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ID PMID Title PublicationDate abstract
19856128 Same question, different answers: a comparison of global health assessments using visual a 2009 Dec PURPOSE: To compare responses to two global health VAS of patients with rheumatoid arthritis at the same assessment within the same questionnaire. METHODS: Secondary analysis of randomised controlled trial data. Patients completed the patient global assessment VAS (PG-VAS) (horizontal 10 cm scale, left (0), right (100), no incremental markers) and EQ-5D-VAS (EQ-VAS) (vertical 20 cm scale, 100 at the top, markers at each increment of 10). Both asked "how good or bad is your health today, in your opinion, from 100 'Best imaginable health state' to 0 'Worst imaginable health state'." Agreement was assessed using intra-class correlation co-efficients (ICC) and Bland-Altman plots. RESULTS: Four hundred and forty-eight patients reported median PG-VAS 66 (IQR 51, 77) and EQ-VAS 65 (IQR 50, 80) scores. Correlation of the VAS scales was moderate at baseline (ICC 0.564) and longitudinally (ICC 0.503). Bland-Altman plots suggested poor concordance of the PG-VAS and EQ-VAS; the limits of agreement were +/-32.3 on a 0-100 scale. PG-VAS scores were evenly distributed; EQ-VAS scores clustered at increments of 10; rounding did not improve agreement. CONCLUSIONS: The EQ-VAS and PG-VAS scores are not interchangeable at the individual level. The EQ-VAS correlated more strongly with disease-specific and health-related quality of life measures, therefore, appears preferable.
20441431 Recent advances in the genetics of systemic lupus erythematosus. 2010 May Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the production of antinuclear autoantibodies and the inflammatory infiltration of many organ systems. SLE is a complex disorder in which multiple genetic variants, together with environmental and hormonal factors, contribute to disease risk. In this article, we summarize our current understanding of the genetic contribution to SLE in light of recent genome-wide association studies, which have brought the total number of confirmed SLE susceptibility loci to 29. In the second section, we explore the functional implications of these risk loci and, in particular, highlight the role that many of these genes play in the Toll-like receptor and type I interferon signaling pathways. Finally, we discuss the genetic overlap between SLE and other autoimmune and inflammatory conditions as several risk loci are shared among multiple disorders, suggesting common underlying pathogenic mechanisms.
19282310 Rapid and sustained health utility gain in anti-tumour necrosis factor-treated inflammator 2010 Feb BACKGROUND: Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and other spondylarthritides impose a great impact on the individual in addition to the costs on society, which may be reduced by effective pharmacological treatment. Industry-independent health economic studies should complement studies sponsored by industry. OBJECTIVE: To study secular trends in baseline health utilities in patients commencing tumour necrosis factor (TNF) blockade for arthritis in clinical practice over 7 years; to address utility changes during treatment; to investigate the influence of previous treatment courses; to study the feasibility of health utility measures and to compare them across diagnostic entities. METHODS: EuroQoL 5 dimensions (EQ-5D) utility data were collected from a structured clinical follow-up programme of anti-TNF-treated patients with RA (N = 2554), PsA (N = 574) or spondylarthritides (N = 586). Time trends were calculated. Completer analysis was used. RESULTS: There were weak or non-significant secular trends for increasing baseline utilities over time for RA, PsA and spondylarthritides. The maximum gain in utilities had already occurred after 2 weeks for all diagnoses and remained stable for patients remaining on therapy. The first and second anti-TNF courses performed similarly. CONCLUSIONS: Utilities at inclusion remained largely unchanged for RA, PsA and spondylarthritides over 7 years. Improvement occurred early during treatment and not beyond 6 weeks at the group level. Improvement during the first course was not consistently greater than the second. There were no major differences between RA, PsA and spondylarthritides. EQ-5D proved feasible and applicable across these diagnoses. These "real world" data may be useful for health economic modelling.
