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ID PMID Title PublicationDate abstract
26515960 Motivational interviewing: relevance in the treatment of rheumatoid arthritis? 2016 Aug Advances in pharmacological treatment options in RA have led to a dramatic potential for improvement in patients' physical and psychological status. Despite advances, poor outcomes, including fatigue, pain, reduced physical activity and quality of life, are still observed. Reasons include non-adherence to medication, insufficient knowledge about the disease and lack of support in coping and effectively self-managing their condition. Motivational interviewing (MI) is a person-centred approach that relies on collaboration and empathy aiming to elicit a person's own motivation for behaviour change. It has been implemented in a variety of long-term conditions, addressing issues such as lifestyle changes with beneficial effects, but it is yet to be widely recognized and adopted in the field of rheumatology. This review will explain the techniques underpinning MI and the rationale for adopting this approach in rheumatology with the aim to increase medication adherence and physical activity and improve patients' coping strategies for pain and fatigue.
26444559 Substance P and Chronic Pain in Patients with Chronic Inflammation of Connective Tissue. 2015 OBJECTIVE: Evidence suggests that substance P (SP) is involved in chronic joint inflammation, such as the pathogenesis of rheumatoid arthritis and osteoarthritis. The goal of the research was to evaluate the correlation between chronic pain and changes in the SP level in patients with chronic inflammation of the connective tissue. METHODS: Patients with osteoarthritis and rheumatoid arthritis were enrolled in this study. The relationship between chronic pain intensity and the serum SP concentration was evaluated in these groups of patients with osteoarthritis and rheumatoid arthritis. RESULTS: The results showed a positive correlation between the serum SP concentrations and chronic pain intensity. CONCLUSIONS: 1. The SP serum concentration was significantly different between the groups of patients with OA and RA. 2. There was a positive correlation between the serum SP concentration and chronic pain intensity in OA and RA patients.
26080569 [Study on biomarker of Tripterygium wilfordii in treatment of rheumatoid arthritis based o 2015 Jan To observe the serum samples and the anti-inflammatory effect of Tripterygium wilfordii in treating RA by using the pharmacokinetic-pharmacodynamic model, make a correlation analysis on concentration-time and effect-time curves, and explore RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in rats by PCR. Methotrexate, tripterine and high-dose T. wilfordii could down-regulate RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in AA rat lymph nodes. The study on PK-PD model showed correlations between inflammatory factors and blood concentration of T. wilfordii. T. wilfordii and its main active constituent tripterine could show the inflammatory effect and treat RA by inhibiting IL-17 cytokine.
25798875 IL-33 and soluble ST2 levels as novel predictors for remission and progression of carotid 2015 Aug OBJECTIVES: To study the association between the baseline IL-33 and soluble ST2 (sST2) levels with disease remission and progression of carotid atherosclerosis in early rheumatoid arthritis (ERA) patients. METHODS: A total of 98 ERA patients were enrolled. Disease activity and the presence of carotid plaque were evaluated at baseline and 12 months later. Plasma IL-33 and sST2 levels were determined using enzyme-linked immunosorbent assay kits. RESULTS: Baseline IL-33 and sST2 levels were associated with inflammatory markers and cardiovascular (CV) risk factors. Overall, 44(45%), 18(18%), and 21(21%) patients achieved remission based on 28-joint disease activity score (DAS28), Boolean, and simplified disease activity score (SDAI) criteria at 12 months, respectively. Patients with detectable IL-33 at baseline were less likely to achieve DAS28 (P = 0.010) and SDAI remission (P = 0.021), while a lower baseline sST2 level was able to predict DAS28, Boolean, and SDAI remission (P = 0.005, 0.001, and <0.001, respectively). Using multivariate analysis, a lower baseline sST2 level independently predict Boolean (OR = 0.789; P = 0.005) and SDAI remission (0.812; P = 0.008). Regarding carotid atherosclerosis, 9/98(9.2%) patients had plaque progression at 12 months. Baseline IL-33 was detectable in 8/9(89%) and 42/83(51%) of patients with and without plaque progression respectively (P = 0.029). Baseline detectable IL-33 was an independent predictor for plaque progression after adjusting for traditional CV risk factors (P = 0.017). CONCLUSIONS: Lower baseline sST2 levels independently predict disease remission and baseline detectable IL-33 independently predicts carotid plaque progression in ERA patients. This study suggests that inflammation induced by the IL-33/ST2 axis may play a significant role in the development of cardiovascular disease in RA.
