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ID PMID Title PublicationDate abstract
25411043 Anti-TNF therapy: past, present and future. 2015 Jan While for a century therapeutics has been dominated by small molecules, i.e. organic chemicals of ~400Da absorbable via the gut, this is no longer the case. There are now a plethora of important medicines which are proteins and injectable, which have dramatically improved the therapy of many inflammatory diseases and of cancer. Most of these are monoclonal antibodies, some are receptor Ig Fc fusion proteins, others are cytokines or enzymes. The key to this new aspect of therapeutics has been the filling of unmet needs, and the consequent commercial success, which promoted further research and development. The first 'biologic' for a common disease, rheumatoid arthritis (RA), was a monoclonal antibody, infliximab, to human tumour necrosis factor (TNF). This was based on our work, which is described in this review, summarizing how TNF was defined as a good target in RA, how it was developed is described here, as well as future indications for anti-TNF and related agents. Biologics are now the fastest growing sector of therapeutics.
23462573 Intradural lumbar disc herniation associated with degenerative spine disease and rheumatoi 2013 May 20 STUDY DESIGN: A case report. OBJECTIVE: To demonstrate a case of intradural lumbar disc herniation including imaging studies, intraoperative imaging, and an intraoperative video. SUMMARY OF BACKGROUND DATA: The first case of lumbar intradural disc herniation was reported as early as 1942; since then more than 150 cases have been reported, mostly in the lumbar spine. Gadolinium-enhanced magnetic resonance image (MRI) is considered the "gold standard" for diagnosing this entity, although it is rarely performed routinely in lumbar disc disease and diagnosis is often made intraoperatively. METHODS: A 70-year-old man presented to the emergency department as a referral complaining of lower back pain, loss of sensation in the right thigh, and difficulty walking. On examination, he showed uneven gait, right-sided foot drop (1/5), hypesthesias in the right inguinal area and ventral thigh, and a positive straight leg raise test on the right. Anal sphincter tone was within normal limits. A magnetic resonance image of the lumbar spine showed a large mediolateral herniated disc at L3-L4, with caudal displacement and unclear signal changes intradurally. RESULTS: Intraoperatively, the herniated disc was found upon opening the dural sac. CONCLUSION: Intradural disc herniations are a rare entity. The opening and inspection of the dural sack should be considered when the correct spinal level can be confirmed and insufficient herniated disc material can be visualized extradurally.
24399233 Angiogenic T cells are decreased in rheumatoid arthritis patients. 2015 May OBJECTIVE: The mechanisms underlying the increased cardiovascular risk (CVR) of rheumatoid arthritis (RA) patients remain unclear. Since the recently discovered angiogenic T cells (Tang) could have a role in endothelial repair through cooperating with endothelial progenitor cells (EPC), the main aim of this study was to analyse the Tang and EPC populations in relation to disease-specific features and traditional CVR factors. METHODS: Tang (CD3(+)CD31(+)CXCR4(+)) and EPC (CD34(+)VEGFR2(+)CD133(+)) populations were quantified by flow cytometry in peripheral blood samples from 103 RA patients and 18 matched healthy controls (HC). Clinical features and traditional CVR factors were obtained from clinical records, and 28-joint Disease Activity Score was used for measuring disease activity. Interferon (IFN) α serum levels were measured by immunoassays. RESULTS: Tang and EPC were strongly decreased in RA patients. In HC, but not in patients, both populations were positively correlated and inversely related to low density lipoprotein- and total-cholesterol levels. Sex, diabetes, dyslipidaemia, hypertension or obesity did not significantly influence Tang in patients, although detected in smokers. However, Tang were closely related to disease activity, autoantibody positivity and IFNα levels. Multiple regression analysis adjusted for traditional CVR factors confirmed that only disease activity, age at diagnosis, antinuclear antibody positivity and smoking habit could predict Tang frequency. Finally, patients who had suffered a CV event since their RA diagnosis presented higher Tang decrease and IFNα levels than those who were CV event-free. CONCLUSIONS: Disease-specific parameters, including disease activity, autoantibody profiles and IFNα levels, are associated with Tang decrease in RA, thus probably accounting for CVR.