19284557 Rheumatoid cachexia is associated with dyslipidemia and low levels of atheroprotective nat 2009 INTRODUCTION: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD) independent of traditional risk factors. The aim of this study was to analyze the associations between diet, body composition, lipids and atheroprotective natural antibodies against phosphorylcholine (anti-PC) in patients with RA. METHODS: A total of 80 RA patients (76% women), mean age (standard deviation (SD)) 61.4 (12) years and median disease duration of 6 years, were assessed by food frequency questionnaire (FFQ), fatty acid profile in adipose tissue and whole-body dual energy x ray absorptiometry (DXA). Rheumatoid cachexia was defined as fat free mass index below the 25th percentile and fat mass index above the 50th percentile of a reference population. Blood lipids, oxidized low-density lipoprotein (oxLDL) and anti-PC levels were determined. RESULTS: The mean body mass index for the women and men was 25.0 and 27.0, respectively. Central obesity was found in 57% of the women (waist circumference >80 cm) and in 89% of the men (waist circumference >94 cm). In all, 18% of the women and 26% of the men had rheumatoid cachexia. These patients had significantly higher total cholesterol (P < 0.033), LDL (P < 0.029), and trendwise oxLDL (P = 0.056) as well as lower anti-PC IgM (P = 0.040), higher frequency of hypertension (69%) and metabolic syndrome (25%) than those without. The patients reported a high dietary intake of saturated fat, which partly correlated with fatty acid composition in adipose tissue and significantly with disease activity. However, patients with or without cachexia did not differ with respect to dietary fat intake or intake of Mediterranean-like diet. Additionally, patients on a Mediterranean-like diet had high levels of anti-PC (P < 0.001). CONCLUSIONS: About one in five patients with low-active RA displayed rheumatoid cachexia. This condition was associated with high levels of LDL cholesterol, low levels of atheroprotective anti-PC and high frequency of hypertension, which is of interest in the context of CVD in RA. The cachexia could not be related to diet fat intake. However, patients on a Mediterranean-like diet had high anti-PC levels in spite of similar frequency of cachexia. High anti-PC levels may provide some protection against CVD.
19523821 Synthesis of calcium phosphate-binding liposome for drug delivery. 2009 Aug 1 Metastatic bone disease is often associated with bone pain, pathologic fractures, and nerve compression syndromes. Effective therapies to inhibit the progression of bone metastases would have important clinical benefits. Therefore, we developed a novel calcium phosphate-binding liposome for a bone-targeting drug delivery system. We synthesized a novel amphipathic molecule bearing a bisphosphonate (BP) head group to recognize and bind to hydroxyapatite (HA). We demonstrated that the liposomes having BP moieties show high affinity for HA. Doxorubicin-loaded liposomes adsorbed on the surface of HA significantly reduce the number of viable human osteosarcoma MG63 cells. This shows that the liposomes can be excellent carriers for anticancer drugs because they specifically target bone tissue. This calcium phosphate-binding liposome system could be used with many drugs for bone-related diseases such as osteoporosis, rheumatoid arthritis, and multiple myeloma.
18718986 Inhibition of radiographic progression with combination etanercept and methotrexate in pat 2009 Jul OBJECTIVE: To determine the effect of changing from etanercept or methotrexate monotherapy to etanercept plus methotrexate combination therapy on radiographic progression in rheumatoid arthritis (RA) patients. METHODS: Patients enrolled in this 1-year open-label study previously completed a 3-year blinded study in which they received methotrexate or etanercept monotherapy or the combination of both. All patients received the combination of etanercept 25 mg subcutaneously twice weekly plus oral methotrexate up to 20 mg/week. The primary radiographic endpoint was a change in modified total Sharp score (TSS), as assessed by blinded readers. RESULTS: At baseline, patients previously receiving methotrexate monotherapy (etanercept-added, n = 52) or etanercept monotherapy (methotrexate-added, n = 68) had moderate disease activity levels (mean disease activity score (DAS) of 2.6 and 2.5, respectively), whereas patients previously receiving combination therapy (n = 90) had a low disease activity level (mean DAS of 2.0). The addition of etanercept to methotrexate monotherapy resulted in a significant reduction in radiographic progression (p<0.05). Mean TSS changes in the previous year versus the current year were +1.79 versus +0.25 for the etanercept-added group (p<0.05); +0.51 versus -0.18 for the methotrexate-added group (NS) and +0.42 versus +0.24 for the combination group (NS). CONCLUSION: In these RA patients with on average moderate disease activity despite previous methotrexate monotherapy, combination treatment with etanercept and methotrexate inhibited radiographic progression and improved radiographic outcomes. These data, in conjunction with the previously published clinical data, support the use of combination therapy in RA patients with moderate disease activity.
