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ID PMID Title PublicationDate abstract
23740226 Efficacy and safety of golimumab as add-on therapy to disease-modifying antirheumatic drug 2014 Aug OBJECTIVES: To evaluate the efficacy and safety of subcutaneous golimumab as add-on therapy in patients with active rheumatoid arthritis (RA) despite disease-modifying antirheumatic drug (DMARD) treatment. To evaluate an intravenous plus subcutaneous (IV+SC) golimumab strategy in patients who had not attained remission. METHODS: GO-MORE was an open-label, multinational, prospective study in patients with active RA in typical clinical practice settings. In part 1, patients received add-on monthly 50-mg subcutaneous golimumab for 6 months. The percentage of patients with good/moderate European League Against Rheumatism (EULAR) 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate (ESR) response was compared in patient subgroups with various concurrent or previous DMARD treatments. In part 2, patients with EULAR responses but not remission were randomly assigned to receive IV+SC or subcutaneous golimumab to month 12; DAS28-ESR remission was measured. RESULTS: 3366 patients were enrolled. At baseline of part 1, 3280 efficacy-evaluable patients had mean disease duration of 7.6 years and mean DAS28-ESR of 5.97 (SD=1.095). At month 6, 82.1% achieved good/moderate EULAR responses and 23.9% attained remission. When EULAR responses were analysed by the number of previously failed DMARD or the concomitant methotrexate dose, DMARD type, or corticosteroid use, no statistically significant differences were observed. Part 2 patients (N=490) who received IV+SC or subcutaneous golimumab achieved similar remission rates (∼25%). Adverse events were consistent with previous reports of golimumab and other tumour necrosis antagonists in this population. CONCLUSIONS: Add-on monthly subcutaneous golimumab resulted in good/moderate EULAR response in most patients; 25% achieved remission after 6 more months of golimumab, but an IV+SC regimen provided no additional efficacy over the subcutaneous regimen.
25050591 Infliximab efficacy in rheumatoid arthritis after an inadequate response to etanercept or 2014 Nov OBJECTIVE: Evaluate efficacy of infliximab with response-driven dosing in patients with active RA. RESEARCH DESIGN AND METHODS: Patients (n = 203) with active RA despite methotrexate + etanercept/adalimumab, participated in this active-infliximab-switch study. Infliximab 3 mg/kg was infused at Weeks 0, 2, 6, 14, and 22 with escalation to 5 or 7 mg/kg depending on EULAR response at Weeks 14 and 22. The primary endpoint was EULAR response at Week 10. Safety was assessed through Week 30. Infliximab levels and antibodies to infliximab (ATI) were measured at Weeks 0, 6, 14, and 26. CLINICAL TRIAL REGISTRATION: NCT 00714493, EudraCT 2007-003288-36. RESULTS: Of 197 evaluable patients, 120/77 previously received etanercept/adalimumab. Baseline mean (SD) swollen and tender joint counts were 17.3 (10.54) and 30.2 (16.89), respectively; mean DAS28-ESR was 6.19 (0.981). At Week 10, 98 (49.7%; 95% CI: 42.6%, 56.9%) patients achieved EULAR response, with a significantly improved DAS28-ESR score (mean [SD] change -1.1 [1.15]; p < 0.001). EULAR response was achieved by 41.7%/62.3% of patients previously receiving etanercept/adalimumab (p = 0.006). At Week 26, 51.8% (95% CI: 44.6%, 58.9%) of patients achieved or maintained EULAR response. Infliximab dose was escalated in 100 patients, 52% of whom achieved EULAR response at Week 26. Median serum concentration levels at Week 26 showed that dose escalation helped EULAR non-responders achieve levels similar to or higher than the levels seen in responders. ATI were associated with lower serum concentrations of infliximab, consistent with lower efficacy rates among ATI-positive patients. CONCLUSION: Infliximab, in treat-to-target settings with individual dose escalation, demonstrated significant efficacy at Weeks 10 and 26 in patients switched to infliximab after inadequate response to etanercept/adalimumab. The observed efficacy indicated that the switch to infliximab and ability to increase dose in a targeted fashion were beneficial. KEY LIMITATIONS: Given the relatively short duration of study follow-up, these safety findings require confirmation in a longer-term study.
