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ID PMID Title PublicationDate abstract
26178280 Nuclear Factor-κB-inducing Kinase Is Expressed in Synovial Endothelial Cells in Patients 2015 Sep OBJECTIVE: The nuclear factor-κB (NF-κB) family of transcription factors is strongly involved in synovial inflammation. We have previously shown that NF-κB-inducing kinase (NIK) is a key regulator of inflammation-induced angiogenesis in rheumatoid arthritis (RA) synovial tissue (ST). Here, we investigated synovial NIK expression in patients with early arthritis and in autoantibody-positive individuals at risk of developing RA. METHODS: ST biopsies were obtained by arthroscopy from 154 patients with early arthritis (duration < 1 yr) with various diagnoses and 54 IgM rheumatoid factor-positive and/or anticitrullinated protein antibodies-positive individuals without evidence of arthritis. ST was stained for NIK and endothelial cell (EC) markers. Additionally, measures of disease activity were collected and contrast-enhanced magnetic resonance imaging (MRI) was performed in a subset of these patients. RESULTS: In patients with early arthritis, NIK was predominantly expressed in EC of small blood vessels. Further, NIK expression correlated with erythrocyte sedimentation rate (r 0.184, p = 0.024), C-reactive protein (r 0.194, p = 0.017), joint swelling (r 0.297, p < 0.001), synovial immune cell markers (lining r 0.585, p < 0.001; sublining macrophages r 0.728, p < 0.001; T cells r 0.733, p < 0.001; and B cells r 0.264, p = 0.040), MRI effusion (r 0.665, p < 0.001), MRI synovitis (r 0.632, p < 0.001), and MRI total score (r 0.569, p < 0.001). In 18.5% of autoantibody-positive individuals, ST NIK(+)EC were present, but this was not predictive of the development of arthritis. CONCLUSION: NIK(+)EC are present in the earliest phase of synovial inflammation and may be indicative of high angiogenic activity in the inflamed ST. Therefore, NIK(+)EC may play an important role in the persistence of synovitis. Collectively, our data underscore the importance of angiogenesis in synovial inflammation and identify NIK as a potential therapeutic target in arthritis.
27338084 Improving the power of clinical trials of rheumatoid arthritis by using data on continuous 2016 Oct OBJECTIVE: In clinical trials of RA, it is common to assess effectiveness using end points based upon dichotomized continuous measures of disease activity, which classify patients as responders or non-responders. Although dichotomization generally loses statistical power, there are good clinical reasons to use these end points; for example, to allow for patients receiving rescue therapy to be assigned as non-responders. We adopt a statistical technique called the augmented binary method to make better use of the information provided by these continuous measures and account for how close patients were to being responders. METHODS: We adapted the augmented binary method for use in RA clinical trials. We used a previously published randomized controlled trial (Oral SyK Inhibition in Rheumatoid Arthritis-1) to assess its performance in comparison to a standard method treating patients purely as responders or non-responders. The power and error rate were investigated by sampling from this study. RESULTS: The augmented binary method reached similar conclusions to standard analysis methods but was able to estimate the difference in response rates to a higher degree of precision. Results suggested that CI widths for ACR responder end points could be reduced by at least 15%, which could equate to reducing the sample size of a study by 29% to achieve the same statistical power. For other end points, the gain was even higher. Type I error rates were not inflated. CONCLUSION: The augmented binary method shows considerable promise for RA trials, making more efficient use of patient data whilst still reporting outcomes in terms of recognized response end points.
26709471 High-density lipoprotein function in rheumatoid arthritis. 2016 Feb PURPOSE OF REVIEW: Patients with rheumatoid arthritis (RA) have accelerated atherosclerosis despite the appearance of having a less atherogenic lipid profile; however, lipoprotein function rather than concentration may be a better indicator of atherosclerotic risk. The purpose of this review is to summarize recent findings concerning HDL function in patients with RA. RECENT FINDINGS: Two major activities of HDL, its antioxidant and cholesterol efflux functions have been examined in RA. HDL antioxidant capacity is inversely associated with inflammation and RA disease activity; however, there is no clear consensus if antioxidant capacity is altered significantly in RA compared with control study participants. Moreover, despite numerous studies there is no consensus whether HDL cholesterol efflux capacity is significantly altered in RA compared with control study participants or influenced by inflammation or disease activity. SUMMARY: Additional studies will be valuable to consolidate existing data and find consensus. Moreover, studies evaluating the impact of various HDL functions on cardiovascular disease in RA are needed.