19552491 Leflunomide treatment in elderly patients with rheumatoid or psoriatic arthritis: retrospe 2009 BACKGROUND: Disease-modifying antirheumatic drugs (DMARDs) play a crucial role in the treatment of persistent chronic synovitis, such as active rheumatoid arthritis (RA) and spondyloarthritis, by inducing or maintaining disease remission, reducing the frequency of flares or relapses, and allowing corticosteroids to be tapered while maintaining disease control. OBJECTIVE: The aim of this retrospective study was to evaluate the safety of, and adherence to treatment with, leflunomide in elderly RA and psoriatic arthritis patients compared with younger patients. METHODS: A total of 90 Italian patients (80 with active RA and 10 with psoriatic arthritis) were retrospectively examined at entry and after 24 months' follow-up. Patients were divided into two groups according to age: those aged 65 years (n = 40). Each patient was analysed for clinical, demographic and laboratory parameters in order to evaluate liver, renal and haematological toxicity. Disease Activity Score including a 28-joint count (DAS28) and physician global assessment of disease activity (MD global) were measured to define disease activity. RESULTS: During the 24-month follow-up period, 30 patients (33.3%) discontinued leflunomide: 17 patients (34.0%) in the group of patients aged 65 years. There were no differences in treatment withdrawal between the two groups. Overall, 10 patients (11.1%) in the entire study population discontinued leflunomide for lack of efficacy, while 21 (23.3%) discontinued the drug because of adverse effects (one patient withdrew because of both inefficacy and adverse effects). There were no significant differences in efficacy or adverse effects between patients aged 65 years. There was also no significant difference in survival rates of leflunomide treatment when patients aged 65 years (p = 0.94). There were no significant differences in withdrawal rates in the overall population when leflunomide monotherapy was compared with leflunomide combination therapy. There were also no significant differences in the types of adverse effects associated with monotherapy or combination therapy when the two age groups were compared. CONCLUSIONS: Leflunomide is a useful and well tolerated DMARD for the treatment of RA and psoriatic arthritis in the elderly. The safety profile of, and adherence to, leflunomide is not different in older patients with chronic inflammatory joint diseases such as RA or psoriatic arthritis to that observed in younger patients.
21077727 Necrotizing group A streptococcal periorbital infection following adalimumab therapy for r 2011 Jun OBJECTIVE: (1) To describe a case of necrotizing group A streptococcal periorbital infection in a patient receiving treatment with adalimumab (Humira, Abbott)-- a fully humanized monoclonal anti-TNF-α agent. (2) To identify bacterial species responsible for infection with different forms of biological therapy. DESIGN: Single interventional case report and literature review. CASE: A 57-year-old woman developed severe right-sided necrotizing periorbital infection whilst receiving treatment with adalimumab for rheumatoid arthritis (RA). Cultures grew Lancefield Group A Streptococcus pyogenes. An extensive literature search for reports of ocular infections associated with biological therapy was conducted. RESULTS: Adalimumab therapy was discontinued and the patient was admitted to an intensive care unit. The patient made a complete recovery after receiving appropriate antibiotic therapy. Overall Gram-positive cocci are the most common infection associated with use of biological therapy. CONCLUSIONS: Anti-TNF-α agents are powerful immune-modulating drugs with potentially serious side effects. This case is the first to link adalimumab to necrotizing periorbital infection. Resolved infection does not preclude reintroduction of anti-TNF therapy however, careful assessment of the risks versus benefits of therapy is required at the individual patient level.
