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ID PMID Title PublicationDate abstract
27294648 Assessment of education requirements for patients with rheumatoid arthritis, based on the 2016 Jun 2 INTRODUCTION: Patients with chronic rheumatoid arthritis (RA) need advice in order to face the problems of everyday life, as well as suffering associated with the disease. Health professionals should attempt to raise the level of resourcefulness and independence of the patient. OBJECTIVE: To assess the relationship between the deficit of knowledge about RA and the degree of pain, fatigue, morning stiffness, assessment of disease activity as well as functional efficiency. MATERIALS AND METHOD: The study was conducted on 277 patients with RA in 7 rheumatologic centres in Poland. The method applied was the questionnaire Pol-ENAT (0-156); HAQ DI (0-3); analog scales (0-100). RESULTS: Mean (SD) age was 53.28 (13.01) and disease duration 13.70 (10.63) years. The mean (SD) value was 54.93 (23.17) for pain, 52.97 (21.98) for fatigue, 48.28 (24.76) for morning stiffness (0-100 mm). HAQ DI was 1.40 (0.66), with an upward trend with duration of disease (p<0.001). There was a positive correlation between the demand for knowledge about the movement (r=0.194; p=0.001), self-care (r=0.134; p=0.026), assistance/support(r =0.163; p=0.006) and morning stiffness experienced. There was a negative correlation between the need for knowledge concerning managing pain, feelings and the arthritis process and daily ability assessed with HAQ DI. CONCLUSIONS: The study shows that health education should be targeted at young patients with early RA. In the case of the severity of morning joints stiffness, there is a need to increase knowledge about the methods of mobility aids, self-care and the possibility of obtaining support.
26449724 Serum 14-3-3η level is associated with severity and clinical outcomes of rheumatoid arthr 2015 Oct 9 INTRODUCTION: Treat-to-target strategies to achieve low disease activity or clinical remission are key in the treatment of rheumatoid arthritis (RA). 14-3-3η is a joint-derived biomarker that is expressed at significantly higher levels in patients with RA than in healthy subjects, other autoimmune diseases, or viral and bacterial arthritides. In this study, we sought to investigate the utility of pretreatment levels of 14-3-3η and serial measurement of 14-3-3η to inform therapeutic outcomes. METHODS: Serum 14-3-3η levels were measured in 149 Japanese patients with RA before the initiation of therapy and at 1-year follow-up. Patients were treated with either methotrexate (MTX), adalimumab (ADA), tocilizumab (TCZ), or tofacitinib (TOF). 14-3-3η positivity was defined as ≥0.19 ng/ml and at two times and four times this cutoff. In contingency analysis, we determined the association of 14-3-3η with disease severity. Wilcoxon matched-pairs test was used to evaluate the significance of pre- to post-treatment changes. Mann-Whitney U test was performed for differences between treatment response groups. Fisher's exact test was used to assess associations of 14-3-3η with a good response defined by European League Against Rheumatism criteria as well as remission defined by the Disease activity Score in 28 joints with erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index score. RESULTS: 14-3-3η-positive patients had more severe disease before the initiation of treatment. When combined with C-reactive protein (CRP), 14-3-3η positivity added significantly and incrementally to the identification of patients with high disease activity. 14-3-3η levels were significantly decreased at 1 year and were modifiable across all classes of therapeutics. Patients who reverted to negative 14-3-3η levels had better clinical response than patients who remained positive at 1 year or became positive. Pretreatment 14-3-3η levels informed 1-year DAS28-ESR remission in the TCZ-treated group, in contrast to the ADA, MTX, or TOF groups, while no differences in pretreatment 14-3-3η expression based on clinical response. CONCLUSIONS: 14-3-3η is a modifiable marker in identifying patients with RA in a high disease state. Patients who achieve a negative 14-3-3η status following 1-year of treatment do better clinically with pretreatment 14-3-3η informing response to TCZ.
