BACKGROUND: Knee osteoarthritis (KOA) is a highly heterogeneous disease encompassing a wide range of clinical phenotypes. Phenotypes based on immune cells and protein pattern in synovial fluid (SF) and their relationship to clinical trajectories have not been described. OBJECTIVE: To assess phenotypes based on immune cells and protein pattern of SF in KOA. DESIGN: SF-derived immune cells were investigated in 119 patients with KOA using flow cytometry. Immune-phenotypes (iPhen) were determined by multivariate patient similarity network analysis and related to clinical trajectory (3-6 months post-sampling) along with protein pattern and macrophage chemokine receptors. RESULTS: Four iPhen were detected based on the distribution of T-lymphocytes, monocyte-macrophage lineage cells and activated CD8+ T-lymphocytes. The 'activated' phenotype (n = 17) had high T-lymphocytes but low monocyte-macrophage lineage cells and neutrophils, all highly activated, and showed improved symptoms in 70% patients. The 'lymphoid progressive' phenotype (n = 31) had high neutrophils, low lymphocytes and monocyte-macrophage lineage cells, low activation and was associated with lower pain levels. The 'myeloid progressive' phenotype (n = 35) had high NK and monocyte-macrophage lineage cells but low T-lymphocytes and activation. The 'aggressive' phenotype (n = 36) had high lymphocytes, macrophages, NK cells and neutrophils and high activation, and only 39% of patients improved during follow-up. Low CXCR4 and CCR7 expression on macrophages and high CXCL10 in SF were linked to improved clinical trajectory. CONCLUSION: We identified four immune-phenotypes that were associated with different clinical trajectories in KOA patients. How these phenotypes can be targeted therapeutically deserves further investigation.

• MeSH
• artróza kolenních kloubů * metabolismus   MeSH
• fenotyp MeSH
• imunofenotypizace MeSH
• lidé MeSH
• makrofágy MeSH
• synoviální tekutina metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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.

• MeSH
• adalimumab 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
• 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 genetika   imunologie   metabolismus   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

OBJECTIVE: To identify expression profiles (EP) associated with aseptic loosening of total knee arthroplasty (TKA) and to compare them with EP observed in total hip arthroplasty (THA), and primary knee and hip osteoarthritis (OA). DESIGN: Gene EP of TNF, IL-6, IL-8, CHIT1, BMP4, CCL3, CCL18, MMP9, RANKL, OPG, DC-STAMP and SOCS3 were assessed using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) on tissues retrieved from patients with aseptically failed TKA (n = 21), THA (n = 41) and primary knee (n = 20) and hip (n = 17) OA. Immunohistochemistry was applied to localize the proteins. RESULTS: When compared to knee OA, the pseudosynovial tissue in TKA exhibit (1) elevation of alternative macrophage activation marker (CHIT1), chemokine (IL-8), and a proteolytic enzyme (MMP9); (2) downregulation of pro-inflammatory cytokine (TNF), osteoclastic regulator (OPG) and a stimulator of bone formation (BMP4); (3) no difference in IL-6, CCL3, CCL18, RANKL, DC-STAMP and SOCS3. The EP in TKA differed from EP in aseptically failed THA by lower CCL3 and DC-STAMP mRNA and protein expression. EP of all studied inflammatory and osteoclastogenic molecules were similar in knee and hip OA. CONCLUSIONS: Comparing to OA, aseptic loosening of TKA is associated with upregulated expression of CHIT1, IL-8 and MMP9, dysregulated RANKL:OPG ratio and low levels of inflammatory cytokines. Similar cytokine profiles were associated with primary knee and hip OA. Further research is required to explain the differences in CCL3 and DC-STAMP expression between failed TKA and THA.

• MeSH
• adaptorové proteiny signální transdukční genetika   metabolismus   MeSH
• artroplastiky kloubů metody   MeSH
• artróza kolenních kloubů genetika   metabolismus   chirurgie   MeSH
• artróza kyčelních kloubů genetika   metabolismus   chirurgie   MeSH
• chemokin CCL3 biosyntéza   genetika   MeSH
• cytokiny biosyntéza   genetika   MeSH
• imunohistochemie MeSH
• kolenní kloub metabolismus   chirurgie   MeSH
• kyčelní kloub metabolismus   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• messenger RNA genetika   MeSH
• náhrada kyčelního kloubu MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• regulace genové exprese * MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• totální endoprotéza kolene MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