28035541 Effect of Artemisia annua extract on treating active rheumatoid arthritis: A randomized co 2017 Jul OBJECTIVE: To investigate the effect and safety of the complementary use of the extract of Artemisia annua L. (EAA) on treating active rheumatoid arthritis (RA). METHODS: A randomized controlled clinical trial was performed. All the 159 participates with active RA were randomly assigned to the control group (80 cases) and EAA group (79 cases) using concealed random allocation method. In the control group, patients were medicated with leflflunomide and methotrexate for 48 weeks; and patients in the EAA group were administrated with leflflunomide, methotrexate plus EAA (30 g/d). At the time points of 0, 12, 24 and 48 weeks, the clinical outcome measures, including objective pain score, tenderness score, number of painful joints, number of swollen joints, health assessment questionnaire (HAQ) score for quality of life, levels of serum rheumatoid factor (RF), anti-cyclic citrullinated protein antibodies (CCP-Ab), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), visual analogue score for pain (VAS), and the overall effificacy were detected and recorded. RESULTS: The objective pain score, number of painful joints and ESR at 12 weeks, tenderness score and HAQ at 24 weeks, and the tenderness score, number of painfull joints, number of swollen joints, HAQ, CRP, RF and CCP-Ab at 48 weeks were signifificantly improved in the EAA group compared with the control group (P<0.01 or P<0.05). At 24 and 48 weeks, the overall effificacy of the EAA group was signifificantly higher than the control group (P<0.01). There were signifificantly higher withdrawal rate of corticosteroids within 12 weeks post-treatment and lower incidence rate of adverse effects in the EAA group compared with the control group (P<0.01 or P<0.05). CONCLUSION: EAA plus methotrexate and leflflunomide were more effective and safer than the routine use of methotrexate and leflflunomide in the treatment of active RA.
26384526 Interstitial pneumonia with autoimmune features and undifferentiated connective tissue dis 2016 Jan BACKGROUND: Interstitial lung diseases (ILDs) are a heterogeneous group of disorders characterized by inflammation and/or fibrosis of the lungs, varying from idiopathic interstitial pneumonias to secondary variants, including the ILDs associated to connective tissue diseases (CTDs). In addition, a number of patients are recognized as unclassifiable ILD (U-ILD), because of the inability to reach a definite diagnosis; some of them show autoimmune manifestations not fulfilling the classification criteria of a given CTD. The term interstitial pneumonia with autoimmune features (IPAF) has been recently proposed for this particular ILD subset. METHODS: Here, we report our experience resulting from the integrated - pneumology/rheumatology - approach to patients with suspected ILDs or CTDs referred to our university-based Center for the Rare Pulmonary Diseases and Rheumatology Unit, from January 2009 to June 2015, with particular attention to the above-mentioned U-ILD, IPAF, and undifferentiated connective tissue disease (UCTD). The comparative analysis of these clinical variants was carried out; moreover, the observed findings were compared with the results of the updated review of the literature. RESULTS: After the first clinical assessment, the U-ILD were identified in 50 patients; afterwards, on the basis of clinico-serological and radiological findings U-ILD group was subdivided into 2 subgroups, namely U-ILD without any clinical extra-thoracic manifestations and/or immunological alterations (15 pts) and IPAF according to the above-mentioned classification criteria (35 pts). Patients with either IPAF or U-ILD were compared with a series of 52 stable UCTD (disease duration ≥3 years), followed at our Rheumatology Unit. Some important differences were evidenced among the 3 series of U-ILD, IPAF, and UCTD: firstly, female gender was more frequent in patients with UCTD (86%) or IPAF (69%) compared with U-ILD (60%) or idiopathic pulmonary fibrosis (24%; p=0.001). In addition, UCTD patients were younger and showed longer disease duration. More interestingly, both UCTD and IPAF series show a comparable prevalence of various clinical manifestations, with the exception of the interstitial lung involvement detectable in a very small percentage of UCTD patients. Concordantly, the review of the literature evidenced two main subsets of U-ILD, one is characterized by isolated unclassifiable interstitial pneumonia and another one composed by subjects with clinically prevalent lung involvement in the setting of not definite CTD, the recently proposed IPAF. CONCLUSION: We hypothesize that IPAF and UCTD might represent two clinical variants of the same systemic autoimmune disorders. The marked difference regarding the prevalence of ILD, which is the clinical hallmark of IPAF but very rare in UCTD, may at least in part reflect a selection bias of patients generally referred to different specialist centers, i.e. pneumology or rheumatology, according to the presence/absence of clinically dominant ILD, respectively. Well-integrated, interdisciplinary teams are recommended for the assessment and management of these patients in the clinical practice. Finally, the cooperation between multidisciplinary groups with different experiences may be advisable for a validation study of the proposed nomenclature and classification criteria of these indefinable ILD/CTD variants.