27344969 Reactive oxygen and nitrogen species in patients with rheumatoid arthritis as potential bi 2016 Aug Reactive oxygen species (ROS) and reactive nitrogen species (RNS) have distinct contribution to the destructive, proliferative synovitis of rheumatoid arthritis (RA) and play a prominent role in cell-signaling events. However, few studies had clarified the role of individual ROS and RNS in the etiopathogenesis of RA. To date, most of the studies were concerned with the measurement of the total oxidative and nitrative stress levels in RA. The aim of this study was to monitor the levels of individual ROS and RNS to emphasize the role that each plays in the pathogenesis of RA and their usefulness as possible biomarkers for the disease activity. In addition, the effect of an antioxidant (ascorbic acid), added to the treatment regimen, on the levels of ROS, RNS and disease activity has been evaluated. Forty-two Saudi RA patients and 40 healthy controls of both genders were included in this study. Serum levels of six different ROS and three different RNS were measured using specific fluorescent probes. The ROS included the hydroxyl radical ((•)OH), the superoxide anion (O2(•-)), hydrogen peroxide (H2O2), the singlet oxygen ((1)O2), the hypochlorite radical (OHCl(•)), and the peroxyl radical (ROO(•)). The RNS included nitric oxide (NO(•)), nitrogen dioxide (ONO-) and peroxynitrite (ONOO-). The main clinical and biochemical markers for disease activity were assessed and correlated with ROS and RNS levels. The clinical markers included the 28 swollen joint count (SJC-28), the 28-tender joint count (TJC-28), morning stiffness and symmetric arthritis, in addition to the disease activity score assessing 28 joints with erythrocyte sedimentation rate (DAS28-ESR). The biochemical markers included undercarboxylated osteocalcin (ucOC), matrix metalloproteinase (MMP-3), ESR, C-reactive protein (CRP), rheumatoid factor (RF) and anticyclic citrullinated polypeptide (Anti-CCP). Ascorbic acid (1mg/day) was added as an antioxidant to the regular treatment regimen of RA patients for two months, and the levels of ROS and RNS, as well as disease activity were re-evaluated. The results have shown significant higher serum levels of individual ROS and RNS in RA patients compared with healthy subjects. Moreover, this study might be the first to report strong positive correlations between most of the reactive species and the clinical and biochemical markers of RA. Interestingly, the addition of ascorbic acid had significantly reduced the levels of all ROS and RNS in RA patients. In conclusion, the role of oxidative and nitrative stress in the pathogenesis of RA has been confirmed by this study. Serum levels of ROS and RNS may effectively serve as biomarkers for monitoring disease progression. Finally, the addition of an antioxidant, such as ascorbic acid, in the management of RA may be of a great value.