25069497 Vitamin D and rheumatic diseases. 2014 Jul 28 Vitamin D has some well-known effects on calcium, phosphate and bone metabolism, but it has recently shown to have many other effects, which may potentially be relevant to patients with extra-skeletal rheumatic diseases. Such effects may be justified by: 1) the presence of the vitamin D receptors also on extra-osseous cells, such as cartilage cells, sinoviocytes, muscle cells; 2) the proven role of vitamin D in the control of the transcription of genes involved in rheumatic diseases; 3) the evidence that vitamin D has multiple endocrine effects not only on calcium homeostasis; 4) the activation of vitamin D not only in the kidneys, but also in monocyte-macrophage and lymphocytic cell lines and in some epithelial cells with additional intracrine and paracrine effects. Vitamin D deficiency has been reported in numerous metabolic, degenerative, inflammatory and autoimmune rheumatic diseases. In some cases this association was also related to the risk of developing a rheumatic disease or the degree of disease activity. However there is no conclusive evidence of the efficacy of a preventive or therapeutic strategy based on vitamin D supplementation in extra-skeletal rheumatic diseases. This review aims to provide an overview of the latest evidence concerning the relationship between vitamin D and the most relevant rheumatic diseases.
25092140 Advances in epigenome-wide association studies for common diseases. 2014 Oct Epigenome-wide association studies (EWASs) provide a systematic approach to uncovering epigenetic variants underlying common diseases. Discoveries have shed light on novel molecular mechanisms of disease and enabled the application of epigenetic variants as biomarkers. Here, we highlight the recent advances in this emerging line of research and discuss key challenges for current and future studies.
24397353 CD38 and E2F transcription factor 2 have uniquely increased expression in rheumatoid arthr 2014 May The purpose of the current study was to find novel rheumatoid arthritis (RA)-specific gene expression by simultaneously comparing the expression profiles of the synovial tissues from patients with RA, osteoarthritis (OA) and ankylosing spondylitis (AS). The Illumina Human HT-12 v4 Expression BeadChip was used to investigate the global gene expression profiles in synovial tissues from RA (n = 12), OA (n = 14) and AS (n = 7) patients. By comparing the profiles in synovial tissues from RA, OA and AS, we identified the CD38, ankyrin repeat domain 38 (ANKRD38), E2F transcription factor 2 (E2F2), craniofacial development protein 1 (CFDP1), cluster of differentiation (CD)7, interferon-stimulated exonuclease gene 20 kDa (ISG20) and interleukin-2 receptor gamma (IL)-2RG genes as differentially expressed gene expression in RA synovial tissues. The increased expression of CD38, E2F2 and IL-2RG, as revealed using real-time polymerase chain reaction (PCR) with synovial tissues from RA (n = 30), OA (n = 26) and AS patients (n = 20), was in agreement with the microarray data. Immunohistochemistry revealed significant CD38 expression and E2F2 in synovial membranes from RA patients (n = 5). The CD38(+) cells had high a percentage in the RA patients' blood (n = 103) and in the CD3(+) and CD56(+) subsets. The CD38(+) cell percentage was correlated significantly with RF level (P = 0·026) in RA patients. The IL-1α and IL-β levels were depressed significantly in the culture medium of RA synovial fibroblast cells (n = 5) following treatment with siRNAs targeting the E2F2 or CD38 genes. This study suggests that the uniquely increased expression of CD38 and E2F2 in RA synovial tissues contribute to the immunoactivation of the disease.
25711751 Adverse drug reactions associated with the use of disease-modifying anti-rheumatic drugs i 2014 Dec This study describes the adverse drug reactions (ADRs) and their incidence in patients with rheumatoid arthritis who were treated in the Colombian health system. A retrospective cohort study was conducted using information from all patients who were diagnosed with rheumatoid arthritis and attended specialized health care centers in the cities of Bogotá, Cali, Manizales, Medellin, and Pereira between 1 December 2009 and 30 August 2013. The ADRs were obtained from medical records and the pharmacovigilance system registry and sorted by frequency and affected tissue according to World Health Organization Adverse Reaction Terminology (WHO-ART). A total of 949 reports of ADRs were obtained from 419 patients (32.8 ADRs per 100 patient-years); these patients were from a cohort of 1,364 patients being treated for rheumatoid arthritis and followed up for an average of 23.8 months (± 12.9). The cohort was mostly female (366, 87.4%) and had a mean age of 52.7 years (± 13.1). The highest numbers of ADRs were reported following the use of tocilizumab, rituximab, and infliximab (28.8, 23.1, and 13.3 reports per 100 patient-years respectively). The most frequently reported ADRs were elevated transaminase levels and dyspepsia. Overall, 87.7% of ADRs were classified as type A, 36.6% as mild, 40.7% as moderate, and 22.7% as severe. As a result, 73.2% of patients who experienced an ADR stopped taking their drugs. The occurrence of ADRs in patients treated for rheumatoid arthritis is common, especially in those associated with the use of biotechnologically produced anti-rheumatic drugs. This outcome should be studied in future research and monitoring is needed to reduce the risks in these patients.
