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ID PMID Title PublicationDate abstract
24286166 Development and assessment of floor and ceiling items for the PROMIS physical function ite 2013 Oct 3 INTRODUCTION: Disability and Physical Function (PF) outcome assessment has had limited ability to measure functional status at the floor (very poor functional abilities) or the ceiling (very high functional abilities). We sought to identify, develop and evaluate new floor and ceiling items to enable broader and more precise assessment of PF outcomes for the NIH Patient-Reported-Outcomes Measurement Information System (PROMIS). METHODS: We conducted two cross-sectional studies using NIH PROMIS item improvement protocols with expert review, participant survey and focus group methods. In Study 1, respondents with low PF abilities evaluated new floor items, and those with high PF abilities evaluated new ceiling items for clarity, importance and relevance. In Study 2, we compared difficulty ratings of new floor items by low functioning respondents and ceiling items by high functioning respondents to reference PROMIS PF-10 items. We used frequencies, percentages, means and standard deviations to analyze the data. RESULTS: In Study 1, low (n = 84) and high (n = 90) functioning respondents were mostly White, women, 70 years old, with some college, and disability scores of 0.62 and 0.30. More than 90% of the 31 new floor and 31 new ceiling items were rated as clear, important and relevant, leaving 26 ceiling and 30 floor items for Study 2. Low (n = 246) and high (n = 637) functioning Study 2 respondents were mostly White, women, 70 years old, with some college, and Health Assessment Questionnaire (HAQ) scores of 1.62 and 0.003. Compared to difficulty ratings of reference items, ceiling items were rated to be 10% more to greater than 40% more difficult to do, and floor items were rated to be about 12% to nearly 90% less difficult to do. CONCLUSIONS: These new floor and ceiling items considerably extend the measurable range of physical function at either extreme. They will help improve instrument performance in populations with broad functional ranges and those concentrated at one or the other extreme ends of functioning. Optimal use of these new items will be assisted by computerized adaptive testing (CAT), reducing questionnaire burden and insuring item administration to appropriate individuals.
23950187 Comparison of the disease activity score using erythrocyte sedimentation rate and C-reacti 2013 Nov OBJECTIVE: The Disease Activity Score based on 28 joints (DAS28) has been increasingly used in clinical practice and research studies of rheumatoid arthritis (RA). Studies have reported discordance between DAS28 based on erythrocyte sedimentation rate (ESR) versus C-reactive protein (CRP) in patients with RA. However, such comparison is lacking in African Americans with RA. METHODS: This analysis included participants from the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis (CLEAR) registry, which enrolls self-declared African Americans with RA. Using tender and swollen joint counts, separate ESR-based and CRP-based DAS28 scores (DAS28-ESR3 and DAS28-CRP3) were calculated, as were DAS28-ESR4 and DAS28-CRP4, which included the patient's assessment of disease activity. The scores were compared using paired t-test, simple agreement and κ, correlation coefficient, and Bland-Altman plots. RESULTS: Of the 233 included participants, 85% were women, mean age at enrollment was 52.6 years, and median disease duration at enrollment was 21 months. Mean DAS28-ESR3 was significantly higher than DAS28-CRP3 (4.8 vs 3.9; p < 0.001). Similarly, mean DAS28-ESR4 was significantly higher than DAS28-CRP4 (4.7 vs 3.9; p < 0.001). ESR-based DAS28 remained higher than CRP-based DAS28 even when stratified by age, sex, and disease duration. Overall agreement was not high between DAS28-ESR3 and DAS28-CRP3 (50%) or between DAS28-ESR4 and DAS28-CRP4 (59%). DAS28-CRP3 underestimated disease activity in 47% of the participants relative to DAS28-ESR3 and DAS28-CRP4 in 40% of the participants relative to DAS28-ESR4. CONCLUSION: There was significant discordance between the ESR-based and CRP-based DAS28, a situation that could affect clinical treatment decisions for African Americans with RA.