26316013 A Randomized Trial Comparing Disease Activity Measures for the Assessment and Prediction o 2015 Dec OBJECTIVE: The aim of the Patient/Physician Reported Efficacy Determination In Clinical Practice Trial (PREDICT; ClinicalTrials identifier NCT01255761) was to compare the patient-reported Routine Assessment of Patient Index Data 3 (RAPID-3) instrument with the investigator-based Clinical Disease Activity Index (CDAI) for assessing certolizumab pegol (CZP) treatment response in rheumatoid arthritis patients at 12 weeks and to predict the treatment response at week 52 using the data from week 12 (coprimary end points). METHODS: Patients received 400 mg of CZP at weeks 0, 2, and 4 (loading dose), followed by 200 mg every 2 weeks thereafter. Patients were randomized 1:1 to assessment with the RAPID-3 or the CDAI. Responder classification was performed at week 12; treatment response was defined as a score of ≤6 or a 20% improvement over baseline on the RAPID-3 or a score of ≤10 or a 20% improvement over baseline on the CDAI. Long-term treatment success was defined as a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) of ≤3.2 at week 52. Comparisons were made for the coprimary end points using noninferiority methods. Patients with improvement of <1 on the CDAI score or with no improvement on the RAPID-3 score at week 12 or patients with high levels of disease activity (CDAI score >22 or RAPID-3 score >12) at 2 consecutive visits were withdrawn from the study. RESULTS: Patients had longstanding disease (mean 8.9 years) and high levels of disease activity (mean scores of 6.3 on the DAS28-ESR, 16.1 on the RAPID-3, and 40.2 on the CDAI). Previous anti-tumor necrosis factor therapy had failed in 55.5% of them. At week 12, a total of 64.7% (by RAPID-3) and 76.4% (by CDAI) of the patients were classified as responders (difference of -11.9% [95% confidence interval -18.4%, -5.3%]). At week 52, a total of 31.5% (by RAPID-3) and 32.3% (by CDAI) of the responders achieved a low level of disease activity on the DAS28-ESR (difference of -1.3% [95% confidence interval -9.3%, 6.6%]). CONCLUSION: The CDAI classified more patients as CZP responders at week 12 than did the RAPID-3. Although these outcome measures were not statistically comparable, the positive predictive value for low disease activity at week 52 was similar. As these tools cover differing domains of therapy response, further evaluation for clinical disease activity assessments and treatment decisions is needed.
26609737 Sex differences in trauma symptoms, body image and intensity of pain in a Polish sample of 2016 Oct The main goal of the current study was to investigate sex differences in the relationship between the level of trauma symptoms appearing in posttraumatic stress disorder (PTSD) and intensity of pain in a sample of 300 Polish patients suffering from chronic pain, specifically rheumatoid arthritis and lower back pain. We also focused on participants' body image with body esteem as a mediator. To assess the intensity of pain among participants, we used the Numerical Rating Scale. The level of trauma symptoms was assessed with the PTSD Factorial Version Inventory. To measure body image among participants, we used the Body Esteem Scale. The results of our study suggest that trauma symptoms and body image dimensions were significant predictors of pain intensity among men suffering from chronic pain. Moreover, trauma symptoms and age were significant predictors of pain intensity among women suffering from chronic pain. Finally, we demonstrated that sex differentiates the reaction to chronic pain.
25997035 In antisynthetase syndrome, ACPA are associated with severe and erosive arthritis: an over 2015 May Anticitrullinated peptide/protein antibodies (ACPA), which are highly specific for rheumatoid arthritis (RA), may be found in some patients with other systemic autoimmune diseases. The clinical significance of ACPA in patients with antisynthetase syndrome (ASS), a systemic disease characterized by the association of myositis, interstitial lung disease, polyarthralgia, and/or polyarthritis, has not yet been evaluated with regard to phenotype, prognosis, and response to treatment. ACPA-positive ASS patients were first identified among a French multicenter registry of patients with ASS. Additionally, all French rheumatology and internal medicine practitioners registered on the Club Rhumatismes et Inflammation web site were asked to report their observations of ASS patients with ACPA. The 17 collected patients were retrospectively studied using a standardized questionnaire and compared with 34 unselected ACPA-negative ASS patients in a case-control study. All ACPA-positive ASS patients suffered from arthritis versus 41% in the control group (P < 0.0001). The number of swollen joints was significantly higher (7.0 ± 5.0 vs 2.9 ± 3.9, P < 0.005), with a distribution resembling that of RA. Radiographic damages were also more frequent in ACPA-positive ASS patients (87% vs 11%, P < 0.0001). Aside from a significantly higher transfer factor for carbon monoxide in ACPA-ASS patients, lung, muscle, and skin involvements had similar incidences, patterns, and severity in both groups. Although Nonbiologic treatments were similarly used in both groups, ACPA-positive patients received biologics more frequently (59% vs 12%, P < 0.0008), mostly due to refractory arthritis (n = 9). Eight patients received anti-Cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) with good efficacy and tolerance, whereas 2 of the 5 patients treated with antitumor necrosis factor drugs had worsened myositis and/or interstitial lung disease. After a >7-year mean follow-up, extra-articular outcomes and survival were not different. ACPA-positive ASS patients showed an overlapping RA-ASS syndrome, were at high risk of refractory erosive arthritis, and might experience ASS flare when treated with antitumor necrosis factor drugs. In contrast, other biologics such as anti-CD20 mAb were effective in this context, without worsening systemic involvements.
