Inhibition of JAK/STAT signaling in rheumatologic disorders: the expanding spectrum

Publication date: Available online 12 September 2019Source: Joint Bone SpineAuthor(s): Thomas El Jammal, Mathieu Gerfaud-Valentin, Pascal Sève, Yvan JamillouxAbstractThree Janus kinase (JAK) inhibitors, ruxolitinib, tofacitinib, and baricitinib, are currently approved by the FDA/EMA for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative rectocolitis. The inhibition of JAK/STAT signaling by these small molecules, downstream of several cytokine receptors, results in lower pro-inflammatory gene expression. Given the cytokine profiles observed in rheumatologic diseases, most of the recent therapeutic strategies target cytokines, either directly or through their receptors. Each cytokine receptor recruits a specific combination of JAKs to activate different programs in cells. The approved drugs are panJAK inhibitors, able to impede more than one pathway. These drugs are being tested in various rheumatologic disorders. At the same time, more specific molecules able to target one specific JAK are being developed. In this review, we describe the expanding spectrum of rheumatologic and autoimmune conditions for which JAK inhibition may represent new avenues in clinical practice.
Source: Joint Bone Spine - Category: Orthopaedics Source Type: research

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ConclusionThe eye could be a responsive marker for the onset or aggravation of an immune reactivation in many rheumatic diseases, furthermore, ocular findings can antedate the diagnosis of the underlying rheumatic disease. By recognizing ocular manifestations of systemic rheumatic diseases it might be possible to avoid or at least delay many long term sequelae.
Source: International Ophthalmology - Category: Opthalmology Source Type: research
Abstract BACKGROUND: Mucosal-associated invariant T (MAIT) cells are gaining more relevance for autoimmune diseases because of its (i) innate and adaptive immune response (ii) tissue homing properties (iii) production of IL-17A. These cells are predominantly CD8+ cells, because of its strong association with MHC-I. Tc17 CD8+/MAIT cells likely to have a critical role in psoriatic arthritis (PsA). Herein, we have explored pathological significance of MAIT cell in PsA. METHODS: Peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) were collected from age/sex matched (n = 10 fo...
Source: Cytokine - Category: Molecular Biology Authors: Tags: Cytokine Source Type: research
In this study, SUA, CRP, creatinine, MCP-1, IFN- α2, IFN-γ, Il-1β, IL-6, IL-8, IL-10, IL-12, IL-17a, IL-18, IL-23, IL-33, TNF-α, and allantoin levels were measured prior to and after 3 months of TNFis treatment in patients with SARDs. The values obtained in the biochemical assays were then tested for associations with the patients’ demograp hic and disease-related data. A total of 128 patients (rheumatoid arthritis,n = 44; ankylosing spondylitis,n = 45; psoriatic arthritis,n = 23; and adults with juvenile idiopathic arthritis,n = 16) ...
Source: Rheumatology International - Category: Rheumatology Source Type: research
CONCLUSIONS: We found very little research investigating the efficacy of smoking cessation intervention specifically in people with IJD. Included studies are limited by imprecision, risk of bias, and indirectness. Neither of the included studies investigated whether smoking cessation intervention reduced disease activity among people with IJD. High-quality, adequately powered studies are warranted. In particular, researchers should ensure that they measure disease markers and quality of life, in addition to long-term smoking cessation. PMID: 31476270 [PubMed - as supplied by publisher]
Source: Cochrane Database of Systematic Reviews - Category: General Medicine Authors: Tags: Cochrane Database Syst Rev Source Type: research
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Source: Discovery Medicine - Category: Research Tags: Discov Med Source Type: research
Abstract Rheumatoid arthritis, psoriatic arthritis and axial spondylarthritis are the most common chronic autoimmune rheumatic diseases. For all three diseases an early diagnosis and initiation of treatment is crucial. The proof of concept network study "Rheuma-VOR" is a further developed version of the predecessor project ADAPTHERA and was extended to several federal states. The aim of this prospective study is to improve the early diagnosis of rheumatoid arthritis, psoriatic arthritis and axial spondylarthritis and thus positively impact the quality of care for patients with the help of multidisciplina...
Source: Zeitschrift fur Rheumatologie - Category: Rheumatology Authors: Tags: Z Rheumatol Source Type: research
There are a large number of potential causes of an inflammatory arthropathy, ranging from self-limiting viral infections to long-term systemic autoimmune diseases. The most common forms of inflammatory arthritis are rheumatoid arthritis and the spondyloarthropathies, a family of related inflammatory diseases including psoriatic arthritis and ankylosing spondylitis. These more common conditions form the basis of this review. There is growing evidence that in both rheumatoid arthritis and psoriatic arthritis, early initiation of treatment and tight control of disease activity improves outcomes.
Source: Orthopaedics and Trauma - Category: Orthopaedics Authors: Tags: Principles of orthopaedics Source Type: research
CONCLUSIONS: These data indicate that GrM levels are increased in RA synovial fluid and that GrM can stimulate proinflammatory IL-29 release from fibroblasts, suggesting a role of GrM in the pathogenesis of RA. PMID: 31172927 [PubMed - as supplied by publisher]
Source: Clinical and Experimental Rheumatology - Category: Rheumatology Tags: Clin Exp Rheumatol Source Type: research
ConclusionWe did not find CD in children with JIA. Long term studies with more JIA patients are needed to provide more precise interpretation.
Source: Arab Journal of Gastroenterology - Category: Gastroenterology Source Type: research
AbstractIn the vast database of peer-reviewed articles, the number of 2018 papers published retrieved using the “autoimmunity” keyword remained unchanged compared with the brilliant results of 2017 while returning above a 5% share within the immunology field, after the brisk decrease of this ratio in 2017. As in the past 12 years, we have now searched PubMed for publications related to autoimmunity in th e major immunology and autoimmunity peer-reviewed journals and provide here an arbitrary discussion of the major themes encountered. Once again, we are happy to notice that similarities between autoimmune ...
Source: Clinical Reviews in Allergy and Immunology - Category: Allergy & Immunology Source Type: research
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