Warning: MagpieRSS: Failed to parse RSS file. (not well-formed (invalid token) at line 17, column 606) in /home/main/public_html/includes/rss_fetch.inc on line 230

Site:

Site: Arthritis Research & Therapy - Latest Articles

Exercise-induced changes in interleukin-10 in patients with knee osteoarthritis: new perspectives?
Osteoarthritis (OA) of the knee is a common chronic disease leading to increased morbidity and reduced quality of life. Although exercise therapy has been shown to be beneficial on both pain and physical functioning, it's underlying mechanism has not been fully understood. However, a recent study found an exercise induced increase in interleukin-10 levels, to which anti-inflammatory and chondroprotective properties are described, in the (peri-)synovial fluid of patients with knee OA. These interesting results provide more insight in the effects of exercise in OA and needs to be validated and confirmed. Hopefully, it offers a promising aspect for further research.

Osteoarthritis and a high-fat diet: the full 'osteoarthritis syndrome' in a small animal model
Obesity is one of the main risk factors for osteoarthritis (OA) and due to the global rise in obesity this will increasingly contribute to OA development. The article of Griffin and co-workers in this issue shows that a high-fat diet leads to obesity and OA in part of the studied animals and that this is related to alterations in locomotor function. Furthermore, a high-fat diet leads to pain sensitization and depression/anxiety-like behavior unrelated to structural OA changes in the knee. Their findings demonstrate that the majority of features of the human "OA syndrome" can be reproduced in a small animal model.

Trait-stratified genome-wide association study identifies novel and diverse genetic associations with serologic and cytokine phenotypes in systemic lupus erythematosus
IntroductionSystemic lupus erythematosus (SLE) is a highly heterogeneous disorder, characterized by differences in autoantibody profile, serum cytokines, and clinical manifestations. SLE-associated autoantibodies and high serum interferon alpha (IFN-alpha) are important heritable phenotypes in SLE which are correlated with each other, and play a role in disease pathogenesis. These two heritable risk factors are shared between ancestral backgrounds. The aim of the study was to detect genetic factors associated with autoantibody profiles and serum IFN-alpha in SLE. Methods: We undertook a case-case genome-wide association study of SLE patients stratified by ancestry and extremes of phenotype in serology and serum IFN-alpha. Single nucleotide polymorphisms (SNPs) in seven loci were selected for follow up in a large independent cohort of 538 SLE patients and 522 controls using a multi-step screening approach based on novel metrics and expert database review. The seven loci were: leucine-rich repeat containing 20 (LRRC20); protein phosphatase 1H (PPM1H); lysophosphatidic acid receptor 1 (LPAR1); ankyrin repeat and sterile alpha motif domain 1A (ANKS1A); protein tyrosine phosphatase, receptor type M (PTPRM); ephrin A5 (EFNA5); and V-set and immunoglobulin domain containing 2 (VSIG2). Results: SNPs in the LRRC20, PPM1H, LPAR1, ANKS1A, and VSIG2 loci each demonstrated strong association with a particular serologic profile (all OR>2.2 and P<3.5x10-4). Each of these serologic profiles was associated with increased serum IFN-alpha. SNPs in both PTPRM and LRRC20 were associated with increased serum IFN-alpha independent of serologic profile (P = 2.2 x 10-6 and P = 2.6 x 10-3 respectively). None of the SNPs were strongly associated with SLE in case-control analysis, suggesting that the major impact of these variants will be upon subphenotypes in SLE. Conclusions: This study demonstrates the power of using serologic and cytokine subphenotypes to elucidate genetic factors involved in complex autoimmune disease. The distinct associations observed emphasize the heterogeneity of molecular pathogenesis in SLE, and the need for stratification by subphenotypes in genetic studies. We hypothesize that these genetic variants play a role in disease manifestations and severity in SLE.

