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ID PMID Title PublicationDate abstract
24313918 Rheumatic manifestations and an epipharyngeal mass accompanied by myelodysplastic syndrome 2015 Jul We herein report two cases of myelodysplastic syndrome with rheumatic manifestations. (Case 1) A 70-year-old man presented with fever, arthritis and bone pain and developed cranial nerve palsy caused by an epipharyngeal mass. Steroid therapy led to a prolonged remission of the febrile condition and mass lesion. (Case 2) An 82-year-old male was treated for intractable polyarthritis and fever with steroid therapy, and serious side effects resulted in lethal pneumonia. We herein describe the entire course of steroid therapy in these two cases. Various rheumatic manifestations in myelodyaplastic syndrome often require empirical steroid therapy. It was effective for the soft tissue mass in Case 1, in which indolent lymphoma could not be denied, and was only partially effective for Case 2 of the febrile and putatively benign conditions, suggesting heterogeneous nature of rheumatic complications in myelodysplastic syndrome.
25935171 Predictors of diastolic dysfunction in rheumatoid arthritis. 2015 May The main objective was to determine the predictors of diastolic dysfunction in rheumatoid arthritis (RA). Articles pertaining to diastolic dysfunction in RA were retrieved from Scopus, EBSCO, PubMed, Web of Science, and Cochrane Library databases. Keywords such as: diastolic, cardiac, left ventricular function, heart failure, rheumatoid arthritis, and cardiac failure were used. Studies, which examined factors, or predictors of diastolic dysfunction in RA, and those with echocardiographic evaluation of diastolic dysfunction, were included. A total of 8 studies met the eligibility criteria. Most studies (6 out of 7 studies) demonstrated a significant inverse relationship between the E (early)/A (late) ratio and disease duration. The pooled analysis using the random effects model revealed a significant but weak inverse relationship between the ratio of the E to A ventricular filling velocities (E/A) ratio and the disease duration (p less than 0.05, r=-0.385). There was a significant relationship between E/A ratio and disease duration in RA.
25370843 Power and color Doppler ultrasound settings for inflammatory flow: impact on scoring of di 2015 Feb OBJECTIVE: To determine how settings for power and color Doppler ultrasound sensitivity vary on different high- and intermediate-range ultrasound machines and to evaluate the impact of these changes on Doppler scoring of inflamed joints. METHODS: Six different types of ultrasound machines were used. On each machine, the factory setting for superficial musculoskeletal scanning was used unchanged for both color and power Doppler modalities. The settings were then adjusted for increased Doppler sensitivity, and these settings were designated study settings. Eleven patients with rheumatoid arthritis (RA) with wrist involvement were scanned on the 6 machines, each with 4 settings, generating 264 Doppler images for scoring and color quantification. Doppler sensitivity was measured with a quantitative assessment of Doppler activity: color fraction. Higher color fraction indicated higher sensitivity. RESULTS: Power Doppler was more sensitive on half of the machines, whereas color Doppler was more sensitive on the other half, using both factory settings and study settings. There was an average increase in Doppler sensitivity, despite modality, of 78% when study settings were applied. Over the 6 machines, 2 Doppler modalities, and 2 settings, the grades for each of 7 of the patients varied between 0 and 3, while the grades for each of the other 4 patients varied between 0 and 2. CONCLUSION: The effect of using different machines, Doppler modalities, and settings has a considerable influence on the quantification of inflammation by ultrasound in RA patients, and this must be taken into account in multicenter studies.
27256290 Internalised stigma in people with rheumatoid arthritis: a cross sectional study to establ 2016 Jun 2 BACKGROUND: Internalised stigma is theorized to be the internalisation and legitimisation of stereotypes of the diagnosis held in society and has not been quantified within patients with Rheumatoid Arthritis. This study aimed to: validate a modified version of a measure of internalised stigma, (the Internalised Stigma of Mental Illness scale, ISMI) for use in a group of patients diagnosed with rheumatoid arthritis; establish the consistency of the construct being measured, and to explore the levels of internalised stigma within this group. METHODS: A cross-sectional survey was conducted in London, UK with participants receiving out-patient treatment for Rheumatoid Arthritis. Participants completed the ISMI-Rheumatoid Arthritis (ISMI-RA) and a measure of self-esteem. RESULTS: One hundred respondents were interviewed by phone. The ISMI-RA was found to be reliable using a measure of internal consistency (α = 0.85) showed concurrent validity with the Index of Self Esteem (r = 0.58, p < 0.01) and discriminant validity with no association with gender (t = 1.43, p = 0.61). A quarter of respondents reported internalised stigma to a 'severe' level. Acceptability and feasibility were established. A confirmatory factor analysis provided some support for the model of internalised stigma. CONCLUSIONS: The application of the ISMI-RA among the Rheumatoid Arthritis population looks promising. Internalised stigma was found to be present within this group. More research is needed to generalize these results and to explore the effects of internalised stigma on treatment adherence and quality of life.
