Rheumatology-Rhumatologie
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Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis

Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis | Rheumatology-Rhumatologie | Scoop.it

Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples. We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA.


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another gut bug?

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RHUMATOLOGIE - RHEUMATOLOGY

Obviously a topic of interest for so many people:

for the patient, it includes aching muscles, tendons and joints..

for MDs and researchers, it covers degenerative diseases as well as arthritis, often associated with various autoimmune diseases (see autoimmunity http://www.scoop.it/t/autoimmunity)

fortunately,

new diagnostic tools are available

and new biotherapies allowed to improve the prognosis and the quality of life of patients

Gilbert C FAURE's insight:

January 2016

still few viewers (#650) for this topic, but >1280 posts and 2000 views

much less than other immunology topics, but growing!


October 2016 1500 scoops and almost 3K views

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Frontiers | Insight into the Endocrine System and the Immune System: A Review of the Inflammatory Role of Prolactin in Rheumatoid Arthritis and Psoriatic Arthritis | Immunology

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects females three times more frequently than males. A potential role for hormones, such as prolactin (PRL), may in part explain this phenomenon. The risk of developing RA is increased in women who are lactating after the first pregnancy, which might be related to breastfeeding and the release of PRL. Other studies found a protective effect of PRL on RA development. Some studies have reported that hyperprolactinemia is more common in RA and serum PRL levels are correlated with several disease parameters, although others could not confirm these findings. Overall the plasma PRL levels are on average not elevated in RA.. Previously, a small number of open label clinical trials using bromocriptine, which indirectly decreases PRL levels, were performed in RA patients and showed clinical benefit, although others found the opposite effect. Locally produced PRL at the site of inflammation may have a crucial role in RA as well, as it has been shown that PRL can be produced by synovial macrophages. Locally produced PRL has both pro-inflammatory and anti-inflammatory effects in arthritis. Psoriatic arthritis (PsA) is also an autoinflammatory disease, in which the PRLR is also expressed in macrophages. The aim of this review is to provide an overview of the potential role of PRL signalling in inflammatory joint diseases (RA and PsA) and its potential as a therapeutic target.
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Rheumatology Online Educational Courses Among Key ARHP Pillars - The Rheumatologist

Rheumatology Online Educational Courses Among Key ARHP Pillars - The Rheumatologist | Rheumatology-Rhumatologie | Scoop.it
Editor’s note: The new Pillar Talk column is developed by the ARHP Executive Committee in an effort to share information about ongoing activities related to our four pillars: Education, Practice, Research and Advocacy. You Might Also Like Online Education for ARHP Members Comprehensive Rheumatology Training Online Rheumatology Health Professionals Should Attend the ACR/ARHP 2014 Meeting... [Read More]
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Nerve growth factor regulation and production by macrophages in osteoarthritic synovium

Nerve growth factor regulation and production by macrophages in osteoarthritic synovium | Rheumatology-Rhumatologie | Scoop.it
Nerve growth factor (NGF) functions to modulate osteoarthritis (OA)‐associated pain. Although recent studies suggest that tumor necrosis factor (TNF)‐α and interleukin (IL)‐1β mediate NGF activity i
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Slideshow: What’s Wrong With My Shoulder?

Slideshow: What’s Wrong With My Shoulder? | Rheumatology-Rhumatologie | Scoop.it
Don’t take your shoulder for granted. It’s a versatile body part that allows an amazing range of motion. Click through to find out what can go wrong with it.
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Autoimmunity Reviews


Recent advances in our understanding of giant cell arteritis pathogenesis

Maxime Samson, Marc Corbera-Bellalta, Sylvain Audia, Ester Planas-Rigol, Laurent Martin, Maria Cinta Cid, Bernard Bonnotte Autoimmunity Reviews, Available online 28 May 2017

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Presence of anticitrullinated protein antibodies in a large population-based cohort from the Netherlands

Presence of anticitrullinated protein antibodies in a large population-based cohort from the Netherlands | Rheumatology-Rhumatologie | Scoop.it
Objectives To determine the prevalence of anticitrullinated protein antibodies (ACPAs) and their association with known rheumatoid arthritis (RA) risk factors in the general population.

