scholarly journals The Role of Posttranslational Protein Modifications in Rheumatological Diseases: Focus on Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Andrea Mastrangelo ◽  
Tania Colasanti ◽  
Cristiana Barbati ◽  
Arbi Pecani ◽  
Danilo Sabatinelli ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Antigen Processing ◽  
Systemic Autoimmune Disease ◽  
Protein Functions ◽  
Citrullinated Proteins ◽  
Wide Group ◽  
Definition Of ◽  
Antigen Processing And Presentation ◽  
Rheumatological Diseases

The definition of posttranslational modification (PTM) encompasses a wide group of chemical reactions that allow modification and modulation of protein functions. The regulation of PTMs is crucial for the activity and survival of the cells. Dysregulation of PTMs has been observed in several pathological conditions, including rheumatoid arthritis (RA). RA is a systemic autoimmune disease primarily targeting the joints. The three PTMs mainly involved in this disease are glycosylation, citrullination, and carbamylation. Glycosylation is essential for antigen processing and presentation and can modulate immunoglobulin activity. Citrullination of self-antigens is strongly associated with RA, as demonstrated by the presence of antibodies directed to anti-citrullinated proteins in patients’ sera. Carbamylation and its dysregulation have been recently associated with RA. Aim of this review is to illustrate the most significant alterations of these PTMs in RA and to evaluate their possible involvement in the pathogenesis of the disease.

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 Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1674
Author(s):  
Sara Tomei ◽  
Ola Ibnaof ◽  
Shilpa Ravindran ◽  
Soldano Ferrone ◽  
Cristina Maccalli
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Immune Responses ◽  
Antigen Processing ◽  
Aberrant Expression ◽  
Immunological Profile ◽  
Malignant Lesions ◽  
Novel Therapeutic Strategies ◽  
Antigen Processing And Presentation

Cancer cells endowed with stemness properties and representing a rare population of cells within malignant lesions have been isolated from tumors with different histological origins. These cells, denominated as cancer stem cells (CSCs) or cancer initiating cells (CICs), are responsible for tumor initiation, progression and resistance to therapies, including immunotherapy. The dynamic crosstalk of CSCs/CICs with the tumor microenvironment orchestrates their fate and plasticity as well as their immunogenicity. CSCs/CICs, as observed in multiple studies, display either the aberrant expression of immunomodulatory molecules or suboptimal levels of molecules involved in antigen processing and presentation, leading to immune evasion. MicroRNAs (miRNAs) that can regulate either stemness properties or their immunological profile, with in some cases dual functions, can provide insights into these mechanisms and possible interventions to develop novel therapeutic strategies targeting CSCs/CICs and reverting their immunogenicity. In this review, we provide an overview of the immunoregulatory features of CSCs/CICs including miRNA profiles involved in the regulation of the interplay between stemness and immunological properties.

EULAR definition of “arthralgia suspicious for progression to rheumatoid arthritis” in a large cohort of patients included in a program for rapid diagnosis: role of auto-antibodies and ultrasound

2020 ◽  
Vol 39 (5) ◽  
pp. 1493-1499 ◽  
Author(s):  
Santiago Ruta ◽  
Einer Sanchez Prado ◽  
Jessica Torres Chichande ◽  
Alvaro Ruta ◽  
Facundo Salvatori ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Rapid Diagnosis ◽  
Large Cohort ◽  
Definition Of

scholarly journals Lipid Peroxidation-Mediated Inflammation Promotes Cell Apoptosis through Activation of NF-κB Pathway in Rheumatoid Arthritis Synovial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Geng Yin ◽  
Ying Wang ◽  
Xiao-min Cen ◽  
Min Yang ◽  
Yan Liang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Apoptosis ◽  
Inflammatory Responses ◽  
Synovial Fibroblasts ◽  
Systemic Autoimmune Disease ◽  
New Strategy ◽  
Significant Clinical Improvement ◽  
Rheumatoid Arthritis Synoviocytes ◽  
Initiation Of Therapy