26332844 Developing clinically relevant biomarkers in inflammatory arthritis: A multiplatform appro 2016 Jun PURPOSE: To identify candidate biomarkers that have the potential to distinguish between patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA) and explore the value of combining different protein discovery platforms for the development of a multiplexed protein biomarker panel. EXPERIMENTAL DESIGN: Serum samples from 32 patients (PsA; n = 16 and RA; n = 16) defined as active, early onset, and treatment naïve were analyzed using unbiased label-free LC-MS/MS, a microsphere bead-based immunoassay (Luminex xMAP) and an aptamer-based assay (SOMAscan). RESULTS: LC-MS/MS was used to quantify 324 proteins, while the Luminex xMAP targeted 48 proteins and SOMAscan supported the measurement of 1129 proteins. The combined data from these techniques gave reproducible quantification of 1501 proteins in total. Of these, 42 (LC-MS/MS), 3 (Luminex xMAP), and 127 (SOMAscan) proteins were found to be differentially expressed between PsA and RA (p < 0.05). CONCLUSION AND CLINICAL RELEVANCE: Using three different and potentially complementary proteomic platforms we identified a total of 172 proteins that are differentially expressed in patients with PsA compared to RA. These proteins collectively represent candidates for inclusion in a protein signature that could be developed as a diagnostic test to discriminate patients with PsA from RA and therefore be of clinical utility.
25817604 ABCB1 genetic variant and its associated tacrolimus pharmacokinetics affect renal function 2015 May 20 BACKGROUND: This study aimed to evaluate the blood exposure of and clinical responses to tacrolimus based on genetic variants of CYP3A5 and ABCB1 in patients with rheumatoid arthritis. METHODS: Seventy rheumatoid arthritis patients treated with oral tacrolimus once daily were enrolled. Blood concentrations of tacrolimus and its major metabolite 13-O-demethylate at 12h after dosing were determined. The relationships between the tacrolimus pharmacokinetics and efficacy, renal function, and CYP3A5 and ABCB1 genotypes were evaluated. RESULTS: Dose-normalized blood concentration of tacrolimus was significantly higher in the CYP3A5*3/*3 group than in the *1 allele carrier group. A lower metabolic ratio of 13-O-demethylate to tacrolimus was observed in the CYP3A5*3/*3 group. The ABCB1 3435TT group had higher dose-normalized blood concentrations of tacrolimus and 13-O-demethylate. The blood tacrolimus concentration was inversely correlated with the estimated glomerular filtration rate (eGFR). ABCB1 C3435T but not CYP3A5 genotype had decreased eGFR. Patients lacking the CYP3A5*3 allele had a higher incidence of tacrolimus withdrawal. CONCLUSION: CYP3A5*3 increased the blood exposure of tacrolimus through its metabolic reduction. ABCB1 C3435T led to a higher blood exposure of tacrolimus and its major metabolite. The ABCB1 genetic variant and its associated tacrolimus pharmacokinetics affected renal function in rheumatoid arthritis patients.