19690516 Computational design and application of endogenous promoters for transcriptionally targete 2009 Nov The promoter regions of genes that are differentially regulated in the synovial membrane during the course of rheumatoid arthritis (RA) represent attractive candidates for application in transcriptionally targeted gene therapy. In this study, we applied an unbiased computational approach to define proximal-promoters from a gene expression profiling study of murine experimental arthritis. Synovium expression profiles from progressing stages of collagen-induced arthritis (CIA) were classified into six distinct groups using k-means clustering. Using an algorithm based on local over-representation and comparative genomics, we identified putatively functional transcription factor-binding sites (TFBS) in TATA-dependent proximal-promoters. Applying a filter based on spacing between TATA box and transcription start site (TSS) combined with the presence of over-represented nuclear factor kappaB (NFkappaB), AP-1, or CCAAT/enhancer-binding protein beta (C/EBPbeta) sites, 382 candidate murine and human promoters were reduced to 66, corresponding to 45 genes. In vitro, 9 out of 10 computationally defined promoter regions conferred cytokine-inducible expression in murine cells and human synovial fibroblasts. Under these conditions, the serum amyloid A3 (Saa3) promoter showed the strongest transcriptional induction and strength. We applied this promoter for driving therapeutically efficacious levels of the interleukin-1 receptor antagonist (Il1rn) in a disease-regulated fashion. These results demonstrate the value of bioinformatics for guiding the selection of endogenous promoters for transcriptionally targeted gene therapy.
20472596 Long-term safety of anti-TNF treatment in patients with rheumatic diseases and chronic or 2010 Jul OBJECTIVES: The aim of this prospective study was to examine the safety of anti-tumour necrosis factor (TNF) therapy in patients with rheumatic disease and hepatitis B virus (HBV) infection. METHODS: 14 patients with chronic HBV infection, 19 HBV-vaccinated patients and 19 patients with resolved HBV infection were included in the study. All HBV-infected patients received combination therapy with oral antivirals and anti-TNF agents. During treatment the levels of hepatitis B surface antibodies (anti-HBs) in HBV-vaccinated patients and of serum HBV DNA in patients with chronic or resolved HBV infection were monitored. RESULTS: No viral reactivation was observed in patients with resolved HBV infection while anti-HBs titres decreased during anti-TNF treatment in vaccinated patients, similarly to patients treated with methotrexate alone. None of the HBV-infected patients developed liver decompensation or a significant increase in alanine aminotransferase levels. One patient (7%) treated with lamivudine and etanercept showed viral reactivation due to the emergence of a lamivudine-resistant mutant strain. CONCLUSIONS: Anti-TNF agents represent a safe option for patients with chronic HBV infection when combined with antiviral therapy, as well as in patients previously exposed to HBV receiving no HBV prophylaxis. Resistant HBV strains may arise in patients with chronic hepatitis B, necessitating the initial use of anti-HBV agents with a low risk of resistance.
21075597 Th17 cells can provide B cell help in autoantibody induced arthritis. 2011 Feb K/BxN mice develop a spontaneous destructive arthritis driven by T cell dependent anti-glucose-6-phosphate isomerase (GPI) antibody production. In this study, a modified version of the K/BxN model, the KRN-cell transfer model (KRN-CTM), was established to determine the contribution of Th17 cells in the development of chronic arthritis. The transfer of naive KRN T cells into B6.TCR.Cα(-/-)H-2(b/g7) T cell deficient mice induced arthritis by day 10 of transfer. Arthritis progressively developed for a period of up to 14 days following T cell transfer, thereafter the disease severity declined, but did not resolve. Both IL-17A and IFNγ were detected in the recovered T cells from the popliteal lymph nodes and ankles. The transfer of KRN Th17 polarized KRN CD4(+) T cells expressing IL-17A and IFNγ induced arthritis in all B6.TCR.Cα(-/-)H-2(b/g7) mice however the transfer of Th1 polarized KRN CD4(+) T cells expressing IFNγ alone induced disease in only 2/3 of the mice and disease induction was delayed compared to Th17 transfers. Th17 polarized KRN/T-bet(-/-) cells induced arthritis in all mice and surprisingly, IFNγ was produced demonstrating that T-bet expression is not critical for arthritis induction, regardless of the cytokine expression. Neutralization of IFNγ in KRN Th17 transfers resulted in earlier onset of disease while the neutralization of IL-17A delayed disease development. Consistent with K/BxN mice, naive KRN T cell transfers and Th17 polarized KRN/T-bet(-/-) transfers induced anti-GPI IgG(1) dominant responses while KRN Th17 cells induced high levels of IgG(2b). These data demonstrate that Th17 cells can participate in the production of autoantibodies that can induce arthritis.
