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ID PMID Title PublicationDate abstract
23651685 Performance of the Dutch SF-36 version 2 as a measure of health-related quality of life in 2013 May 8 BACKGROUND: The aim of this study was to examine the measurement properties of the Dutch SF-36 version 2 (SF-36v2) health survey in patients with rheumatoid arthritis (RA). METHODS: Scaling assumptions, internal reliability, and internal construct validity were examined using available data from 1884 RA patients included in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry. External construct validity and responsiveness to change were examined using baseline and 6-month follow-up data from a subset of 387 early RA patients participating in the DREAM remission induction cohort. RESULTS: The individual items of the SF-36v2 adequately met scaling assumptions, although four items correlated too highly with items from different scales. Internal consistency was high for all eight scales and the physical and mental health components underlying the scales were replicated, supporting the use of the standard scoring algorithms. The SF-36v2 scales demonstrated minimal floor effects and ceiling effects were noteworthy only for the role-physical, social functioning, and role-emotional scales. Correlations with other core measures were as expected and the SF-36v2 showed excellent known-groups validity in distinguishing between patients with low or moderate-high disease activity. All scales related to physical health showed moderate to large responsiveness to change in patients that achieved low disease activity at six months. CONCLUSION: The SF-36v2 appears to be a psychometrically sound tool for the assessment of health-related quality of life of Dutch patients with RA.
24356614 Subacute lupus erythematosus during treatment with golimumab for seronegative rheumatoid a 2014 Feb We report on a 52-year-old woman with a history of severe seronegative rheumatoid arthritis. Several conventional therapies and biological therapy with etanercept and infliximab had been unsuccessful. In 2010 she was given golimumab subcutaneously at a monthly dose of 50 mg. She had a negative ANA titre. After 16 months of uninterrupted therapy and sustained response, she developed skin lesions on the upper trunk, back and upper extremities, which worsened on exposure to the sun. The skin biopsy was compatible with subacute lupus erythematosus. Laboratory findings included an ANA titre 1:640, negative anti-Ro/SSA and anti-DNA antibodies. Topical corticosteroid therapy proved inadequate. The patient's condition improved only after discontinuation of golimumab. The causal relationship between subacute cutaneous lupus erythematosus and golimumab is not dose-related and occurs with some delay (a typical feature of immunological adverse reactions). The association is likely, but not confirmed (because re-challenge was not performed). However, a clear improvement was noted after withdrawal. Based on this case, we hypothesized the aetiological role of golimumab-associated immunogenicity. TNF-α antagonist-induced lupus-like syndrome (TAILS) is a well-known side effect of this class of substances. The British Society of Rheumatology recommends discontinuation of the causal anti-TNF-α treatment in patients with TAILS.
24689929 Expression of TIM-3 on CD4+ and CD8+ T cells in the peripheral blood and synovial fluid of 2014 Oct Rheumatoid arthritis (RA) is characterized by a chronic inflammatory process that targets the synovial lining of diarthrodial joints. TIM-3 plays a key role in the negative regulation of the immune response. In this study, we investigated the expression of TIM-3 on CD4+ and CD8+ T cells from systemic (peripheral blood) and local (synovial fluid) perspectives of RA. Level of TIM-3+ cells from peripheral blood and synovial fluid of patients as well as peripheral blood of healthy controls was measured by flow cytometry. Results showed that TIM-3 expression was significantly increased in both CD4+ and CD8+ T cells in the peripheral blood of RA (p < 0.001 and p < 0.001, respectively). Furthermore, patients revealed even higher expression of TIM-3 in CD4+ and CD8+ T cells in synovial fluid than in peripheral blood. When comparing TIM-3 level with the severity of RA, we identified that the percentage of TIM-3 on both peripheral CD4+ and peripheral CD8+ T cells was negatively correlated with disease activity score 28 (DAS28) of the patients. Similarly, TIM-3 on synovial fluid CD4+ and CD8+ T cells also revealed inverse correlation with DAS28 of the cases. Our data demonstrate a negative correlation between TIM-3 and the disease progression of RA.