Methods Lifelines is a multidisciplinary prospective population-based cohort study in the Netherlands. Cross-sectional data from 40 136 participants were used. The detection of ACPA was performed by measuring anti-CCP2 on the Phadia-250 analyser with levels ≥6.2 U/mL considered positive. An extensive questionnaire was taken on demographic and clinical information, including smoking, periodontal health and early symptoms of musculoskeletal disorders. RA was defined by a combination of self-reported RA, medication use for the indication of rheumatism and visiting a medical specialist within the last year.

Results Of the total 40 136 unselected individuals, 401 (1.0%) had ACPA level ≥6.2 U/mL. ACPA positivity was significantly associated with older age, female gender, smoking, joint complaints, RA and first degree relatives with rheumatism. Of the ACPA-positive participants, 22.4% had RA (15.2% had defined RA according to our criteria and 7.2% self-reported RA only). In participants without RA, 311 (0.8%) were ACPA-positive. In the non-RA group, older age, smoking and joint complaints remained significantly more frequently present in ACPA-positive compared with ACPA-negative participants.

Conclusions In this large population-based study, the prevalence of ACPA levels ≥6.2 U/mL was 1.0% for the total group and 0.8% when excluding patients with RA. Older age, smoking and joint complaints were more frequently present in ACPA-positive Lifelines participants. To our knowledge, this study is the largest study to date on ACPA positivity in the general, mostly Caucasian population.
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Frontiers | Insulin-Like Growth Factor Binding Protein 6 in Rheumatoid Arthritis: A Possible Novel Chemotactic Factor? | Immunology

Objectives: Immune cell migration from the bloodstream to target tissues is a hallmark of rheumatoid arthritis (RA) pathogenesis. The role of chemoattractants, mainly chemokines, and their possible targeting for therapeutic purposes have been under intense investigation over the last years but the results were not as satisfactory as expected. The insulin-like growth factor binding protein 6 (IGFBP6), a direct inhibitor of IGF-II, also exerts IGF-independent effects including tumor cell migration in vitro. We aimed to assess the expression of this protein in serum, synovial fluid and synovial tissue of RA patients and to identify its possible chemotactic role in this disorder. Methods: IGFBP6 was measured in RA patients and healthy donors (HD) sera by LuminexxMAP® technology and in synovial tissue of RA patients and osteoarthritis controls by immunofluorescence. The identification of circulating IGFBP6+ cells was evaluated by flow cytometry and an in vitro migration assay was arranged. Results: We demonstrated that IGFBP6 is able to induce greater in vitro migration of RA as compared to HD and OA T lymphocytes and is overexpressed in serum and synovial tissue of RA patients. This in vitro chemotactic activity can be partially inhibited by dexamethasone. Conclusions: Our findings suggest a pathogenic role of IGFBP6 in RA and support its possible targeting for therapeutic purposes.
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The genetics revolution in rheumatology: large scale genomic arrays and genetic mapping : Nature Reviews Rheumatology : Nature Research

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Etudes approfondies des polyarthrites et maladies systémiques

DIU - Etudes approfondies des polyarthrites et maladies syst�miques
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CD40L-Dependent Pathway Is Active at Various Stages of Rheumatoid Arthritis Disease Progression

CD40L-Dependent Pathway Is Active at Various Stages of Rheumatoid Arthritis Disease Progression | Rheumatology-Rhumatologie | Scoop.it
The inflammatory CD40–CD40L pathway is implicated in various autoimmune diseases, but the activity status of this pathway in various stages of rheumatoid arthritis (RA) progression is unknown. In this study, we used gene signatures of CD40L stimulation derived from human immature dendritic cells and naive B cells to assess the expression of CD40-downstream genes in synovial tissues from anti-citrullinated protein Ab–positive arthralgia, undifferentiated arthritis (UA), early RA, and established RA cohorts in comparison with healthy donors. Interestingly, the expression of CD40LG and active full-length CD40 was increased in the disease tissues, whereas that of a dominant-negative CD40 isoform was decreased. Gene set variation analysis revealed that CD40L-responsive genes in immature dendritic cells and naive B cells were significantly enriched in synovial tissues from UA, early RA, and established RA patients. Additionally, CD40L-induced naive B cell genes were also significantly enriched in synovial tissues from arthralgia patients. In our efforts to characterize downstream mediators of CD40L signaling, we have identified GPR120 and KDM6B as novel components of the pathway. In conclusion, our data suggest that therapeutic CD40–CD40L blocking agents may prove efficacious not only in early and established RA, but also in inhibiting the progression of the disease from arthralgia or UA to RA.
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Osteoarthritis: You can rely on radiography when managing OA, but not too much! : Nature Reviews Rheumatology : Nature Research