19033084 In vivo kinematic analysis of a high-flexion, posterior-stabilized, mobile-bearing knee pr 2009 Sep The objective of this study was to evaluate the kinematics of a high-flexion, posterior-stabilized, mobile-bearing total knee arthroplasty (TKA) in weight-bearing, deep knee bending motion. Thirteen patients implanted with the Legacy Posterior Stabilized Flex (Zimmer, Warsaw, IN) mobile-bearing TKA were examined during a deep knee bending motion using fluoroscopy. Femorotibial motion was determined using a 2-dimensional to 3-dimensional registration technique, which used computer-assisted design models to reproduce the position of metallic implants from single-view fluoroscopic images. The average flexion range of motion between the metallic implants was 116 degrees . The average rotation of the femoral component was 9.3 degrees external rotation. The mean kinematic pathway was early rollback, lateral pivot with external rotation, and bicondylar rollback. We found that the kinematic pattern of the Legacy Posterior Stabilized Flex mobile-bearing TKA was different than normal knee kinematics.
18704426 A comparison study of a recombinant tumor necrosis factor receptor:Fc fusion protein (rhTN 2009 Jan The objective of this study is to evaluate the efficacy and safety of rhTNFR:Fc: a recombinant tumor necrosis factor receptor:Fc fusion protein compared with methotrexate (MTX) in patients with rheumatoid arthritis in China. We treated 238 patients with active rheumatoid arthritis with either twice weekly subcutaneous injection rhTNFR:Fc (25 mg) or weekly oral MTX (mean 15 mg per week) for 24 weeks (registration number: 2003L01264). Clinical responses were defined as the percent improvement in disease activity according to the criteria of the American College of Rheumatology (ACR-N). As compared with MTX-treated patients, more patients who received rhTNFR:Fc had ACR20 improvement in disease activity during the first 2 weeks (P < 0.05). Similarly, more patients treated with rhTNFR:Fc having ACR20, ACR50, ACR70 improvement in disease activity during 8 weeks (P < 0.05). At the end of 12-week treatment, patients received rhTNFR:Fc also had significant improvement at ACR20 (P < 0.05). Compared with oral MTX, patients received rhTNFR:Fc also had significant improvement at ACR70 at the end of 24 weeks treatment (P < 0.05). In conclusion, compared with oral MTX subcutaneous injection, rhTNFR:Fc acted more rapidly to release symptoms and signs of active RA in Chinese patients, and well tolerated in patients with rheumatoid arthritis in China.
19327243 Radiation synovectomy with (90)Yttrium, (186)Rhenium and (169)Erbium: a systematic literat 2009 Jan OBJECTIVE: To perform a systemic review and meta-analysis on the effectiveness of radiosynoviorthesis (RSO). METHODS: A search of medical databases was conducted. Criteria for inclusion: articles in English, minimum follow-up of 6 months, specification of joint disease, reported outcome of at least 5 RSOs. The studies were scored for quality by the Oxford Centre of Evidenced-based Medicine Levels of Evidence, from 1 to 4. RESULTS: Twenty-one (21) studies were included (3 quality 1b, 5 2b and 13 4), analysing 169Erbium/186Rhenium-RSO used predominantly in small joints and 49 (1 quality 1b, 10 2b and 38 4) on 90Yttrium-RSO used predominantly in knee joints. The reported success rates of 169Erbium/186Rhenium-RSO ranged from 69-100% at 6 months, and from 54-100% at > or =12 months; for 90Yttrium they were 24-100% and 29-94%, res-pectively. Studies comparing the effect of RSO with that of glucocorticoid (GC) or saline injection alone were pooled. At 6 months, the pooled odds ratio favouring RSO of the knee with Yttrium over control is 4 (confidence interval (CI) 95% 1.2-14), p=0.02, but at 12 months the ratio was 1.7 (CI95% 0.69-4), p=0.26. For RSO of small joints with Erbium/Rhenium compared to controls, the pooled odds ratio at 6 months is 2 (CI95% 0.66-6), p=0.22 and at 12 months 2 (CI95% 1.09-3.5), p=0.03. CONCLUSION: Reported success rates of RSO are high, but differences in effect with GC injection are less evident, although there is marked heterogeneity in study design of the (small number of) comparative studies.