Increased expression of costimulatory markers CD134 and CD80 on interleukin-17 producing T cells in patients with systemic lupus erythematosus
IntroductionThere is growing evidence that interleukin 17 (IL-17) producing T cells are involved in the pathogenesis of systemic lupus erythematosus (SLE). Previous studies showed that increased percentages of T-cell subsets expressing the costimulatory molecules CD80 and CD134 are associated with disease activity and renal involvement in SLE. The aim of this study was to investigate the distribution and phenotypical characteristics of IL 17 producing T-cells in SLE, in particular in patients with lupus nephritis, with emphasis on the expression of CD80 and CD134. Methods: Thirty-four patients (3 male, 31 female, mean age 41 +/-15 years) fulfilling at least four of the American College of Rheumatology (ACR) revised criteria for the diagnosis of SLE and 24 healthy controls were enrolled. T-cells from the peripheral blood were analysed by fluorescence activated cell sorting (FACS) for their expression levels of CD80, CD134 and CCR6. In vitro stimulated CD3+IL17+ cells were also investigated for the expression of these costimulatory markers. Finally, renal biopsies from SLE patients were evaluated for the presence of CD134 expressing T-cells. Results: Percentages of IL-17 expressing T-cells were significantly increased in patients with active disease as compared to healthy controls (1.46 +/-0.58% versus 0.93 +/-0.30%, P=0.007). The percentage of IL-17 producing T-cells was correlated with disease activity as assessed by systemic lupus erythematosus disease activity index (SLEDAI) (r=0.53, P=0.003). In patients, most of the IL-17 producing T-cells were confined to the CCR6+ T-cell subset (80 +/-13%). Expression of CD80 and CD134 on the IL-17 producing T-cell subset was higher in SLE than in healthy controls (HC) (CD134: 71.78 +/-14.51% versus 51.45 +/-16.58%, P=0.002; CD80: 25.5 +/-14.99% versus 14.99 +/-5.74%, P=0.02). Also, patients with lupus nephritis expressed higher levels of CD134+ on CD3+IL-17+ cells as compared to HC (72.69 +/-11.54% versus 51.45 +/-16.58%, P=0.006). Furthermore, renal biopsies of lupus nephritis patients showed infiltration of CD134+ T cells. Conclusions: Percentages IL-17 expressing T-cells correlate with disease activity. Further, these cells show increased expression of costimulatory markers such as CD134 and CD80. The presence of CD134+ T-cells in renal biopsies of lupus nephritis patients suggest that these cells migrate to the kidney and might contribute to inflammatory processes through IL-17 secretion.

Bcl-xL affects the development of functional CD4 regulatory T cells
None (letter)

Alterations in the self-renewal and differentiation ability of bone marrow mesenchymal stem cells in a mouse model of rheumatoid arthritis
IntroductionRheumatoid arthritis (RA) is a chronic systemic autoimmune disease primarily involving the synovium. Evidence in recent years has suggested that the bone marrow (BM) may be involved, and even be the initiating site of the disease. Abnormalities in haemopoietic stem cells (HSC) survival, proliferation and aging have been described in patients affected by RA and ascribed to abnormal support by the BM microenvironment. Mesenchymal stem cells (MSC) and their progeny constitute important components of the BM niche. In this study we test the hypothesis that the onset of inflammatory arthritis is associated with altered self-renewal and differentiation of bone marrow MSC, which alters the composition of the BM microenvironment. Methods: We have used Balb/C Interleukin-1 receptor antagonist knock-out mice, which spontaneously develop RA-like disease in 100% of mice by 20 weeks of age to determine the number of mesenchymal progenitors and their differentiated progeny before, at the start and with progression of the disease. Results: We showed a decrease in the number of mesenchymal progenitors with adipogenic potential and decreased bone marrow adipogenesis before disease onset. This is associated with a decrease in osteoclastogenesis. Moreover at the onset of disease a significant increase in all mesenchymal progenitors is observed together with a block in their differentiation to osteoblasts. This is associated with accelerated bone loss. Conclusions: Significant changes occur in the BM niche with the establishment and progression of RA-like disease. Those changes may be responsible for aspects of the disease, including advance of osteoporosis. An understanding of the molecular mechanisms leading to those changes may lead to new strategies for therapeutic intervention.