27457885 Evaluation of coping strategies in established rheumatoid arthritis patients: emergence of 2016 Nov AIM: To evaluate coping strategies of Asian RA patients and their associations with health-related quality of life (HRQoL). METHODS: A cross-sectional sample of patients with established RA was evaluated using measures of coping (Coping in Rheumatoid Arthritis Questionnaire [C-RAQ]; appraisal of coping effectiveness and helplessness), HRQoL (Mental and Physical Components [MCS/PCS] of the Short Form 12v2; Rheumatoid Arthritis Impact of Disease score [RAID]) and clinical/laboratory assessments. Principal component analysis was conducted to identify coping strategies. Multiple linear regression analyses were performed to evaluate the associations between coping strategies and HRQoL outcomes. RESULTS: The study sample comprised 101 patients, 81% female, 72.3% Chinese, mean age 54.2 ± 12.6 years. Five coping strategies were identified: Active problem solving (E = 5.36), Distancing (E = 2.30), Concealment (E = 1.89), Cognitive reframing (E = 1.55) and Emotional expression (E = 1.26). Concealment was consistently associated with PCS (r(s) = -0.23, P = 0.049), MCS (r(s) = -0.24, P = 0.04) and RAID (r(s) = 0.39, P < 0.001), and was significant in the multivariate model to explain lower disease-specific HRQoL (RAID) even after adjusting for disease activity, coping effectiveness and helplessness (β = 0.20, P = 0.04). Emotional expression was associated with poorer physical HRQoL (PCS), after adjusting for disease severity, body mass index, coping effectiveness, helplessness and Concealment (β = -0.39, P < 0.001). Perceived coping-related helplessness was significant in multivariate correlates for PCS (β = -0.25, P = 0.036), MCS (β = -0.29, P = 0.02) and RAID (β = 0.53, P < 0.001), after adjusting for covariates. CONCLUSION: Concealment and Emotional expression are associated with lower disease-specific HRQoL and physical HRQoL respectively, with the former coping strategy likely to be culture-specific. Interventions should tailor psychosocial support needs to address not only coping strategies, but patients' perception of their coping.
25303739 Effect of age at menopause on disease presentation in early rheumatoid arthritis: results 2015 May OBJECTIVE: Studies suggest that hormonal states affect disease characteristics in women with rheumatoid arthritis (RA). This study investigated how age at menopause affects disease in women presenting with early RA. METHODS: This was a cross-sectional study of postmenopausal women with early RA under age 65 years at time of enrollment in the Canadian Early Arthritis Cohort. RA-related disease characteristics in women who had early age at menopause (EM; age at menopause <45 years) were compared to those who had usual age at menopause (age at menopause ≥45 years). The t-test was applied to continuous variables and the chi-square test to categorical variables. Multivariate logistic regression analysis was used to adjust for age at menopause, smoking, and use of exogenous hormones. RESULTS: A total of 534 women were included; 93 were in the EM group. The age at RA onset was similar between groups. The EM group had higher mean patient global and pain scores and was more likely to be rheumatoid factor (RF) positive and meet the 1987 American College of Rheumatology criteria for RA. Using multivariate logistic regression, the EM group was more likely to be RF positive (odds ratio 2.2 [95% confidence interval 1.3-3.8], P = 0.005). Symptom duration, joint counts, Disease Activity Score in 28 joints, Health Assessment Questionnaire scores, and inflammatory markers did not differ between groups. CONCLUSION: These data suggest that early age at menopause, compared to usual age at menopause, is associated with seropositivity in women with early RA.
26140463 Evaluation of changes in magnetic resonance images following 24 and 52 weeks of treatment 2016 OBJECTIVES: To compare MRI findings in rheumatoid arthritis (RA) patients treated with biologic disease-modifying anti-rheumatic drugs (DMARDs). METHODS: The study subjects were 43 RA patients treated with biologic DMARDs (13 with infliximab, 15 with tocilizumab, and 15 with abatacept). They were evaluated using Simplified Disease Activity Index (SDAI) and low-field extremity MRI at baseline, and at 24 weeks and 52 weeks of treatment. RESULTS: Synovitis scores were significantly lower by 24 weeks in all groups, compared with baseline (P < 0.05). Significant improvement in bone marrow edema (BME) scores were noted from baseline to 24 weeks in infliximab and abatacept groups (P < 0.05), but from 24 weeks to 52 weeks in tocilizumab group (P < 0.01). No significant change was found in erosion score. The synovitis score at baseline correlated significantly with SDAI at 24 weeks (P < 0.05), and the score at 24 weeks correlated significantly with SDAI at 52 weeks (P < 0.05). CONCLUSIONS: The results suggest that the inflammatory improvement by infliximab and abatacept may express earlier than those by tocilizumab, despite similar improvement in SDAI. MRI-detected synovitis could be a useful predictor of SDAI at 24 weeks of treatment. The MRI remains the best tool to detect and assess the effects of biologic DMARDs in RA.
26471289 The treatment of rheumatoid arthritis using Chinese medicinal plants: From pharmacology to 2015 Dec 24 ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a common worldwide public health problem. Traditional Chinese Medicine (TCM) achieved some results to some extent in the treatment of rheumatoid arthritis (RA). Especially in China, TCM formulas are used in the clinic because of their advantages. Some of these TCM formulas have been used for thousands of years in ancient China, they pays much attention to strengthening healthy qi, cleaning heat, and wet, activating blood, etc. So TCM in anti-RA drug is considered as a simple and effective method. In addition, TCM are also traditionally used as extracts and many Chinese herbs which are considered to be effective for RA. With the advancement of technologies and research methods, researchers have devoted themselves to exploring new therapeutic materials from troves of TCM. The components of TCM are identified and purified, which include alkaloids, coumarins, flavonoids, saponins and so on. However, little or no review works are found in the research literature on the anti-RA drugs from TCM. The present review aims to provide systematically reorganized information on the ethnopharmacology, phytochemistry and pharmacology of TCM used traditionally against RA. The information recorded in this review will provide new directions for researchers in the future. MATERIALS AND METHODS: Relevant scientific literatures were collected from Chinese traditional books and Chinese Pharmacopoeia. Several important pharmacology data, clinical observations, animal experiments on effects of anti-RA drugs from TCM and their mechanisms were extracted from a library and electric search (Pubmed, PubChem Compound, Science Direct, Spring Link, Elsevier, Web of Science, CNKI, Wan Fang, Bai du, The Plant List, etc.). We collected information published between 2002 and 2015 on Chinese medicine in the treatment of RA. Information was also acquired from local classic herbal literature, conference papers, government reports, and PhD and MSc dissertations. RESULTS: This review mainly introduces the current research on anti-RA TCM formulas, extracts and compounds from TCM, pharmacological data and potential mechanisms (inhibit osteoclast proliferation, suppress fibroblast-like synoviocytes (FLSs) growth, decrease the expression of inflammatory cytokines, blocking signal pathways, etc.). CONCLUSIONS: TCM, as a multi-component and multi-target approach, which is a perfect match with the holistic concept of systems biology, is applicable in the treatment of RA. The synergistic connections of Chinese herbs and mechanisms of related active compounds on RA increase the trust for TCM. TCM as alternative remedies for RA not only has an important position in the world market, but also has an irreplaceable role in the treatment of RA in future.
25534420 Risk of venous thromboembolism in patients with rheumatoid arthritis: initiating disease-m 2015 May OBJECTIVES: Recent research suggests that rheumatoid arthritis increases the risk of venous thromboembolism. This study compared the risk of venous thromboembolism in patients with newly diagnosed rheumatoid arthritis initiating a biologic disease-modifying antirheumatic drug (DMARD) with those initiating methotrexate or a nonbiologic DMARD. METHODS: We conducted a population-based cohort study using US insurance claims data (2001-2012). Three mutually exclusive, hierarchical DMARD groups were used: (1) a biologic DMARD with and without nonbiologic DMARDs; (2) methotrexate without a biologic DMARD; or (3) nonbiologic DMARDs without a biologic DMARD or methotrexate. We calculated the incidence rates of venous thromboembolism. Cox proportional hazard models stratified by propensity score (PS) deciles after asymmetric PS trimming were used for 3 pairwise comparisons, controlling for potential confounders at baseline. RESULTS: We identified 29,481 patients with rheumatoid arthritis with 39,647 treatment episodes. From the pairwise comparison after asymmetric PS trimming, the incidence rate of hospitalization for venous thromboembolism per 1000 person-years was 5.5 in biologic DMARD initiators versus 4.4 in nonbiologic DMARD initiators and 4.8 in biologic DMARD initiators versus 3.5 in methotrexate initiators. The PS decile-stratified hazard ratio of venous thromboembolism associated with biologic DMARDs was 1.83 (95% confidence interval [CI], 0.91-3.66) versus nonbiologic DMARDs and 1.39 (95% CI, 0.73-2.63) versus methotrexate. The hazard ratio of venous thromboembolism in biologic DMARD initiators was the highest in the first 180 days versus nonbiologic DMARD initiators (2.48; 95% CI, 1.14-5.39) or methotrexate initiators (1.80; 95% CI, 0.90-3.62). CONCLUSIONS: The absolute risk for venous thromboembolism was low in patients with newly diagnosed rheumatoid arthritis. Initiation of a biologic DMARD seems to be associated with an increased short-term risk of hospitalization for venous thromboembolism compared with initiation of a nonbiologic DMARD or methotrexate.