19070549 Patient barriers to pain management may contribute to poor pain control in rheumatoid arth 2009 Mar We have examined the characteristics of the pain experience as well as barriers to optimal pain management in 60 patients with rheumatoid arthritis (RA) consecutively attending a specialist rheumatology practice. Pain was reported to be moderate to severe in 32 (53%) and mild to absent in 28 (47%). Sixty-five percent of all patients, including almost half of those with moderate to severe pain, reported satisfaction with current pain control. The average number of barriers to pain management for individual patients was 2.6 +/- 1.5, with 33 patients (55%) reporting 3 or more barriers. Specific barriers included concern about side effects of medications in 80%, dislike for "too many pills" in 63%, concern about drug interactions in 57%, fear of addiction in 35%, and fear of masking disease in 27% of the patients. More barriers were significantly associated with higher pain level (r = .33, P = .011) and pain intensity on a visual analogue scale (r = .29, P = .024). Other than the regular use of nonsteroidal anti-inflammatory drugs in 37% of the patients and acetaminophen in 37%, analgesics or other modalities to reduce pain were seldom used. PERSPECTIVE: Moderate to severe pain was present in over half of patients with RA with many reporting the presence of considerable barriers to pain control. These barriers likely contribute to sub optimal pain management. RA patients tolerate pain and use limited mechanisms to deal with the symptom of pain.
19395226 Development and initial validation of a heart disease knowledge questionnaire for people w 2009 Oct OBJECTIVE: To develop and validate two parallel versions of the Heart Disease Fact Questionnaire-Rheumatoid Arthritis (HDFQ-RA), a modified and RA-specific version of the HDFQ. METHODS: The questionnaire was composed of generic questions from the original HDFQ with additional RA-specific questions added. Cognitive interviewing was performed and the questionnaire piloted to generate two parallel questionnaires. For psychometric validation, 130 patients with RA completed the questionnaires at baseline and 2 weeks later. RESULTS: Parallel form reliability of both questionnaires was established; the median score for both questionnaires was 9/13 with no statistical difference in scores. Kuder-Richardson-20 formula was 0.65 and 0.67 for both questionnaires. Test-retest stability showed constant median scores of 9/13 and no statistical difference in scores between baseline and follow-up. Known groups comparison revealed that patients who had self-educated themselves about heart disease, or who were taking CVD medications, had significantly higher scores on the questionnaires. CONCLUSION: The two parallel forms of the HDFQ-RA have been shown to be equivalent measures of CVD knowledge and evidence supporting their reliability and validity is presented. PRACTICE IMPLICATIONS: The HDFQ-RA is an appropriate tool for application in clinical and research settings, e.g., assessing novel educational interventions or tracking participants' progress on an education course.
19195827 Comparison of simultaneous bilateral and staged bilateral total knee arthroplasty in terms 2010 Feb We compared bilateral total knee arthroplasty (TKA) performed at a single session vs those performed at 2 separate sessions with respect to complications, amount of blood loss, and length of hospital stay. Study participants included 119 consecutive patients undergoing simultaneous bilateral TKA and an additional 119 patients undergoing staged bilateral TKA. Systemic complication in the simultaneous bilateral TKA was significantly higher statistically than that in the staged bilateral TKA. Therefore, performing simultaneous bilateral TKA in elderly or high-risk patients results in a significantly higher rate of systemic complications. Simultaneous bilateral TKA is a relatively safe and beneficial procedure with a minimal increase in the risk of systemic complications. However, this procedure should be conducted carefully, particularly in elderly and high-risk patients.