25683200 Specific overexpression of tumour necrosis factor-α-induced protein (TNFAIP)9 in CD14(+) 2015 Jun The tumour necrosis factor (TNF)-α-induced proteins (TNFAIP)9 and TNFAIP3 play an important pathogenic role in murine arthritis. To clarify their pathophysiological roles in patients with rheumatoid arthritis (RA), we examined their expression and localization in peripheral blood mononuclear cells (PBMC). TNFAIP9 and TNFAIP3 mRNA expression was determined in PBMC of RA patients and healthy subjects (control). Flow cytometry was used to analyse the main TNFAIP9- and TNFAIP3-expressing cell populations. TNFAIP9 and TNFAIP3 mRNA expression levels were examined in vitro on CD14(+) cells stimulated with TNF-α and lipopolysaccharide (LPS). The expression levels of TNFAIP9 and TNFAIP3 mRNA were also measured before and 12 weeks after treatment with tocilizumab and abatacept. TNFAIP9 expression was significantly higher, while TNFAIP3 expression was lower in PBMC of RA (n=36) than the control (n=24) (each P < 0.05). TNFAIP9 was expressed on CD14(+) cells, especially in human leucocyte antigen D-related (HLA-DR)(+) CD14(bright) CD16(-) cells, while TNFAIP3 was expressed mainly on CD3(+) T cells. TNF-α and LPS induced TNFAIP9 and TNFAIP3 in human CD14(+) monocytes in vitro. Treatment with tocilizumab (n=13), but not abatacept (n=11), significantly reduced TNFAIP9 mRNA expression in PBMC, which was associated with reduction in the number of circulating CD14(bright) monocytes. The expression of TNFAIP9 in CD14(+) cells was specifically elevated in patients with RA, regulated by TNF-α and LPS, and suppressed by tocilizumab, while TNFAIP3 in PBMC showed different localization and induction patterns.
27062502 BRONJ in patients with rheumatoid arthritis: a multicenter case series. 2016 Sep OBJECTIVE: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of various medications (bisphosphonates, anti-resorptive, and anti-angiogenic drugs). ONJ pathogenesis is still unclear although some risk factors have been recognized. Of these, rheumatoid arthritis (RA) has been hypothesized as a potential risk factor for developing ONJ. This observational study will describe a multicenter case series of patients affected with RA and ONJ, and it will attempt to evaluate the association between features of ONJ and pharmacological, systemic, and site variables. METHODS: Demographic, pharmacological, and clinical data from 18 RA patients with ONJ were collected and registered from three Italian centers (i.e., Palermo, Verona, and Padua) from 2004 to 2013. RESULTS: Sixteen (88.9%) patients were in therapy for RA: 9 of 18 (50.0%) with systemic steroids, 3 of 18 (16.7%) with methotrexate, and 4 of 18 (22.2%) with both medications. Two patients were not receiving treatment for RA. All patients took NBPs for secondary osteoporosis (average NBP duration of 69 months, range: 20-130): Fifteen (83.3%) patients were treated with single NBPs, while three (16.7%) with different molecules; one patient was also treated with denosumab. Mandible was affected more frequently (66.7%) than maxilla (33.3%); one patient presented multiple ONJ events. CONCLUSIONS: This is the first multicenter case series in the international literature regarding our topic. Focusing on our data, it could be hypothesized that patients with RA may be more susceptible to ONJ than the majority of osteometabolic patients. In our opinion, it could be important to monitor also denosumab or other biological drug side effects.