When considering the role of imaging in the management of symptomatic, peripheral joint osteoarthritis (OA) in clinical practice, clinicians should be aware that radiography has its drawbacks, and also consider that the use of advanced imaging techniques such as MRI should not be discouraged.
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The role of stromal cells in inflammatory bone loss

The role of stromal cells in inflammatory bone loss | Rheumatology-Rhumatologie | Scoop.it
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation, local and systemic bone loss and a lack of compensatory bone repair. Fibroblast‐like synoviocytes (FLS) ar
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Pathogenetic insights from the treatment of rheumatoid arthritis

Pathogenetic insights from the treatment of rheumatoid arthritis | Rheumatology-Rhumatologie | Scoop.it
Rheumatoid arthritis is a chronic autoimmune disease that causes progressive articular
damage, functional loss, and comorbidity. The development of effective biologics and
small-molecule kinase inhibitors in the past two decades has substantially improved
clinical outcomes. Just as understanding of pathogenesis has led in large part to
the development of drugs, so have mode-of-action studies of these specific immune-targeted
agents revealed which immune pathways drive articular inflammation and related comorbidities.
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Antigen-specific immunotherapies in rheumatic diseases : Nature Reviews Rheumatology : Nature Research

The main goal of antigen-specific immunotherapy (ASI) in autoimmune and rheumatic diseases is to reprogramme or remove autoreactive cells and/or induce immune tolerance to self-antigens. Current therapies in these diseases either treat symptoms or slow down disease progression but are not yet curative or preventative — disease-specific treatments are urgently needed. In contrast to the nonspecific treatments in current use that induce generalized immune suppression, which is associated with several adverse effects including increased risk of infections, ASIs target a restricted subset of B cells or T cells, and thus do not compromise systemic immunity and host defence. This Review provides a summary of novel approaches for identifying autoepitopes and detecting and targeting autoreactive cells that might help in the development of ASIs. Promising approaches include the use of tolerizing peptides coupled to MHC constructs and/or nanocompounds, tolerizing dendritic cells and antigen-specific vaccines. Following studies in animal models of rheumatoid arthritis and systemic lupus erythematosus, several of these strategies have now entered clinical trials. However, to use these approaches in humans, several important limitations must first be addressed, such as; selecting the proper immunodominant autoantigen; identifying the optimal timing, dosing and route of administration; finding biomarkers for monitoring the therapy; and optimizing methodology.
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Nature Reviews Rheumatology (2017) doi:10.1038/nrrheum.2017.107 Published online 13 July 2017

Antigen-specific immunotherapies in rheumatic diseases 

 Judit Pozsgay, Zoltán Szekanecz & Gabriella Sármay
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Fondation Arthritis | Fardeau des maladies ostéoarticulaires: L’étude « Global Burden of Disease »

Fondation Arthritis | Fardeau des maladies ostéoarticulaires: L’étude « Global Burden of Disease » | Rheumatology-Rhumatologie | Scoop.it
Les maladies ostéoarticulaires sont la première cause d'incapacité dans le monde.
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5th World Congress on Controversies in BMJD by CongressMed - Events

5th World Congress on Controversies in BMJD by CongressMed - Events | Rheumatology-Rhumatologie | Scoop.it
The 5th World Congress on Controversies, Debates & Consensus in Bone, Muscle & Joint Diseases (BMJD) aims to continue facilitating effective debates on unresolved clinical and therapeutic dilemmas.
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Rao and Poulin Finding pathologic T cells in rheumatoid arthritis by mass cytometry

To watch this webinar please go to LabRoots at: https://www.labroots.com/ms/webinar/finding-pathologic-cells-rheumatoid-arthritis-mass-cytometry Determinin
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Efficacy, safety, pharmacokinetics, and pharmacodynamics of filgotinib, a selective Janus kinase 1 inhibitor, after short‐term treatment of rheumatoid arthritis: Results of two randomized Phase IIA...