23672124 [Total hip arthroplasty with double-tapered cementless femoral stem for hip bony]. 2013 Mar OBJECTIVE: To investigate the effectiveness of total hip arthroplasty with double-tapered cementless femoral stem for hip bony fusion by comparing with anatomical cementless femoral stem. METHODS: A retrospective analysis was made on clinical data of 50 cases (80 hips) of hip bony fusion undergoing total hip arthroplasty between October 1999 and January 2008. The patients were divided into 2 groups: 31 cases (49 hips) using BetaCone double-tapered cementless femoral stem (trial group), and 19 cases (31 hips) using Ribbed anatomical cementless femoral stem (control group). There was no significant difference in gender, age, disease duration, preoperative Harris score, and abduction angle of the hip between 2 groups (P > 0.05). After operation, X-ray films were used to calculate the ratio of force arm of abductor (a) to the force arm of gravity (b) and analyze the stability of the prosthesis. The abduction angle of the hip and Harris score were measured during follow-up. RESULTS: Fracture occurred during operation in 9 hips of 9 cases (5 in trial group and 4 in control group), and was cured after fixation. The mean follow-up time was 49 months (range, 12-98 months) in trial group and was 53 months (range, 6-105 months) in control group. The ratio of a/b was 0.65 +/- 0.25 in trial group and was 0.56 +/- 0.37 in control group, showing significant difference (t = 2.19, P = 0.03). The abduction angle of hip was (34.49 +/- 7.58) degrees in trial group and was (30.97 +/- 7.24) degrees in control group at 6 months after operation, which was significantly improved when compared with preoperative value in 2 groups (P < 0.05), and significant difference was found between 2 groups (t = 2.06, P = 0.04). Postoperative Harris score was significantly improved in 2 groups when compared with preoperative score (P < 0.05); trial group was better than control group in Harris score at 1 month after operation (t = 3.62, P = 0.01), but no significant difference was found between 2 groups at last follow-up (t = 1.61, P = 0.11). At last follow-up, X-ray films showed stabilized prosthesis in 2 groups. Grade I or II ectopic ossification occurred in 12 cases (14 hips) of trial group and 8 cases (9 hips) of control group at 2 years after operation. CONCLUSION: The total hip arthroplasty with both double-tapered and anatomical cementless femoral stems for hip bony fusion can obtain satisfactory effectiveness, while the double-tapered cementless femoral stem has better abduction angle of hip.
24253594 Confirmation of -174G/C interleukin-6 gene promoter polymorphism as a genetic marker predi 2014 Jan BACKGROUND: The IL-6 -174G/C genetic variant has recently been associated with the clinical response to etanercept therapy in rheumatoid arthritis (RA) patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the antitumor necrosis factor (anti-TNF) treatment outcome in RA. MATERIALS AND METHODS: Our study population was composed of 199 Spanish patients with RA receiving anti-TNF therapy. The IL-6 -174G/C (rs1800795) genetic variant was genotyped using the TaqMan allelic discrimination technology. Patients were classified, according to the European League Against Rheumatism (EULAR) criteria, as responders (good and moderate response) and nonresponders at 6, 12, 18, and 24 months after the first infusion. RESULTS: The -174*G allele was significantly associated with a good or moderate EULAR response at 12 [P=0.015, odds ratio (OR)=2.93, 95% confidence interval (CI) 1.29-6.70], 18 (P=4.54E-03, OR=5.17, 95% CI 1.80-14.85), and 24 months (P=4.54E-03, OR=14.86, 95% CI 2.91-75.91). A meta-analysis combining these data with the results from a previous study confirmed this association (P=1.89E-02, OR=1.80, 95% CI 1.13-2.87, at 12 months). CONCLUSION: Our results support the role of the -174G/C IL-6 polymorphism as a genetic marker of responsiveness to anti-TNF therapy.