28010120 Interleukin-6-174G > C (rs1800795) polymorphism distribution and its association with 2017 May The association of interleukin-6 (IL-6)-174G > C (rs1800795) single nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) is a relevant issue because of conflicting and consensus lacking reports published in literature. We investigated IL-6-174G > C promoter polymorphism in 34 RA patients, attending a tertiary care hospital in north India. We also performed a meta-analysis, of the previously published studies reporting this genetic relationship, in overall population, and independently in Asian and Caucasian ethnicities to further elucidate this association. A total of 13 studies, including the current one, involving 3291 RA cases and 3812 controls were analyzed. Out of the 13 studies, 6 were from Asian, 6 from Caucasian and 1 from a mixed population. Our case-control study showed significant association of IL-6-174G > C SNP with increased RA risk: allelic (OR = 3.750, 95% CI = 1.800-7.813, p < 0.001); dominant (OR = 2.800, 95% CI = 1.167-6.721, p = 0.021); and recessive (OR = 36.72, 95% CI = 2.004-672.7, p = 0.015). The meta-analysis revealed the increased RA risk associated with IL-6-174G > C SNP in overall population: allelic (OR = 1.650, 95% CI = 1.169-2.329, p = 0.004); homozygous (OR = 1.380, 95% CI = 0.906-2.101, p = 0.133); heterozygous (OR = 1.559, 95% CI = 1.001-2.428, p = 0.049); dominant (OR = 1.663, 95% CI = 1.078-2.567, p = 0.022); and recessive (OR = 1.366, 95% CI = 0.964-1.935, p = 0.079). Subgroup analysis also showed this polymorphism to be associated with increased RA risk in Asian population: allelic (OR = 3.724, 95% CI = 1.361-10.190, p = 0.010); dominant (OR = 3.823, 95% CI = 1.320-11.074, p = 0.013); and recessive (OR = 4.357, 95% CI = 1.634-11.623, p = 0.003), but not in Caucasian population. This meta-analysis shows that IL-6-174G > C SNP is significantly associated with increased RA risk in overall, and specifically in Asian population.
25505001 Drug adherence, response and predictors thereof for tocilizumab in patients with rheumatoi 2015 Jul OBJECTIVE: To evaluate drug adherence, clinical response and predictors thereof for tocilizumab in patients with RA in routine care based on prospectively collected data from the Swedish biologics register, Anti-Rheumatic Therapies in Sweden. METHODS: RA patients who had started with tocilizumab from September 2008 until March 2012 were identified. Cox regression and logistic regression models were used. RESULTS: A total of 530 RA patients were included, of whom 80.6% were female, 64.7% were on concomitant DMARDs, of which 300 were on MTX and 12% were biologic naive. The overall 6 month, 1 and 2 year estimated drug continuations were 79%, 64% and 50%, respectively. In the multivariate analyses, a low initial level of CRP [hazard ratio (HR) 0.76/1 S.D. (95% CI 0.63, 0.91)], high HAQ score [HR 1.23/1 S.D. (95% CI 1.06, 1.44)] and prior exposure to different biologics [HR 1.43 (95% CI 1.12, 1.83)] were predictors for drug termination, whereas concomitant DMARD therapy was not. European League Against Rheumatism (EULAR) good, moderate, and no response were achieved by 184 (46.7%), 133 (33.8%) and 77 (19.5%) patients, respectively. Predictors for EULAR good response vs no response (at 2.5-8 months) were low HAQ [odds ratio (OR) 0.56/1 S.D. (95% CI 0.40, 0.78)], high 28-joint DAS [OR 2.0/1 S.D. (95% CI 1.44, 2.78)] and not being on prednisolone [OR 0.47 (95% CI 0.25, 0.88)] at baseline. CONCLUSION: In this RA cohort treated with tocilizumab, the estimated 1 year drug continuation was 64% and 80% of the patients achieved a EULAR response. Drug discontinuation was not predicted by no concomitant DMARD, but by low CRP, high HAQ and prior exposure to biologics.