26414681 Can Creatine Supplementation Improve Body Composition and Objective Physical Function in R 2016 Jun OBJECTIVE: Rheumatoid cachexia (muscle wasting) in rheumatoid arthritis (RA) patients contributes to substantial reductions in strength and impaired physical function. The objective of this randomized controlled trial was to investigate the effectiveness of oral creatine (Cr) supplementation in increasing lean mass and improving strength and physical function in RA patients. METHODS: In a double-blind design, 40 RA patients were randomized to either 12 weeks' supplementation of Cr or placebo. Body composition (dual x-ray absorptiometry and bioelectrical impedance spectroscopy [BIS]), strength, and objectively assessed physical function were measured at baseline, day 6, week 12, and week 24. Data analysis was performed by analysis of covariance. RESULTS: Cr supplementation increased appendicular lean mass (ALM; a surrogate measure of muscle mass) by mean ± SE 0.52 ± 0.13 kg (P = 0.004 versus placebo), and total LM by 0.60 ± 0.37 kg (P = 0.158). The change in LM concurred with the gain in intracellular water (0.64 ± 0.22 liters; P = 0.035) measured by BIS. Despite increasing ALM, Cr supplementation, relative to placebo, failed to improve isometric knee extensor strength (P = 0.408), handgrip strength (P = 0.833), or objectively assessed physical function (P = 0.335-0.764). CONCLUSION: In patients with RA, Cr supplementation increased muscle mass, but not strength or objective physical function. No treatment-related adverse effects were reported, suggesting that Cr supplementation may offer a safe and acceptable adjunct treatment for attenuating muscle loss; this treatment may be beneficial for patients experiencing severe rheumatoid cachexia.
27735145 Anti CCP Antibodies in Tuberculosis. 2016 May INTRODUCTION: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been considered very specific for rheumatoid arthritis (RA). Some studies have shown that these antibodies can be positive in infectious diseases like TB, HIV, etc. METHODS: Fifty patients of tuberculosis both pulmonary and extra-pulmonary were enrolled in the study from inpatient and outpatient departments from May 2012 to November 2013. Anti-CCP antibody test was done in all the patient by ELISA. RESULTS: Thirty one were pulmonary and 17 were extra-pulmonary and two were disseminated extra-pulmonary TB. Of the 31 cases of pulmonary tuberculosis, 12 cases (38.7%) were positive for anti-CCP antibodies and 19 cases (61.3%) were negative for same. Of the 19 cases of extra-pulmonary tuberculosis, two cases (10.52%) were positive for anti-CCP antibodies and 17 cases (89.48%) were negative. Of the 31 patients of pulmonary TB, nine were sputum positive and 22 were negative. Of those with sputum positive five (55.56%) were positive for anti-CCP antibodies and those with sputum negative 7 cases (31.81%) were positive for anti-CCP antibodies. CONCLUSIONS: Anti-CCP can be falsely positive in cases of tuberculosis. Positivity of anti-CCP antibodies for tuberculosis is more for pulmonary (more for sputum-positive than sputum-negative) than extra-pulmonary TB. Anti-CCP thus is not very specific for rheumatoid arthritis.