24139404 Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic 2013 Oct 18 BACKGROUND: Tofacitinib is a disease-modifying antirheumatic drug (DMARD) which was recently approved by US Food and Drug Administration (FDA). There are several randomised clinical trials (RCTs) that have investigated the efficacy and safety of tofacitinib in adult patients with rheumatoid arthritis (RA). A systematic review with a meta-analysis of RCTs was undertaken to determine the efficacy and safety of tofacitinib in treating patients with RA. METHODS: Electronic and clinical trials register databases were searched for published RCTs of tofacitinib between 2009 and 2013. Outcomes of interest include 20% and 50% improvement in the American College of Rheumatology Scale (ACR20 and ACR50) response rates, rates of infection, the number of immunological/haematological adverse events (AEs), deranged laboratory results (hepatic, renal, haematological tests and lipoprotein level) and the incidence of drug withdrawal. RESULTS: Eight RCTs (n = 3,791) were reviewed. Significantly greater ACR20 response rates were observed in patients receiving tofacitinib 5 and 10 mg bid (twice daily) versus placebo at week 12, with risk ratios (RR) of 2.20 (95% CI 1.58, 3.07) and 2.38 (95% CI 1.81, 3.14) respectively. The effect was maintained at week 24 for 5 mg bid (RR 1.94; 95% CI 1.55, 2.44) and 10 mg bid (RR 2.20; 95% CI 1.76, 2.75). The ACR50 response rate was also significantly higher for patients receiving tofacitinib 5 mg bid (RR 2.91; 95% CI 2.03, 4.16) and 10 mg bid (RR 3.32; 95% CI 2.33, 4.72) compared to placebo at week 12. Patients in the tofacitinib group had significantly lower mean neutrophil counts, higher serum creatinine, higher percentage change of LDL/HDL and a higher risk of ALT/AST > 1 ULN (upper limit of normal) versus placebo. There were no significant differences in AEs and withdrawal due to AEs compared to placebo. CONCLUSION: Tofacitinib is efficacious and well tolerated in patients with MTX-resistant RA up to a period of 24 weeks. However, haematological, liver function tests and lipoproteins should be monitored. Long-term efficacy and pharmacovigilance studies are recommended.
23934131 Kaempferol inhibits IL-1β-induced proliferation of rheumatoid arthritis synovial fibrobla 2013 Oct Inflammatory cytokines, matrix metalloproteinases (MMPs) and cyclooxygenase (COX)-2 released from rheumatoid arthritis synovial fibroblasts (RASFs) are involved in the destruction of both articular bone and cartilage. Kaempferol has been reported to act as an antioxidant and anti-inflammatory agent by inhibiting nitric oxide synthase and COX enzymes. The aim of the present study was to determine the effects of kaempferol on the interleukin-1β (IL-1β)-induced proliferation of RASFs and the production of MMPs, COX and prostaglandin E2 (PGE2) by RASFs. The proliferation of the RASFs stimulated with IL-1β and treated with/without kaempferol was evaluated by CCK-8 assay. The expression of MMPs, TIMP metallopeptidase inhibitor-1 (TIMP-1), COXs, PGE2 and that of intracellular MAPK signaling molecules, including p-ERK, p-p38, p-JNK and nuclear factor-κB (NF-κB) was examined by immunoblotting or semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and ELISA under the conditions described above. Kaempferol inhibited the proliferation of both unstimulated and IL-1β‑stimulated RASFs, as well as the mRNA and protein expression of MMP-1, MMP-3, COX-2 and PGE2 induced by IL-1β. Kaempferol also inhibited the phosphorylation of ERK-1/2, p38 and JNK, as well as the activation of NF-κB induced by IL-1β. These results indicate that kaempferol inhibits synovial fibroblast proliferation, as well as the production of and MMPs, COX‑2 and PGE2, which is involved in articular inflammation and destruction in rheumatoid arthritis (RA). Our data suggest that kaempferol may be a novel therapeutic agent for the treatment of RA.