25637346 The association between reduction in inflammation and changes in lipoprotein levels and HD 2015 Jan 30 BACKGROUND: Potent anti-inflammatory rheumatoid arthritis (RA) treatments are associated with reduced cardiovascular risk as well as increases in low-density lipoprotein (LDL) cholesterol. This apparent paradox may be explained by favorable changes in other lipid measurements. The objective of this study was to determine the longitudinal association between changes in inflammation with advanced lipoprotein measurements and high-density lipoprotein (HDL) cholesterol efflux capacity. METHODS AND RESULTS: We conducted this study in a longitudinal RA cohort from a large academic center, including subjects with high-sensitivity C-reactive protein (hs-CRP) reduction ≥10 mg/L at 2 time points 1 year apart. Subjects receiving statins during the study period or preceding 6 months were excluded. We compared total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B, and apolipoprotein A1 levels and HDL cholesterol efflux capacity at baseline and 1-year follow-up by using the paired t test. We also assessed the correlations between reductions in hs-CRP with percentage change in lipid parameters. We studied 90 RA subjects (mean age 57 years, 89% female), all of whom were receiving disease-modifying antirheumatic drugs. We observed a 7.2% increase in LDL cholesterol levels (P=0.02) and improvement in efflux capacity by 5.7% (P=0.002) between baseline and follow-up, with a median hs-CRP reduction of 23.5 mg/L. We observed significant correlations between reductions in hs-CRP with increases in apolipoprotein A1 (r=0.27, P=0.01) and HDL cholesterol efflux capacity (r=0.24, P=0.02). CONCLUSION: Among RA subjects experiencing reductions in hs-CRP, we observed increased LDL cholesterol levels and concomitant improvements in HDL cholesterol efflux capacity. These findings provide further insight into lipid modulation and the beneficial effect of reduction in inflammation on lipids in vivo.
25932604 An involvement of SR-B1 mediated p38 MAPK signaling pathway in serum amyloid A-induced ang 2015 Aug Serum amyloid A (SAA) has been reported high expression in autoimmune diseases, such as rheumatoid arthritis (RA). However, detailed molecular mechanisms induced by SAA in the pathogenesis of RA are still unclear. Herein, we focused on the role of SAA-SR-B1 mediated p38 MAPK signaling pathway in the process of RA angiogenesis. Our results showed that both SAA and SR-B1 predominantly localized to vascular endothelial cells, lining and sublining layers in RA synovium. In a series of in vitro experiments with human umbilical vein endothelial cells (HUVECs), SAA induced the endothelial cells (ECs) proliferation, migration and tube formation. However, blockage of SR-B1 and p38 MAPK inhibited SAA-induced cells proliferation, migration and tube formation. In conclusion, our data showed a possible molecular mechanism for SAA-SR-B1 induced angiogenesis events via p38 MAPK signaling pathway.
27457515 Histone deacetylase 3 regulates the inflammatory gene expression programme of rheumatoid a 2017 Jan OBJECTIVES: Non-selective histone deacetylase (HDAC) inhibitors (HDACi) have demonstrated anti-inflammatory properties in both in vitro and in vivo models of rheumatoid arthritis (RA). Here, we investigated the potential contribution of specific class I and class IIb HDACs to inflammatory gene expression in RA fibroblast-like synoviocytes (FLS). METHODS: RA FLS were incubated with pan-HDACi (ITF2357, givinostat) or selective HDAC1/2i, HDAC3/6i, HDAC6i and HDAC8i. Alternatively, FLS were transfected with HDAC3, HDAC6 or interferon (IFN)-α/β receptor alpha chain (IFNAR1) siRNA. mRNA expression of interleukin (IL)-1β-inducible genes was measured by quantitative PCR (qPCR) array and signalling pathway activation by immunoblotting and DNA-binding assays. RESULTS: HDAC3/6i, but not HDAC1/2i and HDAC8i, significantly suppressed the majority of IL-1β-inducible genes targeted by pan-HDACi in RA FLS. Silencing of HDAC3 expression reproduced the effects of HDAC3/6i on gene regulation, contrary to HDAC6-specific inhibition and HDAC6 silencing. Screening of the candidate signal transducers and activators of transcription (STAT)1 transcription factor revealed that HDAC3/6i abrogated STAT1 Tyr701 phosphorylation and DNA binding, but did not affect STAT1 acetylation. HDAC3 activity was required for type I IFN production and subsequent STAT1 activation in FLS. Suppression of type I IFN release by HDAC3/6i resulted in reduced expression of a subset of IFN-dependent genes, including the chemokines CXCL9 and CXCL11. CONCLUSIONS: Inhibition of HDAC3 in RA FLS largely recapitulates the effects of pan-HDACi in suppressing inflammatory gene expression, including type I IFN production in RA FLS. Our results identify HDAC3 as a potential therapeutic target in the treatment of RA and type I IFN-driven autoimmune diseases.
26191188 Expression and function of microRNA-188-5p in activated rheumatoid arthritis synovial fibr 2015 Activated synovial fibroblasts in rheumatoid arthritis (RASF) play a critical role in the pathology of rheumatoid arthritis (RA). Recent studies suggested that deregulation of microRNAs (miRs) affects the development and progression of RA. Therefore, we aimed to identify de-regulated miRs in RASF and to identify target genes that may contribute to the aggressive phenotype of RASF. Quantitative real-time PCR revealed a marked downregulation of miR-188-5p in synovial tissue samples of RA patients as well as in RASF. Exposure to the cytokine interleukine-1β lead to a further downregulation of miR-188-5p expression levels compared to control cells. Re-expression of miR-188-5p in RASF by transient transfection significantly inhibited cell migration. However, miR-188-5p re-expression had no effects on glycosaminoglycan degradation or expression of repellent factors, which have been previously shown to affect the invasive behavior of RASF. In search for target genes of miR-188-5p in RASF we performed gene expression profiling in RASF and found a strong regulatory effect of miR-188-5p on the hyaluronan binding protein KIAA1199 as well as collagens COL1A1 and COL12A1, which was confirmed by qRT-PCR. In silico analysis revealed that KIAA1199 carries a 3'UTR binding site for miR-188-5p. COL1A1and COL12A1 showed no binding site in the mRNA region, suggesting an indirect regulation of these two genes by miR-188-5p. In summary, our study showed that miR-188-5p is down-regulated in RA in vitro and in vivo, most likely triggered by an inflammatory environment. MiR-188-5p expression is correlated to the activation state of RASF and inhibits migration of these cells. Furthermore, miR-188-5p is directly and indirectly regulating the expression of genes, which may play a role in extracellular matrix formation and destruction in RA. Herewith, this study identified potential novel therapeutic targets to inhibit the development and progression of RA.
27333261 Efficacy of a Rheumatoid Arthritis-Specific Smoking Cessation Program: A Randomized Contro 2017 Jan OBJECTIVE: Smoking adversely influences comorbidities in rheumatoid arthritis (RA). The aim of this pilot study was to investigate whether smoking cessation is increased following a 3-month smoking cessation intervention tailored for people with RA. METHODS: Thirty-nine current smokers with RA were recruited. Participants were randomized into the control group to receive the current local standard of care for smoking cessation (i.e., ABC = brief advice and subsidized nicotine replacement therapy [NRT], or into the intervention group to receive ABC plus additional smoking cessation advice for 3 months (ABC+), including face-to-face, telephone, and e-mail contact. Advice was tailored to the participants' specific needs from a range of intervention tools focused on education about smoking and RA, pain control, exercise, coping, and support. The primary outcome was smoking cessation at 6 months. The secondary outcome was sustained reduction in smoking at 6 months. Disease and psychosocial characteristics of quitters and nonquitters were examined. RESULTS: The overall smoking cessation rate was 24%. There was no significant difference in smoking cessation rates between the ABC and ABC+ groups (21% versus 26%; P = 0.70). The mean number of cigarettes smoked daily was reduced by 44% (P < 0.001) but did not differ between ABC and ABC+ groups (mean reduction 47% versus 41%; P = 0.72). Successful quitters had more years in education and had smoked less across their lifetime, but these differences were not statistically significant. CONCLUSION: Smoking cessation in RA may lead to a reduced comorbid burden. The lack of added benefit of the tailored intervention suggests that brief advice and NRT are currently the best practice for supporting people with RA who wish to quit smoking.
26417004 Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory 2015 Oct 19 Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. Through evaluation of synovial tissues from rheumatoid arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression corresponds with an increased incidence of ELS and gene signatures associated with their development and activity. The presence of synovial ELS was also noted in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory arthritis. Here, pathology was associated with increased synovial expression of pro-inflammatory cytokines, homeostatic chemokines, and transcriptional regulators linked with lymphoid neogenesis. In both clinical and experimental RA, synovial ELS coincided with the heightened local expression of cytokines and transcription factors of the Th17 and T follicular helper (Tfh) cell lineages, and included podoplanin-expressing T cells within lymphoid aggregates. IL-27 inhibited the differentiation of podoplanin-expressing Th17 cells, and an increased number of these cells were observed in IL-27R-deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector T cells. These studies open new opportunities for patient stratification and treatment.
25587165 Successful Colchicine Therapy in a Patient With Follicular Bronchiolitis Presumed to Be As 2015 Jul Follicular bronchiolitis (FB) is a rare small-airway pathology that is associated mainly with connective tissue diseases. This case report presents a new, diagnosed, different airway disease in a non-smoker with rheumatoid arthritis in remission who was treated for presumed asthma, but was not controlled. She was ultimately diagnosed with FB after video-assisted thoracoscopic surgery. The clinical findings of FB were controlled successfully by colchicine after she did not respond to systemic steroid therapy. This is the first case report of FB associated with rheumatoid arthritis that responded to colchicine.