25593243 Variation in rheumatoid hand and wrist surgery among medicare beneficiaries: a population- 2015 Mar OBJECTIVE: To examine the rate and variation in rheumatoid arthritis (RA)-related hand and wrist surgery among Medicare (elderly) beneficiaries in the United States, and to identify the patient and provider factors that influence surgical rates. METHODS: Using the 2006-2010 100% Medicare claims data of beneficiaries with RA diagnosis, we examined rates of rheumatoid hand and wrist arthroplasty, arthrodesis, and hand tendon reconstruction in the United States. We used multivariate logistic regression models to examine variation in receipt of surgery by patient and regional characteristics (density of providers, intensity of use of biologic disease-modifying antirheumatic drugs). RESULTS: Between 2006 and 2010, the annual rate of RA-related hand and wrist arthroplasty or arthrodesis was 23.1 per 10,000 patients, and the annual rate of hand tendon reconstruction was 4.2 per 10,000 patients. The rates of surgery varied 9-fold across hospital referral regions in the United States. Younger patient age, female sex, white race, higher socioeconomic status (SES), and rural residence were associated with a higher likelihood of undergoing arthroplasty and arthrodesis. We observed a significant decline in rate of arthroplasty and arthrodesis with increasing density of rheumatologists. Tendon reconstruction was not influenced by provider factors, but was correlated with age, race, SES, and rural status of the patients. CONCLUSION: Surgical reconstruction of rheumatoid hand deformities varies widely across the United States, driven by both regional availability of subspecialty care in rheumatology and individual patient factors.
26443608 Anticarbamylated protein antibodies are associated with long-term disability and increased 2016 Jun OBJECTIVES: Anticarbamylated protein (anti-CarP) antibodies are a novel family of autoantibodies recently identified in patients with inflammatory arthritis. The aim of this study was to investigate their association with long-term outcomes of disability and disease activity over 20 years' follow-up in a cohort of patients with inflammatory polyarthritis (IP). METHODS: Norfolk Arthritis Register recruited adults with recent-onset swelling of ≥2 joints for ≥4 weeks from 1990 to 2009. At baseline, Health Assessment Questionnaire (HAQ) and 28 joint disease activity scores (DAS28) were obtained, and C reactive protein, rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA) and anti-CarP antibodies were measured. Further HAQ scores and DAS28 were obtained at regular intervals over 20 years. Generalised estimating equations were used to test the association between anti-CarP antibody status and longitudinal HAQ and DAS28 scores; adjusting for age, gender, smoking status, year of inclusion and ACPA status. Analyses were repeated in subgroups stratified by ACPA status. The relative association of RF, ACPA and anti-CarP antibodies with HAQ and DAS28 scores was investigated using a random effects model. RESULTS: 1995 patients were included; 1310 (66%) were female. Anti-CarP antibodies were significantly associated with more disability and higher disease activity, HAQ multivariate β-coefficient (95% CI) 0.12 (0.02 to 0.21), and these associations remained significant in the ACPA-negative subgroups. The associations of RF, ACPA and anti-CarP antibodies were found to be additive in the random effects model. CONCLUSIONS: Anti-CarP antibodies are associated with increased disability and higher disease activity in patients with IP. Our results suggest that measurement of anti-CarP antibodies may be useful in identifying ACPA-negative patients with worse long-term outcomes. Further, anti-CarP antibody status provided additional information about RF and ACPA.