25265764 A comparative study of serum and synovial fluid levels of uric acid between patients with 2014 Jul BACKGROUND: The urate levels and the correlations of urate levels between the serum and synovial fluid (SF) of many arthritic diseases have not been well described. OBJECTIVE: Compare urate levels in the serum and SF of gouty arthritis, calcium pyrophosphate dihydrate deposition disease (CPPD), rheumatoid arthritis (RA), septic arthritis, ankylosing spondylitis (AS), and osteoarthritis (OA) patients. MATERIAL AND METHOD: Paired samples of serum and SF from 95 patients comprised of 33 patients with gout, 22 with CPPD, 18 with RA, nine with septic arthritis, three with AS, and 10 with OA were collected simultaneously for urate measurement by photometric test. RESULTS: Ninety-five patients, including 53 males, with mean (SD) age of 64.1 (15.3) years were recruited. In gout, serum and SF urate levels were significantly higher than those of CPPD, RA, septic arthritis, AS, and OA ( p 0..01). In all the study population, the serum/SF ratios of urate levels of gout were not different across all groups. However, after excluding 24 patients with creatinine >1.5 mg/dl, the serum/SF ratios of urate were significantly lower in gout compared with the others ( 0.02). There were strongly positive correlations between serum and SF urate levels in gout similar to CPPD, RA, septic arthritis, AS, an dOA (r = 0.81-0.91, p 0O.01). CONCLUSION: Despite the highest level of serum and SF urate across all groups, the serum/SF urate ratio in gout patients was the lowest, which suggests that SF urate levels are uniquely higher than their serum. In addition, the levels of serum urate of the entire groups strongly reflect their SF levels.
25085953 Myelitis and optic neuritis induced by a long course of etanercept in a patient with rheum 2014 Aug 1 A 64-year-old woman presented with an acute onset of myelitis and optic neuritis after 47 months of etanercept use for rheumatoid arthritis. Etanercept was discontinued and pulse methylprednisolone therapy (1000 mg/day for 3 days) was started, followed by a quick and complete resolution. Demyelination associated with antitumor necrosis factor agents, reported to develop mostly from 1 week to 12 months after the initiation of the agents, could develop after a few years and thus warrants vigilant monitoring.
25082646 Efficacy and safety of rituximab with and without methotrexate in the treatment of rheumat 2014 Dec INTRODUCTION: Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX). OBJECTIVES: To evaluate the efficacy and safety of RTX-MTX combination therapy compared with RTX alone in the treatment of RA. METHODS: We analyzed data from a prospective cohort study, the Italian biologic register GISEA, to investigate the efficacy and safety of rituximab. Moreover, the adverse events (AE) and the causes of discontinuation therapy were analyzed. RESULTS: We identified 338 RA patients, 162 treated with RTX and 176 with RTX-MTX. After 52 and 104 weeks of therapy the disease activity score in 28 joints and the Health Assessment Questionnaire Score were available in 168 patients (78 with RTX-MTX and 60 with RTX alone), showing significant reduction without differences among the two groups. AE were reported in 142 patients (42%), for a total of 368 recorded side effects. The majority (90.5%) of AE were mild to moderate in severity. Comparable percentages of severe AE were reported in the 2 groups (9.9% for RTX alone and 9.3% for RTX+MTX). A poor disease control was observed in 14.2% and 13.5% of patients treated with RTX+MTX and RTX, respectively; while 12 patients (4.5% in RTX+MTX, and 2.5% in RTX group) suspended therapy for AE. CONCLUSIONS: RTX showed a good efficacy and safety profile in the real-life management of RA patients regardless of the association with MTX.
22987832 Performance of different screening methods for the determination of urinary glycosaminocly 2013 Feb BACKGROUND: The study aim was to compare the performance of three different methods used for determining urinary glycosaminoglycans (GAG) levels in spot and 24-h urine samples. METHODS: Performance characteristics were studied for cetylpyridinium chloride (CPC), and manual and automated dimethylmethylene blue (DMB) methods. RESULTS: For automated DMB method, within-run precisions were 9.10% and 1.98%, and between-day precisions were 13.0% and 5.81% in low- and high-urine pools, respectively. The method was linear up to 100 mg/L of GAG concentration. The detection limit of the method was 0.71 mg/L. Mean recovery was 95.7%. CONCLUSIONS: The automated DMB method was found to give better performance characteristics than cetylpyridinium chloride (CPC) and manual DMB methods. It is a fast, cheap, simple and reliable method and can be applied in many diseases in which GAG is used as a screening test.
