Response to 'Serum level of adiponectin is a surrogate independent biomarker of radiographic disease progression in early rheumatoid arthritis: results from the ESPOIR cohort'- authors' reply

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Harnessing Apoptotic Cell Clearance to Treat Autoimmune Arthritis

Early-stage apoptotic cells possess immunomodulatory properties. Proper apoptotic cell clearance during homeostasis has been shown to limit subsequent immune responses. Based on these observations, early-stage apoptotic cell infusion has been used to prevent unwanted inflammatory responses in different experimental models of autoimmune diseases or transplantation. Moreover, this approach has been shown to be feasible without any toxicity in patients undergoing allogeneic hematopoietic cell transplantation to prevent graft-versus-host disease. However, whether early-stage apoptotic cell infusion can be used to treat ongoing inflammatory disorders has not been reported extensively. Recently, we have provided evidence that early-stage apoptotic cell infusion is able to control, at least transiently, ongoing collagen-induced arthritis. This beneficial therapeutic effect is associated with the modulation of antigen-presenting cell functions mainly of macrophages and plasmacytoid dendritic cells, as well as the induction of collagen-specific regulatory CD4+ T cells (Treg). Furthermore, the efficacy of this approach is not altered by the association with two standard treatments of rheumatoid arthritis (RA), methotrexate and tumor necrosis factor (TNF) inhibition. Here, in the light of these observations and recent data of the literature, we discuss the mechanisms of early-stage apoptotic cell infusion and how this therapeutic approach can be transposed to patients with RA

Elevated Adiponectin Serum Levels in Women with Systemic Autoimmune Diseases

Adipose tissue produces a wide range of proteins that may influence the immune system. In this study, we assessed the serum levels of leptin, adiponectin, and ghrelin, in association with the measurements of body composition, in 15 female patients with various autoimmune diseases (systemic lupus erythematosus, primary Sjögren's syndrome, sarcoidosis, mixed connective tissue disease, vasculitis, CREST syndrome, and polymyositis) and in 15 healthy female controls. There were no statistically significant differences between the patients and controls with regard to serum leptin, serum ghrelin, global fat mass, adiposity, and fat mass in the android or gynoid regions, whereas serum adiponectin levels were higher in patients than controls (16.3 ± 1.6 μg/mL versus 9.7 ± 0.6 μg/mL; P = .01). As adiponectin is known to exhibit potent anti-inflammatory properties, a high adiponectinemia in patients with systemic autoimmune disease may mitigate the inflammatory response. However, the precise consequences of these elevated serum adiponectin levels on the metabolic syndrome development and atherosclerotic cardiovascular risk in this patient population still needs to be determined

Apoptotic cell infusion treats ongoing collagen-induced arthritis, even in the presence of methotrexate, and is synergic with anti-TNF therapy

International audienceAbstractBackgroundApoptotic cell-based therapies have been proposed to treat chronic inflammatory diseases. The aim of this study was to investigate the effect of intravenous (i.v.) apoptotic cell infusion in ongoing collagen-induced arthritis (CIA) and the interaction of this therapy with other treatments used in rheumatoid arthritis (RA), including methotrexate (MTX) or anti-TNF therapy.MethodsThe effects of i.v. apoptotic cell infusion were evaluated in a CIA mouse model in DBA/1 mice immunized with bovine type II collagen. The number and functions of antigen-presenting cells (APC), regulatory CD4+ T cells (Treg), and circulating anti-collagen auto-antibodies were analyzed in CIA mice.ResultsTreatment of arthritic mice with i.v. apoptotic cell infusion significantly reduced the arthritis clinical score. This therapeutic approach modified T cell responses against the collagen auto-antigen with selective induction of collagen-specific Treg. In addition, we observed that APC from apoptotic-cell-treated animals were resistant to toll-like receptor ligand activation and favored ex vivo Treg induction, indicating APC reprogramming. Apoptotic cell injection-induced arthritis modulation was dependent on transforming growth factor (TGF)-β, as neutralizing anti-TGF-β antibody prevented the effects of apoptotic cells. Methotrexate did not interfere, while anti-TNF therapy was synergic with apoptotic-cell-based therapy.ConclusionOverall, our data demonstrate that apoptotic-cell-based therapy is efficient in treating ongoing CIA, compatible with current RA treatments, and needs to be evaluated in humans in the treatment of RA