27188857 Inflammatory cytokine levels, disease activity, and function of patients with rheumatoid a 2016 Jul The objective of this study was to compare the effects of treatment by combined conventional disease-modifying antirheumatic drugs (cDMARDs) or biologics on cytokines, disease activity, and function in rheumatoid arthritis (RA). Sera from a cohort of 81 patients with long-standing RA treated with combined cDMARDs or biologics were measured for 12 cytokines. Comparisons of serum cytokine concentrations with treatment types (combination 2, 3 cDMARDs or biologics), serologic status (positivity for RF and anti-cyclic citrullinated peptide antibody (anti-CCP Ab)), DAS28-ESR, and function were performed. Spearman correlation coefficients between individual cytokines and clinical parameters were explored. Approximately half of the patients were prescribed two cDMARDs. Mean duration of current treatment was 42 months. More than 70 % had moderate disease activity or normal function/slight disability. Serum concentrations of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-23, IL-33, interferon (IFN)-γ, granulocyte monocyte-colony stimulating factor (GM-CSF), and TNF-α in patients taking combined cDMARDs did not significantly differ from those on biologics. Seventy-nine serum samples (97.5 %) had undetectable levels of 1 to 10 cytokines. Concentrations of several cytokines were significantly higher in patients with moderate to high disease activity, seropositive or poor functional status. Weak correlations between cytokine levels and RA disease activity or function were demonstrated. The highest correlation coefficients were observed with IL-33, IL-8, and IL-6. Long-term treatment with cDMARDs did not differ from biologics with respect to cytokine concentrations, disease activity, and function. The cytokine profiles in established RA were mainly those produced from effector cells, especially IL-6, IL-8, and IL-33. Both IL-8 and IL-33 may be potential biomarkers and/or treatment targets in patients with late RA.
25050521 Effect of etanercept, infliximab and methotrexate in the treatment of arthritis. 2015 Feb BACKGROUND: Rheumatoid arthritis a chronic inflammatory autoimmune disease with inflammation of the joint, leading to damage of bone and surrounding cartilage. OBJECTIVES: Our study was designed to find the efficacy of etanercept, infliximab and methotrexate in effective therapeutic management against arthritis patients. METHODS: A total of 315 patients, including both the sexes in the age group of 45-70 years with active rheumatoid arthritis attending Hospital of Academy of Military Medical Sciences, Beijing, China during the period of December 2012 to November 2013 were included in the study. 100 patients with joint pains, but not with rheumatoid arthritis were taken as a control group. All the patients were treated with infliximab, methotrexate and etanercept. RESULTS: In our study, patients responded, 75% to infliximab and etanercept combinations than to methotrexate. The combination therapy also showed a radiological decrease in the joint damage. There is significant when combinations of these drugs were used for the therapy (P<0.001). CONCLUSION: In our study, use of infliximab and etanercept combinations lowered the joint damage and helped in the improvement of the patient's life.
27579330 The Relationship of Cytokines IL-13 and IL-17 with Autoantibodies Profile in Early Rheumat 2016 Aims. In the present study, we aimed to assess the concentrations of IL-13 and IL-17 in serum of patients with early rheumatoid arthritis (eRA), the investigation of correlation between the concentrations of these cytokines and disease activity score, and the concentration of some autoantibodies and the evaluation of the utility of IL-13 and -17 concentration measurements as markers of disease activity. Materials and Methods. Serum samples were collected from 30 patients and from 28 controls and analysed parameters. Results. The serum concentrations of IL-13, IL-17, anti-CCP, and IgM-RF were statistically significantly higher in patients with eRA, compared to the controls. IL-13 concentrations in the severe and moderate groups with eRA were statistically higher than in the mild and control groups. Also, in the case of IL-17, serum concentrations increased proportionally with the disease activity of eRA. We observe that concentrations of IL-13 and -17 did not correlate with autoantibodies. IL-17 concentration significantly positively correlated with CRP, while IL-13 concentration significantly negatively correlated with CRP. Disease activity score, DAS28, was strongly positively correlated with levels of ESR and weakly positively correlated with concentrations of anti-RA33 autoantibodies. IL-13 has a higher diagnostic utility than IL-17, CRP, ESR, IgM-RF, and anti-CCP as markers of disease activity. Conclusions. The presence of higher IL-13 and IL-17 serum levels in patients, compared with those of controls, confirms that these markers, found with high specificity, might be involved in the pathogenesis of eRA. IL-13 and IL-17 might be of better usefulness in the prediction of eRA activity status than IgM-RF and anti-CCP.
