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ID PMID Title PublicationDate abstract
23123533 New biomarkers in rheumatoid arthritis. 2012 Nov Rheumatoid arthritis (RA) is a common autoimmune disease affecting around 1% of the population. Although major advances have been made in the treatment of RA, still relatively little is known on disease pathogenesis and aetiology. From treatment studies it has become clear that treating patients early in their disease course will provide the best results. However, especially in the early phase of arthritis, in particular when the patients do not yet fulfil the criteria for RA, it is difficult to decide which patients would benefit most from an early and aggressive intervention. Good biomarkers are important to guide decisions in the clinical management of RA. Next to the well-known rheumatoid factor (RF) and the anti-citrullinated protein antibodies (ACPA), several new markers are now likely to become available with interesting potential. Besides antibody responses directed against citrullinated proteins, also antibodies against carbamylated proteins (anti-CarP) have recently been shown to be present in RA. Interestingly these anti-CarP antibodies are also present in around 20% of the ACPA-negative RA patients and are associated with more severe joint damage in this group. Apart from the antibodies that help in establishing the diagnosis and prognosis, also novel biomarkers that reflect clinical disease activity scores are being discovered. The development of biomarker-based disease activity scores might allow easy and frequent monitoring of patients to rapidly adjust treatment.
21120535 Osteoblast physiology in normal and pathological conditions. 2011 Feb Osteoblasts are mononucleated cells that are derived from mesenchymal stem cells and that are responsible for the synthesis and mineralization of bone during initial bone formation and later bone remodelling. Osteoblasts also have a role in the regulation of osteoclast activity through the receptor activator of nuclear factor κ-B ligand and osteoprotegerin. Abnormalities in osteoblast differentiation and activity occur in some common human diseases such as osteoporosis and osteoarthritis. Recent studies also suggest that osteoblast functions are compromised at sites of focal bone erosion in rheumatoid arthritis.
22854556 [Health-related quality of life in Korean patients with rheumatoid arthritis: association 2012 Jun PURPOSE: The purpose of this predictive study was to identify factors affecting health related quality of life (HRQoL) in patients with rheumatoid arthritis (RA). METHODS: The participants in this study were 131 patients with RA who were recruited from the outpatient clinic of a university hospital in Seoul. Disease activity in rheumatoid arthritis was evaluated by calculating the Disease Activity Score 28. Disability in activities of daily living (ADL) was assessed with the Korean Health Assessment Questionnaire, and depression with The Center for Epidemiologic Studies Depression Scale. HRQoL was evaluated using The Short Form 36 Health Survey. Data were analyzed using descriptive statistics, correlation, and hierarchical multiple regression. RESULTS: Pain, disability in ADL, disease activity, and depression correlated negatively with physical and mental dimensions of HRQoL. But hierachical multiple regression analysis revealed that disability in ADL and depression were the only variables negatively influencing physical and mental QoL after adjustment for influences of sociodemographic variables. CONCLUSION: Results of this study suggest that disability in ADL and depression, rather than disease activity and pain have profound effects on HRQoL in patients with RA. Further studies are needed to assess the predictive ability of disease activity and pain on HRQoL in this population.
22999943 Autoimmune manifestations in large granular lymphocyte leukemia. 2012 Dec Large granular lymphocyte (LGL) leukemia features a group of indolent lymphoproliferative diseases that display a strong association with various autoimmune conditions. Notwithstanding, these autoimmune conditions have not been comprehensively characterized or systematized to date. As a result, their clinical implications remain largely unknown. The authors offer a comprehensive review of the existing literature on various autoimmune conditions documented in the course of T-cell LGL (T-LGL) leukemia. Though some of them are thought be secondary to the LGL leukemia, others could be primary and might even play a role in its pathogenesis. A considerable clinico-laboratory overlap between T-LGL leukemia associated with rheumatoid arthritis and Felty's syndrome suggests that they are just different eponyms for the same clinical entity.
22042491 Prevalence of overweight in Moroccan patients with rheumatoid arthritis and its relationsh 2012 Mar We aimed to estimate the prevalence of overweight in Moroccan patients with rheumatoid arthritis (RA) and its relationships with disease activity, functional disability, structural damage, and immunological status. Two hundred fifty patients with RA were consecutively included. Patients' characteristics were specified. The following data were collected: age, disease duration, disease activity (evaluated with physical examination data, biological tests (erythrocyte sedimentation rate and C-reactive protein), and the disease activity score (DAS28)), radiographic changes (assessed by the Sharp's method), functional disability (assessed by using the Health Assessment Questionnaire), extra-articular manifestations, immunological status, and treatment details. Overweight was defined according to the body mass index (BMI) values: underweight, <18.5; normal weight, 18.5-24.9; overweight, 25-29.9; and obesity, ≥30. The mean age of patients was 46.31 ± 12.64 years. The mean disease duration was 9.46 ± 8.43 years. Seventy-five patients (30%) were overweight, 42 (16.8%) were obese, and 133 (53.2%) were normal. Increased BMI was associated with the activity of disease (DAS28) (r = 0.426), structural damage (Sharp total score) (r = 0.297), the rate of rheumatoid factor (r = 0.311), and with the rate of anti-cyclic citrullinated protein antibodies (for all p ≤ 0.01). There were no statistically significant differences in BMI according to gender, dose and duration of corticosteroids, or functional impairment. In our sample, overweight seems to be prevalent in our RA patients. Overweight seems to occur independently of treatment and shown to be mainly associated to disease activity, structural damage, and immunological status. Large studies are needed to confirm those results.
22772459 Usefulness of ultrasonography-proven tenosynovitis to monitor disease activity of a patien 2013 May We introduced abatacept (ABT) in a very early rheumatoid arthritis (RA) patient with active tenosynovitis of hands defined by musculoskeletal ultrasonography (MSKUS). MSKUS-proven tenosynovitis remarkably improved at 2 months in spite of clinical exacerbation, followed by clinical remission at 5 months. MSKUS abnormalities also disappeared. Although ABT was discontinued due to an adverse event after the sixth infusion, she remained in clinical remission as well as imaging remission by MSKUS at 13 months.
23200062 Vitamin D in rheumatoid arthritis: panacea or placebo? 2012 Nov Vitamin D deficiency is highly prevalent in the general population including individuals with rheumatoid arthritis (RA). Autocrine regulation of vitamin D modulates important biologic processes including immune responses. Vitamin D deficiency has been implicated in the pathogenesis of several autoimmune diseases including RA. Vitamin D regulates both the innate and adaptive immune responses. Recent evidence indicates that vitamin D's effects on the innate immune system are predominantly through the toll-like receptors (TLR) and on the adaptive immune system through T cell differentiation, particularly the Th17 response. As Th17 cells are critical in the pathogenesis of RA, this has led to an interest in the effects of vitamin D deficiency in RA. Several studies have looked at the association of vitamin D deficiency with markers of disease activity in RA with somewhat mixed results. Based on these results, although the role of vitamin D in mediating various biological processes is well defined, this has not translated into meaningful clinical associations in RA. Herein, we review the immune-modulatory role of vitamin D and its effects on pathogenesis, disease activity, and cardiovascular risk in RA.
22819082 Genetics of rheumatoid arthritis: an impressionist perspective. 2012 May Rheumatoid arthritis (RA) is the most common rheumatic disease. The genetic basis of RA is supported through the identification of more than 30 susceptibility genetic variants. Each of these genes individually makes only a slight contribution to the risk of disease. Moreover, there is significant disparity in the genetic variants associated with different RA subgroups and patient ethnicities, which emphasizes the intricate nature of the disease's pathogenesis, and the complexities involved in large-scale genetic studies. This review evaluates critically the recent literature on the genetic contribution to RA and assesses the methodology used to identify these risk alleles.
20864373 MicroRNAs as new player in rheumatoid arthritis. 2011 Jan MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression at the post-transcriptional level. Currently, there are 939 mature human miRNA sequences listed in the Sanger updated miRNA registry. There are approximately 1500 predicted miRNAs in the human genome that may regulate the expression of one third of our genes. By controlling the accumulation of the target protein(s) in cells, these regulatory RNA molecules participate in key functions in many physiological networks and their deregulation has been implicated in the pathogenesis of serious human disorders, such as cancer and infection. The implication of miRNAs in immune-mediated disorders such as rheumatoid arthritis (RA) has recently emerged suggesting that miRNA-based therapeutic approaches may have a promising potential in these diseases. Here, we provide an overview of the state-of-the-art on miRNAs in RA, focusing on both systemic and local features of the pathology.
22841830 Lipid and lipid mediator profiling of human synovial fluid in rheumatoid arthritis patient 2012 Nov Human synovial fluid (SF) provides nutrition and lubrication to the articular cartilage. Particularly in arthritic diseases, SF is extensively accumulating in the synovial junction. During the last decade lipids have attracted considerable attention as their role in the development and resolution of diseases became increasingly recognized. Here, we describe a capillary LC-MS/MS screening platform that was used for the untargeted screening of lipids present in human SF of rheumatoid arthritis (RA) patients. Using this platform we give a detailed overview of the lipids and lipid-derived mediators present in the SF of RA patients. Almost 70 different lipid components from distinct lipid classes were identified and quantification was achieved for the lysophosphatidylcholine and phosphatidylcholine species. In addition, we describe a targeted LC-MS/MS lipid mediator metabolomics strategy for the detection, identification and quantification of maresin 1, lipoxin A(4) and resolvin D5 in SF from RA patients. Additionally, we present the identification of 5S,12S-diHETE as a major marker of lipoxygenase pathway interactions in the investigated SF samples. These results are the first to provide a comprehensive approach to the identification and profiling of lipids and lipid mediators present in SF and to describe the presence of key anti-inflammatory and pro-resolving lipid mediators identified in SF from RA patients.
21622631 Reliability and validity of the INFOOT three-dimensional foot digitizer for patients with 2011 May BACKGROUND: Abnormal foot posture and deformities are identified as important features in rheumatoid arthritis. There is still no consensus regarding the optimum technique(s) for quantifying these features; hence, a foot digitizer might be used as an objective measurement tool. We sought to assess the validity and reliability of the INFOOT digitizer. METHODS: To investigate the validity of the INFOOT digitizer compared with clinical measurements, we calculated Pearson correlation coefficients. To investigate the reliability of the INFOOT digitizer, we calculated intraclass correlation coefficients, SEMs, smallest detectable differences, and smallest detectable difference percentages. RESULTS: Most of the 38 parameters showed good intraclass correlation coefficients, with values greater than 0.9 for 30 parameters and greater than 0.8 for seven parameters. The left heel bone angle expressed a moderate correlation, with a value of 0.609. The SEM values varied between 0.31 and 3.51 mm for the length and width measures, between 0.74 and 5.58 mm for the height data, between 0.75 and 5.9 mm for the circumferences, and between 0.78° and 2.98° for the angles. The smallest detectable difference values ranged from 0.86 to 16.36 mm for length, width, height, and circumference measures and from 2.17° to 8.26° for the angle measures. For the validity of the INFOOT three-dimensional foot digitizer, Pearson correlation coefficients varied between 0.750 and 0.997. CONCLUSIONS: In this rheumatoid arthritis population, good validity was demonstrated compared with clinical measurements, and most of the obtained parameters proved to be reliable.
23154729 Foot ulcers caused by rheumatoid vasculitis in a patient with rheumatoid arthritis undergo 2012 A 59-year-old woman with a 10-year history of rheumatoid arthritis (RA) presented with chronic ulcers on both feet while undergoing treatment with etanercept. Rheumatoid vasculitis (RV) was diagnosed, and the patient was treated with immunosuppressant drugs and skin grafting. Although anti-tumor necrosis factor (TNF) agents are known to induce vasculitis, vasculitis can also be caused by active RA. Accordingly, the cause of vasculitis in RA patients receiving anti-TNF therapy must be evaluated carefully.
22101695 Complementary and alternative medicine in rheumatoid arthritis. 2011 Oct There are studies that have evidence for and are against to suggest that some of the complementary and alternative medicines (CAM) are effective against rheumatoid arthritis (RA). However, there are no adequate studies that have evaluated the role that can be played by CAM in the management of RA. A focused approach in defining the role and limitation as well as the possible adverse events and safety should help in integrating both CAM and mainstream treatment of RA. This review discussed the limitations in the available literature and the direction for future research, which can accelerate the defining role of CAM in RA.
23981749 Patterns of angiotensin converting enzyme insertion/deletion gene polymorphism among an Eg 2013 Jun AIM: This case control study was designed to determine the patterns of angiotensin converting enzyme insertion/deletion (ACE I/D) gene polymorphism in rheumatoid arthritis (RA) patients and healthy controls. METHODS: The study population was divided into two groups: the study group included 66 RA patients diagnosed according to the American College of Rheumatology (ACR) classification criteria for RA, and the control group included 66 healthy adults who were age-and sex-matched to the RA group. All RA patients were assessed by Disease Activity Score (DAS28), ACR Classification of Global Functional Disability Status and Sharp's score as outcome measures. Gene investigations for ACE I/D polymorphism were performed by polymerase chain reaction (PCR) in both groups. RESULTS: The ACE I/D polymorphism was the (D/D) genotype in 60.6% (n = 40) of RA patients, the (I/D) genotype in 31.8% (n = 21) and the (I/I) genotype in 7.6% (n = 5). The frequency of (D) carriage was significantly higher in the RA cases than in the control group (76.5% vs. 53.8%, respectively, P = 0.0002). ACE D allele carriers were at higher risk of RA, 2.8 times higher than (I) carriers and those who had the homozygote (DD) genotype had 5.6 times the possibility of having RA. No correlations were observed between the homozygote (DD) genotype and disease activity or severity in RA patients. CONCLUSIONS: Our study suggests that high frequency of the ACE D allele contributes to the heritability of RA susceptibility compared to other ACE alleles. On the other hand, no association was detected between ACE I/D polymorphism and the severity of RA.
22505270 Early rheumatoid arthritis in Latin America: low socioeconomic status related to high dise 2012 Aug OBJECTIVE: To determine the influence of socioeconomic factors on disease activity in a Latin American (LA) early rheumatoid arthritis (RA) multinational inception cohort at baseline. METHODS: Clinical evaluation, ethnicity, socioeconomic status (SES), 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR), Health Assessment Questionnaire (HAQ) disability index (DI), and erosions were recorded in 1,093 patients with early RA (<1 year from onset). Multivariate analyses evaluated influences of sex, age, marital status, education, medical coverage, SES, and ethnicity on HAQ DI, DAS28-ESR, and presence of erosions. RESULTS: Ethnicities included 43% Mestizo, 31% Caucasian, 19% African LA, 4% Amerindian, and 3% other. Fifty-eight percent were of low/low-middle SES, 42% had <8 years of education, 21% had no medical coverage, median disease duration was 6 months (25th, 75th percentiles 4, 9 months), median HAQ DI score was 1.25 (25th, 75th percentiles 0.63, 2.00), median DAS28-ESR score was 6.2 (25th, 75th percentiles 4.9, 7.2), and 25% had erosions. Women and Mestizos, African LA, and Amerindians had earlier onset than men or Caucasians (P < 0.01). When adjusted by country, the analysis of covariance model showed that low/low-middle SES, female sex, partial coverage, and older age were associated with worse HAQ DI scores; only low/low-middle SES was associated with higher DAS28 scores. Statistically significant differences were found in HAQ DI and DAS28 scores between countries. When excluding country, low/low-middle SES, female sex, and no coverage were associated with worse HAQ DI and DAS28 scores, whereas separated/divorced/widowed status was associated with worse HAQ DI scores and age was associated with worse DAS28 scores. Logistic regression showed that older age, no coverage, and the Amerindian and other ethnic groups were associated with erosions. CONCLUSION: We compared early RA patients from the main LA ethnic groups. Our findings suggest that low/low-middle SES is important in determining disease activity. A more genetic-related background for erosions is possible.
22183424 Association of anticytomegalovirus seropositivity with more severe joint destruction and m 2012 Jun OBJECTIVE: Expansion of autoreactive CD4+CD28(null) T cells is associated with extraarticular disease manifestations, including rheumatoid vasculitis, and it has recently been demonstrated that expansion of these T cells is associated with anticytomegalovirus (anti-CMV) seropositivity. This study was undertaken to investigate a possible link between latent CMV infection and rheumatoid arthritis (RA). METHODS: In a retrospective analysis, anti-CMV antibodies and clinical, serologic, and radiologic parameters of joint destruction were examined in 202 RA patients and 272 healthy controls. In addition, frequencies of CD4+CD28(null) T cells; concentrations of the cytokines monocyte chemotactic protein 1 (MCP-1), interferon-α (IFNα), and IFN-inducible protein 10; and anti-CMV-specific T cell responses were analyzed in RA patients. RESULTS: Overall, no significant difference in the frequency of anti-CMV seropositivity between RA patients and healthy controls was observed. Among individuals older than age 55 years, however, anti-CMV IgG antibodies were significantly more frequent in RA patients than controls (65.3% and 54.7%, respectively; P = 0.05). Anti-CMV seropositivity in RA patients was associated with an increased frequency of CD4+CD28(null) T cells and increased serum concentrations of MCP-1. The frequency of anti-CMV-specific CD4+ T cells producing IFNγ was increased in RA patients compared to controls. Most importantly, anti-CMV-seropositive RA patients showed radiographic evidence of more advanced joint destruction and had increased frequencies of joint-related surgical procedures, indicating more severe joint disease. CONCLUSION: Our findings indicate that latent CMV infection aggravates the clinical course of RA and is associated with increased frequencies of CD4+CD28(null) T cells and of CMV-specific IFNγ-secreting CD4+ T cells.
22328469 Adaptation and crosscultural validation of the Foot Impact Scale for Rheumatoid Arthritis 2012 Jul OBJECTIVE: To adapt and crossculturally validate the Foot Impact Scale for Rheumatoid Arthritis (FIS-RA) using Rasch analysis. METHODS: The FIS-RA was translated from English to German, Hungarian, and Dutch target languages and administered to 653 rheumatoid arthritis patients. Rasch analysis was undertaken on the impairment/footwear (FIS-RA(IF) ) and activity limitation/participation restriction subscales for each language version separately and for pooled data. Overall fit to the Rasch model, item and person fit, unidimensionality, differential item function (DIF), and local response dependency were tested. To meet Rasch model assumptions, item deletion, subtests analysis, and item-splitting strategies were adopted. RESULTS: With the exception of the Hungarian FIS-RA(IF) subscale, preliminary fit to the Rasch model was unsuccessful for all target languages individually and for pooled data. Multidimensionality, misfitting items, local dependency, and DIF by age, sex, disease duration, and language were observed. With adjustment, fit to the Rasch model was satisfactorily achieved for all language versions. For the pooled data, the Rasch model assumptions for crosscultural validity were met following item deletion, subtest analysis, and item splitting for language DIF. CONCLUSION: With adaptations, the FIS-RA was successfully translated and crossculturally validated for use in 4 European languages. The 2 subscales can be used at the individual level for patient assessment and at the group level for research purposes.
22609344 Pannus regression after posterior decompression and occipito-cervical fixation in occipito 2013 Feb OBJECTIVES: Several techniques have been proposed for treating cervical spine instability due to rheumatoid arthritis. The aim of this study was to screen the different treatment options used in this pathology to evaluate the best form of treatment when the progression of rheumatoid disease affected the cranio-vertebral junction (CVJ) stability. The most important purpose of this study was to achieve both the efficacy of occipito-cervical fusion (OCF) to stabilize the occipitocervical junction and stop pannus progression. The authors describe their case example and stress, in the light of a literature review, the hypothesis that a stable biomechanical system extended to all the spaces involved, has both direct and indirect effects on RA pannus progression and the condition responsible for its formation, such as inflammation and articular hypermobility. Hence, the aim of this study is to advance this thesis, which may be extended to a wider statistical sample, with the same characteristics. METHOD: A systematic literature research of case report articles, review articles, original articles, and prospective cohort studies, published from 1978 to 2011, was performed using PUBMED to analyze the different surgical strategies of RA involving CVJ and the role of OCF in these conditions. The key words used for the search the were: "inflammatory cervical pannus regression", "rheumatoid arthritis of the cranio-cervical junction", "occipito-cervical fusion", "treatment option in rheumatoid cervical instability", "altanto-axial dislocation", "craniovertebral junction" and "surgical technique". In addition, the authors reported their experience in a patient affected by erosive rheumatoid arthritis (ERA) with an anterior and posterior pannus involving C0-C1-C2. They decided to report this exemplative case to emphasize their own assumptions concerning the association between a posterior bony fusion, the arrest of anterior pannus progression and the improvement of functional outcome, without, however, a direct intervention on the anterior pannus. RESULT: Thirty-seven different studies were identified that reflected search criteria, five of which were literature reviews. The different surgical treatment options in cervical RA disease are described in relation to neurological outcome according to the Ranawat grading system, functional outcome or quality of life according to the Steinbrocker classification, and progression of cervical instability and radiographic index of cranial settling, focusing on the role of OCF.
21434343 [Effect of methotrexate in treating patients with rheumatoid arthritis of different Chines 2011 Jan OBJECTIVE: To study whether the effects of methotrexate were different in treating patients with rheumatoid arthritis (RA) of different Chinese medical syndrome patterns. METHODS: Retrospective analysis was conducted in 312 RA patients treated with methotrexate, the Chinese medical syndrome patterns in them were differentiated into the cold-dampness blocking collateral type (SA), the heat-dampness blocking collateral type (SB), the phlegm blood-stasis intermingling type (SC), and the heat-cold complex type (SD). Parameters including numbers of joint with tenderness (Njt) and that with arthroncus (Nja); patient's morning stiffness duration (MSD), scores estimated by visual analog scale (VAS) and health assessment questionnaire (HAQ); as well as laboratory indices involving rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), etc. were recorded before and after treatment and statistically analyzed. RESULTS: After treatment, improvements were shown in all patients in terms of Njt, Nja, MSD, VAS scores and ESR, showing significant difference as compared with those before treatment (P < 0.05); and the improvements among patients with different Chinese medical syndrome types were different in degree, the best curative effect was shown in patients of SB type (chi2 = 45.3, P < 0.05). CONCLUSIONS: Referring to Chinese medical syndrome patterns, the curative effect of methotrexate on patients with Heat-Dampness blocking collateral pattern is better than on those of other pattern.
22039166 Optimising treatment in rheumatoid arthritis: a review of potential biological markers of 2011 Dec Following a greater understanding of the pathogenesis of rheumatoid arthritis (RA), the treatment of this chronic disease has improved with the availability of biological agents targeting key molecules. Despite this, initial treatment produces an inadequate response in many patients and guidance on the optimal treatment for these patients is needed. Research in specific patient populations aims to define predictive biomarkers of response to identify those patients most likely to benefit from treatment with specific agents. Although there have been conflicting results from studies of various genetic markers, single nucleotide polymorphisms in the tumour necrosis factor (TNF) -308 promoter region may play a role in response to specific TNF inhibitors. Microarray analysis of mRNA expression levels has identified unique sets of genes with differentially regulated expression in responders compared with non-responders to the TNF inhibitor infliximab. Of the various protein biomarkers studied, rheumatoid factor and/or anticitrullinated protein autoantibodies may have a future role in predicting response or guiding the order in which to use biological agents. Further research is needed with larger, well-designed studies to clarify the current understanding on the role of biomarkers in predicting treatment response in RA to help guide clinical decision-making. Individualised treatment has the potential to improve the therapeutic outcomes for patients.