OBJECTIVES: Prolactin (PRL) is a hormone with cytokine-like activities that has been demonstrated to be involved in immune responses. However, there are inconsistent results related to the role of PRL in rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the levels of PRL in serum and synovial fluid in patients with RA and osteoarthritis (OA) and examine whether PRL might be associated with laboratory and clinical disease activity of RA. METHODS: A total of 29 patients with RA and 26 patients with OA were included in the study. The concentration of PRL in the serum and synovial fluid was measured by immunoradiometric assays, and the levels of serum anti-citrullinated protein/peptide autoantibodies (ACPA) and IgM rheumatoid factor (IgM-RF) were analysed by ELISA. Disease activity score (DAS 28) and radiological (Larsen) score were assessed. RESULTS: The levels of PRL in serum (299.55±27.28 vs. 230.59±16.61 mIU/l, p=0.041) as well as in synovial fluid (338.85±33.49 vs. 245.97±21.88 mIU/l, p=0.024) were significantly higher in patients with RA than in patients with OA. A moderate correlation was found between disease activity of RA and levels of PRL in synovial fluid (r=0.485, p=0.010) and the serum PRL levels correlated significantly with the total Larsen score (r=0.484, p=0.014). CONCLUSIONS: The findings of increased prolactin levels in patients with RA lead to the assumption that prolactin may play a role in disease severity and the process of joint damage in RA.

• MeSH
• artróza kolenních kloubů metabolismus   patologie   radiografie   MeSH
• autoprotilátky krev   MeSH
• imunoglobulin M krev   MeSH
• kolenní kloub patologie   radiografie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prolaktin metabolismus   MeSH
• revmatoidní artritida metabolismus   patologie   radiografie   MeSH
• revmatoidní faktor krev   MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• synoviální tekutina metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

PURPOSE OF THE STUDY A failure of total hip or knee artroplasty is associated with an increased production of joint fluid. This contains wear particles and host cells and proteins, and is assumed to be involved in the pathogenesis of aseptic loosening and periprosthetic osteolysis. This study investigated the effect of synovial fluid from patients with aseptically failed joint prostheses on osteoblast cultures. MATERIAL AND METHODS Synovial fluid samples were obtained from patients with failed total joint prostheses (TJP; n=36) and from control patient groups (n=16) involving cases without TJP and osteoarthritis, without TJP but with osteoarthritis, and with stable TJP. The samples were treated in the standard manner and then cultured with the SaOS-2 cell line which shows the characteristics and behaviour of osteoblasts. Each fluid sample was also examined for the content of proteins, cells and selected cytokines (IL-1?, TNF-&alfa;, IL-6, RANKL and OPG detected by ELISA). We tested the hypothesis assuming that the fluids from failed joints would show higher cytotoxicity to osteoblast culture and we also expected higher levels of IL-1?, TNF-&alfa;, IL-6, and RANKL in patients with TJP failure and/ or with more severe bone loss. The statistical methods used included the Kruskal-Wallis ANOVA and Mann-Whitney U test. RESULTS The fluids from failed TJPs showed the highest RANKL and the lowest OPG levels resulting in the highest RANKL/OPG ratio. However, there was no evidence suggesting that the joint fluids from failed TJPs would be more toxic to osteoblast culture than the fluids from control groups. In addition, no correlation was found between the fluid levels of molecules promoting inflammation and osteoclastic activity and the extent of bone loss in the hip (in terms of Saleh's classification) or the knee (AORI classification). In fact, the fluids from failed TJPs had higher protein levels in comparison with the controls, but the difference was not significant. DISCUSSION The finding of high RANKL levels and low OPG concentrations is in agreement with the theory of aseptic loosening and periprosthetic osteolysis. The other cytokines, particularly TNF-&alfa; and IL-1?, were found in low levels. This can be explained by the stage of particle disease at which the samples were taken for ELISA analysis. It is probable that the level of signal molecules reflects osteolytic process activity and is therefore not constant. The reason for no correlation found between cytokine levels and the extent of bone loss may also lie in the use of therapeutic classifications of bone defects that is apparently less sensitive to the biological activity of aseptic loosening and/or periprosthetic osteolysis. CONCLUSIONS Synovial fluids from failed total hip or knee joint prostheses are not toxic to osteoblast cultures. Cytotoxicity indicators and levels of pro-inflammatory and pro-osteoclastic cytokines (IL-1?, TNF-&alfa;, IL-6, RANKL and OPG) do not correlate well with the extent of periprosthetic bone loss.