25561362 The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflamm 2015 Mar The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010-2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003). In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk.
26287504 MicroRNA-150: A potential regulator in pathogens infection and autoimmune diseases. 2015 MicroRNAs (miRNAs) are short non-coding RNAs that play an important role in post-transcriptional regulation of gene expression. The past studies showed that miR-150 might emerge as a master regulator of gene expression during the immune cells differentiation and immune response process. Its regulation ability in immune cellular process might contribute to the host defense against invading pathogens, and dysregulated expression of miR-150 in immune cells might result in autoimmune diseases. This review summarized that miR-150 could regulate B cells, T cells and NK/iNKT cells differentiation and immune response. And also, this review provides a comprehensive view on the association of miR-150 and autoimmune diseases such as systemic sclerosis (SSc), multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and contact sensitivity. Especially, the duplex role of miR-150 in the fibrosis process might contribute to the pathomechanism of SSc. Though much remains to be explored about the roles of miR-150 in pathogenic infection and autoimmune diseases, targeting miR-150 may serve as a promising therapy strategy.
26880831 Increased levels of peptidylarginine deiminase 2 in synovial fluid from anti-CCP-positive 2016 May OBJECTIVE: To quantify peptidylarginine deiminase 2 (PAD2) in SF of RA patients and OA patients, and to determine the association between PAD2 levels, disease activity and inflammatory markers in RA. METHODS: Blood and SF samples were obtained from 39 RA patients and 40 patients with OA. PAD2 content and PAD activity were measured by means of in-house assays. TNF-α, IL-1β, IL-6, IL-8, IL-10 and IL-12 were measured using flow cytometry. RESULTS: PAD2 levels and PAD activity were higher in SF from RA than OA patients (P < 0.0001 and P = 0.03, respectively), as were all cytokine levels (P < 0.0001-0.05). SF PAD2 levels were higher among anti-CCP-positive patients than among anti-CCP-negative patients (P = 0.005). PAD2 levels in SF from RA patients correlated with disease activity, as assessed by DAS28 (P < 0.005). Moreover, SF PAD2 levels correlated with circulating CRP and anti-CCP levels (P < 0.0006), as well as with leucocyte count, IL-6, IL-8 and IL-10 levels in SF (P < 0.0001-0.02). PAD activity in SF was higher in RA patients than in OA patients, and correlated with PAD2 concentration. CONCLUSION: Extracellular PAD2 levels in SF correlate with disease activity in RA patients. Anti-CCP-positive RA patients have higher PAD2 levels in SF than anti-CCP-negative RA patients and OA patients. Since we could demonstrate enzymatically active PADs in SF, we propose that free, extracellular PAD is of pathogenic relevance.
27609119 Generation of Functional Cardiomyocytes from the Synoviocytes of Patients with Rheumatoid 2016 Sep 9 Cardiovascular disease is a leading cause of morbidity in rheumatoid arthritis (RA) patients. This study aimed to generate and characterise cardiomyocytes from induced pluripotent stem cells (iPSCs) of RA patients. Fibroblast-like synoviocytes (FLSs) from patients with RA and osteoarthritis (OA) were successfully reprogrammed into RA-iPSCs and OA-iPSCs, respectively. The pluripotency of iPSCs was confirmed by quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining. Established iPSCs were differentiated into cardiomyocytes using a small molecule-based monolayer differentiation protocol. Within 12 days of cardiac differentiation from patient-specific and control-iPSCs, spontaneously beating cardiomyocytes (iPSC-CMs) were observed. All iPSC-CMs exhibited a reliable sarcomeric structure stained with antibodies against cardiac markers and similar expression profiles of cardiac-specific genes. Intracellular calcium signalling was recorded to compare calcium-handling properties among cardiomyocytes differentiated from the three groups of iPSCs. RA-iPSC-CMs had a lower amplitude and a shorter duration of calcium transients than the control groups. Peak tangential stress and the maximum contractile rate were also decreased in RA-iPSC-CMs, suggesting that contractility was reduced. This study demonstrates the successful generation of functional cardiomyocytes from pathogenic synovial cells in RA patients through iPSC reprogramming. Research using RA-iPSC-CMs might provide an opportunity to investigate the pathophysiology of cardiac involvement in RA.