27993172 Immune reconstitution 20 years after treatment with alemtuzumab in a rheumatoid arthritis 2016 Dec 20 BACKGROUND: Alemtuzumab, an anti-CD52 monoclonal antibody, was administered to patients with RA between 1991 and 1994. We have followed a cohort of recipients since that time and previously reported significant delays in immune reconstitution. Here we report >20 years of follow-up data from this unique cohort. METHOD: Surviving alemtuzumab recipients were age, sex and disease duration matched with RA controls. Updated mortality and morbidity data were collected for alemtuzumab recipients. For both groups antigenic responses were assessed following influenza, Pneumovax II and combined diphtheria/tetanus/poliovirus vaccines. Circulating cytokines and lymphocyte subsets were also quantified. RESULTS: Of 16 surviving alemtuzumab recipients, 13 were recruited: 9 recipients underwent a full clinical assessment and 4 had case notes review only. Since our last review 10 patients had died from causes of death consistent with long-standing RA, and no suggestion of compromised immune function. Compared with controls the alemtuzumab cohort had significantly reduced CD4(+) and CD8(+) central memory T-cells, CD5(+) B cells, naïve B cells and CD19(+)CD24(hi)CD38(hi) transitional (putative regulatory) B cells. Nonetheless vaccine responses were comparable between groups. There were significantly higher serum IL-15 and IFN-γ levels in the alemtuzumab cohort. IL-15 levels were inversely associated with CD4(+) total memory and central memory T cells. CONCLUSION: After 20 years the immune system of alemtuzumab recipients continues to show differences from disease controls. Nonetheless mortality and morbidity data, alongside vaccination responses, do not suggest clinical immune compromise. As lymphodepleting therapies, including alemtuzumab, continue to be administered this work is important with regard to long-term immune monitoring and stages of immune recovery.
27435295 Prediction of the therapeutic response to methotrexate at 24 weeks by methotrexate-polyglu 2017 May OBJECTIVES: The objective of this study is to evaluate the pharmacokinetics and pharmacodynamics of methotrexate-polyglutamates (MTX-PGs) in erythrocytes in patients with rheumatoid arthritis and correlate them with the efficacy. METHODS: MTX-PG concentrations in erythrocytes were measured in 42 MTX-naïve patients repeatedly for 24 weeks by high-performance liquid chromatography. In 56 patients receiving stable MTX doses for at least 12 weeks, the correlation between MTX doses and MTX-PG concentrations was examined. The efficacy was measured by the change of DAS28CRP (ΔDAS28CRP). RESULTS: There were moderate correlations between MTX dose and MTX-PG 3, 4, and 5. At 24 weeks, MTX-PG2, 3, 4, and 1-5 were higher in patients with ΔDAS28CRP >1.2 than in those with ≤1.2. The cutoff value of MTX-PG1-5 to discriminate ΔDAS28CRP >1.2 from ≤1.2 at 24 weeks was 68.7 nM. Among 20 patients with MTX-PG1-5 > 50.6 nM at 8 weeks, seven already improved at 8 weeks and additional 11 improved at 24 weeks (p < 0.001). On the contrary, among the nine patients with MTX-PG1-5 ≤ 50.6 nM at 8 weeks, none improved at 8 weeks and only one improved at 24 weeks (p = 0.500). CONCLUSIONS: Erythrocyte MTX-PGs might be a potential indicator and predictor of MTX efficacy.
26261853 The European League Against Rheumatism (EULAR) - 16th Annual European Congress (June 10-13 2015 Jun The 16th Annual European Congress of Rheumatology, organized by the European League Against Rheumatism (EULAR), provided the latest advances in the field of rheumatologic diseases to around 14,000 participants from more than 120 countries. This congress has become the primary platform for exchange of scientific and clinical information and the biggest rheumatology event in Europe. The congress covered a broad spectrum of the rheumatic diseases through 400 lectures, workshops, 300 oral presentations, 2,000 posters, 350 invited speakers, and basic science and clinical symposia.