24815806 Genetic determinants of pulmonary fibrosis: evolving concepts. 2014 May Interstitial lung diseases encompass a wide range of diffuse lung disorders that are often complicated by the development of pulmonary fibrosis and that can occur in isolation or in systemic diseases. In the past decade, availability of high-throughput genotyping and large collaborative clinical networks has led to the identification of many genetic variants associated with sporadic and familial fibrotic interstitial pneumonias. Susceptibility to idiopathic pulmonary fibrosis seems to involve a combination of polymorphisms related to epithelial cell injury and dysfunction and abnormal wound healing, whereas chronic inflammation seems important in the development of pulmonary fibrosis in sarcoidosis or collagen vascular diseases such as systemic sclerosis or rheumatoid arthritis; however, each of the disease-associated variants typically has a small effect and they are therefore not helpful in prediction of risk. Genetic studies have substantially expanded understanding of the pathogenesis of pulmonary fibrosis. Future challenges will be to assess how multiple susceptibility alleles interact with each other and environmental factors to determine disease risk and several different phenotypes, to define the mechanism of action and cellular pathways involving susceptibility alleles, and to identify which of the gene products and molecular mechanisms implicated in disease pathobiology are good therapeutic targets.
24564598 Determinants of adrenal androgen hypofunction in premenopausal females with rheumatoid art 2014 The aim of our study was to investigate adrenocortical function in the context of disease activity and inflammatory status in premenopausal RA females. Adrenal glucocorticoid and androgen responses to the 1 microg ACTH 1-24 test were investigated in 23 premenopausal RA and in 15 age- and BMI-matched healthy females. Twelve RA patients were on low-dose prednisone (<8.5 mg/day). Patients with DAS28>3.2 had lower (p<0.05) total plasma cortisol, 17-hydroxyprogesterone, dehydroepiandrosterone and androstenedione responses in the ACTH test compared to healthy controls. Patients with DAS28>3.2 had lower (p<0.05) dehydroepiandrosterone response in the ACTH test compared to patients with DAS28
24127342 Decline in hand bone mineral density indicates increased risk of erosive change in early r 2014 Apr OBJECTIVE: Despite better disease suppression with combination disease-modifying antirheumatic drugs (DMARDs), some patients with rheumatoid arthritis (RA) have progressive erosive disease. The objective of this study was to determine whether hand bone mineral density (BMD) loss in the first 6 months of treatment indicates increased risk of erosions at 12 months. METHODS: Patients with DMARD-naive early RA receiving treat-to-target therapy were studied (n = 106). Hand BMD was measured at baseline and 6 months by dual x-ray absorptiometry. Hand and feet radiographs were performed at baseline and 12 months and scored using the van der Heijde modification of the Sharp method. A K-means clustering algorithm was used to divide patients into 2 groups: the BMD loss group or the no loss group, according to their absolute change in BMD from baseline to 6 months. Multiple regression analysis (hurdle model) was performed to determine the risk factors for both erosive disease and erosion scores. RESULTS: Hand BMD loss at 6 months was associated with erosion scores at 12 months (P = 0.021). In a multiple regression analysis, hand BMD loss (P = 0.046) and older age at onset (≥50 years; P = 0.014) were associated with erosive disease, whereas baseline erosion scores (P = 0.001) and anti-cyclic citrullinated peptide (P = 0.024) were correlated with erosion severity/progression. CONCLUSION: In RA patients receiving treat-to-target therapy, early hand BMD loss could identify patients who are at risk of developing erosive disease at 12 months, potentially allowing intensification of treatment to prevent erosive damage.