27909083 Continual Maintenance of Remission Defined by the ACR/EULAR Criteria in Daily Practice Lea 2017 Feb OBJECTIVE: To evaluate longterm functional outcomes in rheumatoid arthritis (RA) based on the number of times that the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) or the 28-joint Disease Activity Score (DAS28) remission criteria were fulfilled. METHODS: Patients with RA who participated in all 6 data collections in an observational cohort from 2008 to 2010 and who fulfilled the DAS28 remission criteria at baseline were studied. Patients were classified by the number of times they fulfilled the ACR/EULAR [Boolean trial, Boolean practice, Simplified Disease Activity Index (SDAI), or Clinical Disease Activity Index (CDAI)] or DAS28 remission criteria at each collection. The OR for the Japanese version of the Health Assessment Questionnaire (J-HAQ) progression, based on the number of times each set of remission criteria was fulfilled, were calculated by logistic regression. RESULTS: A total of 915 patients were studied. The OR (95% CI) for J-HAQ progression were 0.54 (0.33-0.87), 0.55 (0.33-0.92), 0.48 (0.28-0.82), 0.29 (0.16-0.51), 0.24 (0.13-0.47), and 0.07 (0.03-0.15) for those fulfilling the Boolean trial remission from 1 to 6 times. This tendency was also observed for the other 4 criteria. The OR (95% CI) for J-HAQ progression in patients who achieved remission at all 6 data collections were 0.07 (0.03-0.14) for the Boolean practice, 0.10 (0.05-0.20) for the SDAI, and 0.07 (0.04-0.15) for the CDAI, whereas 0.15 (0.08-0.29) for the DAS28. CONCLUSION: Continual fulfillment of any remission criteria was strongly effective in preventing patients from progression of functional disability; however, the ACR/EULAR criteria appear to be preferable.
26697483 CRISPR/CAS9-Mediated Genome Editing of miRNA-155 Inhibits Proinflammatory Cytokine Product 2015 MicroRNA 155 (miR-155) is a key proinflammatory regulator in clinical and experimental rheumatoid arthritis (RA). Here we generated a miR-155 genome knockout (GKO) RAW264.7 macrophage cell line using the clustered regulatory interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (CAS9) technology. While upregulating the Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP1), the miR-155 GKO line is severely impaired in producing proinflammatory cytokines but slightly increased in osteoclastogenesis upon treatment with receptor activator of nuclear factor-κB ligand (RANKL). Taken together, our results suggest that genome editing of miR-155 holds the potential as a therapeutic strategy in RA.
26608859 [Efficacy of disease modifying anti-rheumatic drugs on bone destruction in rheumatoid arth 2015 Dec There had been proved the efficacy of preventing bone destruction by using disease modifying anti-rheumatic drugs (DMARDS) such as methotrexate(MTX). A certain combination of DMARDS is more effective than treated alone. But the data about DMARDS combination therapy or DMARDS used mainly in Japan is not abundant, and there needed to establish the evidences of them.