23294500 Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumato 2013 Feb 9 BACKGROUND: Rheumatoid arthritis is a heterogeneous chronic disease, and no therapeutic agent has been identified which is universally and persistently effective in all patients. We investigated the effectiveness of tofacitinib (CP-690,550), a novel oral Janus kinase inhibitor, as a targeted immunomodulator and disease-modifying therapy for rheumatoid arthritis. METHODS: We did a 6-month, double-blind, parallel-group phase 3 study at 82 centres in 13 countries, including North America, Europe, and Latin America. 399 patients aged 18 years or older with moderate-to-severe rheumatoid arthritis and inadequate response to tumour necrosis factor inhibitors (TNFi) were randomly assigned in a 2:2:1:1 ratio with an automated internet or telephone system to receive twice a day treatment with: tofacitinib 5 mg (n=133); tofacitinib 10 mg (n=134); or placebo (n=132), all with methotrexate. At month 3, patients given placebo advanced to either tofacitinib 5 mg twice a day (n=66) or 10 mg twice a day (n=66). Primary endpoints included American College of Rheumatology (ACR)20 response rate, mean change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI), and rates of disease activity score (DAS)28-4(ESR) less than 2·6 (referred to as DAS28<2·6), all at month 3. The full analysis set for the primary analysis included all randomised patients who received at least one dose of study medication and had at least one post-baseline assessment. This trial is registered with www.ClinicalTrials.gov, number NCT00960440. FINDINGS: At month 3, ACR20 response rates were 41·7% (55 of 132 [95% CI vs placebo 6·06-28·41]; p=0·0024) for tofacitinib 5 mg twice a day and 48·1% (64 of 133; [12·45-34·92]; p<0·0001) for tofacitinib 10 mg twice a day versus 24·4% (32 of 131) for placebo. Improvements from baseline in HAQ-DI were -0·43 ([-0·36 to -0·15]; p<0·0001) for 5 mg twice a day and -0·46 ([-0·38 to -0·17]; p<0·0001) for 10 mg twice a day tofacitinib versus -0·18 for placebo; DAS28<2·6 rates were 6·7% (eight of 119; [0-10·10]; p=0·0496) for 5 mg twice a day tofacitinib and 8·8% (11 of 125 [1·66-12·60]; p=0·0105) for 10 mg twice a day tofacitinib versus 1·7% (two of 120) for placebo. Safety was consistent with phase 2 and 3 studies. The most common adverse events in months 0-3 were diarrhoea (13 of 267; 4·9%), nasopharyngitis (11 of 267; 4·1%), headache (11 of 267; 4·1%), and urinary tract infection (eight of 267; 3·0%) across tofacitinib groups, and nausea (nine of 132; 6·8%) in the placebo group. INTERPRETATION: In this treatment-refractory population, tofacitinib with methotrexate had rapid and clinically meaningful improvements in signs and symptoms of rheumatoid arthritis and physical function over 6 months with manageable safety. Tofacitinib could provide an effective treatment option in patients with an inadequate response to TNFi. FUNDING: Pfizer.
24453423 Marked independent relationship between circulating interleukin-6 concentrations and endot 2013 We examined the potential impact of conventional compared with nonconventional cardiovascular risk factors including interleukin-6 levels on endothelial activation in RA. Circulating soluble E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 concentrations were measured in 217 African patients (112 black and 105 white) with RA. In comprehensive confounder adjusted mixed regression models, 5 conventional and 4 nonconventional cardiovascular risk factors were associated (P = 0.05 to <0.0001) with endothelial activation. Interleukin-6 was the only risk factor related to each endothelial activation molecule and independently contributed by 18% and significantly more than other risk factors to the variation in overall endothelial activation as estimated by an SD (z) score of endothelial activation molecule concentrations. The independent interleukin-6-overall endothelial activation relationships were reproduced in various subgroups. Interleukin-6 concentrations relate consistently, markedly, and to a larger extent than other cardiovascular risk factors to endothelial activation in RA. Assessment of interleukin-6 concentrations may enhance cardiovascular risk stratification in RA.
23727609 Replication study of STAT4 rs7574865 G/T polymorphism and risk of rheumatoid arthritis in 2013 Sep 10 AIM: Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are common systemic autoimmune diseases with genetic and environmental predisposing factors. Signal transducer and activator of transcription 4 (STAT4) transmits signals induced by interleukin-12, interleukin-23 and interferon-γ, which are key cytokines and play important roles in the development of autoimmune diseases. Previous studies confirmed the STAT4 rs7574865 G/T locus to be associated with RA. Thus we conducted a replication study to investigate STAT4 rs7574865 G/T polymorphism and RA/AS susceptibility in a Chinese population. METHODS: We studied STAT4 rs7574865 G/T gene polymorphism in 520 patients with RA, 100 AS patients and 520 controls in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: When the STAT4 rs7574865 GG homozygote genotype was used as the reference group, the GT or GT/TT genotypes were associated with the risk for RA. After stratification analyses, a significantly increased risk for RA associated with the STAT4 rs7574865 GT genotype was evident among the rheumatoid factor (RF)-positive patients, patients with higher erythrocyte sedimentation rate (ESR) level and patients with higher RA disease activity score (DAS28) compared with the STAT4 rs7574865 GG genotype. A significantly increased risk for RA associated with the STAT4 rs7574865 TT genotype was evident among older patients and RF-negative patients compared with the STAT4 rs7574865 GG genotype. STAT4 rs7574865 G/T was not associated with susceptibility to AS. CONCLUSION: This replication study confirmed that STAT4 rs7574865 G/T polymorphism was associated with the risk of RA. CONDENSED ABSTRACT: STAT4 polymorphisms are associated with rheumatoid arthritis risk.
24913965 Antineutrophil cytoplasm antibody: positivity and clinical correlation. 2015 Jan OBJECTIVE: To determine positivity and clinical correlation of anti-neutrophil cytoplasmic antibodies (ANCA), taking into account the interference of antinuclear antibodies (ANA). MATERIAL AND METHODS: A prospective study was conducted in the Laboratory of Immunology of the National Cuban Center of Medical Genetic during one year. Two hounded sixty-seven patients with indication for ANCA determination were included. ANCA and ANA determinations with different cut off points and assays were determined by indirect immunofluorescense. Anti proteinase 3 and antimyeloperoxidase antibodies were determined by ELISA. RESULTS: Most positivity for ANCA was seen in patients with ANCA associated, primary small-vessel vasculitides, rheumatoid arthritis and systemic lupus erythematosus. Presence of ANCA without positivity for proteinase 3 and myeloperoxidase was higher in patients with ANA and little relation was observed between the perinuclear pattern confirmed in formalin and specificity by myeloperoxidase. Highest sensibility and specificity values for vasculitides diagnostic were achieved by ANCA determination using indirect immunofluorescense with a cut off 1/80 and confirming antigenic specificities with ELISA. CONCLUSION: ANCA can be present in a great number of chronic inflammatory or autoimmune disorders in the population studied. This determination using indirect immunofluorescence and following by ELISA had a great value for vasculitis diagnosis. Anti mieloperoxidasa assay has a higher utility than the formalin assay when ANA is present.
24552146 Anti-invasive effects of Celastrus Orbiculatus extract on interleukin-1 beta and tumour ne 2014 Feb 19 BACKGROUND: Invasion of fibroblast-like synoviocytes (FLSs) is critical in the pathogenesis of rheumatoid arthritis (RA). The metalloproteinases (MMPs) and activator of nuclear factor-kappa B (NF-κB) pathway play a critical role in RA-FLS invasion induced by interleukin-1 beta (IL-1β) and tumour necrosis factor-alpha (TNF-α). The present study aimed to explore the anti-invasive activity and mechanism of Celastrus orbiculatus extract (COE) on IL-1β and TNF-α combination-stimulated human RA-FLSs. METHODS: We investigated the effect of COE on IL-1β and TNF-α combination-induced FLS invasion as well as MMP expression and explored upstream signal transduction. RESULTS: COE suppressed IL-1β and TNF-α combination-stimulated FLSs invasion by inhibiting MMP-9 expression and activity. Furthermore, our results revealed that COE inhibited the transcriptional activity of MMP-9 by suppression of the binding activity of NF-κB in the MMP-9 promoter, and inhibited IκBα phosphorylation and nuclear translocation of NF-κB. CONCLUSIONS: COE inhibits IL-1β and TNF-α combination-induced FLSs invasion by suppressing NF-κB-mediated MMP-9 expression.
23589893 Deficiency of β-arrestin1 ameliorates collagen-induced arthritis with impaired TH17 cell 2013 Apr 30 Rheumatoid arthritis (RA) is an inflammatory disease in which interleukin 17 (IL-17)-producing T helper 17 (T(H)17) cells have been critically involved. We show that in patients with RA, the expression of a multifunctional regulator β-arrestin1 was significantly up-regulated in peripheral and synovial CD4(+) T cells, which correlated well with active phases of RA. In collagen-induced arthritis, deficiency of β-arrestin1 ameliorated disease with decreased T(H)17 cell differentiation, proinflammatory cytokine production, synovitis, and cartilage and bone destruction. Further mechanistic study reveals that β-arrestin1 promoted signal transducer and activator of transcription 3 (STAT3) activation required for T(H)17 cell differentiation through scaffolding the interaction of Janus kinase 1 and STAT3. These findings indicate a critical role for β-arrestin1 in the pathogenesis of collagen-induced arthritis and T(H)17 cell differentiation and suggest β-arrestin1 as a potential diagnostic biomarker and therapeutic target for RA.
22955636 Retinal vasculitis in rheumatic diseases: an unseen burden. 2013 Jan Retinal vascular inflammation, a potentially blinding condition (herein: retinal vasculitis (RV)) is commonly associated with a heterogeneous group of diseases characterized by systemic inflammatory cell infiltration and/or necrosis of blood vessel walls. RV may arise as an isolated ocular disorder, as part of systemic vasculitis (Wegener's granulomatosis and Adamantiadis-Behcet Disease), or it can be secondary to an underlying connective tissue disease (systemic lupus erythematosus, sarcoidosis, and rheumatoid arthritis), systemic infection, or malignancy. Depending on the type of RV, it can be a potentially disabling condition, in the short or long term. Early diagnosis is the key to successful treatment and better prognosis. However, early diagnosis can be difficult, because these conditions usually present with nonspecific visual symptoms for a long period before diagnostic manifestations occur. The retina should be examined in warranted patients with verified rheumatic disease, since retinal vasculitis may be asymptomatic at the beginning (peripheral retinal disease). RV can be detected clinically (often accompanied by uveitis, scleritis, or macular edema) or revealed on fluorescein fundus angiography, even if minimal signs of retinal vessel inflammation are present. RV may also represent one of the possible extra-articular manifestations of the rheumatic disease. Rheumatologists should be familiar with the ocular manifestations of these disorders, since they may not only be sight-threatening, but more importantly, could be the presenting or even the very first manifestations of active, potentially lethal systemic disease in a patient with nonspecific rheumatologic presentation.
23606709 Rheumatoid arthritis synovial tissue harbours dominant B-cell and plasma-cell clones assoc 2014 Apr OBJECTIVE: To identify potential autoreactive B-cell and plasma-cell clones by quantitatively analysing the complete human B-cell receptor (BCR) repertoire in synovium and peripheral blood in early and established rheumatoid arthritis (RA). METHODS: The BCR repertoire was screened in synovium and blood of six patients with early RA (ERA) (<6 months) and six with established RA (ESRA) (>20 months). In two patients, the repertoires in different joints were compared. Repertoires were analysed by next-generation sequencing from mRNA, generating >10 000 BCR heavy-chain sequence reads per sample. For each clone, the degree of expansion was calculated as the percentage of the total number of reads encoding the specific clonal sequence. Clones with a frequency ≥ 0.5% were considered dominant. RESULTS: Multiple dominant clones were found in inflamed synovium but hardly any in blood. Within an individual patient, the same dominant clones were detected in different joints. The majority of the synovial clones were class-switched; however, the fraction of clones that expressed IgM was higher in ESRA than ERA patients. Dominant synovial clones showed autoreactive features: in ERA in particular the clones were enriched for immunoglobulin heavy chain gene segment V4-34 (IGHV4-34) and showed longer CDR3 lengths. Dominant synovial clones that did not encode IGHV4-34 also had longer CDR3s than peripheral blood. CONCLUSIONS: In RA, the synovium forms a niche where expanded--potentially autoreactive--B cells and plasma cells reside. The inflamed target tissue, especially in the earliest phase of disease, seems to be the most promising compartment for studying autoreactive cells.
23225308 A diclofenac suppository-nabumetone combination therapy for arthritic pain relief and a mo 2013 Mar Diclofenac suppository, a non-steroidal anti-inflammatory drug (NSAID), is used widely in rheumatoid arthritis (RA) patients with severe arthritic pain. As the binding percentage of diclofenac to serum proteins is high, its free (unbound) concentration after rectal administration is low. To increase temporarily the free concentration of diclofenac and to enhance its analgesic effect by inhibiting the protein binding of diclofenac, the analgesic effect of diclofenac was examined before and after the start of an inhibitor administration to RA patients with insufficient control of arthritic pain, and the protein binding capacity of diclofenac was evaluated. Binding experiments were performed by ultrafiltration, and arthritic pain was recorded by the face scale. Free fractions of diazepam and diclofenac were augmented by increasing 6-methoxy-2-naphthylacetic acid (6-MNA; the active metabolite of the NSAID nabumetone) concentrations. The free fraction of diazepam increased after the start of nabumetone administration to RA patients, and arthritic pain relief was observed. These results suggest that 6-MNA has an inhibitory effect on the protein binding of diclofenac and the free fraction of diazepam can be used to evaluate the binding capacity of diclofenac. It is considered that diclofenac suppository-nabumetone combination therapy and the method for protein binding monitoring by diazepam can positively benefit RA patients with insufficient control of arthritic pain.
24840285 Biologics-induced autoimmune renal disorders in chronic inflammatory rheumatic diseases: s 2014 Aug The use of biologic drugs has been linked with the paradoxical development of systemic and organ specific autoimmune processes. The aim of this study was to describe the features of biologics-induced autoimmune renal disorders (AIRD) through a systematic review and a cohort study of 707 adult patients affected with Rheumatoid Arthritis (RA), Ankylosing Spondylitis (SA) and Psoriatic Arthritis (PsA). The literature search identified 2687 articles of which 21 were considered relevant for the present study, accounting for 26 case reports. The cohort analysis retrieved 3 cases. According to clinical manifestations and kidney histology the identified AIRD cases were classified as: a) glomerulonephritis associated with systemic vasculitis (GNSV), b) glomerulonephritis in lupus-like syndrome (GNLS), c) isolated autoimmune renal disorders (IARD). Twenty-two out of 29 cases with AIRD were reported in patients affected by RA, 5 in AS and 2 in PsA. The biologic drug most frequently associated with development of AIRD was Etanercept (15 cases, 51.7%), followed by Adalimumab (9 cases, 31.0%) and Infliximab (3 cases, 10.3%) while Tocilizumab and Abatacept were reported in 1 case (3.4%) for each. Thirteen out of 29 (44.8%) cases were classified as affected by IARD, 12 (41.3%) as GNSV and 4 (13.9%) as GNLS. Worse prognosis was associated with GNSV and lack of biologic withdrawal. Although rare, AIRD may be life-threatening and may lead to renal failure and death. If AIRD occurs, biologic drugs must be stopped and patient should be treated according to clinical manifestations and kidney biopsy findings.
25324392 Detection of T cell responses to a ubiquitous cellular protein in autoimmune disease. 2014 Oct 17 T cells that mediate autoimmune diseases such as rheumatoid arthritis (RA) are difficult to characterize because they are likely to be deleted or inactivated in the thymus if the self antigens they recognize are ubiquitously expressed. One way to obtain and analyze these autoimmune T cells is to alter T cell receptor (TCR) signaling in developing T cells to change their sensitivity to thymic negative selection, thereby allowing their thymic production. From mice thus engineered to generate T cells mediating autoimmune arthritis, we isolated arthritogenic TCRs and characterized the self antigens they recognized. One of them was the ubiquitously expressed 60S ribosomal protein L23a (RPL23A), with which T cells and autoantibodies from RA patients reacted. This strategy may improve our understanding of the underlying drivers of autoimmunity.
24288552 Induction of Th17 lymphocytes and Treg cells by monocyte-derived dendritic cells in patien 2013 Dendritic cells (DCs) have a key role in the regulation of immune response. We herein explored, in patients with inflammatory diseases, the role of monocyte derived DC's (mo-DCs) on the generation of Th17 and T regulatory (Treg) lymphocytes. Peripheral blood was obtained from thirty-five patients with rheumatoid arthritis (RA), twelve with systemic lupus erythematosus (SLE), and twenty healthy subjects. Mo-DCs were generated under standard (IL-4/GM-CSF) or tolerogenic (IL-4/GM-CSF plus recombinant P-selectin or PD-1 or IL-10) conditions, and their ability to induce Th17 and Treg lymphocytes was tested. We detected that mo-DCs from patients with RA showed an enhanced release of IL-6 and IL-23 as well as an increased capability to induce Th17 cells. Although mo-DCs from SLE patients also released high levels of IL-6/IL-23, it did not show an increased ability to induce Th17 lymphocytes. In addition, mo-DCs, from patients with RA and SLE generated under the engagement of PSGL-1, showed a defective capability to induce Foxp3+ Treg cells. A similar phenomenon was observed in SLE, when DC's cells were generated under PDL-1 engagement. Our data indicate that DCs from patients with rheumatic inflammatory disease show an aberrant function that may have an important role in the pathogenesis of these conditions.
24653565 In vitro anti-inflammatory mechanism of Folium Hibisci Mutabilis leaves ethanol extracts. 2014 BACKGROUND: Folium Hibisci Mutabilis was one of the traditional Chinese medicines with pharmacological activities of wound healing, antibacterial and anti-inflammatory, normally applied to the clinical treatment of local purulent infection, scald, and epidemic parotitis. However, few people reported that its effects of extracts on RAW264.7, cells and TNF-α, IL-6, and NO levels in rats serum of inflammation rats. MATERIALS AND METHODS: We mainly adopted the RAW264.7, macrophage cell line which was intervened by lipopolysaccharide (L PS), to establish the model of inflammatory cells. The secretion changes of TNF, and IL-6, level in the model cell acted by the FHMAEs, were detected by ELISA, NO level changes were determined by nitrate reductase method; Arthritis model induced by Collagen Type II were chose, and regulatory role of FHMAEs on IL-6 and NO level in serum were observed, FHMAEs mechanism of action were investigated in the treatment of rheumatoid arthritis. The states of the model rats were recorded. RESULTS: Release of TNF-α, IL-6, and NO in LPS-induced RAW264.7, cells were significantly inhibited and has a clear dose-response relationship; The TNF-α, IL-6 and NO levels were reduced by FHMAEs in experimental arthritis rats serum, and the status of rats were improved. At last, we found that IL-6, NO and TNF-α levels in the inflammatory cells could be reduced by FHMAEs greatly. CONCLUSION: Both synovial inflammation and synovial proliferation could be reduced or inhibited by FHMAEs, all of this may provide experimental effective data for the novel drugs development and the clinical treatment of rheumatoid arthritis.
24448344 Identification of secreted phosphoprotein 1 gene as a new rheumatoid arthritis susceptibil 2015 Mar OBJECTIVE: To evaluate the contribution of the SPP1 rs11439060 and rs9138 polymorphisms, previously reported as autoimmune risk variants, in the rheumatoid arthritis (RA) genetic background according to anti-citrullinated protein antibodies (ACPAs) status of RA individuals. METHODS: We analysed a total of 11,715 RA cases and 26,493 controls from nine independent cohorts; all individuals were genotyped or had imputed genotypes for SPP1 rs11439060 and rs9138. The effect of the SPP1 rs11439060 and rs9138 risk-allele combination on osteopontin (OPN) expression in macrophages and OPN serum levels was investigated. RESULTS: We provide evidence for a distinct contribution of SPP1 to RA susceptibility according to ACPA status: the combination of ≥3 SPP1 rs11439060 and rs9138 common alleles was associated mainly with ACPA negativity (p=1.29×10(-5), ORACPA-negative 1.257 (1.135 to 1.394)) and less with ACPA positivity (p=0.0148, ORACPA-positive 1.072 (1.014 to 1.134)). The ORs between these subgroups (ie, ACPA-positive and ACPA-negative) significantly differed (p=7.33×10(-3)). Expression quantitative trait locus analysis revealed an association of the SPP1 risk-allele combination with decreased SPP1 expression in peripheral macrophages from 599 individuals. To corroborate these findings, we found an association of the SPP1 risk-allele combination and low serum level of secreted OPN (p=0.0157), as well as serum level of secreted OPN correlated positively with ACPA production (p=0.005; r=0.483). CONCLUSIONS: We demonstrate a significant contribution of the combination of SPP1 rs11439060 and rs9138 frequent alleles to risk of RA, the magnitude of the association being greater in patients negative for ACPAs.
24470327 Interleukin-17+CD8+ T cells are enriched in the joints of patients with psoriatic arthriti 2014 May OBJECTIVE: Psoriatic arthritis (PsA) is associated with HLA class I genes, in contrast to the association with HLA class II in rheumatoid arthritis (RA). Since IL-17+ cells are considered important mediators of synovial inflammation, we sought to determine whether IL-17-producing CD8+ T cells may be found in the joints of patients with PsA and whether these cells might contribute to the disease process. METHODS: Mononuclear cells from paired samples of synovial fluid (SF) and peripheral blood (PB) from patients with PsA or patients with RA were stimulated ex vivo, and CD4- T cells were examined by flow cytometry for cytokine expression, cytotoxic markers, and frequencies of γ/δ or mucosal-associated invariant T cells. Clinical measures of arthritis activity (C-reactive protein [CRP] level, erythrocyte sedimentation rate [ESR], Disease Activity Score in 28 joints [DAS28]) and power Doppler ultrasound (PDUS) scores for the presence of active synovitis in the aspirated knee were recorded and assessed for correlations with immunologic markers. RESULTS: Within the CD3+ T cell compartment, both IL-17+CD4- (predominantly CD8+) and IL-17+CD4+ T cells were significantly enhanced in the SF compared to the PB of patients with PsA (P = 0.0003 and P = 0.002, respectively; n = 21), whereas in patients with RA, only IL-17+CD4+ T cells were increased in the SF compared to the PB (P = 0.008; n = 14). The frequency of IL-17+CD4- T cells in PsA SF was positively correlated with the CRP level (r = 0.52, P = 0.01), ESR (r = 0.59, P = 0.004), and DAS28 (r = 0.52, P = 0.01), and was increased in patients with erosive disease (P < 0.05). In addition, the frequency of IL-17+CD4- T cells positively correlated with the PDUS score, a marker for active synovitis (r = 0.49, P = 0.04). CONCLUSION: These results show, for the first time, that the PsA joint, but not the RA joint, is enriched for IL-17+CD8+ T cells. Moreover, the findings reveal that the levels of this T cell subset are correlated with disease activity measures and the radiographic erosion status after 2 years, suggesting a previously unrecognized contribution of these cells to the pathogenesis of PsA.
25243130 Evaluation of the TMJ by means of clinical TMD examination and MRI diagnostics in patients 2014 This study included 30 patients with diagnosed rheumatoid arthritis (RA) and 30 test subjects without RA (control group). The objective of the study was to examine both groups for the presence of temporomandibular disorders (TMD) and morphological changes of the temporomandibular joint (TMJ). All individuals were examined using a systematic detailed clinical TMD examination as well as magnetic resonance imaging (MRI). The clinical TMD examination yielded significant differences between the RA patients and the control group concerning crepitus of the TMJ, and palpation tenderness of the masticatory muscles as well as the unassisted mandibular opening. The evaluation of the MRI images for the RA group showed significantly more frequent deformations of the condyle, osteophyte formations and erosions in the condylar compacta, and degenerative changes in the spongiosa. Increased intra-articular accumulation of synovial liquid and signs of inflammatory changes of the spongiosa were only found in the RA group. Statistical analysis showed a significant correlation between crepitus and specific osteoarthrotic changes (MRI), respectively, and between crepitus and a complete anterior disk displacement without reduction (MRI). The duration of the RA disease correlated neither with the anamnestic and clinical dysfunction index by Helkimo nor with RA-specific MRI findings.
23081991 Serial block-face scanning electron microscopy combined with double-axis electron beam tom 2013 Apr To evaluate the advantages of combination of two advanced electron microscopic technologies such as serial block-face scanning electron microscopy and double-axis electron beam tomography, we analyzed the three-dimensional morphology of cellular relationships between dendritic and plasma cells in the synovial membrane from patients with rheumatoid arthritis, using the combined approach.
24299607 Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis: study protoc 2013 Nov BACKGROUND: Rheumatoid arthritis (RA), as a common systemic inflammatory autoimmune disease, affects approximately 1 in 100 individuals. Effective treatment for RA is not yet available because current research does not have a clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a patent Chinese herbal medicine, has been used in the treatment of RA in recent years. Despite its reported clinical efficacy, there are no large-sample, multicenter, randomized trials that support the use of Xinfeng Capsule for RA. Therefore, we designed a randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of Xinfeng Capsule in the treatment of RA. METHODS AND DESIGN: This is a 12-week, randomized, placebo-controlled, double-blind, multicenter trial on the treatment of RA. The participants will be randomly assigned to the experimental group and the control group at a ratio of 1:1. Participants in the experimental group will receive Xinfeng Capsule and a pharmaceutical placebo (imitation leflunomide). The control group will receive leflunomide and an herbal placebo (imitation Xinfeng Capsule). The American College of Rheumatology (ACR) Criteria for RA will be used to measure the efficacy of the Xinfeng Capsule. The primary outcome measure will be the percentage of study participants who achieve an ACR 20% response rate (ACR20), which will be measured every 4 weeks after randomization. Secondary outcomes will include the ACR50 and ACR70 responses, the side effects of the medications, the Disease Activity Score 28, RA biomarkers, quality of life, and X-rays of the hands and wrists. The first four of the secondary outcomes will be measured every 4 weeks and the others will be measured at baseline and after 12 weeks of treatment. DISCUSSION: The result of this trial will help to evaluate whether Xinfeng Capsule is effective and safe in the treatment of RA. TRIAL REGISTRATION: This trial has been registered in ClinicalTrials.gov. The identifier is NCT01774877.