23517397 Clinical significance of interleukin-32 expression in patients with rheumatoid arthritis. 2013 Mar OBJECTIVE: To explore the clinical significance of interleukin (IL)-32 in the treatment of rheumatoid arthritis (RA) patients and analyze the correlations of IL-32 with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF). METHODS: A total of 97 patients with RA and 36 patients with non-RA connective tissue diseases (CTD) were included. The mRNA levels of IL-32 and TNF-α in peripheral blood mononuclear cells (PBMCs) were determined using a quantitative real-time polymerase chain reaction. The plasma concentrations of IL-32 and TNF-α were determined using enzyme-linked immunosorbent assays. Data were analyzed using one-way ANOVA and Spearman's method. RESULTS: The mRNA levels of IL-32 and TNF-α in the active RA groups were significantly higher than those in the healthy control, stable RA, and non-RA CTD groups (P < 0.01). There was no significant difference between the stable RA, healthy control, and non-RA CTD groups (P > 0.05). The concentrations of IL-32 and TNF-α in the active RA groups were significantly higher than those in the stable RA and control groups (P < 0.01). IL-32 expression was positively correlated with TNF-α, ESR, CRP, RF, and DAS28 in patients with RA (P < 0.01). CONCLUSION The levels of IL-32 and TNF-α in the peripheral blood of patients with active RA are significantly higher than in that of patients with stable RA and healthy people. The IL-32 level in peripheral blood may provide a reference for the detection of RA activity.
25775286 [Contribution of dynamic radiographs in atlantoaxial subluxation in rheumatoid arthritis]. 2014 Jul BACKGROUND: Cervical spine (CS) involvement is common during rheumatoid arthritis (RA) and it is distinguished by its potential gravity. AIM: To determinate the occurrence of atlantoaxial subluxation (AAS) by dynamic incidences X-Ray and to assess its predictive factors. METHODS: Our study included a cohort of 40 patients carrying RA, who fulfilled the American College of Rheumatology criteria, for more than 2 years. All patients had a complete physical and laboratory evaluation. Radiological evaluation included CS radiographs in anteroposterior, lateral, and lateral in full flexion and extension views. RESULTS: The occurrence of CS involvement was about 47.5% by XRay dominated by AAS which found in 42,5% of the cases. Among AAS, anterior AAS was the most frequent with a prevalence of 22,5% followed by lateral AAS in 12,5% then vertical and rotatory AAS in 10% of cases each one and posterior AAS in 2,5% of the cases. Comparison between patients with and without CS involvement indicated the presence of two predictive factors: the sharp modified score and the C - reactive protein (p=0.002 and p=0.004 respectively). CONCLUSION: Our study demonstrated that AAS is frequent in RA particularly in active forms with structural lesions. AAS can be asymptomatic, for this reason systematic diagnosis by X-Ray with dynamic views is important.
25339638 Use of a 12-week observational period for predicting low disease activity at 52 weeks in R 2015 May OBJECTIVE: Only a few studies have assessed predictive factors for the long-term efficacy of abatacept. This study aimed to provide clinical evidence of an adequate observational period for predicting low disease activity (LDA) achievement at 52 weeks in RA patients treated with abatacept. METHODS: Participants were all patients registered in a Japanese multicentre registry who were treated with abatacept and had at least 52 weeks of follow-up (n = 254). RESULTS: Areas under the receiver operating characteristic curves for the 28-joint count with CRP (DAS28-CRP) at each time point for LDA achievement at 52 weeks were: 0.686 (cut-off score: 4.6) at baseline, 0.780 (3.8) at 4 weeks, 0.875 (3.3) at 12 weeks, and 0.900 (3.0) at 24 weeks. Although patients with a DAS28-CRP score < 3.0 at 24 weeks had the highest proportion of LDA achievement at 52 weeks (79.3%), the proportion for those with a score < 3.3 at 12 weeks was comparable (77.2%, P = 0.697). Proportions were significantly lower in patients with a score < 3.8 at 4 weeks or < 4.6 at baseline. Multivariate logistic regression demonstrated that a DAS28 score of < 3.3 at 12 weeks was an independent strong predictor for LDA at 52 weeks (adjusted odds ratio: 15.2, P < 0.001). CONCLUSION: Twelve weeks is an adequate observational period to judge the long-term clinical efficacy of abatacept, and is about as early as the period for assessing TNF blockade therapy.