27628666 Patient and physician perspectives of hand function in a cohort of rheumatoid arthritis pa 2016 Sep 15 BACKGROUND: In 2004, we initiated an inception cohort of patients with recent-onset rheumatoid arthritis (RA). Hand function was incorporated into evaluations from 2014 onward. The objectives were to examine hand function in our cohort, compare hand function with function in healthy controls and determine the factors associated with impaired function. METHODS: From February 2014 to June 2015, 139 patients (97.2 % of the cohort) had disease activity scored (28 joints, [DAS28]); the Michigan Hand Outcome Questionnaire (MHQ) and Disabilities of the Arm, Shoulder and Hand Outcome Measure (DASH) were completed, and the tip-, key- and palmar-pinch and grip strengths were measured. Sixty-nine healthy controls underwent the same evaluations. Ninety-nine patients underwent a second evaluation one year after their baseline. Descriptive statistics and linear regression models were used. Patients and controls signed informed consent. RESULTS: Patients were primarily middle-aged females with a median disease duration of 7 years; 91 patients had DAS28-remission, and 16, 23, and 9 patients had low, moderate and high disease activity, respectively. Controls scored better than did patients with (any) disease activity level; remission patients had similar DASH and key pinch function as did controls with poorer MHQ and both tip and palmar pinch and grip strength. DAS28 was consistently associated with impaired hand function. Among the patients with a one-year re-assessment, changes in DAS28 correlated (rho = 0.34 to 0.63) with changes in hand function (p ≤ 0.01 for all comparisons), but there was no correlation with palmar pinch strength. CONCLUSIONS: Disease activity was associated with hand function impairment in RA patients with variable follow-up. MHQ discriminated poorer hand function in remission patients who otherwise had similar DASH scores as the controls did.
25800216 Active-comparator design and new-user design in observational studies. 2015 Jul Over the past decade, an increasing number of observational studies have examined the effectiveness or safety of treatments for rheumatoid arthritis. Unlike randomized controlled trials (RCTs), however, observational studies of drug effects have methodological limitations such as confounding by indication. Active-comparator designs and new-user designs can help mitigate such biases in observational studies and improve the validity of their findings by making them more closely approximate RCTs. In an active-comparator study, the drug of interest is compared with another agent commonly used for the same indication, rather than with no treatment (a 'non-user' group). This principle helps to ensure that treatment groups have similar treatment indications, attenuating both measured and unmeasured differences in patient characteristics. The new-user study includes a cohort of patients from the time of treatment initiation, enabling assessment of patients' pretreatment characteristics and capture of all events occurring during follow-up. These two principles should be considered when designing or reviewing observational studies of drug effects.
26223686 Monocyte chemotactic protein-1 elevation prior to the onset of rheumatoid arthritis among 2015 OBJECTIVE: To examine monocyte chemotactic protein-1 (MCP-1) concentration and future rheumatoid arthritis (RA) risk, and investigate effect modification by human leukocyte antigen-shared epitope (HLA-SE) and several lifestyle factors. METHODS: We conducted a nested case-control study using stored plasma samples from the Nurses' Health Studies. Each pre-RA case was matched to three controls (N case = 220, N control = 675). Odds ratios (OR) for RA associated with MCP-1 concentration and interactions with HLA-SE, smoking, BMI and alcohol intake were estimated. RESULTS: MCP-1 concentration was associated with both seropositive and seronegative RA, in particular <5 years of blood draw (OR: 2.42), and among HLA-SE positive (OR: 2.05). No interactions with smoking, BMI or alcohol were detected. CONCLUSION: MCP-1 was associated with risk of RA, especially among HLA-SE positive, but did not differ by smoking status, BMI or alcohol intake.
