such as multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), hematologic immune cytopenia (HIC) and Crohn’s disease are difficult to be treated. High-dose immunosuppressive therapy followed by autologous stem cells transplantation is reliable option for a successive treatment of this group of patients. Aim. To determine the safety of the procedure of autologous stem cell transplantation in patients with autoimmune diseases and concomitant malignant hematological disorders. Methods. During a period of 15 years (from September 2000 to September 2015) at the University Clinic of Hematology in Skopje we have treated 6 patients with autoimmune disease and concomitant hematological neoplasm. None of the patients was treated for primary autoimmune diseases. Two men and 4 women, with median age of 47 years were treated. Sjogren syndrome and multiple myeloma were found in 2 patients, polyartheritis nodosa and multiple myeloma in 1 patient, rheumatoid arthritis and acute myeloblastic leukemia in 1, systemic lupus erythematosus and non-Hodgkin lymphoma in 1; severe psoriasis and acute myeloblastic leukemia in 1 patient. Results. All treated patients are alive after trans-planted procedure, with transplant related mortality day +100: 0. Conclusion. Autologous stem cell transplantation is safe and recommended option for treatment ofpatients with autoimmune disease and hematologic neoplasm.

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