25263357 [Proteomics study of synovial lesions in rats with Mtb-induced rheumatoid arthritis]. 2014 Aug OBJECTIVE: To characterize the proteomic profiles of joint synovial tissue in normal rats and rats with rheumatoid arthritis (RA) and identify the proteins related with the occurrence of RA to explore the pathogenesis of RA. METHODS: SD rat models of RA were established using Mtb (heat-killed Mycobacterium tuberculosis H37Ra). Two-dimensional gel electrophoresis proteomics technology was employed to analyze the difference in synovial tissue protein profiles between RA model rats and normal rats, and two of the differentially expressed proteins were verified with Western blotting and fluorescence quantitative PCR. RESULTS: Comparison of the two-dimensional gel electrophoresis patterns from the model rats and normal rats showed 4 up-regulated and 4 down-regulated proteins by 2 folds in the RA model rats. Western blotting and fluorescent quantitative PCR of 2 of the 8 proteins yielded consistent results with those by proteomics analysis. CONCLUSION: Arthritis synovial lesions in RA represent very complex pathological processes involving a variety of proteins, and these differentially expressed proteins may contribute to the progression of RA.
24128086 The validity of the diagnosis of inflammatory arthritis in a large population-based primar 2013 Jun 7 BACKGROUND: Large population-based databases based on electronic medical records (EMRs) of patients in primary care are a useful data source to investigate morbidity and health care utilization. Diagnoses recorded in EMRs are doctor-defined, but their validity can be disputed. In this study we investigated the validity of the diagnosis inflammatory arthritis (IA), a group of chronic rheumatic diseases, including rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, in primary care based EMRs. METHODS: In five general practices, participating in the Netherlands Information Network of General Practice (LINH), EMRs of 219 patients with a diagnostic code of IA were systematically reviewed on characteristics which are not routinely extracted for the LINH database. The diagnosis IA was confirmed when we found, based on a correspondence with a medical specialist, the following diagnoses in the free text fields of the EMR: oligoarthritis, polyarthritis, rheumatoid arthritis and/or spondyloarthropathy. These results were used to determine the validity of the diagnosis IA in EMRs and to develop an algorithm to improve diagnostic validity. RESULTS: From the 219 patients diagnosed as IA in the database, the diagnosis IA was confirmed in 155 patients (70.8%). The algorithm, which resulted in a group of patients with as many as possible confirmed IA-diagnosed patients without excluding too many patients from our dataset, was when patients fulfilled at least one of the following three criteria: 1) a repeat prescription for a disease-modifying antirheumatic drug (DMARD) and/or biological agent, 2) ≥ four contacts or one episode with a diagnostic code for IA, combined with at least two IA-related prescriptions (excluding DMARDs/biological agents), and 3) age at diagnosis ≥ 61 years. After applying this algorithm, the percentage of correctly diagnosed IA patients increased from 71% to 78% reducing the size of our study population by 36%. CONCLUSIONS: Based on additional diagnostic information, the diagnosis IA from EMRs of patients in primary care is sufficiently valid when using the proposed algorithm. After applying the algorithm, the percentage of correctly diagnosed IA patients increased from 71% to 78%.
24914609 What to do with all of these lung nodules? 2014 May Caplan syndrome is a rare entity that is specific to rheumatoid arthritis and presents with multiple, well-defined necrotic nodules in patients with occupational dust exposure. The present report describes a case of Caplan syndrome involving a 71-year-old man with a known diagnosis of seropositive rheumatoid arthritis who presented to the authors' centre with a five-year history of multiple, bilateral cavitary lung nodules with mild dyspnea on exertion. He was an ex-smoker (30 pack-years) and had previously worked with silica. The case highlights the clinical, radiological and pathological features of this syndrome and outlines the importance of considering a broad differential in the management of pulmonary nodules, especially in patients with rheumatoid arthritis.
