OBJECTIVE: To develop evidence-based European Alliance of Associations for Rheumatology (EULAR) points to consider (PtCs) for the management of difficult-to-treat rheumatoid arthritis (D2T RA). METHODS: An EULAR Task Force was established comprising 34 individuals: 26 rheumatologists, patient partners and rheumatology experienced health professionals. Two systematic literature reviews addressed clinical questions around diagnostic challenges, and pharmacological and non-pharmacological therapeutic strategies in D2T RA. PtCs were formulated based on the identified evidence and expert opinion. Strength of recommendations (SoR, scale A-D: A typically consistent level 1 studies and D level 5 evidence or inconsistent studies) and level of agreement (LoA, scale 0-10: 0 completely disagree and 10 completely agree) of the PtCs were determined by the Task Force members. RESULTS: Two overarching principles and 11 PtCs were defined concerning diagnostic confirmation of RA, evaluation of inflammatory disease activity, pharmacological and non-pharmacological interventions, treatment adherence, functional disability, pain, fatigue, goal setting and self-efficacy and the impact of comorbidities. The SoR varied from level C to level D. The mean LoA with the overarching principles and PtCs was generally high (8.4-9.6). CONCLUSIONS: These PtCs for D2T RA can serve as a clinical roadmap to support healthcare professionals and patients to deliver holistic management and more personalised pharmacological and non-pharmacological therapeutic strategies. High-quality evidence was scarce. A research agenda was created to guide future research.

• Klíčová slova
• arthritis, fibromyalgia, inflammation, rheumatoid, ultrasonography,
• MeSH
• adherence k farmakoterapii MeSH
• antirevmatika aplikace a dávkování   terapeutické užití   MeSH
• cvičení MeSH
• hepatitida B komplikace   farmakoterapie   MeSH
• hepatitida C komplikace   farmakoterapie   MeSH
• kognitivně behaviorální terapie MeSH
• komorbidita MeSH
• lidé MeSH
• revmatoidní artritida komplikace   diagnóza   farmakoterapie   terapie   MeSH
• určení symptomu MeSH
• vzdělávání pacientů jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• směrnice pro lékařskou praxi MeSH
• Názvy látek
• antirevmatika MeSH

BACKGROUND: Interleukin 40 (IL-40) is a newly identified B cell-associated cytokine implicated in humoral immune responses and B cell homeostasis. As B cells play a pivotal role in autoimmunity, we investigated the function of IL-40 in rheumatoid arthritis (RA). METHODS: IL-40 expression was determined in the synovial tissue from RA and osteoarthritis (OA) patients. IL-40 was analysed in the serum/synovial fluid of patients with RA (n=50), systemic lupus erythematosus (SLE, n=69), OA (n=44), and healthy controls (HC, n=50). We assessed the changes of IL-40 levels in RA patients following the B cell depletion by rituximab (n=29) or after the TNF inhibition by adalimumab (n=25). We examined the relationship between IL-40, disease activity, autoantibodies, cytokines, and NETosis markers. Effect of IL-40 on synovial fibroblasts was determined. RESULTS: IL-40 was overexpressed in RA synovial tissue, particularly by synovial lining and infiltrating immune cells. The levels of IL-40 were up-regulated in the synovial fluid of RA versus OA patients (p<0.0001). Similarly, IL-40 was increased in the serum of RA patients compared to HC, OA, or SLE (p<0.0001 for all) and decreased after 16 and 24 weeks (p<0.01 and p<0.01) following rituximab treatment. No significant effect of adalimumab on IL-40 was observed. IL-40 levels in RA patients correlated with rheumatoid factor-IgM and anti-cyclic citrullinated peptides (anti-CCP) in the serum (p<0.0001 and p<0.01), as well as in the synovial fluid (p<0.0001 and p<0.001). Synovial fluid IL-40 was also associated with disease activity score DAS28 (p<0.05), synovial fluid leukocyte count (p<0.01), neutrophil attractants IL-8 (p<0.01), MIP-1α (p<0.01), and markers of neutrophil extracellular traps externalization (NETosis) such as proteinase 3 (p<0.0001) and neutrophil elastase (p<0.0001). Synovial fibroblasts exposed to IL-40 increased the secretion of IL-8 (p<0.01), MCP-1 (p<0.05), and MMP-13 (p<0.01) compared to the unstimulated cells. CONCLUSIONS: We show the up-regulation of IL-40 in RA and its decrease following B cell depleting therapy. The association of IL-40 with autoantibodies, chemokines, and markers of NETosis may imply its potential involvement in RA development. Moreover, IL-40 up-regulates the secretion of chemokines and MMP-13 in synovial fibroblasts, indicating its role in the regulation of inflammation and tissue destruction in RA.

• Klíčová slova
• B cells, NETosis, autoantibodies, disease activity, interleukin-40, rheumatoid arthritis,
• MeSH
• adalimumab terapeutické užití   MeSH
• antirevmatika farmakologie   terapeutické užití   MeSH
• artróza kolenních kloubů imunologie   metabolismus   MeSH
• autoprotilátky krev   MeSH
• B-lymfocyty účinky léků   imunologie   MeSH
• biologické markery MeSH
• cytokiny analýza   MeSH
• dospělí MeSH
• extracelulární pasti imunologie   MeSH
• fibroblasty MeSH
• interleukiny metabolismus   MeSH
• kohortové studie MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfocytární deplece MeSH
• matrixová metaloproteinasa 13 analýza   MeSH
• regulace genové exprese účinky léků   MeSH
• revmatoidní artritida imunologie   terapie   MeSH
• rituximab farmakologie   terapeutické užití   MeSH
• senioři MeSH
• synoviální membrána chemie   imunologie   MeSH
• synoviální tekutina chemie   imunologie   MeSH
• systémový lupus erythematodes imunologie   metabolismus   MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adalimumab MeSH
• antirevmatika MeSH
• autoprotilátky MeSH
• biologické markery MeSH
• C17orf99 protein, human MeSH Prohlížeč
• cytokiny MeSH
• interleukiny MeSH
• matrixová metaloproteinasa 13 MeSH
• rituximab MeSH
• TNF-alfa MeSH