23904438 Phagocyte dysfunction in polymyalgia rheumatica and other age-related, chronic, inflammato 2013 Nov This study was conducted to evaluate phagocyte function in patients with age-related chronic inflammatory conditions. It included 95 patients with PMR, 17 with GCA, 40 with EORA, and 25 age-matched HCs. Serum IL-8 was determined with a bead array. The chemotactic capacity, phagocytic ability, and oxidative burst activity of circulating leukocytes were determined with flow cytometry kits. Patients with active chronic inflammatory diseases showed a significant increase in circulating levels of IL-8 that remained elevated in patients with PMR or EORA, despite treatment. No correlation was found between circulating IL-8 and the migratory capacity of neutrophils. Neutrophils from patients with active EORA without stimulus and after fMLP stimuli showed a higher capacity to migrate than those of the HCs (P=0.033). The phagocytic activity of granulocytes in the patients with GCA was significantly higher than in the HCs and the patients with PMR or EORA (P<0.05). The percentage and MFI of phagocytes that produce ROIs when stimulated with Escherichia coli was significantly reduced in neutrophils and monocytes from the patients with age-restricted inflammatory conditions. We concluded that the effector functions of phagocytes, determined to be chemotaxis, phagocytosis, and oxidative burst, are deregulated in age-restricted inflammatory disorders and may have a pathogenic role.
23633118 Evidence that CXCL16 is a potent mediator of angiogenesis and is involved in endothelial p 2013 Jul OBJECTIVE: To examine the possibility that CXCL16 recruits endothelial cells (ECs) to developing neovasculature in rheumatoid arthritis (RA) synovium. METHODS: We utilized the RA synovial tissue SCID mouse chimera system to examine human microvascular EC (HMVEC) and human endothelial progenitor cell (EPC) recruitment into engrafted human synovium that was injected intragraft with CXCL16-immunodepleted RA synovial fluid (SF). CXCR6-deficient and wild-type (WT) C57BL/6 mice were primed to develop K/BxN serum-induced arthritis and evaluated for angiogenesis. HMVECs and EPCs from human cord blood were also examined for CXCR6 expression, by immunofluorescence and assessment of CXCL16 signaling activity. RESULTS: CXCR6 was prominently expressed on human EPCs and HMVECs, and its expression on HMVECs could be up-regulated by interleukin-1β. SCID mice injected with CXCL16-depleted RA SF exhibited a significant reduction in EPC recruitment. In experiments using the K/BxN serum-induced inflammatory arthritis model, CXCR6(-/-) mice showed profound reductions in hemoglobin levels, which correlated with reductions in monocyte and T cell recruitment to arthritic joint tissue compared to that observed in WT mice. Additionally, HMVECs and EPCs responded to CXCL16 stimulation, but exhibited unique signal transduction pathways and homing properties. CONCLUSION: These results indicate that CXCL16 and its receptor CXCR6 may be a central ligand/receptor pair that is closely associated with EPC recruitment and blood vessel formation in the RA joint.
24631368 Sour cherry (Prunus cerasus) seed extract increases heme oxygenase-1 expression and decrea 2014 May Sour cherry seed extract (SCE) was evaluated for its capacity to inhibit lipopolysaccharide-treated human peripheral blood T cells expressing tumor necrosis factor-alpha, and the chemokine interleukin-8. Both proteins are diagnostic biomarkers for inflammatory pathologies. Peripheral blood leukocytes from 11 rheumatoid arthritis (RA) patients and 8 healthy control subjects were co-cultured for 24h in lipopolysaccharide and the extract, then evaluated by flow cytometry for T cell activation and by enzyme-linked immunoassay for lymphocyte-associated heme oxygenase-1 (HO-1) expression. There was a dose-dependent decrease in expression of the immunophenotypes: CD3+TNF-α+, and CD3+IL8+ in cultures from RA patients to a greater extent than in cells from healthy participants. These results suggest that the extract may have a modulatory roll in RA and other inflammatory disorders via the induction of HO-1, thus abating oxidative stress and strengthening regulation of pro-inflammatory signaling pathways.