24676986 MRI in rheumatoid arthritis: a useful tool for the clinician? 2014 Jun Over the last two decades, MRI has emerged as an important clinical tool to assist in the diagnosis and management of rheumatic disease. In rheumatoid arthritis (RA), MRI has improved our understanding of the pathological basis of disease and has provided new information about imaging features that reflect joint inflammation and damage. Using MRI, we can now directly observe inflammation involving the synovial membrane and tenosynovium, plus joint damage including bone erosion and cartilage thinning. Inflammation of bone beneath the joint (osteitis) appears as bone oedema which is a feature unique to MRI and yields important diagnostic and prognostic information in patients with inflammatory arthritis. With the introduction of biologics to rheumatology clinical practice, sensitive tools are required to monitor disease activity and progression, so that the disease suppressing effect of these new agents can be measured. MRI fits the bill for this role as it can inform the clinician about the development of bone erosions well before plain radiography, and its ability to reveal cartilage damage is emerging. The use of MRI as a marker of outcome in clinical trials is being paralleled by its increasing role in the clinic. Both extremity and high field MRI have clinical applications in RA and need to be considered along with other advanced imaging techniques as useful tools to add to the clinician's armamentarium. This review will summarise recent advances in this field and will apply current knowledge to specific clinical scenarios relevant to modern rheumatology practice.
24491820 Autoimmunity: from black water fever to regulatory function. 2014 Feb Autoimmunity is a field that has only been around for a little over a century. Initially, it was thought that autoimmunity could not happen, that the body would never turn on itself (i.e. "horror autotoxicus"). It was only around the First World War that autoimmunity was recognized as the pathogenesis of various diseases, including rheumatoid arthritis. The discovery of Compound E led to successful treatment of patients with autoimmune diseases, but it was not till later that the adverse effects of this class of drugs were elucidated. The "modern" age of autoimmunity began around 1945 with the description of blackwater fever, and most of the subsequent research on hemolytic anemia and the role of an autoantibody in its pathogenesis led to a description of the anti-globulin reaction. The lupus erythematous (LE) cell was recognized in the mid-1940s by Hargreaves. His research carried on into the 1960s. Rheumatoid factor was also first described in the 1940s as yet another serum factor with activity against globulin-coated sheep red blood cells. The concept of autoimmunity really gained a foothold in the 1950s, when autoimmune thyroid disease and idiopathic thrombocytopenia were first described. Much has happened since then, and our understanding of autoimmunity has evolved now to include mechanisms of apoptosis, signaling pathway derangements, and the discovery of subsets of T cells with regulatory activity. The modern day study of autoimmunity is a fascinating area of research, and full understanding of the pathogenesis of autoimmune diseases is far from being completely elucidated.
23961676 [Anti-cytokine treatment, newly developed]. 2013 Jul Rheumatoid arthritis (RA) is characterized by chronic inflammatory synovitis that causes pain, loss of function and disability, and can significantly reduce health-related quality of life. Improved understanding of the pathogenesis has led to the development of new biologic treatments that target specific cytokines. Large randomized controlled trials (RCTs) have been conducted to show the efficacy of anti-TNF and IL-6. However, despite these treatments, some patients fail to respond to these therapies. Recently other anti-ctyokine treatments had been developed and introduced. Here, we discuss about new anti-cytokine treatments for RA.
24907153 Associations between serum 25-hydroxyvitamin D and disease activity, inflammatory cytokine 2014 Nov OBJECTIVE: The aim of this study was to describe the associations between serum levels of 25-hydroxyvitamin D [25(OH)D] and disease activity, inflammatory cytokines and bone loss/erosions in patients with RA. METHODS: The study included 130 patients with RA and 80 healthy controls. Serum 25(OH)D, IL-17 and IL-23 levels were detected by ELISA. Radiographic bone erosion was assessed using the van der Heijde modified Sharp score and BMD was measured using DXA. RESULTS: There were no significant differences in age, gender and BMI between the RA and control groups. Serum level of 25(OH)D was markedly lower in the RA group than in the control group [43.12 nmol/l (s.d. 15.59) vs 57.93 (15.95), P < 0.01]. In RA patients, 25(OH)D levels were significantly and negatively associated with clinical parameters of disease activity including swollen joint count, tender joint count, joint pain degree, morning stiffness time and HAQ score and laboratory measures including platelets and ESR after adjustment for gender, age and BMI. They were also negatively associated with serum levels of IL-17 and IL-23. While 25(OH)D levels were not associated with radiographic bone erosions of RA, they were significantly lower in those with osteopenia and osteoporosis than in those with normal BMD (P < 0.01). CONCLUSION: 25(OH)D levels were reduced in patients with RA and were negatively associated with disease activity, IL-17/IL-23 and bone loss in RA. These suggest that vitamin D deficiency may play a role in the aetiology of RA.
24324211 CX3CL1 and CX3CR1 expression in tertiary lymphoid structures in salivary gland infiltrates 2014 Apr OBJECTIVES: Primary SS is an autoimmune disease characterized by chronic lymphocytic inflammation and ectopic germinal centre (GC) formation within salivary glands. Fractalkine (CX3CL1), associated with the pathogenesis of RA, is the sole member of the CX3C chemokine (CK) family and acts as an adhesion and chemotactic molecule. The objectives of this work are to determine to what extent CX3CL1 and its receptor CX3CR1 expression might be altered in salivary glands obtained from patients and to establish whether these CKs might be involved in SS ectopic lymphoneogenesis. METHODS: We assessed the presence of CX3CL1 protein in sera by ELISA in 21 patients with primary SS, 11 patients with Sicca syndrome (Sicca), 20 RA patients and 10 blood donors. Histological evaluation was performed on sequential sections of salivary gland tissue. Using TaqMan RT-PCR we studied CX3CL1 and CX3CR1 mRNA expression in salivary gland tissues from a molecular point of view. RESULTS: Increased serum levels of CX3CL1 protein were observed in SS patients compared with controls (P < 0.0001) and in RA patients compared with controls (P < 0.0001), but no difference was found between Sicca patients and controls (P = 0.22). We identified histologically the cells expressing CX3CL1 and CX3CR1 in salivary glands of SS patients and we localized the molecule within tertiary lymphoid structures. Finally, the mRNA levels of the CK and its receptor were up-regulated in SS salivary glands. CONCLUSION: We believe that our findings point to the need for future studies on CX3CL1 and CX3CR1 proteins as contributors to the formation of ectopic GCs and possibly as a new tool in the evaluation and diagnosis of SS.
24037554 Determining best practices in early rheumatoid arthritis by comparing differences in treat 2013 Nov OBJECTIVE: To determine site variation by comparing outcomes across sites in an early rheumatoid arthritis cohort. METHODS: Sites from the Canadian Early Arthritis Cohort database with at least 40 patients were studied. Comparisons were made among sites in change in 28-joint Disease Activity Score (DAS28), proportion of patients in DAS28 remission, and treatment strategies. RESULTS: The study included 1138 baseline patients at 8 sites, with baseline (SD) age 52 years (16.9); 72% women; 23% erosions; 54% ever smokers; 51% rheumatoid factor-positive; 37% anticitrullinated protein antibody-positive; disease duration 187 (203) days; DAS28 4.5 (1.4). Site had an effect on outcomes when adjusting for confounders. At 6 and 12 months, sites B and H, the 2 largest sites, had the best changes in DAS28 (-1.82 and -2.09, respectively, at 6 mos, and -2.27 for both at 12 mos; p < 0.001). Site H had the most patients in DAS28 remission at 6 months [64.5% compared to other sites that had from 34.1% to 51.7% (p < 0.001)], and at the last followup, sites B and H had the most in remission. Subcutaneous methotrexate was used more overall and earlier at sites B and H. Those sites used less steroid therapy, and site B had the second-highest use of triple disease-modifying antirheumatic drugs at any visit. Medications were increased more in 2 of the 3 smallest sites. Biologics were used by 9 months most in the smallest (50.0%) and then largest (19.6%) sites. CONCLUSION: Sites in an early inflammatory arthritis cohort yielded different outcomes. Better outcomes up to 12 months may result from initial treatment with early combination therapy and/or subcutaneous methotrexate.