26175470 The effect on treatment response of fibromyalgic symptoms in early rheumatoid arthritis pa 2015 Dec OBJECTIVE: To evaluate whether patients with RA who belong to the spectrum of fibromyalgic RA (FRA) have an impaired response to treatment measured by traditional activity scores. METHODS: Patients from the ESPOIR cohort were analysed. This prospective cohort included 813 patients with early arthritis not initially receiving DMARDs. Among the 697 patients who met RA classification criteria, we studied two groups, one with and the other without FRA. The following endpoints were compared at 6, 12 and 18 months using a mixed linear regression model: 28-joint DAS (DAS28), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and HAQ. In addition, attainment of low disease activity (LDA; DAS28 <3.2) and remission (DAS28 <2.6, SDAI <3.3, CDAI <2.8) at these time points was analysed. RESULTS: Patients with FRA (n = 120) had higher DAS28, SDAI, CDAI and HAQ scores than patients with RA and no fibromyalgic characteristics (n = 548). DAS28 and other DASs started out higher in subjects with FRA, and while they improved to a similar extent to in the isolated RA group, they remained consistently higher among FRA patients. Achievement of LDA and remission was significantly less likely in subjects with FRA. CONCLUSION: Patients with FRA and RA will have a similar response to treatment according to the decrease in indexes of disease activity, but may miss the target of remission or LDA.
26577945 Is RANKL inhibition both anti-resorptive and anabolic in rheumatoid arthritis? 2015 Nov 17 A small peptide, OP3-4, blocks receptor activator of NF-κB from binding to its ligand, receptor activator of NF-κB ligand (RANKL), and was reported recently to inhibit bone resorption, promote bone formation and protect cartilage in a preclinical rheumatoid arthritis model. The latter effects may result from inhibition of RANKL reverse signalling in osteoblasts and chondrocytes. Whether other RANKL inhibitors, such as denosumab, share this action is not known, but OP3-4 at least has potential to provide anabolic treatment for both systemic and focal bone loss in inflammatory arthritis.
27198590 Ranges of motion after reverse shoulder arthroplasty improve significantly the first year 2016 Jul OBJECTIVES: To evaluate the trajectory of the change in range of motion after reverse shoulder joint replacement during 3-year follow-up among patients with rheumatoid arthritis. METHODS: Retrospective cohort longitudinal study of 76 shoulder replacements performed in a university clinic. The range of shoulder motion was assessed by a physiotherapist using a manual goniometer with 5-degree precision before the surgery and 1, 3, 6, 12, and 36 months postoperatively. RESULTS: The shapes of the regression curves suggest that the improvement or decline observed in joint motion was happening mostly during the first year after surgery. After 1 year, the trajectories become flat and they remained unchanged until the end of follow-up. CONCLUSIONS: After shoulder joint replacement, the range of shoulder motion showed substantial changes during the first year only. This should be taken into account when scheduling control visits, planning rehabilitation, and predicting the use of community services after the surgery.
26970491 Autoantibodies in inflammatory arthritis. 2016 Jul Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone with joint destruction. The lack of immunological tolerance in RA represents the first step toward the development of autoimmunity. Susceptible individuals, under the influence of environmental factors, such as tobacco smoke, and silica exposure, develop autoimmune phenomena that result in the presence of autoantibodies. HLA and non-HLA haplotypes play a major role in determining the development of specific autoantibodies differentiating anti-citrullinated antibodies (ACPA)-positive and negative RA patients. Rheumatoid factor (RF) and ACPA are the serological markers for RA, and during the preclinical immunological phase, autoantibody titers increase with a progressive spread of ACPA antigens repertoire. The presence of ACPA represents an independent risk factor for developing RA in patients with undifferentiated arthritis or arthralgia. Moreover, anti-CarP antibodies have been identified in patients with RA as well as in individuals before the onset of clinical symptoms of RA. Several autoantibodies mainly targeting post-translational modified proteins have been investigated as possible biomarkers to improve the early diagnosis, prognosis and response to therapy in RA patients. Psoriatic arthritis (PsA) is distinguished from RA by infrequent positivity for RF and ACPA, together with other distinctive clinical features. Actually, specific autoantibodies have not been described. Recently, anti-CarP antibodies have been reported in sera from PsA patients with active disease. Further investigations on autoantibodies showing high specificity and sensibility as well as relevant correlation with disease severity, progression, and response to therapy are awaited in inflammatory arthritides.
26282936 How to use biologic agents in patients with rheumatoid arthritis who have comorbid disease 2015 Aug 17 Although biologic disease modifying anti-rheumatic drugs (bDMARDs) have improved the quality of life of patients with rheumatoid arthritis, side effects remain a problem, especially for patients with pre-existing comorbidities. Randomized controlled trials of such drugs in rheumatoid arthritis typically exclude patients with comorbidities and are of short duration, so they do not provide data on adverse events in these people. Other data sources such as national bDMARD registries are limited by the preselection of patients for both conventional synthetic chemical compound disease modifying anti-rheumatic drugs (csDMARDs) and bDMARDs, and although these databases document comorbidity, they rarely report its severity. This too limits definitive statements on the progression or resolution of pre-existing disease. Although bDMARDs may not be contraindicated in patients with rheumatoid arthritis and certain comorbid diseases, additional assessments or precautions are recommended. This review summarizes current data on the use of bDMARDs in people with rheumatoid arthritis and common comorbid diseases. It provides an evidence base for doctors and their patients when discussing and selecting the appropriate bDMARDs.
27573797 Sonography Is Superior to Serum-Based Biomarkers for Measuring Disease Status in Experimen 2016 Oct OBJECTIVES: Progress in developing novel rational treatments for rheumatoid arthritis (RA) critically depends on preclinical work in experimental animals. However, there is lack of insight into the most appropriate mode of noninvasive measurement of disease status in experimental RA. This study compared sonography with serum biomarkers in a rabbit model of RA. METHODS: Six-month-old male New Zealand White rabbits were randomized into 2 groups: antigen-induced arthritis group (n = 25), which was subjected to ovalbumin immunization and intra-articular injection; and control group (n = 5). Pathologic changes in the knee joints were evaluated by sonography, and serum C-reactive protein, tumor necrosis factor TNF-α, and interleukin 1 were measured by enzyme-linked immunosorbent assay. Synovial pathologic scores were obtained by ultrasound-guided biopsy. RESULTS: A total of 23 rabbits (2 rabbits died before the end of the study) in the antigen-induced arthritis group and 5 rabbits in the control group completed the study. Sonographic scores for all rabbits were graded from 0 to 3, according to grayscale sonography, synovitis, and blood flow. Synovial lesions were evident on sonography before week 4; however, serum biomarkers slowly increased until weeks 5 and 6 (P < .05). Although both sonography and serum biomarkers correlated significantly with synovitis scoring, the correlations for the sonographically derived parameters were better. The correlation indices between pathologic scores and synovial membranes thickness, blood flow, and resistive index were 0.798, 0.557, and -0.320, respectively, whereas the correlation indices between pathologic scores and tumor necrosis factor α, interleukin 1, and C-reactive protein levels were 0.451, 0.503, and 0.529. CONCLUSIONS: Sonographic findings had better correlations with histologic scoring than serologic biomarkers of disease activity in the RA rabbit model, especially at early stages. Local pathologic assessment of disease status by sonography is possible.
25512675 MRI assessment of early response to certolizumab pegol in rheumatoid arthritis: a randomis 2015 Jun OBJECTIVES: To identify the first time point of an MRI-verified response to certolizumab pegol (CZP) therapy in patients with rheumatoid arthritis (RA). METHODS: Forty-one patients with active RA despite disease-modifying antirheumatic drug therapy were randomised 2:1 to CZP (CZP loading dose 400 mg every 2 weeks at weeks 0-4; CZP 200 mg every 2 weeks at weeks 6-16) or placebo→CZP (placebo at weeks 0-2; CZP loading dose at weeks 2-6; CZP 200 mg every 2 weeks at weeks 8-16). Contrast-enhanced MRI of one hand and wrist was acquired at baseline (week 0) and weeks 1, 2, 4, 8 and 16. All six time points were read simultaneously, blinded to time, using the Outcome Measures in Rheumatology Clinical Trials RA MRI scoring system. Primary outcome was change in synovitis score in the CZP group; secondary outcomes were change in bone oedema (osteitis) and erosion scores and clinical outcome measures. RESULTS: Forty patients were treated (27 CZP, 13 placebo→CZP), and 36 (24 CZP, 12 placebo→CZP) completed week 16. In the CZP group, there were significant reductions from baseline synovitis (Hodges-Lehmann estimate of median change, -1.5, p=0.049) and osteitis scores (-2.5, p=0.031) at week 16. Numerical, but statistically insignificant, MRI inflammation reductions were observed at weeks 1-2 in the CZP group. No significant change was seen in bone erosion score. Improvements across all clinical outcomes were seen in the CZP group. CONCLUSIONS: CZP reduced MRI synovitis and osteitis scores at week 16, despite small sample size and the technical challenge of reading six time points simultaneously. This study provides essential information on optimal MRI timing for subsequent trials. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT01235598.
27098309 Ureido group-specific antibodies are induced in rabbits immunized with citrulline- or homo 2016 Nov The specificities and cross-reactions of antibodies induced by citrulline- and homocitrulline-containing proteins may give implications on the role of citrulline- and homocitrulline-binding antibodies in the pathogenesis and progression of rheumatoid arthritis (RA). Here we use rabbits as an experimental model of antibody development in RA. Thirty-two animals were immunized with peptide antigens containing either homocitrulline or citrulline. The sera were tested for binding to CCP and MCV antigens and to peptide sequences related to carboxyterminal telopeptides of type I and II collagens and containing arginine, citrulline, or homocitrulline. The binding of CCP and MCV antigens to antisera against homocitrulline-containing immunogens could be inhibited by human serum albumin containing homocitrulline, whereas similar binding to sera against citrulline-containing immunogens was not inhibited. The antisera induced with citrulline-containing collagen telopeptides recognized type I collagen-related antigens in a sequence-specific manner, as antibody binding to both citrulline- and homocitrulline-containing peptides was inhibited by corresponding citrullinated and native peptides. In contrast, type II collagen-related peptides were recognized by the antisera in a ureido group-specific manner, as their binding to homocitrulline-containing peptide was inhibited by both citrulline- and homocitrulline-containing, but not native peptide. Binding of the citrullinated type II collagen peptide could only be inhibited by the similarly citrullinated peptide. In conclusion, antibodies induced with citrulline or homocitrulline-containing antigens bound antigens in a ureido group-specific manner, recognizing citrulline and homocitrulline also in other sequences than those used in the original immunization. In competitive situations the amino acid present in the immunization antigen was favored.
26692147 Association of XRCC1 and OGG1 DNA repair gene polymorphisms with rheumatoid arthritis in E 2016 Mar 1 Rheumatoid arthritis (RA) is a chronic autoimmune disease and can lead to deformities and severe disabilities, due to irreversible damage of tendons, joints, and bones. Previous studies indicated that the DNA repair system was involved in the pathology of RA. In this study, we investigated the association of two XRCC1 (X-ray repair cross-complementing group 1) (rs25487 and rs25489) gene polymorphisms and two OGG1 (8-oxoguanine glycosylase 1) gene polymorphisms (rs159153 and rs3219008) with the susceptibility to RA in 320 Egyptians individuals (160 RA patients and 160 controls). Genotyping was performed using restriction fragment length polymorphism polymerase chain reaction. We found an association between variant XRCC1 (rs25487 and rs25489) genotype polymorphisms, OGG1 (rs3219008) genotype polymorphism, and RA disease susceptibility. Moreover, the presence of the Gln/Gln, Arg/His, and His/His genotypes of XRCC1 was significantly more likely to have bone erosion and extra-articular features in RA patients. Further, patient's carrying the OGG1 A/G and G/G genotypes more likely to have bone erosion. However, the AA genotype and A allele were significantly more likely to have extra-articular features. Also, there were no significant associations between C/T OGG1 gene polymorphism and RA susceptibility, bone erosion, and extra-articular features occurrence in RA patients. We concluded that the XRCC1-Arg/Gln, XRCC1-Arg/His, and OGG1 A/G polymorphism have a role in the development of rheumatoid arthritis disease. Also, these variant are associated with the severity of RA.