24472267 Plasma osteopontin is correlated with bone resorption markers in rheumatoid arthritis pati 2014 Jan AIM: To assess whether any form of osteopontin (OPN) is correlated with bone resorption markers or treatment effects in rheumatoid arthritis (RA). METHOD: Subjects comprised 119 patients with RA. RA disease activity was evaluated by Disease Activity Score (DAS) 28, erythrocyte sedimentation rate (ESR), and levels of C-reactive protein (CRP), rheumatoid factor (RF) and matrix metalloproteinase (MMP)-3. OPN levels in plasma and urine were measured by enzyme-linked immunosorbent assay (ELISA). Levels of tartrate-resistant acid phosphatase (TRACP) 5b in serum and C-terminal telopeptide of type 1 collagen (CTX)-1 in urine were measured by ELISA. Patients were divided into responder and nonresponder groups, and OPN levels were compared at baseline and after treatment. RESULTS: Levels of full-length OPN in plasma (P-fOPN) were significantly correlated with levels of TRACP 5b (r = 0.44, P < 0.001), urine CTX-1 (r = 0.26, P = 0.004) and MMP-3 (r = 0.34, P < 0.001). Levels of TRACP 5b were significantly correlated with age (r = 0.25, P = 0.007), but levels of P-fOPN were not. After treatment, plasma OPN levels were significantly decreased in responders (P = 0.003). Levels of full-length or thrombin-cleaved forms of OPN in urine were not correlated with TRACP 5b or CTX-1. CONCLUSION: Our results suggest that plasma OPN may reflect inflammatory bone destruction in RA patients.
23686569 Performance of anti-cyclic citrullinated Peptide assays differs in subjects at increased r 2013 Sep OBJECTIVE: To compare the diagnostic accuracy and agreement of commonly available assays for anti-citrullinated protein antibodies in patients with established rheumatoid arthritis (RA) and subjects at increased risk of RA. METHODS: Tests for anti-cyclic citrullinated peptide (anti-CCP) antibodies were performed using CCP2 IgG and CCP3.1 IgA/IgG enzyme-linked immunosorbent assays in the following groups: probands with established RA (n = 340) from the Studies of the Etiology of Rheumatoid Arthritis (SERA) cohort and their first-degree relatives (FDRs) without inflammatory arthritis (n = 681), Department of Defense Serum Repository (DoDSR) RA cases with pre-RA diagnosis samples (n = 83; 47 cases also had post-RA diagnosis samples), and blood donor and DoDSR control subjects (n = 283). RESULTS: In patients with established RA, the CCP2 assay was more specific (99.2% versus 93.1%; P < 0.01) but less sensitive (58.7% versus 67.4%; P = 0.01) than the CCP3.1 assay; the specificity of the CCP3.1 assay increased to 97.2% when cutoff levels ≥3-fold the standard level were considered. In all subjects, CCP3.1 assay positivity (using standard cutoff levels) was more prevalent. Among DoDSR cases, the CCP2 assay was more specific than the CCP3.1 for predicting a future diagnosis of RA, and higher CCP levels trended toward increasing specificity for the development of RA within 2 years. At standard cutoff levels, assay agreement was good in patients with established RA (κ = 0.76) but poor in FDRs without inflammatory arthritis (κ = 0.25). CONCLUSION: Anti-CCP assays differ to an extent that may be meaningful for diagnosing RA in patients with inflammatory arthritis and evaluating the natural history of RA development in subjects at risk of RA. The mechanisms underlying these differences in test performance need further investigation.
25437288 Challenges in imaging in preclinical rheumatoid arthritis. 2014 Nov There exists a preclinical phase to the disease progression of rheumatoid arthritis, in which there is evidence of autoimmunity but no overt clinical arthritis. Identifying patients in this phase would allow for early treatment, to potentially halt manifestation of the disease. Imaging, because it is noninvasive, provides an appealing alternative to gold-standard synovial biopsies for identification of these preclinical patients. Ultrasonography, magnetic resonance imaging, and positron emission tomography all have their advantages and disadvantages as imaging modalities in this regard. Further research into alternative imaging modalities with larger cohorts is required to determine the most effective technique.