• MeSH
• artróza kolenních kloubů chirurgie   metabolismus   MeSH
• artróza kyčelních kloubů chirurgie   metabolismus   MeSH
• interleukin-6 analýza   MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• ligand RANK analýza   MeSH
• náhrada kyčelního kloubu MeSH
• osteoblasty cytologie   MeSH
• osteoprotegerin analýza   MeSH
• selhání protézy MeSH
• senioři MeSH
• synoviální tekutina fyziologie   chemie   MeSH
• TNF-alfa analýza   MeSH
• totální endoprotéza kolene MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

• MeSH
• artróza kolenních kloubů metabolismus   MeSH
• cytokiny analýza   MeSH
• GPI-vázané proteiny MeSH
• lektiny analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• revmatoidní artritida metabolismus   MeSH
• senioři MeSH
• serpiny analýza   MeSH
• synoviální tekutina chemie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

Our purpose in this randomized, double blind, placebo controlled study was to find out the possible effect of a polyphenolic pine bark extract, Pycnogenol® (Pyc) on the level of 8-oxo-7,8-dihydroguanine (8-oxoG) as representative of oxidative damage to DNA and on the DNA repair ability of elderly people. According to our results, three months of Pyc administration had no effect on the level of oxidative damage to DNA or on repair ability, but we found a relationship between the level of 8-oxoG and repair ability of DNA in this group. To conclude, even if the positive effect of Pyc was not confirmed in the case of elderly people it is important to highlight the necessity of further investigations about the mechanisms of Pyc acting on different age groups.

• MeSH
• artróza kolenních kloubů metabolismus   MeSH
• borovice MeSH
• dvojitá slepá metoda MeSH
• financování organizované MeSH
• flavonoidy farmakologie   MeSH
• guanin analogy a deriváty   metabolismus   MeSH
• kometový test MeSH
• lidé středního věku MeSH
• lidé MeSH
• oprava DNA účinky léků   MeSH
• oxidační stres účinky léků   MeSH
• poškození DNA účinky léků   MeSH
• randomizované kontrolované studie jako téma MeSH
• rostlinné extrakty farmakologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

BACKGROUND: Resistin is a newly identified adipocytokine which has demonstrated links between obesity and insulin resistance in rodents. In humans, proinflammatory properties of resistin are superior to its insulin resistance-inducing effects. OBJECTIVES: To assess resistin expression in synovial tissues, serum and synovial fluid from patients with rheumatoid arthritis, osteoarthritis and spondylarthropathies (SpA), and to study its relationship with inflammatory status and rheumatoid arthritis disease activity. METHODS: Resistin expression and localisation in synovial tissue was determined by immunohistochemistry and confocal microscopy. Serum and synovial fluid resistin, leptin, interleukin (IL)1beta, IL6, IL8, tumour necrosis factor alpha, and monocyte chemoattractant protein-1 levels were measured. The clinical activity of patients with rheumatoid arthritis was assessed according to the 28 joint count Disease Activity Score (DAS28). RESULTS: Resistin was detected in the synovium in both rheumatoid arthritis and osteoarthritis. Staining in the sublining layer was more intensive in patients with rheumatoid arthritis compared with those with osteoarthritis. In rheumatoid arthritis, macrophages (CD68), B lymphocytes (CD20) and plasma cells (CD138) but not T lymphocytes (CD3) showed colocalisation with resistin. Synovial fluid resistin was higher in patients with rheumatoid arthritis than in those with SpA or osteoarthritis (both p<0.001). In patients with rheumatoid arthritis and SpA, serum resistin levels were higher than those with osteoarthritis (p<0.01). Increased serum resistin in patients with rheumatoid arthritis correlated with both CRP (r=0.53, p<0.02), and DAS28 (r=0.44, p<0.05), but not with selected (adipo) cytokines. CONCLUSION: The upregulated resistin at local sites of inflammation and the link between serum resistin, inflammation and disease activity suggest a role for resistin in the pathogenesis of rheumatoid arthritis.

• MeSH
• artróza kolenních kloubů krev   metabolismus   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• financování organizované MeSH
• imunoenzymatické techniky MeSH
• konfokální mikroskopie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu analýza   MeSH
• resistin analýza   krev   MeSH
• revmatoidní artritida krev   metabolismus   MeSH
• senioři MeSH
• spondylartropatie krev   metabolismus   MeSH
• stupeň závažnosti nemoci MeSH
• synoviální membrána chemie   MeSH
• synoviální tekutina chemie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

• MeSH
• arginin analogy a deriváty   analýza   krev   MeSH
• artróza kolenních kloubů krev   metabolismus   radiografie   MeSH
• extracelulární matrix - proteiny analýza   MeSH
• finanční podpora výzkumu jako téma MeSH
• glykoproteiny analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lysin analogy a deriváty   analýza   krev   MeSH
• synoviální tekutina chemie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH