Arthritis in idiopathic inflammatory myopathy: clinical features and autoantibody associations.

OBJECTIVE: To determine the prevalence, distribution, and clinical manifestations of arthritis in a cohort of patients with idiopathic inflammatory myopathies (IIM). Associations with autoantibody status and HLA genetic background were also explored. METHODS: Consecutive patients with IIM treated in a single center were included in this cross-sectional study (n = 106). History of arthritis, 68-joint and 66-joint tender and swollen joint index, clinical features of IIM, and autoantibody profiles were obtained by clinical examination, personal interview, and review of patient records. High-resolution genotyping in HLA-DRB1 and HLA-DQB1 loci was performed in 71 and 73 patients, respectively. RESULTS: A combination of patients' medical history and cross-sectional physical examination revealed that arthritis at any time during the disease course had occurred in 56 patients (53%). It was present at the beginning of the disease in 39 patients (37%) including 23 cases (22%) with arthritis preceding the onset of muscle weakness. On physical examination, 29% of patients had at least 1 swollen joint. The most frequently affected areas were wrists, and metacarpophalangeal and proximal interphalangeal joints. Twenty-seven out of the 29 anti-Jo1-positive patients had arthritis at any time during the course of their illness; this prevalence was significantly higher compared to patients without the anti-Jo1 autoantibody (p < 0.0001). No association of arthritis with individual HLA alleles was found. CONCLUSION: Our data suggest that arthritis is a common feature of myositis. It is frequently present at the onset of disease and it may even precede muscular manifestations of IIM. The most common presentation is a symmetrical, nonerosive polyarthritis affecting particularly the wrists, shoulders, and small joints of the hands. We have confirmed a strong association of arthritis with the presence of the anti-Jo1 antibody.

The metastasis-associated protein S100A4 promotes the inflammatory response of mononuclear cells via the TLR4 signalling pathway in rheumatoid arthritis.

OBJECTIVES: S100A4 has been implicated in cancer and several inflammatory diseases, including RA. The aim of the present study was to determine whether S100A4 can stimulate proinflammatory cytokine production in mononuclear cells. METHODS: Peripheral blood mononuclear cells (PBMCs) isolated from patients with RA were stimulated with S100A4, S100A8, S100A9 and S100A12. The production of IL-1ß, IL-6 and TNF-α was measured by ELISA. Receptor for advanced glycation end products (RAGEs) and Toll-like receptor 4 (TLR4) signalling were examined. For signalling pathway blocking studies, inhibitors of myeloid differentiation primary response gene 88 (MyD88), nuclear factor kappa B (NF-κB) and the mitogen activated protein (MAP) kinases p38, extracellular signal-regulated kinase 1/2 (ERK1/2) and Jun N-terminal kinase (JNK) were used. MAP kinase activation was evaluated by western blotting. RESULTS: Stimulation of PBMCs with S100A4 significantly up-regulated IL-1ß, IL-6 and TNF-α production compared with unstimulated cells (P < 0.001). Importantly, the production of these cytokines was markedly enhanced in response to S100A4 compared with S100A8 and S100A12; however, it was less pronounced compared with S100A9. Furthermore, enhanced production of proinflammatory cytokines in S100A4-stimulated PMBCs was at least partly mediated via TLR4, but not RAGEs, and by activation of the transcription factor NF-κB and the MAP kinases p38 and ERK1/2. CONCLUSION: This is the first study to demonstrate that S100A4 can induce an inflammatory response mediated by TLR4 and by the activation of NF-κB and the kinases p38 and ERK1/2 in mononuclear cells from patients with RA. Therefore S100A4 may be a potential therapeutic target for immune-mediated diseases.

The expression profile of miR-23b is not altered in peripheral blood mononuclear cells of patients with idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIM) belong to a group of autoimmune disorders, primarily characterized by chronic inflammation of human skeletal muscle tissue. The etiology of these diseases is unknown, however, genetic predisposition plays a significant role in disease onset. Beside the known genetic risk located in the MHC complex, the epigenetic modifications including changes in miRNAs expression profiles have been recently implicated recently in many autoimmune diseases. Micro RNA molecules are involved in many physiological processes, including the regulation of the immune response. In our study we have focused on the miR-23b, as it represents a novel promising autoimmunity regulator molecule. Downregulation of miR-23b was recently described in patients with rheumatoid arthritis and systemic lupus erythematosus. We have measured the expression miR-23b peripheral blood mononuclear cells of patients with dermatomyositis and polymyositis. No meaningful difference was found in comparison with healthy controls.