25973089 Significance of liver biopsy for the evaluation of methotrexate-induced liver damage in pa 2015 It is well recognized that long-term administration of methotrexate (MTX) in patients with rheumatoid arthritis (RA) can induce liver fibrosis via a steatohepatitis-like inflammatory process. Several non-invasive tests have been investigated as alternatives to liver biopsy, which is, however, still recognized as a final diagnostic modality to detect the MTX-induced liver damage. To clarify whether there is a significant discrepancy between clinical estimations and pathologic findings of this hepatic condition, we performed a following comparative study. Four RA patients (4 women, age 67-80 yr) with MTX-induced liver damage were reviewed. The severity of hepatic damage estimated clinically was compared with histopathologic findings. Consequently, the liver biopsies showed the relatively earlier stages of and milder degrees of hepatic damages than the clinical estimations. The histopathologic findings were more reliable and useful than any other clinical examinations, to plan and modify the treatment strategies, especially in cases of liver damages with multiple etiologies besides MTX. These findings suggest that liver biopsy is an unavoidable examination to assess precisely MTX-induced liver damage. Non-invasive tests may be useful to monitor the hepatic condition of RA patients receiving MTX but do not constitute an acceptable alternative to liver biopsy.
27267524 Metabolic syndrome in patients with rheumatoid arthritis followed at a University Hospital 2016 Mar INTRODUCTION: Patients with rheumatoid arthritis (RA) are 30-60% more likely to develop cardiovascular disease (CV) than the general population. Metabolic syndrome (MS), defined by a number of cardiovascular risk factors, confers a greater risk of CVdisease and diabetes. The association of MS with RA is not yet fully understood and its prevalence varies from 19 to 63% across studies. OBJECTIVES: To assess the prevalence of MS in a population of RA patients followed in a hospital in Northeastern Brazil and analyze associations of demographic and clinical factors with MS. METHODS: Outpatients with RA were evaluated in a cross-sectional study regarding demographic, clinical, laboratory and anthropometric data. The criteria for defining MS were those adopted by NCEPIII (2005) and IDF (2006). RESULTS: 110 patients with RA were studied; 97.3% were female, with a mean age of 55.5 years (SD=12.9) and duration of illness of 11.2 years (SD=7.3). The MS prevalence from NCEPIII (2005) and IDF (2005) were, respectively, 50% and 53.4%. Advanced age (57.9±11.9 versus 52.9±13.5; p=0.04) and smoking load >20 packs/year (29% versus 9%, p=0.008) were associated with MS. The major components of the metabolic syndrome were abdominal obesity (98.1%), hypertension (80%) and low HDL cholesterol (72.2%). CONCLUSIONS: RA patients in a tertiary center in Northeastern Brazil showed high prevalence of MS. It is worth noting that almost all patients had MS and abdominal obesity, which has important practical implications. In addition to the components of MS, age and smoking were associated with this syndrome.
27197661 Program Death-1 Suppresses Autoimmune Arthritis by Inhibiting Th17 Response. 2016 Oct Program death-1 (PD-1) is a co-inhibitory receptor inducibly expressed on activated T cells. PD-1 has been reported to be associated with the development of several autoimmune diseases including rheumatoid arthritis, but the precise cellular and molecular mechanisms have not been fully elucidated. To study the role of PD-1 in the pathogenesis of rheumatoid arthritis and the possible underlying mechanisms, we performed collagen-induced arthritis (CIA) in C57BL/6 mice. Here, we show that PD-1 deficiency leads to the development of severe CIA in mice. When analyzing T cells from CIA mice ex vivo, we noticed aberrant antigen-specific Th17 responses in mice lacking PD-1. This is possibly due to deregulated activation of PKC-θ and Akt. In support of this notion, treating Pdcd1 (-/-) mice with an inhibitor of PI3-kinase that is upstream of PKC-θ and Akt significantly suppressed the disease severity. Therefore, our data indicate that PD-1 dampens antigen-specific Th17 response, thus inhibiting the disease.