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of multiple joints. The central pathogenesis of RA is the proliferation of synovial fibroblasts in response to inflammatory cytokines. However, some of the targeted therapies for inflammation reactions do not display significant clinical improvement after initiation of therapy. Thus, the relationship between inflammatory responses and RA therapy is still incompletely understood. In the present study, we proposed to determine whether enhanced inflammations may lead to cell apoptosis in rheumatoid arthritis synoviocytes. Our results indicated that products of lipid peroxidations, 4-HNE, may induce synovial intrinsic inflammations by activating NF-κB pathways and it may lead to cell apoptosis. Pharmacological inhibition of NF-κB activation may reduce the 4-HNE mediated inflammation responses and subsequent cell apoptosis. Our results may help to clarify the role of inflammations on RA development and imply that blocking NF-κB activation may be partly beneficial for human RA therapy. These findings might provide a mechanism-based rationale for developing new strategy to RA clinical therapy.

scholarly journals Responsiveness in Rheumatoid Arthritis. A Report from the OMERACT 11 Ultrasound Workshop

2013 ◽  
Vol 41 (2) ◽  
pp. 379-382 ◽  
Author(s):  
Annamaria Iagnocco ◽  
Esperanza Naredo ◽  
Richard Wakefield ◽  
George A.W. Bruyn ◽  
Paz Collado ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Task Force ◽  
Power Doppler ◽  
Consensus Definition ◽  
Synovitis Score ◽  
The Us ◽  
Definition Of ◽  
Acceptable Reliability ◽  
Power Doppler Signal

Objective.To summarize the work performed by the Outcome Measures in Rheumatology (OMERACT) Ultrasound (US) Task Force on the validity of different US measures in rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) presented during the OMERACT 11 Workshop.Methods.The Task Force is an international group aiming to iteratively improve the role of US in arthritis clinical trials. Recently a major focus of the group has been the assessment of responsiveness of a person-level US synovitis score in RA: the US Global Synovitis Score (US-GLOSS) combines synovial hypertrophy and power Doppler signal in a composite score detected at joint level. Work has also commenced examining assessment of tenosynovitis in RA and the role of US in JIA.Results.The US-GLOSS was tested in a large RA cohort treated with biologic therapy. It showed early signs of improvement in synovitis starting at Day 7 and increasing to Month 6, and demonstrated sensitivity to change of the proposed grading. Subsequent voting questions concerning the application of the US-GLOSS were endorsed by > 80% of OMERACT delegates. A standardized US scoring system for detecting and grading severity of RA tenosynovitis and tendon damage has been developed, and acceptable reliability data were presented from a series of exercises. A preliminary consensus definition of US synovitis in pediatric arthritis has been developed and requires further testing.Conclusion.At OMERACT 11, consensus was achieved on the application of the US-GLOSS for evaluating synovitis in RA; and work continues on development of RA tenosynovitis scales as well as in JIA synovitis.

scholarly journals Pharmacokinetics-Based Chronoefficacy of Semen Strychni and Tripterygium Glycoside Tablet Against Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingpan Lin ◽  
Lu Gao ◽  
Yanke Lin ◽  
Shuai Wang ◽  
Zemin Yang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Destruction ◽  
Systemic Exposure ◽  
Inflammatory Factors ◽  
Systemic Autoimmune Disease ◽  
Active Ingredients ◽  
Tnf Α ◽  
Exposure Levels ◽  
Semen Strychni