24377493 The effects of sandals on postural stability in patients with rheumatoid arthritis: an exp 2014 Mar BACKGROUND: Rheumatoid arthritis results in postural instability, pain and functional limitations. As rheumatoid arthritis progresses, localised forefoot deformities such as hallux valgus and clawing of the lesser toes occur, leading to a high proportion of people with rheumatoid arthritis wearing sandals. Sandals may affect postural stability due to poor motion control. The aim was to assess two different open-toe sandals on postural stability in people with rheumatoid arthritis. METHODS: Twenty women with rheumatoid arthritis were assessed in quiet standing under four conditions: (1) open-back sandal; (2) closed-back sandal; (3) own footwear and (4) bare feet. Postural stability was assessed as postural sway in the anterior-posterior and medial-lateral directions, with eyes open and eyes closed, using a pressure mat. Repeated measures analysis of variance tested the interaction effect of the footwear and eye conditions on anterior-posterior and medial-lateral sway. FINDINGS: In eyes-open, there was no significant difference in anterior-posterior sway (P=.169) and medial-lateral sway (P=.325) for footwear conditions. In eyes-closed testing, compared with barefoot conditions, increased anterior-posterior sway was observed with participants' footwear (P<.0001), the open-back sandal (P=.005), and the closed-back sandal (P=.017). With eyes closed, increased anterior-posterior sway was also observed with the participants' footwear compared with the closed-back sandal (P=.041). Increased medial-lateral sway was observed with the closed-back sandal compared with bare feet (P=.014). INTERPRETATION: Sandals may be detrimental to older women with well-established rheumatoid arthritis when eyes are closed. Further investigation is needed to evaluate the effect of sandals on dynamic tasks.
23983001 Barriers to optimal disease control for rheumatoid arthritis patients with moderate and hi 2014 Feb OBJECTIVE: To evaluate barriers that prevent rheumatoid arthritis (RA) patients from achieving Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) scores within the current recommended levels for low disease activity (LDA) or clinical remission (DAS28-ESR score <3.2). METHODS: Using an electronic medical record program, clinical data for RA patients treated in Optimising Patient Outcomes in Australian Rheumatology clinics, with a recorded DAS28-ESR score, were collected at one point in time. The data included demographics, medications, disease measures, and the rheumatologist's opinion of the main barriers preventing improvement to the recommended DAS28 score. RESULTS: Of the 4,037 patients with a recorded DAS28-ESR score, 304 patients (7.5%) had high disease activity (HDA) and 1,211 patients (30%) had moderate disease activity (MDA). For 584 HDA or MDA patients, the barriers to disease control (BTCs) were recorded by the rheumatologist when there was no adjustment to disease-modifying antirheumatic drug (DMARD) therapy. The recorded BTCs were irreversible joint damage (19.7%), patient-driven preference (14.7%), noninflammatory musculoskeletal pain (9.2%), insufficient time to assess the effect of recently initiated DMARDs (9.2%), safety concerns (7.5%), comorbidities (6.5%), resistant disease (6.3%), and other less common reasons. These patients received DMARDs (97.4%), including biologic agents (34.1%), methotrexate (74.8%), and oral corticosteroids (41.8%). CONCLUSION: This study identified clinical situations in which rheumatologists elected to continue RA patients with MDA or HDA on DMARD therapy without adjustment to achieve clinical remission or an LDA target of a DAS28-ESR score <3.2.
22839595 Physical inactivity and arterial dysfunction in patients with rheumatoid arthritis. 2013 OBJECTIVES: The increased risk of cardiovascular (CV) disease associated with rheumatoid arthritis (RA) is partly attributable to chronic inflammation, but traditional CV risk factors such as physical inactivity are also likely to be important. This study assessed the cross-sectional relationship between physical activity (PA) and arterial dysfunction in patients with RA. METHODS: Participants free of overt arterial disease aged 40-65 years were recruited from a consecutive series of RA patients attending a rheumatology clinic. A research nurse measured the 'augmentation index' (AIX%) on a single occasion (a higher AIX% indicates arterial dysfunction) using SphygmoCor radial pulse wave analysis (PWA) according to current recommendations. Participants provided a fasting blood sample and self-completed a patient questionnaire that included the modified Godin PA score (mGPAS). Analysis was adjusted for age, sex, CV and rheumatological factors using multiple linear regression. RESULTS: Among 114 patients (mean age 54 years, median arthritis duration 10 years, 82% women), mean AIX% was 31.5 (SD 7.7) and median mGPAS 15 (IQR 10-35). AIX% was correlated with mGPAS (rho -0.21, p = 0.02). AIX% decreased with more frequent vigorous PA. On unadjusted analysis, a 10-point higher mGPAS was associated with a -0.9 [95% confidence interval (CI) -1.3 to -0.4, p = 0.0005] lower AIX%. On adjusted analysis, the reduction was attenuated to -0.5 (95% CI -0.8 to -0.1, p = 0.03). CONCLUSIONS: A higher level of self-reported PA in RA patients is associated with a lower level of arterial dysfunction independently of other CV and rheumatological factors. Longitudinal studies are required to demonstrate that increased PA improves arterial dysfunction in RA patients.
24906551 Functional and patient-reported outcome of partial wrist denervation versus the Mannerfelt 2014 Jul INTRODUCTION: Wrist arthrodesis offers high success rates in patients with rheumatoid arthritis; however, loss of residual mobility may cause unnecessary disability. This makes wrist denervation an appealing alternative. However, there is a distinct lack of patient-reported outcome measure studies comparing these two procedures. The aim of this study was to report any change in function, pain and satisfaction following wrist arthrodesis compared to denervation in a single surgeon series of rheumatoid patients. PATIENTS AND METHODS: The results of 16 wrist arthrodesis in 15 patients and 14 partial (PIN) wrist denervations in 13 patients were compared with a mean follow-up period of 39 and 22 months, respectively. The primary outcome measures were the same for both groups and included the validated patient-rated wrist evaluation questionnaire and a satisfaction questionnaire. RESULTS: Wrist arthrodesis significantly improved the mean total pain and functional outcome scores by 54 and 36 %, respectively, at the time of follow-up. Wrist denervation patients also reported significant improvements of 44 and 42 % in total pain and functional outcomes, respectively; 87 % reported being very satisfied with their wrist arthrodesis procedure compared to 78 % in the denervation group. No statistically significant difference in response between the groups was observed in this series of patients. CONCLUSIONS: Both procedures enjoyed favourable results amongst patients with excellent satisfaction outcomes. PIN denervation is a simple procedure with low complication rates and we therefore consider it a valid alternative to more difficult treatment options, such as partial or total wrist arthrodesis.
25073613 Presence of comorbidity affects both treatment strategies and outcomes in disease activity 2015 Mar To clarify the impact of comorbidities on treatment strategies and outcomes in patients with rheumatoid arthritis (RA) using a large observational RA cohort, the presence of comorbidities was assessed using the Charlson Comorbidity Index (CCI). Changes in medication, disease activity by Disease Activity Score-28 joint count (DAS28) over 6 months, disability assessed by the Japanese version of the Health Assessment Questionnaire (J-HAQ), and quality of life by EuroQOL-5-Dimensions (EQ-5D) over 1 year in patients with high disease activity (DAS28 > 5.1) at baseline were assessed according to age-adjusted CCI (CCI(A)) and categorized into four groups (CCI(A) 0, 1-2, 3-4, and ≥5). Among 5,317 patients, 975 patients (18.3%) had at least one comorbidity listed by CCI. DAS28, J-HAQ, and EQ-5D increased in severity with increased CCI(A) levels. Among patients with high disease activity (n = 267), treatment with methotrexate and/or biologics and improved DAS28 scores, shown by attenuated intensity, were associated with increased CCI(A) levels. J-HAQ improved from 1.29 ± 0.31 to 0.87 ± 0.37 in 1 year in the CCI(A) 0 group. The adjusted difference (standard error) in J-HAQ at 1 year in CCI(A) 1-2, 3-4, and ≥5 groups was worse than J-HAQ in the CCI(A) 0 group by 0.32 (0.09, p < 0.001), 0.45 (0.10, p < 0.001), and 0.45 (0.15, p < 0.01), respectively. The magnitude of improvement of EQ-5D was significantly attenuated with increasing CCI(A) levels. Thus, patients with comorbidities may not experience the same degree of benefit from recent RA treatments compared with patients without comorbidities in daily practice.
25355728 MRI assessment of suppression of structural damage in patients with rheumatoid arthritis r 2016 Jan OBJECTIVE: To evaluate changes in structural damage and joint inflammation assessed by MRI following rituximab treatment in a Phase 3 study of patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) who were naive to biological therapy. METHODS: Patients were randomised to receive two infusions of placebo (n=63), rituximab 500 mg (n=62), or rituximab 1000 mg (n=60) intravenously on days 1 and 15. MRI scans and radiographs of the most inflamed hand and wrist were acquired at baseline, weeks 12 (MRI only), 24 and 52. The primary end point was the change in MRI erosion score from baseline at week 24. RESULTS: Patients treated with rituximab demonstrated significantly less progression in the mean MRI erosion score compared with those treated with placebo at weeks 24 (0.47, 0.18 and 1.60, respectively, p=0.003 and p=0.001 for the two rituximab doses vs placebo) and 52 (-0.30, 0.11 and 3.02, respectively; p<0.001 and p<0.001). Cartilage loss at 52 weeks was significantly reduced in the rituximab group compared with the placebo group. Other secondary end points of synovitis and osteitis improved significantly with rituximab compared with placebo as early as 12 weeks and improved further at weeks 24 and 52. CONCLUSIONS: This study demonstrated that rituximab significantly reduced erosion and cartilage loss at week 24 and week 52 in MTX-inadequate responder patients with active RA, suggesting that MRI is a valuable tool for assessing inflammatory and structural damage in patients with established RA receiving rituximab. TRIAL REGISTRATION NUMBER: NCT00578305.
23559669 Rituximab treatment for 'rhupus syndrome': clinical and power-Doppler ultrasonographic mon 2013 May OBJECTIVE: To evaluate the safety and efficacy of rituximab in patients suffering from rhupus unresponsive to therapy with non-biological disease-modifying anti-rheumatic drugs (DMARDs). METHODS: Six patients fulfilling criteria for both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and with a DAS28 score >5.1 were enrolled to receive two fortnightly 1000 mg rituximab doses at baseline and after 28 weeks. All patients underwent clinical, laboratory, and power- Doppler (PD) ultrasonographic (US) assessment at baseline and after 14, 28 and 56 weeks. RESULTS: A sustained improvement in DAS28, SLEDAI, HAQ, laboratory markers and ultrasound indices together with a significant reduction in the daily dose of prednisone were observed throughout follow-up. CONCLUSION: Rituximab may be a safe and effective therapeutic option in refractory rhupus patients.
25267142 Fish consumption and risk of rheumatoid arthritis: a dose-response meta-analysis. 2014 Sep 30 INTRODUCTION: The association between fish consumption and rheumatoid arthritis (RA) is unclear. The aim of this paper was to summarize the available evidence on the association between fish consumption and risk of RA using a dose-response meta-analysis. METHODS: Relevant studies were identified by a search of MEDLINE and EMBASE through December 2013, with no restrictions. A random-effects dose-response meta-analysis was conducted to combine study specific relative risks. Potential non-linear relation was investigated using restricted cubic splines. A stratified analysis was conducted by study design. RESULTS: Seven studies (four case-controls and three prospective cohorts) involving a total of 174 701 participants and 3346 cases were included in the meta-analysis. For each one serving per week increment in fish consumption, the relative risk (RR) of RA was 0.96 (95% confidence interval (CI) 0.91 to 1.01). Results did not change when stratifying by study design. No heterogeneity or publication bias was observed. When fish consumption was modeled using restricted cubic splines, the risk of RA was 20 to 24% lower for 1 up to 3 servings per week of fish (RR =0.76, 95% CI: 0.57 to 1.02) as compared to never consumption. CONCLUSIONS: Results from this dose-response meta-analysis showed a non-statistically significant inverse association between fish consumption and RA.
25012729 Estimating effectiveness and cost of biologics for rheumatoid arthritis: application of a 2014 Jul 1 PURPOSE: The aim of this analysis was to implement a claims-based algorithm to estimate biologic cost per effectively treated patient for biologics approved for moderate to severe rheumatoid arthritis (RA). METHODS: This retrospective analysis included commercially insured adults (aged 18-63 years) with RA in a commercial database, who initiated biologic treatment with abatacept, adalimumab, etanercept, golimumab, or infliximab between 2007 and 2010. The algorithm defined effectiveness as having all of the following: high adherence, no biologic dose increase, no biologic switching, no new nonbiologic disease-modifying antirheumatic drug, no increased or new oral glucocorticoid use, and no more than 1 glucocorticoid injection. For each biologic, cost per effectively treated patient was defined as total drug and administration costs (from allowed amounts on claims), divided by the number of patients categorized as effectively treated. FINDINGS: Of 15,351 patients, 12,018 (78.3%) were women, and the mean (SD) age was 49.7 (9.6) years. The algorithm categorized treatment as effective in the first year for 30% (1899/6374) of etanercept, 30% (1396/4661) of adalimumab, 20% (560/2765) of infliximab, 27% (361/1338) of abatacept, and 29% (62/213) of golimumab treated patients. The 1-year biologic cost per effectively treated patient, as defined by the algorithm, was nominally lower for subcutaneously injected biologics than for infused biologics. The 1-year biologic cost per effectively treated patient, as defined by the algorithm, was lowest for etanercept ($49,952), followed by golimumab ($50,189), adalimumab ($52,858), abatacept ($71,866), and infliximab ($104,333). IMPLICATIONS: Algorithm-defined effectiveness was similar for biologics other than infliximab. The 1-year biologic cost per effectively treated patient, as defined by the algorithm, was nominally lower for subcutaneously injected biologics than for infused biologics.
24990480 Inducible tyrosine kinase inhibitors: a review of the patent literature (2010 - 2013). 2014 Sep INTRODUCTION: The non-receptor tyrosine kinase, inducible tyrosine kinase (Itk), plays an important role in thymus(T)-cell signalling and the production of pro-inflammatory cytokines. Itk, and the other Tec family members, Rlk and Tec, are viewed as attractive drug targets for new agents for the treatment of autoimmune and inflammatory diseases. Interest in Itk inhibitors is still modest compared to other kinases such as the Janus kinase (JAK) family or Syk. AREAS COVERED: This article reviews the patent filings published from January 2010 to April 2014 that claim Itk inhibitors. It first considers those applications that claim selective, or apparently selective, Itk inhibitors. It then considers those applications that claim less-selective Itk inhibitors. The recent interest in irreversible Itk inhibitors is also discussed. EXPERT OPINION: There is a difference of opinion as to the preferred utility for Itk inhibitors. Progress has been made in designing selective Itk inhibitors but little clinical progress. Until clinical data are available, it remains difficult to assess how well Itk inhibitors compare with JAK inhibitors as potential treatments for rheumatoid arthritis. However, animal data suggest that irreversible Itk inhibitors could be useful in treating asthma, whereas dual Itk inhibitors may have more utility in treating rheumatoid arthritis.
24641943 Patients with regular physical activity before onset of rheumatoid arthritis present with 2014 Aug OBJECTIVES: Physical activity has been shown to decrease inflammatory markers; here we investigate the effect on the clinical presentation of rheumatoid arthritis (RA). METHODS: We used the cases from the population-based EIRA study (N=617), followed in the Swedish Rheumatology Quality Register, calculating the odds of having above median level of 28-joint disease activity score (DAS28), physician assessment, pain (visual-analogue scale (VAS), VAS-pain) and activity limitation (health assessment questionnaire (HAQ)) at diagnosis, as an effect of physical activity 5 years before diagnosis, investigated both in categories and dichotomised. RESULTS: Dose-response relationships were seen for all measures; the higher the level of physical activity, the lower the likelihood of having outcome measure above median. Further, regular physical activity associated with 42% reduced odds of having DAS28 above median (OR=0.58 (95% CI 0.42 to 0.81)). Effects were similar for VAS-pain (OR=0.62 (95%CI 0.45 to 0.86)) and physician assessment (OR=0.67 (95%CI 0.47 to 0.95)) but not for HAQ. Statistically significant effects were also found both for the combined objective components and the combined subjective components of DAS28. CONCLUSIONS: Physically active individuals seem to present with milder RA, which adds to the evidence of beneficial effects of physical activity on inflammatory diseases. The observation should be important for both health professionals and individuals seeking to reduce their risk.
23276819 The long-term immunosuppressive effects of disulfide-linked HLA-G dimer in mice with colla 2013 Apr HLA-G, a natural immunosuppressant present in the human placenta during pregnancy, prevents fetal destruction by the maternal immune system. The immunosuppressive effect of HLA-G is mediated by the immune cell inhibitory receptors, LILRB1 and LILRB2. HLA-G forms disulfide-linked dimers by natural oxidation, and the dimer associates with LILRB1/B2 much more strongly than the monomer. Furthermore, the dimer formation remarkably enhanced the LILRB-mediated signaling. In this report, we studied the in vivo immunosuppressive effect of the HLA-G dimer, using the collagen-induced arthritis model mouse. Mice were treated with the HLA-G monomer or dimer intracutaneously at the left foot joint, once or for 5 days, and the clinical severity was evaluated daily in a double-blind study. The HLA-G monomer and dimer both produced excellent anti-inflammatory effects with a single, local administration. Notably, as compared to the monomer, the dimer exhibited significant immunosuppressive effects at lower concentrations, which persisted for about two months. In accordance with this result, a binding study revealed that the HLA-G dimer binds PIR-B, the mouse homolog of the LILRBs, with higher affinity and avidity than the monomer. The HLA-G dimer is expected to be quite useful as an anti-rheumatoid arthritis agent, in small amounts with minimal side effects.