Synovial effusion and synovial fluid biomarkers in psoriatic arthritis to assess intraarticular tumor necrosis factor-alpha blockade in the knee joint
IntroductionEvaluation of synovial effusion (SE), synovial fluid (SF) and synovial tissue (ST) biomarkers in relation to disease activity indexes to assess the response to intraarticular (IA) tumor necrosis factor (TNF)-alpha blockers in psoriatic arthritis (PsA). Methods: Systemic and local disease activity indexes (disease activity score [DAS]; the Ritchie articular index [mRAI], erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); Thompson articular [THOMP] and joint articular [KJAI]-Index ) and ST samples were assessed at baseline, throughout treatment, and during the follow-up in 14 patients affected with PsA who underwent IA injections (0.5 ml - 12.5 mg) in the knee joint of etanercept (E) or placebo (P) once every two weeks for a ten week period. Total SF white blood cell (WBC) counts (WBC/ mul) and SF cytokine/chemokine (CK/CCK) levels were measured before IA-E at baseline, after IA-E, and as long as there were adequate amounts of SF for knee aspiration (post). Characterization of synovial mononuclear cell infiltration and synovial vessels was carried out in 8/14 knees by staining serial sections of synovial tissue biopsies for CD45, CD3, CD68, CD31 and CD105. Results: At baseline, CRP and/or ESR were significantly correlated with SF-CK (IL-1beta, IL-1Ra, IL-6, IL-8) and CCK (CCL2, CCL3 and CCL4). Post-IA injections, there was a decrease in SE in the knees in which aspiration following IA-E injection was possible as well as a significant reduction in SF WBC/mul and in SF-CK (TNF-alpha, IL- 1beta, IL-1Ra, IL-6 and IL-22). Pre- and post- IA-E injections, there were significant correlations between ST markers and SF-CK (IL-1beta with CD45; IL-1beta and IL-6 with CD31) and between SF-CCK (CCL4 and CCL3 with CD3). At the end of the study, there was a significant reduction in disease activity indexes (CRP, DAS, RAI, THOMP, KJAI) as well as in the ST markers (CD45; CD3). Conclusions: Synovial effusion regression is a reliable indicator of the response to IA TNF-alpha blockers in PsA patients as it is confirmed by the correlation between SF biomarkers to disease activity and synovial tissue inflammation.

Liposomal encapsulation enhances and prolongs the anti-inflammatory effects of water-soluble dexamethasone phosphate in experimental adjuvant arthritis
IntroductionThe objective was to evaluate the efficacy of intravenous (i.v.) injection of liposomally encapsulated dexamethasone phosphate (DxM-P) in comparison to free DxM-P in rats with established adjuvant arthritis (AA). This study focused on polyethylene glycol (PEG)-free liposomes, to minimize known allergic reactions caused by neutral PEG-modified (PEG-ylated) liposomes. Methods: Efficacy was assessed clinically and histologically using standard scores. Non-specific and specific immune parameters were monitored. Activation of peritoneal macrophages was analyzed via cytokine profiling. Pharmacokinetics/biodistribution of DxM in plasma, synovial membrane, spleen, and liver were assessed via mass spectrometry. Results: Liposomal DxM-P (3 x 1 mg/kg body weight; administered i.v. on days 14, 15, 16 of AA) strongly and long-lastingly suppressed established AA, including histological signs, erythrocyte sedimentation rate, white blood cell count, circulating anti-mycobacterial IgG, and production of interleukin-1beta (IL-1 and IL-6 by peritoneal macrophages. The clinical effects of liposomal DxM-P were dose-dependent for dosages between 0.01 and 1.0 mg/kg. Single administration of 1 mg/kg liposomal DxM-P and 3 x 1 mg/kg of free DxM-P showed comparable effects consisting of a partial and transient suppression. Moreover, the effects of medium-dose liposomal DxM-P (3 x 0.1 mg/kg) were equal (in the short term) or superior (in the long term) to those of high-dose free DxM-P (3 x 1 mg/kg), suggesting a potential dose reduction by a factor between 3 and 10 by liposomal encapsulation. For at least 48h after the last injection, liposomal drug achieved significantly higher levels in plasma, synovial membrane, spleen, and liver than free drug. Conclusions: This new PEG-free formulation of macrophage-targeting liposomal DxM-P considerably reduces the dose and/or frequency required to treat AA, with a potential to enhance/prolong therapeutic efficacy and limit side-effects also in the therapy of rheumatoid arthritis. Depot and/or recirculation effects in plasma, inflamed joint, liver, and spleen may contribute to this superiority of liposomally encapsulated DxM-P.