27102374 Free and nanoencapsulated vitamin D3 : effects on E-NTPDase and E-ADA activities in an ani 2016 Jun The effect of vitamin D3 in oral solution (VD3 ) and vitamin D3 -loaded nanocapsules (NC-VD3 ) was analysed in animals with complete Freund's adjuvant (CFA) induced arthritis (AR). For this purpose, we evaluated scores for arthritis, thermal hyperalgesia and paw oedema, as well as histological analyses and measurements of the activity of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) and ecto-adenosine deaminase (E-ADA) enzymes in rat lymphocytes. Haematological and biochemical parameters were also determined. The doses administered were 120 UI/day of VD3 and 15.84 UI/day of NC-VD3 . Fifteen days after the induction of AR, the groups were treated for 15 days with vitamin D3 . The results demonstrated that VD3 was able to reduce arthritis scores, thermal hyperalgesia and paw oedema in rats with CFA-induced arthritis. However, treatment with NC-VD3 did not reduce arthritis scores. The histological analyses showed that both formulations were able to reduce the inflammatory changes induced by CFA. The activity of E-NTPDase in rat lymphocytes was higher in the AR compared with the control group, while the activity of E-ADA was lower. This effect was reversed after the 15-day treatment. Data from this study indicates that both forms of vitamin D3 seem to contribute to decreasing the inflammatory process induced by CFA, possibly altering the activities of ectoenzymes. Copyright © 2016 John Wiley & Sons, Ltd. SIGNIFICANCE OF THE STUDY: The effects promoted by both formulations of vitamin D3 , either in oral solution or nanoencapsulated form, strongly suggests the softening of the inflammatory process induced by complete Freund's adjuvant (CFA), possibly altering the E-NTPDase and E-ADA activities. However, it is known that vitamin D has a beneficial effect on the modulation of the immune system components responsible for the inflammatory process. Moreover, the establishment of responses to treatment with vitamin D3 may provide an alternative for inhibiting the proinflammatory response, assisting in our understanding of the immunopathology of this disease and possibly improving the signs and symptoms that hinder the quality of life of patients with rheumatoid arthritis. HIGHLIGHTS: Evaluation of the effects on the E-NTPDase and E-ADA activities in an animal model of induced arthritis. Two formulations of vitamin D3 were used: form oral solution and nanoencapsulated. Vitamin D3 seems to contribute to the inflammatory process induced by CFA. Vitamin D3 possibly alters the E-NTPDase and E-ADA activities. Vitamin D3 may be an alternative supplementary treatment for chronic arthritis.
26848119 Granulocyte colony-stimulating factor (G-CSF) plays an important role in immune complex-me 2016 May Neutrophils are an abundant cell type in many chronic inflammatory diseases such as rheumatoid arthritis (RA); however, their contribution to the pathology of RA has not been widely studied. A key cytokine involved in neutrophil development and function is granulocyte-colony stimulating factor (G-CSF). In this study we used the K/BxN serum-transfer arthritis (STA) model, mimicking the effector phase of RA, to investigate the importance of G-CSF in arthritis development and its relation to neutrophils. Here, we show for the first time in this model that G-CSF levels are increased both in the serum and in inflamed paws of arthritic mice and importantly that G-CSF blockade leads to a profound reduction in arthritis severity, as well as reduced numbers of neutrophils in blood. Moreover, CXCL1 and CXCL2 levels in the arthritic joints were also lowered. Our data demonstrate that G-CSF is a pivotal driver of the disease progression in the K/BxN STA model and possibly acts in part by regulating neutrophil numbers in the circulation. Therefore, our findings suggest that G-CSF might be a suitable target in RA, and perhaps in other immune complex-driven pathologies.
25722987 Anti-CCP antibody levels are not associated with MS: results from a case-control study. 2015 Citrullinated proteins have been suggested to play a critical role in the pathogenesis of multiple sclerosis (MS). Anticyclic citrullinated peptide (anti-CCP) antibody is used in the early diagnosis of rheumatoid arthritis (RA). The objective of this study was to investigate the presence of anti-CCP antibody in patients with MS compared to RA patients and healthy controls. Fifty patients with MS (38 females, 12 males; mean age 36.72 ± 8.82 years), 52 patients with RA (40 females, 12 males; mean age 40.87 ± 10.17 years), and 50 healthy controls (32 females, 18 males; mean age 38.22 ± 11.59 years) were included in this study. The levels of serum anti-CCP antibody were measured using an enzyme-linked immunosorbent assay (ELISA). The results of the study showed that anti-CCP antibody levels were significantly higher in RA patients versus MS or healthy controls (P < 0.001). Moreover, anti-CCP antibody was positive in 43 (83%) patients with RA, while it was negative in all MS patients as well as in all healthy controls. Also, no significant correlation was found between the anti-CCP levels and EDSS scores (r = -0.250). In conclusion, the results of this study did not support a positive association between serum anti-CCP antibody and MS.