Rheumatoid arthritis is a systemic autoimmune disease characterized by synovial inflammation and bone destruction. Identifying drugs with time-varying efficacy and toxicity, and elucidating the mechanisms would help to improve treatment efficacy and reduce adverse effects. Here, we aimed to determine the chronoefficacy of semen strychni (SS) and tripterygium glycoside tablet (TGT) against rheumatoid arthritis in mice, and to investigate a potential role of circadian pharmacokinetics in generating chronoefficacy. SS extract and TGT suspension were prepared with ultrasonication. Effects of SS and TGT on collagen-induced arthritis (CIA) were evaluated by measuring TNF-α and IL-6 levels. SS dosed at ZT18 was more effective in protecting against CIA than drug dosed at ZT6 (i.e., lower levels of key inflammatory factors at ZT18 than at ZT6). This was accompanied by higher systemic exposure levels of strychnine and brucine (two main putative active ingredients of SS) in ZT18-treated than in ZT6-treated CIA mice. TGT dosing at ZT2 showed a better efficacy against CIA as compared to herb doing at ZT14. Consistently, ZT2 dosing generated a higher exposure of triptolide (a main putative active ingredient of TGT) as compared to ZT14 dosing in CIA mice. Moreover, strychnine, brucine, and triptolide significantly inhibited the proliferation of fibroblast-like synoviocytes, and reduced the production of TNF-α and IL-6 and the mRNAs of TNF-α, IL-6, COX-2, and iNOS, suggesting that they possessed an anti-arthritis activity. In conclusion, SS and TGT display chronoefficacy against rheumatoid arthritis in mice, that is attributed to circadian pharmacokinetics of main active ingredients. Our findings have implications for improving treatment outcomes of SS and TGT via timed delivery.

scholarly journals Proteoglycan Aggrecan Conducting T Cell Activation and Apoptosis in a Murine Model of Rheumatoid Arthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
A. Hanyecz ◽  
K. Olasz ◽  
O. Tarjanyi ◽  
P. Nemeth ◽  
K. Mikecz ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Systemic Autoimmune Disease ◽  
T Cell Epitopes ◽  
T Cell Apoptosis ◽  
Autoreactive T Cell

Rheumatoid arthritis (RA) is a systemic autoimmune disease and its targeting of the joints indicates the presence of a candidate autoantigen(s) in synovial joints. Patients with RA show immune responses in their peripheral blood to proteoglycan (PG) aggrecan. One of the most relevant animal models of RA appears to be proteoglycan-induced arthritis (PGIA), and CD4+T cells seem to play a crucial role in the initiation of the disease. In this review, the role of various T cell epitopes of aggrecan in the induction of autoreactive T cell activation and arthritis is discussed. We pay special attention to two critically important arthritogenic epitopes, 5/4E8 and P135H, found in the G1 and G3 domains of PG aggrecan, respectively, in the induction of autoimmune arthritis. Finally, results obtained with the recently developed PG-specific TCR transgenic mice system showed that altered T cell apoptosis, the balance of activation, and apoptosis of autoreactive T cells are critical factors in the development of autoimmunity.

scholarly journals The Role of Antigen Processing and Presentation in Cancer and the Efficacy of Immune Checkpoint Inhibitor Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 134
Author(s):  
Anastasia Mpakali ◽  
Efstratios Stratikos
Keyword(s):  
Immune Checkpoint ◽  
Antigen Processing ◽  
Current Knowledge ◽  
Checkpoint Inhibitors ◽  
Clinical Results ◽  
Therapeutic Benefit ◽  
Complementary Approach ◽  
Intracellular Antigen ◽  
Antigen Processing And Presentation

Recent clinical successes of cancer immunotherapy using immune checkpoint inhibitors (ICIs) are rapidly changing the landscape of cancer treatment. Regardless of initial impressive clinical results though, the therapeutic benefit of ICIs appears to be limited to a subset of patients and tumor types. Recent analyses have revealed that the potency of ICI therapies depends on the efficient presentation of tumor-specific antigens by cancer cells and professional antigen presenting cells. Here, we review current knowledge on the role of antigen presentation in cancer. We focus on intracellular antigen processing and presentation by Major Histocompatibility class I (MHCI) molecules and how it can affect cancer immune evasion. Finally, we discuss the pharmacological tractability of manipulating intracellular antigen processing as a complementary approach to enhance tumor immunogenicity and the effectiveness of ICI immunotherapy.

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