24792332 The in vitro addition of methotrexate and/or methylprednisolone determines peripheral redu 2015 Jan The aim of our study was to evaluate methotrexate (MTX) and methylprednisolone (MP) effect on peripheral Th17 and Treg subsets in patients with rheumatoid arthritis (RA). We enrolled 15 patients (10 early RA and 5 long-standing disease) with active RA and 10 age-matched healthy donors as controls. Frequencies of Th17 and Treg were quantified using flow cytometry before and after in vitro addition of MTX, MP or both drugs. Our results showed a reduction in the overall Th17 population followed by an increase in Th17 IL-10(+) and Treg, after in vitro treatment of PBMCs with the drugs in patients with early RA. Long-standing disease patients showed a less evident increase in Treg cells and less enhancement of IL-10 Th17 cells. We suggest that the treatment with MTX and MP could ameliorate RA disease activity by normalizing the distribution/imbalance of Th17/Treg and indicate a new regulatory role of IL-17(+) cells in RA patients.
23543349 T cell responses to citrullinated self-peptides in patients with rheumatoid arthritis. 2013 Sep Antibodies to citrullinated peptides(ACPA) have high specificity for diagnosis and prognosis in rheumatoid arthritis (RA). ACPA are of IgG isotype and have an association with shared epitope-bearing HLA DR allele, suggesting that T cell help is needed for their generation. In mice models, T cell reactive to citrullinated self-peptide have been reported however, the human data is limited. Patients with RA satisfying ACR criteria were included and peripheral blood obtained for lymphoproliferative assay, antibody level and HLA typing. Citrullinated (Cit) and native peptides of Vimentin and Aggrecan were used for stimulating peripheral blood mononuclear cells in 5-day cultures. A SI value above >2.0 was taken as significant. HLA typing was done by SSCP and ACPA were tested by ELISA. A total of 50 patients (45 females; mean age 42 years; mean duration of disease 7 years) with RA were included in the study. A total of 90 % were RF positive and 78 % were ACPA positive. A total of 28 patients showed response to Agg peptide with 21 of them showing higher response to CitAgg as compared to native Agg peptide as well as the median SI was higher with CitAgg (6.07 Vs. 5.09; p = 0.009). A total of 31 patients showed response to Vim peptide with response to native peptide being higher than CitVim peptide in 22 of the patients. There was no association of T cell response with presence of shared epitope. Nearly half the patients with RA show T cell response to aggrecan and vimentin peptides; however, citrullination is not crucial for T cell response.
23740233 Senescence marker killer cell lectin-like receptor G1 (KLRG1) contributes to TNF-α produc 2014 Jun OBJECTIVES: Killer cell lectin-like receptor G1 (KLRG1) is an NK cell marker also expressed on T cells showing an immunosenescent phenotype. KLRG1 binding to its ligand E-cadherin inhibits functional responses. It was recently shown that soluble E-cadherin (sE-cadherin) also influences KLRG1 signalling, although its involvement in arthritis is unknown. Our goal was to evaluate the contribution of KLRG1(+) T cells to synovitis. METHODS: Paired peripheral blood (PB) and synovial fluid (SF) mononuclear cells from 21 patients with spondyloarthritis (SpA) or rheumatoid arthritis (RA), eight with crystal-induced arthritis and 10 controls were obtained. T cells were characterised for KLRG1 expression directly ex vivo, while TNF-α/IFN-γ production was assessed after polyclonal stimulation. Assays of chemotaxis response towards SF were conducted. Additionally, sE-cadherin levels in our paired samples were determined. Moreover, TNF-α/IFN-γ production by antigen-specific T cells was evaluated in the presence of sE-cadherin. RESULTS: KLRG1(+) T cells were enriched in SF as opposed to PB of SpA and RA patients, which contrasts with results obtained in crystal-induced arthritides. KLRG1(+) T cells were more functionally active as opposed to KLRG1(-) T cells and migrated preferentially towards SpA and RA SF. sE-cadherin levels were higher in SF versus plasma. The presence of sE-cadherin enhanced the number of KLRG1(+) CD4(+) T cells able to produce TNF-α but not IFN-γ. CONCLUSIONS: sE-cadherin contributes to the local proinflammatory environment in the joint by favouring TNF-α production by KLRG1(+) CD4(+) T cells. This pathway seems to be operational in both SpA and RA, but not in crystal-induced arthritis.