Both immune and non-immune mechanisms are involved in muscle damage and dysfunction occurring in idiopathic inflammatory myopathies (IIMs). Crosstalk among inflammatory cells, muscle and endothelial cells is essential in the pathogenesis of IIMs. Resistin, originally described as an adipokine linking obesity and insulin resistance in rodents, has been shown a pro-inflammatory molecule in humans. Besides its direct effect on production of several inflammatory mediators, resistin influences chemotaxis, migration, proliferation, cell survival, endothelial dysfunction and metabolism--all aspects implicated in the pathogenesis of IIMs. Up-regulation of resistin in muscle tissue and elevated serum resistin levels have been recently demonstrated in patients with IIMs. In addition, serum levels of resistin reflected global disease activity, including extramuscular organ involvement, in patients with this disease. However, there are currently not sufficient data to distinguish the features of resistin that cause injury of muscle tissue from those that promote muscle regeneration and repair. The aim of this review is therefore to summarize current knowledge about potential implication of resistin in idiopathic inflammatory myopathies.

• MeSH
• biologické markery metabolismus   MeSH
• cévní endotel metabolismus   patologie   MeSH
• chemotaxe fyziologie   MeSH
• cytokiny metabolismus   MeSH
• endoteliální buňky metabolismus   patologie   MeSH
• lidé MeSH
• myozitida krev   etiologie   patologie   MeSH
• pohyb buněk fyziologie   MeSH
• proliferace buněk MeSH
• resistin fyziologie   MeSH
• upregulace MeSH
• viabilita buněk fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH
• cytokiny MeSH
• resistin MeSH
• RETN protein, human MeSH Prohlížeč

INTRODUCTION: The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity. METHODS: Serum resistin levels were determined in 42 patients with inflammatory myopathies and 27 healthy controls. The association among resistin levels, inflammation, global disease activity and muscle strength was examined. The expression of resistin in muscle tissues from patients with inflammatory myopathies and healthy controls was evaluated. Gene expression and protein release from resistin-stimulated muscle and mononuclear cells were assessed. RESULTS: In patients with inflammatory myopathies, the serum levels of resistin were significantly higher than those observed in controls (8.53 ± 6.84 vs. 4.54 ± 1.08 ng/ml, P < 0.0001) and correlated with C-reactive protein (CRP) levels (r = 0.328, P = 0.044) and myositis disease activity assessment visual analogue scales (MYOACT) (r = 0.382, P = 0.026). Stronger association was observed between the levels of serum resistin and CRP levels (r = 0.717, P = 0.037) as well as MYOACT (r = 0.798, P = 0.007), and there was a trend towards correlation between serum resistin and myoglobin levels (r = 0.650, P = 0.067) in anti-Jo-1 positive patients. Furthermore, in patients with dermatomyositis, serum resistin levels significantly correlated with MYOACT (r = 0.667, P = 0.001), creatine kinase (r = 0.739, P = 0.001) and myoglobin levels (r = 0.791, P = 0.0003) and showed a trend towards correlation with CRP levels (r = 0.447, P = 0.067). Resistin expression in muscle tissue was significantly higher in patients with inflammatory myopathies compared to controls, and resistin induced the expression of interleukins (IL)-1β and IL-6 and monocyte chemoattractant protein (MCP)-1 in mononuclear cells but not in myocytes. CONCLUSIONS: The results of this study indicate that higher levels of serum resistin are associated with inflammation, higher global disease activity index and muscle injury in patients with myositis-specific anti-Jo-1 antibody and patients with dermatomyositis. Furthermore, up-regulation of resistin in muscle tissue and resistin-induced synthesis of pro-inflammatory cytokines in mononuclear cells suggest a potential role for resistin in the pathogenesis of inflammatory myopathies.

• MeSH
• imunohistochemie MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida krev   imunologie   patologie   MeSH
• resistin krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• resistin MeSH

To investigate the effect of intensive physiotherapy on disease activity and serum levels of adipocytokines in patients with ankylosing spondylitis (AS). Twenty-six patients with AS were included in this study. Intensive physiotherapy was performed twice a week for a period of 3 months. The Bath AS Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI) were assessed at inclusion and after 3 months. Leptin, adiponectin, resistin and visfatin serum levels were analysed by ELISA assays. Patients had mild to moderate disease activity. Baseline levels of adipocytokines did not correlate with indicators of disease activity, functional status or acute-phase reactants. After the 3 months of intensive physiotherapy, BASDAI significantly decreased from 2.98 to 1.8 (p = 0.01) and BASFI improved from 2.31 to 1.37 (p = 0.05), while there were no changes in serum levels of CRP, ESR and adipocytokines. In addition, baseline levels of adipocytokines did not predict the change of disease activity or functional ability. Intensive physiotherapy effectively reduces all clinical measures of disease activity, but it is not associated with a significant change in acute-phase reactants or serum levels of adipocytokines.

• MeSH
• adipokiny krev   MeSH
• ankylózující spondylitida krev   patofyziologie   terapie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• stupeň závažnosti nemoci MeSH
• terapie cvičením metody   MeSH
• výsledek terapie MeSH
• zdravotní stav MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adipokiny MeSH