TAM receptor ligands in lupus: Protein S but not Gas6 levels reflect disease activity in systemic lupus erythematosus
IntroductionThe TAM (tyro 3, axl, mer) kinases are key regulators of innate immunity and are important in the phagocytosis of apoptotic cells. Gas6 and protein S are ligands for these TAM kinases and bind to phosphatidyl serine residues exposed during apoptosis. In animal models, absence of TAM kinases is associated with lupus-like disease. To test whether human systemic lupus erythematosus (SLE) patients might have deficient levels of TAM ligands, we measured Gas 6 and protein S levels in SLE. Methods: 107 SLE patients were recruited. Of these, 45 SLE patients were matched age, gender and ethnicity with normal controls (NC). Gas6 and free protein S were measured with sandwich enzyme linked immunosorbent assays (ELISAs). Results: Overall, the plasma concentrations of Gas6 and free protein S were not different between 45 SLE patients and 45 NC. In SLE patients, the levels of free protein S were positively correlated with age (r=0.2405, P=0.0126), however those of Gas6 were not. There was no correlation between the concentrations of Gas6 and free protein S in individuals. Levels of free protein S were significantly lower in SLE patients with a history of serositis, neurologic disorder, hematologic disorder and immunologic disorder. Gas6 levels were elevated in patients with a history of neurologic disorder. The SLE patients with anti-Sm or anti-cardiolipin IgG showed lower free protein S levels. Circulating free protein S was positively correlated with complement component 3 (C3) (r=0.3858, P<0.0001) and complement component 4 (C4) (r=0.4275, P<0.0001). In the patients with active BILAG hematologic involvement, the levels of free protein S were lower and those of Gas6 were higher. Conclusions: In SLE, free protein S was decreased in patients with certain types of clinical history and disease activity. Levels of free protein S were strongly correlated with C3 and C4 levels. Gas6 levels in SLE patients differed little from levels in NC, but they were elevated in the small numbers of patients with a history of neurological disease. The correlation of decreased protein S levels with lupus disease activity is consistent with a role for the TAM receptors in scavenging apoptotic cells and controlling inflammation. Protein S appears more important functionally in SLE patients than Gas6 in this regard.

Risk factors for total joint arthroplasty infection in patients receiving tumor necrosis factor alpha-blockers: a case-control study
IntroductionThe objective of this study was to assess natural microbial agents, history and risk factors for total joint arthroplasty (TJA) infections in patients receiving tumor necrosis factor (TNF)alpha-blockers, through the French RATIO registry and a case-control study. Methods: Cases were TJA infections during TNFalpha-blocker treatments. Each case was compared to two controls (with TJA and TNFalpha-blocker therapy, but without TJA infection) matched on age (+/-15 years), TJA localization, type of rheumatic disorder and disease duration (+/-15 years). Statistical analyses included univariate and multivariate analyses with conditional logistic regression. Results: In the 20 cases (18 rheumatoid arthritis), TJA infection concerned principally the knee (n=12, 60%) and the hip (n=5, 25%). Staphylococcus was the more frequent microorganism involved (n=15, 75%). Four patients (20%) were hospitalized in an intensive care unit and two died from infection. Eight cases (40%) versus 5 controls (13%) had undergone primary TJA or TJA revision for the joint subsequently infected during the last year (P=0.03). Of these procedures, 5 cases versus 1 control were performed without withdrawing TNFalpha-blockers (P=0.08). In multivariate analysis, predictors of infection were primary TJA or TJA revision for the joint subsequently infected within the last year (odds ratio, OR=88.3; 95%CI 1.1-7,071.6; P=0.04) and increased daily steroid intake (OR=5.0 per 5 mg/d increase; 1.1-21.6; P=0.03). Case-control comparisons showed similar distribution between TNFalpha-blockers (P=0.70). Conclusions: In patients receiving TNFalpha-blockers, TJA infection is rare but potentially severe. Important risk factors are primary TJA or TJA revision within the last year, particularly when TNFalpha-blockers are not interrupted before surgery, and the daily steroid intake.

Warning: MagpieRSS: Failed to fetch http://www.arthritisusa.net/index2.php?option=com_rss&feed=RSS2.0&no_html=1. (HTTP Response: HTTP/1.1 404 Not Found ) in /home/main/public_html/includes/rss_fetch.inc on line 230

Site: