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ID PMID Title PublicationDate abstract
22736091 Differential synovial Th1 cell reactivity towards Escherichia coli antigens in patients wi 2012 Sep OBJECTIVE: Ankylosing spondylitis (AS) is associated with clinical and subclinical mucosal inflammation, suggesting that commensal bacteria contribute to the pathogenesis of the disease. METHODS: The frequency of Th1 cells reacting towards conserved Escherichia coli (E coli) proteins and pathogenicity factors in peripheral blood mononuclear cells (PBMNC) and synovial fluid mononuclear cells (SFMNC) of patients with AS and those with rheumatoid arthritis (RA) was determined. PBMNC from healthy individuals were included as controls. RESULTS: Higher frequencies of Th1 cells reacting to conserved E coli proteins were observed in SFMNC and, to a lesser extent, in PBMNC of patients with AS compared with patients with RA (SFMNC, p<0.01; PBMNC, p<0.05). In contrast, the frequencies of cytomegalovirus- and staphylococcal enterotoxin B (SEB)-induced Th1 cells did not differ between patients with AS and those with RA in SFMNC, and SEB-induced Th1 cell frequencies in PBMNCs were even higher in patients with RA than in those with AS (p<0.05). CONCLUSIONS: The high frequency and enrichment of E coli-specific CD4 T cells in the inflamed joints of patients with AS but not those with RA suggests that commensal bacteria are relevant antigens in AS that might trigger the disease.
21821989 [Extranodal NK/T-cell lymphoma, nasal type, developed in a patient with rheumatoid arthrit 2011 Jul It is well known that patients with rheumatoid arthritis (RA) have a higher risk of developing malignant lymphoma (ML) than the general population. Most of these lymphomas occur in patients receiving immunosuppressive (IS) agents such as methotrexate (MTX). Spontaneous regression of tumors is often observed after the discontinuation of IS drugs, especially in patients with Epstein-Barr virus-positive lymphoma. Here we encountered an RA patient who developed extranodal NK/T-cell lymphoma, nasal type during treatment of RA with MTX and etanercept. Despite the discontinuation of MTX and etanercept, the tumor did not show any regression. Complete response was achieved after treatment with concurrent chemoradiotherapy. ML of NK-cell origin is extremely rare, while the majority of ML cases associated with RA are of B-cell origin. This report describes extranodal NK/T-cell lymphoma, nasal type case associated with RA. Such cases should be accumulated to evaluate the mechanism of onset and clinical characteristics of NK/T-cell lymphoma associated with RA.
22753774 Circulating endothelial cells and their progenitors in systemic lupus erythematosus and ea 2012 Oct OBJECTIVE: The aim of this study was to investigate the endothelial progenitor cell population in SLE and early RA patients and its potential relationships with disease features and cytokine serum levels. METHODS: Endothelial progenitor cells (EPCs), mature EPCs (mEPCs) and endothelial cells (ECs) were measured in peripheral blood samples from 83 SLE and 85 early RA patients and 39 healthy controls by flow cytometry on the basis of CD34, VEGF receptor 2 and CD133 expression. Serum levels of IL-1β, IL-6, IL-8, IL-17, VEGF-A, IFN-α, TGF-β and GM-CSF were quantified by immunoassays. Clinical and immunological data were obtained by reviewing clinical histories. RESULTS: Circulating EPCs were increased in SLE but not in early RA patients associated with an enhanced CD34(+) bone marrow-progenitor cell release but unrelated to disease features. The amount of mEPCs, however, was significantly higher in SLE patients presenting anti-SSA/SSB antibodies and/or malar rash, whereas the presence of specific autoantibodies was associated with EC counts in early RA and SLE patients. As expected, most cytokines tested were altered in both diseases but, interestingly, IFN-α levels, and to a lesser extent IL-6 and IL-1β, were associated with CD133 loss and increased mEPC number, whereas VEGF and TGF-β seem to exert an opposite effect. CONCLUSION: Our results show that high IFN-α levels and/or the presence of disease-specific antibodies may identify a group of SLE patients with increased mEPC and EC counts, and consequently probably defective endothelial repair, thus supporting their use as surrogate biomarkers of endothelial damage and high cardiovascular risk.
24082324 Active compound of Zingiber cassumunar Roxb. down-regulates the expression of genes involv 2012 Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovium. It is involved in up-regulation of pro-inflammatory cytokines and matrix metalloproteinases (MMPs), resulting in joint inflammation and erosion. Zingiber cassumunar Roxb. has long been used to reduce joint pain and inflammation. This study aimed to investigate the inhibitory activities of an active compound of Z. cassumunar, (E)-4-(3',4'-dimethoxyphenyl)but-3-en-1-ol (compound D), against cytokine-induced up-regulation of catabolic genes involved in cartilage degradation in RA. Synovial fibroblast cell line, SW982, was cultured in media containing interleukin-1β (IL-1β), in the presence or absence of compound D at the concentration range of 1 to 100 µM. After 24 hours, the cells were analyzed for the expressions of MMPs, IL-1β and interleukin-1β-converting enzyme (ICE) by RT-PCR. MMPs activities in the culture media were analyzed by zymographic techniques. Dexamethasone was used as the positive control. It was found that compound D at the concentration of 10 - 100 µM significantly decreased the mRNA expressions of MMP-1, -2, -3, and -13 which was induced by IL-1β (P<0.05) concomitantly with a decrease in activities of these MMPs in the culture media. An increase in the mRNA expression of IL-1β and ICE was also suppressed by compound D. The results suggest that the potent activities of this compound may be involved in the reduction of IL-1β protein synthesis in both pro-form and active form which played an important role in up-regulation of MMPs. This study first revealed the chondroprotective activity of Z. cassumunar in the transcriptional level by suppressing cytokine-induced catabolic genes which caused cartilage erosion in RA.
21497722 [Etiology and evolution of bronchiectasis in women]. 2011 Apr INTRODUCTION: Although considered as an orphan disease in the developed countries, bronchiectasis are frequent in our country as in all emerging ones. They are most common in women and they represent a frequent cause for consultation and hospitalization in pulmonology departments. PATIENTS AND METHODS: To determine the etiology and prognosis of the bronchectasies in women, a retrospective study was performed including 200 patients. RESULTS: The mean age was 55.60 years. The diagnosis of bronchiectasis was confirmed in all patients. Bronchiectasis were post-tuberculosis in 56.5% of cases and primitive in 29.5% of cases. The systemic diseases, in particular the rheumatoid polyarthritis represented 3% of cases. The infectious complications and the chronic respiratory failure were more frequent in patients with primitive bronchiectasis than those with secondary bronchiectasis. However this difference was statistically significant only for the chronic respiratory failure. CONCLUSION: The bronchiectasis remains frequent in women in our country, as a sequel of pulmonary tuberculosis more than primitive forms. Bronchiectasis secondary to systemic diseases, although rare, must be known.
22165979 Certolizumab pegol for the treatment of rheumatoid arthritis. 2012 Feb INTRODUCTION: Improved understanding of the pathogenesis of rheumatoid arthritis (RA), and subsequent development of targeted therapies, have greatly advanced the management of this chronic inflammatory disease. The aim of treatment is a state of clinical remission. Certolizumab pegol (CZP) is a novel pegylated TNF alpha inhibitor (TNFi) therapy and is the focus of this review. AREAS COVERED: CZP is different from other TNFi as it contains a polyethylene glycol (PEG) moiety, and lacks the constant fragment (Fc) of immunoglobulin; therefore it does not activate complement. In this review in addition to clinical efficacy of CZP, effects on radiographic and patient-reported outcomes, are discussed. Adverse event data from clinical trials and extension studies are also reviewed. EXPERT OPINION: The addition of novel TNFi therapies to treat RA is welcomed. As well as displaying clinical efficacy, there is evidence to suggest that CZP has unique characteristics, including reduced transfer across the placenta and reduced frequency of injection site reactions. Furthermore, randomised controlled trials (RCTs) of CZP have demonstrated rapid improvements in workplace and home productivity in patients contributing to reducing the significant socioeconomic burden of RA.
22627098 Rituximab-induced hepatitis C virus reactivation in rheumatoid arthritis. 2013 Feb The B-cell depletion agent rituximab (RTX) is used in lymphoma and rheumatoid arthritis (RA), and there have been several case reports of an RTX-induced reactivation of hepatitis C virus in patients with lymphoma. However, there have been no papers detailing hepatitis C virus reactivation after RTX therapy in a patient with RA. Here we report a case of RTX-induced hepatitis C virus reactivation in a patient with RA. Physicians should be aware that a close follow-up of liver function and viral load is mandatory after RTX therapy in patients with RA and concomitant hepatitis C.
22288450 Chronotherapy with modified-release prednisone in patients with rheumatoid arthritis. 2012 Feb Glucocorticoids are indispensable for the treatment of systemic inflammatory diseases such as rheumatoid arthritis (RA), though their beneficial effects have to be balanced with potential complications arising from high doses, prolonged use or dose splitting. A glucocorticoid formulation (modified-release prednisone) has been developed to be taken in accordance with biological rhythms (chronotherapy). Morning symptoms of RA are caused by elevated nocturnal levels of proinflammatory cytokines, particularly IL-6. Endogenous cortisol levels may be insufficient to counter the inflammatory effects of IL-6. The early morning rise in cortisol can be supplemented with exogenous glucocorticoid replacement therapy if this is given as the recently developed chronotherapy formulation. There is no adverse impact of modified-release prednisone on the hypothalamic-pituitary-adrenal (HPA) axis; indeed, there might be evidence of a beneficial effect on HPA axis function. This review summarizes the development of modified-release prednisone, pharmacokinetic characteristics and clinical experience in patients with RA.
22367473 High-resolution ultrasound evaluation of extrinsic wrist ligaments in patients affected by 2012 Jul OBJECTIVES: To evaluate the ultrasound features of the extrinsic wrist ligaments in rheumatoid arthritis (RA) patients in comparison with healthy volunteers. METHODS: Twenty-one consecutive patients affected by RA (12 men, 9 women; mean age 57 ± 14.6 years) were compared with 21 controls (12, 9; 54 ± 12.1, respectively). Wrists were evaluated using ultrasound on both palmar and dorsal sides along each ligament, using carpal bones as references. The following ligaments were studied: radioscaphocapitate, radiolunotriquetral, palmar ulnolunate, palmar ulnotriquetral, dorsal radiotriquetral, dorsal ulnotriquetral, and radial collateral ligament. Ligament number and thickness were noted. Echotexture was rated as fibrillar, fragmented, or heterogeneous; the surface was rated as smooth or blurred. RESULTS: The number of palmar ulnolunate and palmar ulnotriquetral ligaments detected by ultrasound in patients was significantly lower than in controls (P = 0.031 and P = 0.037, respectively). All ligaments had significantly more fragmented or heterogeneous echotexture and blurred surface and were significantly thinner in patients than in controls (P < 0.001). No correlation was found between ligament thickness and RA duration or clinical parameters. CONCLUSIONS: Extrinsic wrist ligaments were less detectable and thinner in patients affected by RA compared with healthy volunteers matched for age and sex. Ligament thinning did not directly correlate with RA duration and clinical parameters. KEY POINTS: • Ultrasound is increasingly used to evaluate normal anatomy of extrinsic wrist ligaments. • Extrinsic wrist ligaments are thinner in rheumatoid arthritis patients than in controls. • Extrinsic wrist ligaments are less easy to detect in rheumatoid arthritis patients. • Ligament thinning and detectability are not related to clinical parameters.
22110122 The association of treatment response and joint damage with ACPA-status in recent-onset RA 2012 Feb OBJECTIVE: Anticitrullinated protein antibodies (ACPAs) are suggested to identify different subsets of patients with rheumatoid arthritis (RA). The authors compared the clinical and radiological responses to Disease Activity Score (DAS)-steered treatment in patients with RA positive or RA negative for ACPA. METHODS: In the BehandelStrategieën (BeSt) study, 508 patients with recent-onset RA were randomised to four treatment strategies aimed at a DAS ≤2.4. Risks of damage progression and (drug-free) remission in 8 years were compared for ACPA-positive and ACPA-negative patients using logistic regression analysis. Functional ability and DAS components over time were compared using linear mixed models. RESULTS: DAS reduction was achieved similarly in ACPA-positive and ACPA-negative patients in all treatment strategy groups, with a similar need to adjust treatment because of inadequate response. Functional ability and remission rates were not different for ACPA-positive and ACPA-negative patients. ACPA-positive patients had more radiological damage progression, especially after initial monotherapy. They had a lower chance of achieving (persistent) drug-free remission. CONCLUSION: Clinical response to treatment was similar in ACPA-positive and ACPA-negative patients. However, more ACPA-positive patients, especially those treated with initial monotherapy, had significant radiological damage progression, indicating that methotrexate monotherapy and DAS- (≤2.4) steered treatment might be insufficient to adequately suppress joint damage progression in these patients.
22539478 Physical activity and energy expenditure in rheumatoid arthritis patients and matched cont 2012 Aug OBJECTIVES: To compare daily energy expenditure between RA patients and matched controls, and to explore the relationship between daily energy expenditure or sedentariness and disease-related scores. METHODS: One hundred and ten patients with RA and 440 age- and sex-matched controls were included in this study. Energy expenditure was assessed using the validated physical activity (PA) frequency questionnaire. Disease-related scores included disease activity (DAS-28), functional status (HAQ), pain visual analogue scale (VAS) and fatigue VAS. Total energy expenditure (TEE) and the amount of energy spent in low- (TEE-low), moderate- (TEE-mod) and high-intensity (TEE-high) PAs were calculated. Sedentariness was defined as expending <10% of TEE in TEE-mod or TEE-high activities. Between-group comparisons were computed using conditional logistic regression. The effect of disease-related scores on TEE was investigated using linear regression. RESULTS: TEE was significantly lower for RA patients compared with controls [2392 kcal/day (95% CI 2295, 2490) and 2494  kcal/day (2446, 2543), respectively, P = 0.003]. A significant difference was found between groups in TEE-mod (P = 0.015), but not TEE-low (P = 0.242) and TEE-high (P = 0.146). All disease-related scores were significantly poorer in sedentary compared with active patients. TEE was inversely associated with age (P < 0.001), DAS-28 (P = 0.032) and fatigue VAS (P = 0.029), but not with HAQ and pain VAS. CONCLUSION: Daily energy expenditure is significantly lower in RA patients compared with matched controls, mainly due to less moderate-intensity PAs performed. Disease activity and fatigue are important contributing factors. These points need to be addressed if promoting PA in RA patients is a health goal. Trial registration. ClinicalTrials.gov, http://clinicaltrials.gov, NCT01228812.
22313326 Economic evaluation of tocilizumab combination in the treatment of moderate-to-severe rheu 2012 OBJECTIVE: This study was designed to evaluate the cost utility of tocilizumab in rheumatoid arthritis (RA) patients, with inadequate responses to traditional disease-modifying anti-rheumatic drugs (tDMARDs) from a payer's perspective in Italy. METHODS: An individual patient simulation model was used to project lifetime medical costs (payer's perspective) and quality-adjusted life-years (QALYs). Treatment sequences starting with tocilizumab or the most commonly prescribed biologics (etanercept, adalimumab, or infliximab) were compared. The addition of tocilizumab to standard of care, without the replacement of anti-tumor necrosis factor (TNF)-α treatments, was also evaluated. Patient characteristics, treatment efficacy, and quality-of-life data were based on three phase 3 tocilizumab clinical trials (TOcilizumab Pivotal Trial in Methotrexate Inadequate respONders [OPTION], Tocilizumab in cOmbination With traditional DMARD therapy [TOWARD], and TociLIzumab Safety and THE Prevention of Structural Joint Damage [LITHE]). Mixed-treatment comparison was used to estimate response probabilities. Resource utilization, treatment acquisition, administration, and monitoring costs were estimated using Italian secondary sources. Uncertainty in model parameters was evaluated by probabilistic sensitivity analysis. RESULTS: Replacement of anti-TNF-α treatments with tocilizumab reduced total costs over a patient's lifetime (base-case analysis: tocilizumab sequence, €141,100 vs standard of care sequence, €143,500). Patients receiving tocilizumab realized more QALYs than patients receiving standard of care (9.8881 vs 9.3502 QALYs). Therefore, according to the base-case analysis, the tocilizumab sequence dominated the standard of care. In a sensitivity analysis, the model base-case result was robust to input changes. When tocilizumab was added to standard of care, without replacing anti-TNF-α treatments, the incremental cost-effectiveness ratio was €17,100 per QALY. CONCLUSION: The analysis demonstrates that, in Italy, replacing another biologic DMARD with tocilizumab or adding tocilizumab to the current standard of care is a cost-effective strategy in the treatment of RA patients with inadequate responses to tDMARDs.
21439777 The prevalence of dysphonia, its association with immunomediated diseases and correlation 2012 Mar INTRODUCTION: Patients with autoimmune diseases may suffer from hoarseness and voice disorders because of anatomical and functional alterations. OBJECTIVES: To assess the prevalence of dysphonia in rheumatic patients and its impact on their quality of life (QOL). To analyze the association of voice disorders in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren syndrome (SS). To determine if voice disorders during the acute phase of these diseases are correlated with specific biochemical parameters. METHODS: Present an observational and transverse analytic study of 140 patients selected from February 2009 to January 2010. The subjects (80) were diagnosed with RA (44), SLE (32), and SS (4), and the control group (60) presented no voice disorders or rheumatic diseases. Patients were evaluated using the Voice Handicap Index (VHI) and a three items outcome scale (TIOS). A biochemical and C-reactive protein study was performed on 40 patients with a disease outbreak, measuring their complement, sedimentation velocity (VSG), and anti-DNA antibodies. RESULTS: The prevalence of dysphonia among the subjects was 32-38% as opposed to 5-8% in the control group. The rheumatic patients presented an odds ratio (OR) for dysphonia of 2.82 (VHI) and 5.04 (TIOS) when compared with healthy individuals (P<0.05). We found statistically significant differences in functional, physical, occupational, and emotional subscales of these tests. No significant differences were found when studying the biochemical parameters. A higher incidence of voice disorders (OR=3.07) was associated with SLE, followed by RA (OR=2.8; 95% CI). CONCLUSIONS: Systemic immunomediated diseases may associate voice disorders. Patients with SLE are those who develop these disorders more frequently. The biochemical parameters most affected during a crisis are VSG and anti-DNA antibodies.
22920235 Serum soluble receptor for advanced glycation end products levels and aortic augmentation 2013 Feb OBJECTIVE: We assessed whether a serum soluble receptor for advanced glycation end product (sRAGE) levels were associated with a progression of carotid atherosclerosis and arterial stiffness indexes in a cohort of early rheumatoid arthritis (RA) patients. METHODS: RA patients with symptoms onset <2 years were recruited. Vascular assessments and serum sRAGE levels were measured at baseline and 1 year later. Arterial stiffness was determined by pulse wave velocity and aortic augmentation index (AIx). Carotid intima-media thickness was measured using high-resolution ultrasound. RESULTS: Ninety-four patients completed the 1-year study. Fifty-three (56.4%) achieved disease remission [28-joint disease activity score (DAS28 < 2.6)] at 12 months. Improvement in arterial stiffness was observed as reflected by the significant reductions in AIx and pulse wave velocity. At 12 months, the sRAGE levels increased significantly compared with baseline (939.8 ± 517.7 pg/ml to 1272.1 ± 567.3 pg/ml, P < 0.001). Changes in sRAGE levels were significantly higher in men compared to women (768 ± 510 pg/ml versus 271 ± 490 pg/ml, P < 0.05) and was negatively associated with the change in AIx (r = -0.259, P = 0.023). Changes in sRAGE level were not associated with other demographic, clinical, cardiovascular risk factors or treatment. Using multivariate analysis, the change in sRAGE levels and baseline high-density lipoprotein were independent predictors associated with the change in AIx. CONCLUSIONS: Arterial stiffness improved significantly in patients with early RA after effective control of inflammation. Increase in sRAGE level was associated with a decrease in AIx, suggesting that sRAGE may play an important role in the ligand-soluble receptor for advanced glycation end product interaction propagated inflammation and vascular stiffness in these patients.
22616846 Limited effect of anti-rheumatic treatment on 15-prostaglandin dehydrogenase in rheumatoid 2012 May 22 INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which prostaglandin E2 (PGE2) displays an important pathogenic role. The enzymes involved in its synthesis are highly expressed in the inflamed synovium, while little is known about 15- prostaglandin dehydrogenase (15-PGDH) that metabolizes PGE2. Here we aimed to evaluate the localization of 15-PGDH in the synovial tissue of healthy individuals or patients with inflammatory arthritis and determine the influence of common RA therapy on its expression. METHODS: Synovial tissue specimens from healthy individuals, psoriatic arthritis, ostheoarthritis and RA patients were immunohistochemically stained to describe the expression pattern of 15-PGDH. In addition, the degree of enzyme staining was evaluated by computer analysis on stained synovial biopsies from two groups of RA patients, before and after RA specific treatment with either intra-articular glucocorticoids or oral methotrexate therapy. Prostaglandins derived from the cyclooxygenase (COX) pathway were determined by liquid-chromatography mass spectrometry in supernatants from interleukin (IL) 1β-activated fibroblast-like synoviocytes (FLS) treated with methotrexate. RESULTS: 15-PGDH was present in healthy and inflamed synovial tissue, mainly in lining macrophages, fibroblasts and vessels. Intra-articular glucocorticoids showed a trend towards reduced 15-PGDH expression in RA synovium (p = 0.08) while methotrexate treatment left the PGE2 pathway unaltered both in biopsies ex vivo and in cultured FLS. CONCLUSIONS: Early methotrexate therapy has little influence on the expression of 15-PGDH and on any of the PGE2 synthesizing enzymes or COX-derived metabolites. Thus therapeutic strategies involving blocking induced PGE2 synthesis may find a rationale in additionally reducing local inflammatory mediators.
23277489 Regulation of DNA methylation in rheumatoid arthritis synoviocytes. 2013 Feb 1 Rheumatoid arthritis (RA) is a chronic inflammatory disease in which fibroblast-like synoviocytes (FLS) exhibit an aggressive phenotype. Although the mechanisms responsible are not well defined, epigenetic determinants such as DNA methylation might contribute. DNA methyltransferases (DNMTs) are critical enzymes that establish and maintain DNA methylation. We evaluated whether proinflammatory cytokines might contribute to differential DNA methylation previously described in RA FLS through altered DNMT expression. FLS were obtained from RA and osteoarthritis (OA) synovium at the time of total joint replacement. Gene expression was determined by quantitative real-time PCR and protein expression by Western blot analysis. DNMT activity was measured with a functional assay, and global methylation was determined by an immunoassay that detects methylcytosine. Resting expression of DNMT1, -3a, and -3b mRNA were similar in RA and OA FLS. Western blot showed abundant DNMT1 and DNMT3a protein. Exposure to IL-1 decreased DNMT1 and DNMT3a mRNA expression in FLS. Dose responses demonstrated decreased DNMT expression at concentrations as low as 1 pg/ml of IL-1. DNMT mRNA levels decreased rapidly, with significant suppression after 2-8 h of IL-1 stimulation. IL-1 stimulation of OA FLS did not affect methylation of LINE1 sites but led to demethylation of a CHI3L1 locus that is hypomethylated in RA FLS. Chronic IL-1 stimulation also mimicked the effect of a DNMT inhibitor on FLS gene expression. Exposure to proinflammatory mediators reversibly alters DNA methylation in FLS by decreasing DNMT expression and function. These data suggest that IL-1 can potentially imprint cells in chronic inflammatory diseases.
22104130 Genetic polymorphisms in metabolic and cellular transport pathway of methotrexate impact c 2012 The aim of this study was to investigate the impact of genetic polymorphisms in the metabolic and cellular transport pathway of methotrexate (MTX) on the clinical outcome of MTX monotherapy in Japanese rheumatoid arthritis (RA) patients. Fifty-five patients were treated with MTX monotherapy at a dose of 4-10 mg/week. The total concentration of MTX-polyglutamates (MTX-PGs) was measured at steady-state in red blood cells (RBCs) by high performance liquid chromatography. The genotype at 16 polymorphic sites in 11 genes (ABCB1, ABCG2, ABCC2, RFC1, PCFT, SLCO1B1, MTHFR, GGH, ATIC, MTR, and MTRR) was analyzed. No significant association between the total concentration of MTX-PGs in RBCs and clinical outcome was found. However, patients with the ABCB1 3435TT genotype had a significantly lower mean disease activity score (DAS) 28 than did patients with the ABCB1 3435CC genotype (p = 0.02). Similarly, patients with the ABCB1 2677AA/AT/TT genotypes had a significantly lower mean DAS28 than did patients with the ABCB1 2677GG/GA/GT genotypes (p = 0.04). The patients with the MTHFR 1298AA genotype had a significantly lower mean DAS28 than those with the MTHFR 1298AC/CC genotypes (p = 0.04). In conclusion, the ABCB1 3435C>T, ABCB1 2677G>A/T, and MTHFR 1298A>C polymorphisms influenced the efficacy of MTX monotherapy.
22013740 Spirulina platensis protects neurons via suppression of glial activation and peripheral se 2011 Oct Spirulina platensis treatment (400 mg kg(-1) for 25 days) effectively suppressed peripheral sensitization via modulation of glial activation and improved motor coordination and restoration of functional motor activity in collagen-induced arthritic rats. Spirulina treatment also resulted in an appreciable reduction of the NF200 accumulation in the spinal cord neurons of arthritic rats. This is indicative of neuroprotective action of S. platensis against glutamate excitotoxicity-induced central sensitization produced by the peripheral joint inflammation in the collagen-induced arthritis. The results suggest that effects of S. platensis may be due to its counter regulation of spinal glial activation and could be a potential strategy for the treatment of arthritis.
20422193 The investigation of toll-like receptor 3, 9 and 10 gene polymorphisms in Turkish rheumato 2011 Oct Toll-like receptors (TLRs) play an important role in the induction and regulation of the innate immune system or adaptive immune responses. Genetic variations within human TLRs have been reported to be associated with a range of immune-related diseases. This study was conducted to investigate the frequencies of TLR3 rs3775290, TLR9 rs187084, and TLR10 rs4129009 polymorphisms and to detect between polymorphisms and autoantibody positive as RF, collagen type II, anti-RNP, and anti-CCP in patient group. We performed a case-control study of 100 rheumatoid arthritis (RA) cases and 100 healthy controls matched on age, sex, and residence. All polymorphisms in TLRs were determined by polymerase chain reaction-based restriction fragment length polymorphism. Serum autoantibody level was measured using quantitative ELISA. SNPs were genotyped in all samples. Our results showed that TT genotype for SNP 1237 T/C increased the RA risk significantly (p < 0.05). No statistically significant differences were found in the TLR3 and TLR10 genotypes or allele distribution between RA patients and control individuals. No associations were noted with autoantibody production and TLR3, TLR9, and TLR10 polymorphisms genotypes (p > 0.05). Our study suggests that a single nucleotide polymorphism (rs187084) in TLR9 gene may be a susceptibility factor for RA in Turkish population. Further studies are required to explore the role of TLRs gene polymorphisms in the risk of RA, especially in ethnically different populations to confirm our results.
23224330 Risk of alanine transferase (ALT) elevation in patients with rheumatoid arthritis treated 2013 May OBJECTIVE: To determine incidence of increased levels of alanine transferase (ALT) >2× upper limit of normal (ULN) in patients receiving methotrexate (MTX), treated according to a dynamic strategy, and to identify predictors of ALT of >2× ULN. METHODS: Data of 508 recent-onset rheumatoid arthritis (RA) patients from the BeSt study, randomized to initial monotherapy or combination therapy, were used. Treatment was dynamic, aiming at a disease activity score = ≤ 2.4. ALT was measured every three months. With logistic regression analyses, baseline variables predictive of first ALT of >2× ULN were identified and the association between use of concomitant antirheumatic drugs, the actual and cumulative dose of MTX and ALT of >2× ULN was determined. RESULTS: In total, 498 patients ever initiated MTX, with a total duration on MTX of 1,416 patient-years. In 89 patients, a first incidence of ALT of >2× ULN occurred. Incidence rate was 6.3 per 100 patient-years and cumulative incidence 18 %. ACPA positivity and baseline ALT of >1× ULN were independent predictors of later ALT of >2× ULN (OR 1.8 (95 % CI, 1.1-3.1) and OR 3.1 (95 % CI, 1.6-6.2), respectively). Smoking showed a trend (OR 1.6 (95 % CI, 0.98-2.7)). Mean MTX dosage over time was higher in patients with an ALT of >2× ULN. Patients who did not have an ALT of >2× ULN used more concomitant disease-modifying antirheumatic drugs and longer. CONCLUSIONS: In RA patients treated with MTX according to a dynamic strategy resembling daily clinical practice, incidence of increased ALT of >2× ULN was lower than previously reported, and also without treatment adjustments, persistence was rare. The recommendations for ALT monitoring may be reevaluated.