19931339 miR-223 is overexpressed in T-lymphocytes of patients affected by rheumatoid arthritis. 2010 Feb miRNAs have recently emerged as key regulators of the immune system, being involved in lymphocyte selection and proliferation, in T(reg) cells differentiation, and in hematopoiesis in general. Rheumatoid arthritis (RA) is an autoimmune pathology the etiology of which is still obscure. Although a multifactorial pathogenesis has been hypothesized, the precise mechanisms leading to the disease are still poorly understood at the molecular level. miRNA expression profile analysis highlighted that miR-223 is the only miRNA that is strikingly deregulated in peripheral T-lymphocytes from RA patients compared with healthy donors. Further analysis by quantitative reverse transcription-polymerase chain analysis confirmed that miR-223 is overexpressed in T-lymphocytes from RA patients (n = 28) compared with healthy donors (n = 10). Moreover, purification of different T-lymphocyte populations from RA patients highlights that miR-223 is expressed at higher levels in naive CD4(+) lymphocytes, whereas its expression is barely detectable in T(h)-17 cells. In summary, our data provide a first characterization of the miRNA expression profiles of peripheral T-lymphocytes of RA patients, identifying miR-223 as overexpressed in CD4(+) naive T-lymphocytes from these individuals. A deeper analysis of the biologic functions and effects of the expression of miR-223 in T-lymphocytes is needed to clarify the exact link between our observation and the disease.
21255181 Possible involvement of peptidylprolyl isomerase Pin1 in rheumatoid arthritis. 2011 Feb The peptidylprolyl isomerase Pin1 is over-expressed in some human diseases including malignancies and chronic inflammatory diseases, this suggests that it contributes to the constitutive activation of certain intracellular signaling pathways that promote cell proliferation and cell invasion. Here, we investigate the possible role of Pin1 in rheumatoid arthritis (RA). Pin1 expression was immunohistochemically analyzed in synovial tissue (ST) obtained from patients with RA and osteoarthritis (OA). To investigate the correlation between Pin1 and motility and proliferation of synovial cells, Pin1 localization was immunohistochemically compared with matrix metalloproteinase (MMP)-1, MMP-3, and proliferating cell nuclear antigen (PCNA). Double immunofluorescent staining for Pin1 and p65 was performed to determine whether Pin1 is involved in nuclear factor κB (NF-κB) activation in RA-ST. Results showed Pin1 expression was significantly higher in RA-ST than in OA-ST. The expression of MMP-1, MMP-3, and PCNA was also significantly elevated in RA-ST. Double immunofluorescent staining revealed colocalization of Pin1 and p65 in the nuclei of RA-ST. These results suggest that Pin1 may be involved in the pathogenesis of RA binding with p65 to activate the proteins MMP-1, MMP-3, and PCNA. Therefore, Pin1 may play a pivotal role in the pathogenesis of RA.
19350558 Semi-mature DC are immunogenic and not tolerogenic when inoculated at a high dose in colla 2009 May Semi-mature DC (smDC) have been shown to be tolerogenic and thus applicable to the treatment of autoimmune disease. However, in our repeated experiments, even the same batches of smDC were found to be profoundly immunogenic rather than tolerogenic when inoculated at high doses into arthritic mice. In a cytokine chip assay, smDC were characterized by remarkable production of IL-2, IL-3, IL-5, and IL-13 together with well-known Th2 cytokines. Low doses (2 x 10(5)) of smDC showed excellent anti-arthritic activity in collagen-induced arthritis animals, whereas high doses (2 x 10(6)) of smDC uniformly accelerated arthritic symptoms. SmDC, vaccinated at lower doses, markedly induced forkhead box P3 Treg, Th2 cytokines (IL-4/IL-10), and TGF-â in their immune deviation. Interestingly, however, as the number of smDC increased from 2 x 10(5) to 2 x 10(6) in the same assay, the Treg population, Th2 cytokines, and TGF-beta were dramatically reduced. Our present study clearly indicates that smDC could induce either T-cell tolerance or T-cell activation, depending on the inoculum size. Special attention should be paid to the optimal range of smDC in DC-mediated immunotherapy for the treatment of rheumatoid arthritis.