Clinical, ultrasonographic and CT markers for botulinum toxin injections into the piriformis muscle

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ATHLETIQUE: interest of an adapted physical activity program in patients with juvenile idiopathic arthritis: a feasibility and preliminary effectiveness study

BackgroundJuvenile Idiopathic Arthritis (JIA) is associated with joint inflammation, pain and limited joint mobility, impacting the practice of physical activities. Adapted Physical Activities (APA) are an increasingly used method of rehabilitation, but additional studies are needed to define the nature of the most appropriate physical activity for patients with JIA. The “ATHLETIQUE” project aims to evaluate the impact of a program integrating APA sessions with use of a pedometer watch, on disease activity in patients with JIA.MethodsThis study will be a randomized, multicenter, open-label, controlled clinical trial with 2 parallel arms. The patients included in this study will be children and adolescents with JIA, aged 6 to 17 years. The experimental group (30 patients) will participate in an APA program for 3 months and will use a pedometer watch for one year. We will evaluate and compare the change in disease activity measurements (primary objective), fatigue, pain, quality of life, level of physical activity, functional capacities, and muscle strength (secondary objectives) after 14, 26 and 50 weeks. The control group (10 patients) will undergo the same evaluations as the experimental group but will not participate in the APA program and will not wear the pedometer watch.Expected resultsThe APA program may help to promote an active lifestyle with regular physical activity, preventing comorbidities and motor disability. Promising results on disease activity, functional capacities and quality of life would enable us to envisage a larger research program with a view to optimizing and assessing APA for children with JIA.DiscussionThis study will be conducted in the short and medium-term, with one-year follow-up, including 3 months of APA sessions for the experimental group. The sessions proposed during the APA program will mainly be aerobic and bodyweight exercises. Furthermore, in contrast to previous studies on this topic, our study will integrate a novel element, namely the use of a pedometer watch. This watch will help to implement strategies to address motivation. This study aims to improve physical and mental well-being, provide a basis for the design of a larger study, and propose recommendations adapted to children with JIA.Trial registrationRegistered with ClinicalTrials.gov under the number NCT0557242

Increased production of soluble CTLA-4 in patients with spondylarthropathies correlates with disease activity

International audienceINTRODUCTION: Spondylarthropathies (SpA) are characterized by abnormal immune responses including T cell activation. Cytotoxic T lymphocyte associated molecule-4 (CTLA-4) is involved in down-regulating immune responses. A soluble form of CTLA-4 (sCTLA-4), resulting from an alternative splicing, has been identified and was found increased in several autoimmune diseases. Here, we evaluated circulating levels of sCTLA-4 as a marker of immune dysregulation in SpA. Intracellular CTLA-4 and levels of CTLA-4 transcript expression in peripheral blood lymphocytes (PBL) were also studied. METHODS: Sera from 165 patients with SpA were evaluated for sCTLA-4 measurements. Results were compared with those from 71 patients with rheumatoid arthritis (RA) and 88 healthy subjects. In 32 patients with SpA, 22 patients with RA and 15 healthy controls, we analyzed the intracellular CTLA-4 expression in CD4+ T cells, CD8+ T cells, activated (HLA-DR+Foxp3-) CD4+ T cells, CD4+ regulatory (CD25+Foxp3+) T cells and in CD3 negative cells by flow cytometry. Expression of the full length (coding for membrane CTLA-4) and spliced form (coding for sCTLA-4) of CTLA-4 transcripts in PBL were analyzed by quantitative real-time polymerase chain reaction (QRT-PCR). RESULTS: High levels of sCTLA-4 were found in the SpA group compared to the RA group and healthy controls (P < 0.0001). Soluble CTLA-4 serum levels strongly correlated with clinical index of disease activity BASDAI (r = 0.42, P < 0.0001) and C-reactive protein (CRP) levels (r = 0.17, P = 0.037). In contrast to RA patients, SpA patients did not exhibit changes in intracellular CTLA-4 expression in the different PBL subsets tested. Finally, the SpA group showed a preferential expression of the spliced CTLA-4 mRNA (P = 0.0014) in PBL. CONCLUSIONS: SpA patients exhibit high levels of circulating sCTLA-4 that may result from an alternative splicing of CTLA-4 transcripts. This may influence immune activation and regulation in SpA