25079933 Rheumatoid factor and anti-CCP do not predict progressive joint damage in patients with ea 2014 Jul 30 OBJECTIVE: To analyse if predictors of radiographic progression differ between patients treated with or without prednisolone in early rheumatoid arthritis (RA). Radiographs of hands and feet were assessed using the modified Sharp/van der Heijde score and radiographic progression was defined as an increase in the total Sharp score above 5.8 (the smallest detectable change). DESIGN: Prospective, randomised study of patients with early RA. SETTING: Secondary level of care; six participating centres from southern Sweden; both urban and rural populations. PARTICIPANTS: In all, 225 patients, 64% women, with a diagnosis of RA according to the American College of Rheumatology criteria, were included if they were between 18 and 80 years of age and had a disease duration of less than 1 year. INTERVENTION: The patients were randomised to 7.5 mg prednisolone daily for 2 years (P-group; n=108) or no prednisolone (NoP-group; n=117) when they started with their first disease-modifying anti-rheumatic drug and were prospectively followed for 2 years. RESULTS: The frequency of patients with radiographic progression after 2 years was 26% in the P-group and 39% in the NoP-group (p=0.033). Relevant interactions between treatment and rheumatoid factor (RF) (p=0.061) and between treatment and anti-cyclic citrullinated peptide 2 (anti-CCP) (p=0.096) were found. RF and anti-CCP independently predicted radiographic progression only in the NoP-group, OR (95% CI) 9.4 (2.5 to 35.2), p=0.001 and OR (95% CI) 8.7 (2.5 to 31.3), p=0.001, respectively. CONCLUSIONS: The presence of RF and anti-CCP predicted radiographic progression in patients not treated with prednisolone but failed to predict progression in patients treated with this drug. The data suggest that early treatment with prednisolone may modulate not only inflammation but also autoimmunity-associated pathogenetic mechanisms. TRIAL REGISTRATION NUMBER: ISRCTN20612367.
25713628 Utility of different cardiovascular disease prediction models in rheumatoid arthritis. 2014 Oct BACKGROUND: Rheumatoid arthritis comes with a 30% higher probability for cardiovascular disease than the general population. Current guidelines advocate for early and aggressive primary prevention and treatment of risk factors in high-risk populations but this excess risk is under-addressed in RA in real life. This is mainly due to difficulties met in the correct risk evaluation. This study aims to underline the differences in results of the main cardiovascular risk screening models in the real life rheumatoid arthritis population. METHODS: In a cross-sectional study, patients addressed to a tertiary care center in Romania for an biannual follow-up of rheumatoid arthritis and the ones who were considered free of any cardiovascular disease were assessed for subclinical atherosclerosis. Clinical, biological and carotidal ultrasound evaluations were performed. A number of cardiovascular disease prediction scores were performed and differences between tests were noted in regard to subclinical atherosclerosis as defined by the existence of carotid intima media thickness over 0,9 mm or carotid plaque. RESULTS: In a population of 29 Romanian rheumatoid arthritis patients free of cardiovascular disease, the performance of Framingham Risk Score, HeartSCORE, ARIC cardiovascular disease prediction score, Reynolds Risk Score, PROCAM risk score and Qrisk2 score were compared. All the scores under-diagnosed subclinical atherosclerosis. With an AUROC of 0,792, the SCORE model was the only one that could partially stratify patients in low, intermediate and high-risk categories. The use of the EULAR recommended modifier did not help to reclassify patients. CONCLUSION: The only score that showed a statistically significant prediction capacity for subclinical atherosclerosis in a Romanian rheumatoid arthritis population was SCORE. The additional calibration or the use of imaging techniques in CVD risk prediction for the intermediate risk category might be warranted.