PREVALENCE OF PERIPHERAL AND EXTRA-ARTICULAR DISEASE IN ANKYLOSING SPONDYLITIS VERSUS NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: A META-ANALYSIS

Pathophysiology and treatment of rheumatic disease

Prevalence of peripheral and extra-articular disease in ankylosing spondylitis versus non-radiographic axial spondyloarthritis: a meta-analysis

Pathophysiology and treatment of rheumatic disease

Dickkopf-1 and interleukin 6 interaction as a potential mechanism of Wnt pathway inhibition in rheumatoid arthritis

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Clinical Response and Remission in Patients with Non-Radiographic Axial Spondyloarthritis after Three Years of Adalimumab Therapy

Pathophysiology and treatment of rheumatic disease

Soluble biomarkers of cartilage and bone metabolism in early proof of concept trials in psoriatic arthritis: Effects of adalimumab versus placebo

Background: There is growing interest in soluble biomarkers that could be used on the group level for screening purposes in small proof of principle studies during early drug development. We investigated early changes in serum levels of several candidate biomarkers involved in cartilage and bone metabolism following the initiation of adalimumab as a prototypic active treatment in psoriatic arthritis (PsA) compared to placebo. Materials and Methods: Twenty-four PsA patients were randomized to receive either adalimumab 40 mg s.c. every other week or placebo for 4 weeks, followed by an open label extension phase. Serum samples were obtained at baseline and after 4 and 12 weeks of treatment and analyzed for levels of CPII and PINP (synthesis of type II and type I procollagen), melanoma inhibitory activity (MIA) (chondrocyte anabolism), matrix metalloproteinase (MMP)-3, C2C and cartilage oligomeric matrix protein (COMP) (type II collagen degradation), osteocalcin (OC) (bone formation), NTX-I and ICTP (both type I collagen degradation). Results: After 4 weeks, there was a significant decrease in serum MMP-3 levels in adalimumab-treated patients (P<0.005), while no change was observed in the placebo group. A significant increase in serum MIA was noted after adalimumab therapy (P<0.005) but not after placebo treatment. After 12 weeks, there was a marked reduction in serum MMP-3 in both groups (P<0.005), whereas other markers did not show significant changes compared to baseline. Conclusion: MMP-3 and MIA could serve as soluble biomarkers associated with inflammation as well as joint remodelling and destruction and may, together with clinical evaluation and in combination with other biomarkers, assist in distinguishing between effective and ineffective therapy in small, proof-of-principle studies of short duration in PsA. © 2010 van Kuijk et al

Systematic validation of specific phenotypic markers for in vitro polarized human macrophages.

Item does not contain fulltextBACKGROUND: Polarization of macrophages by specific micro-environmental conditions impacts upon their function following subsequent activation. This study aimed to systematically validate robust phenotypic markers for in vitro polarized human macrophages in order to facilitate the study of macrophage subsets in vivo. METHODS: Human peripheral blood monocytes were polarized in vitro with IFN-gamma, IL-4, or IL-10. Similar experiments were performed with TNF, IL-13, dexamethasone, M-CSF and GM-CSF as polarizing stimuli. Phenotypic markers were assessed by flow cytometry and qPCR. RESULTS: IFN-gamma polarized macrophages (MPhi(IFN-gamma)) specifically enhanced membrane expression of CD80 and CD64, IL-4 polarized macrophages (MPhi(IL-4)) mainly upregulated CD200R and CD206, and downregulated CD14 levels, and IL-10 polarized macrophages (MPhi(IL-10)) selectively induced CD163, CD16, and CD32. The expression profiles of the most specific markers were confirmed by qPCR, dose-response experiments, and the use of alternative polarizing factors for each macrophage subset (TNF, IL-13, and dexamethasone, respectively). GM-CSF polarized macrophages (MPhi(GM-CSF)) upregulated CD80 but not CD64 expression, showing a partial phenotypic similarity with MPhi(IFN-gamma), and also upregulated the expression of the alternative activation marker CD206. M-CSF polarized macrophages (MPhi(M-CSF)) not only expressed increased levels of CD163 and CD16, resembling MPhi(IL-10,) but also displayed high levels of CD64. The phenotype of MPhi(M-CSF) could be further modulated by additional polarization with IFN-gamma, IL-4, or IL-10, whereas MPhi(GM-CSF) showed less phenotypic plasticity. CONCLUSION: This study validated CD80 as the most robust phenotypic marker for human MPhi(IFN-gamma), whereas CD200R was upregulated and CD14 was specifically downregulated on MPhi(IL-4). CD163 and CD16 were found to be specific markers for MPhi(IL-10). The GM-CSF/M-CSF differentiation model showed only a partial phenotypic similarity with the IFN-gamma/IL-4/IL-10 induced polarization

The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis synovium

BACKGROUND: Interleukin (IL)-36α is a recently described member of the IL-1 cytokine family with pro-inflammatory and clearly pathogenic properties in psoriasis. OBJECTIVE: To determine the IL-36α expression in psoriatic arthritis (PsA) compared to rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial tissues obtained from arthritis patients were stained for IL-36α, IL-36 receptor (IL-36R) and IL-36R antagonist (IL-36Ra) by immunohistochemistry and immunofluorescence. Lysates were examined for IL-36α by western blot analysis. Synovial fibroblasts (FLS) cultured in the presence of IL-36α were assayed for cytokine expression by quantitative real time PCR and multiplex assay. IL-36α-induced signal transduction in FLS was analysed by immunoblotting. RESULTS: Expression of IL-36R and its ligands IL-36α and IL-36Ra was detected in the synovial lining layer and cellular infiltrates of patients with inflammatory arthritis. IL-36α was expressed significantly higher in PsA and RA than in OA synovium. CD138-positive plasma cells were identified as the main cellular source of IL-36α. No differences were observed for the expression of IL-36R and IL-36Ra between PsA, RA and OA. Functionally, IL-36α induced the expression of IL-6 and IL-8 in FLS through p38/NFkB activation. CONCLUSIONS: IL-36α is up-regulated in PsA and RA synovium, expressed by tissue plasma cells and leads to IL-6 and IL-8 production by synovial fibroblasts. Hence, IL-36α links plasma cells to inflammatory cytokine production by FLS and may represent a key link between autoimmunity and the induction of synovitis