Efficacy, safety, pharmacokinetics, and pharmacodynamics of filgotinib, a selective Janus kinase 1 inhibitor, after short‐term treatment of rheumatoid arthritis: Results of two randomized Phase IIA... | Rheumatology-Rhumatologie | Scoop.it
Objective. Janus kinase (JAK) inhibitors have shown efficacy in rheumatoid arthritis (RA). We hypothesized that selective inhibition of JAK1 would combine good efficacy with a differentiated safet
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Autoimmunity Reviews


Intravenous immunoglobulins in systemic sclerosis: Data from a French nationwide cohort of 46 patients and review o
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Biologics registers in RA: methodological aspects, current role and future applications : Nature Reviews Rheumatology : Nature Research

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New Interleukins in Psoriasis and Psoriatic Arthritis Patients: The Possible Roles of Interleukin-33 to Interleukin-38 in Disease Activities and Bone Erosions

Objectives: New interleukins (ILs), especially members of IL-1 and IL-12 families, have recently been reported to be involved in the development and regulation of autoimmune and inflammatory diseases. In this study, we aimed to explore the impact of these new ILs in psoriasis (Ps) and psoriatic arthritis (PsA). Methods: Forty PsA patients, 20 Ps patients, and 20 healthy controls (HCs) were recruited. Blood samples were obtained for detecting the levels of ILs, IL-12/23p40, and tumor necrosis factor α (TNF-α). The severity of skin lesions was assessed by the Psoriasis Area and Severity Index (PASI). Arthritis activities of PsA patients were assessed by the PsA Joint Activity Index. For PsA patients, circulating osteoclastogenesis-related cytokines (osteoprotegerin and receptor activator of nuclear factor-#x03BA;B ligand) and numbers of osteoclast precursors were evaluated. Radiographic features of affected joints in these patients were scored for erosion, joint-space narrowing, osteolysis, and new bone formation. Correlations among levels of these ILs, Ps, and PsA disease activities and bone erosions were studied. Results: Ps and PsA patients had higher serum levels of TNF-α, IL-12/23p40, and IL-33. Serum levels of IL-34 and IL-35 were higher in PsA patients than in Ps patients and HCs. Patients with pustular Ps had higher serum levels of IL-36α and IL-38 than patients with Ps vulgaris or HCs. Increased serum levels of IL-36α were positively correlated with PASI. Conclusion: Certain ILs were elevated in the circulation of patients with Ps and PsA, which might contribute to the pathogenesis of skin lesions and arthritis.
Dermatology
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Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis

Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis | Rheumatology-Rhumatologie | Scoop.it
Imbalance in the autonomic nervous system (ANS) has been observed in many established chronic autoimmune diseases, including rheumatoid arthritis (RA), which is a prototypic immune‐mediate
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Largest Psoriasis Meta-Analysis to Date Yields New Genetic Clues

Largest Psoriasis Meta-Analysis to Date Yields New Genetic Clues | Rheumatology-Rhumatologie | Scoop.it
The identification of 16 additional genetic markers will help researchers get closer to understanding how — and why — psoriasis develops.
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Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study

Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study | Rheumatology-Rhumatologie | Scoop.it
Objective To evaluate the effect of secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic changes through 2 years in patients with ankylosing spondylitis (AS).

Methods In the phase III MEASURE 1 study, patients were randomised to receive intravenous secukinumab 10 mg/kg (at baseline, week 2 and week 4) followed by subcutaneous secukinumab 150 mg (intravenous 150 mg; n=125) or 75 mg (intravenous 75 mg; n=124) every four weeks, or matched placebo (n=122). Placebo-treated patients were re-randomised to subcutaneous secukinumab 150 or 75 mg from week 16. Clinical efficacy assessments included Assessment of SpondyloArthritis international Society 20 (ASAS20) response rates through week 104. Radiographic changes at week 104 were assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS).

Results 97 (77.6%) and 103 (83.1%) patients in the intravenous 150 mg and intravenous 75 mg groups, respectively, completed week 104. In the full analysis set (intent-to-treat), ASAS20 response rates at week 104 were 73.7% and 68.0% in the intravenous 150 mg and intravenous 75 mg groups, respectively. Among patients with evaluable X-rays who were originally randomised to secukinumab (n=168), mean change in mSASSS from baseline to week 104 was 0.30±2.53. Serious adverse events were reported in 12.2% and 13.4% of patients in the 150 mg and 75 mg groups, respectively.

Conclusions Secukinumab improved AS signs and symptoms through 2 years of therapy, with no unexpected safety findings. Data from this study suggest a low mean progression of spinal radiographic changes, which will need to be confirmed in longer-term controlled studies.

Trial registration number NCT01358175.
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