23844744 Epstein-Barr virus infection transforms CD25+ B cells into antibody-secreting cells in rhe 2013 Dec Epstein-Barr virus (EBV) infection may initiate production of autoantibodies and development of cancer and autoimmune diseases. Here we outline phenotypic and functional changes in B cells of patients with rheumatoid arthritis (RA) related to EBV infection. The B-cell phenotype was analysed in blood and bone marrow (BM) of RA patients who had EBV transcripts in BM (EBV(+) , n = 13) and in EBV(-) (n = 22) patients with RA. The functional effect of EBV was studied in the sorted CD25(+) and CD25(-) peripheral B cells of RA patients (n = 18) and healthy controls (n = 9). Rituximab treatment results in enrichment of CD25(+) B cells in peripheral blood (PB) of EBV(+) RA patients. The CD25(+) B-cell subset displayed a more mature phenotype accumulating IgG-expressing cells. It was also enriched with CD27(+) and CD95(+) cells in PB and BM. EBV stimulation of the sorted CD25(+) B cells in vitro induced a polyclonal IgG and IgM secretion in RA patients, while CD25(+) B cells of healthy subjects did not respond to EBV stimulation. CD25(+) B cells were enriched in PB and synovial fluid of RA patients. EBV infection affects the B-cell phenotype in RA patients by increasing the CD25(+) subset and by inducing their immunoglobulin production. These findings clearly link CD25(+) B cells to the EBV-dependent sequence of reactions in the pathogenesis of RA.
23318705 Severe deficiency of 25-hydroxyvitamin D₃ (25-OH-D₃) is associated with high disease a 2013 May This study aims to measure the serum level of 25-hydroxyvitamin D₃ (25-OH-D₃) in 302 patients with rheumatoid arthritis (RA), studying the association to disease activity. Three hundred two RA patients underwent clinical examination and serological analysis. 25-Hydroxyvitamin D₃ was determined by high-performance liquid chromatography-tandem mass spectrometry. Vitamin D₃ deficiency defined as serum levels of 25-hydroxyvitamin D₃ below 50 nmol/l was detected in 101 RA patients (33.4 %). There was no significant correlation between the serum level of 25-hydroxyvitamin D₃ and Disease Activity Score 28 (DAS28) (3w) score. In a subpopulation of RA patients with very low serum level of 25-OH-D₃ (≤15 nmol/l) (n = 15), there were significant differences compared to patients with normal 25-OH-D3 (n = 200): higher percentage of patients with positive rheumatoid factor (100.0 versus 77.5 %; p = 0.05), higher CRP (28.7 versus 14.8 mg/l; p = 0.001), higher number of patients treated with at least three disease-modifying antirheumatic drugs (DMARDs) (40.0 versus 14.5 %; p = 0.02), higher number of patients with high disease activity DAS28 score of ≥5.1 (20.0 versus 4.5 %; p = 0.01), lower age (54.5 versus 64.0 years; p = 0.003) and shorter disease duration (5.1 versus 10.3 years; p = 0.06). Deficiency of 25-hydroxyvitamin D₃ was detected in 33.4 % of the RA patients. A subpopulation of patients with severe deficiency of vitamin D₃ serum level of ≤15 nmol/l was characterised by all being positive for rheumatoid factor, high percentage of patients with very high disease activity and high percentage of patients treated with at least three DMARDs.