24562503 Decreased expression of miR-146a and miR-155 contributes to an abnormal Treg phenotype in 2015 Jun OBJECTIVES: MicroRNAs (miRNAs) have been implicated in the pathogenesis of autoimmune diseases, not least for their critical role in the regulation of regulatory T cell (Treg) function. Deregulated expression of miR-146a and miR-155 has been associated with rheumatoid arthritis (RA). We therefore investigated miR-146a and miR-155 expression in Tregs of patients with RA and their possible impact on Treg function and disease activity. METHODS: Expression of miR-146a and miR-155 was assessed in RA patients and controls. MiRNA expression was correlated with disease activity and expression of target genes. Interference with biological activity of miRNAs was evaluated in functional Treg assays. RESULTS: Diminished upregulation of miR-146a and miR-155 in response to T cell stimulation was found in Tregs of RA patients. Diminution of miR-146a expression was observed in particular in patients with active disease, and correlated with joint inflammation. In patients with active RA, Tregs demonstrated a pro-inflammatory phenotype characterised by inflammatory cytokine expression. This was due to an augmented expression and activation of signal transducer and activator transcription 1 (STAT1), a direct target of miR-146a. CONCLUSIONS: Our results suggest that in RA miR-146a facilitates a pro-inflammatory phenotype of Tregs via increased STAT1 activation, and contributes thereby to RA pathogenesis.
26581676 Unconventional T-cell recognition of an arthritogenic epitope of proteoglycan aggrecan rel 2016 Apr It has been proposed that peptide epitopes bind to MHC class II molecules to form distinct structural conformers of the same MHC II-peptide complex termed type A and type B, and that the two conformers of the same peptide-MHC II complex are recognized by distinct CD4 T cells, termed type A and type B T cells. Both types recognize short synthetic peptides but only type A recognize endosomally processed intact antigen. Type B T cells that recognize self peptides from exogenously degraded proteins have been shown to escape negative selection during thymic development and so have the potential to contribute to the pathogenesis of autoimmunity. We generated and characterized mouse CD4 T cells specific for an arthritogenic epitope of the candidate joint autoantigen proteoglycan aggrecan. Cloned T-cell hybridomas specific for a synthetic peptide containing the aggrecan epitope showed two distinct response patterns based on whether they could recognize processed intact aggrecan. Fine mapping demonstrated that both types of T-cell recognized the same core epitope. The results are consistent with the generation of aggrecan-specific type A and type B T cells. Type B T cells were activated by supernatants released from degrading cartilage, indicating the presence of antigenic extracellular peptides or fragments of aggrecan. Type B T cells could play a role in the pathogenesis of proteoglycan-induced arthritis in mice, a model for rheumatoid arthritis, by recognizing extracellular peptides or protein fragments of joint autoantigens released by inflamed cartilage.
26093279 Targeting bromodomain-containing protein 4 (BRD4) benefits rheumatoid arthritis. 2015 Aug We aimed to explore the effects of bromodomain-containing protein 4 (BRD4) inhibition on tumor necrosis factor (TNF)-α-stimulated human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) behavior and the therapeutic implications using BRD4 inhibitor JQ1 were explored in vivo. The levels of interleukin (IL)-1β, IL-6, IL-17 and IL-18 in cultural supernatants from TNFα-stimulated RA-FLS were measured by ELISA. RA-FLS migration and invasion in vitro were investigated using wound healing and Matrigel assay. Expression of signaling pathway proteins was measured by Western blot. The in vivo effects of BRD4 inhibitor JQ1 were elucidated using collagen-induced arthritis (CIA) mice. We found BRD4 silencing reduced the secretion of IL-1β, IL-6, IL-17 and IL-18 from TNFα-stimulated human RA-FLS. Downregulation of BRD4 inhibited FBS-induced migration and invasion of human RA-FLS. BRD4 silencing decreased the phosphorylation of c-Jun and activation of NFκB in TNFα-stimulated RA-FLS. In vivo, BRD4 inhibitor JQ1 reduced the inflammatory response, autoantibody production and joint damage of CIA model. Our data suggest for the first time that BRD4 inhibition has anti-inflammatory property in RA.
26344397 Development of ultrasound enthesitis score to identify patients with enthesitis having spo 2015 Nov OBJECTIVES: To distinguish patients (pts) with enthesitis having spondyloarthritis (SpA) from pts with enthesitis without SpA by ultrasound (US) enthesitis score. METHODS: The study sample included 127 pts with enthesitis (76 pts with SpA, 26 pts with rheumatoid arthritis, 25 pts with mechanically-related enthesitis). The entheses of plantar fascia, Achilles, patellar, quadriceps and common extensor tendon on lateral epicondyle were examined by US. Two operators, blinded to clinical diagnosis and enthesitis symptoms, assessed enthesis thickness, echogenicity, enthesophytes, power Doppler signal and erosions. Logistic regression and receiver operating characteristic (ROC) curve analysis were used to determine the predictive value of each enthesitis lesion for diagnosis of SpA. The best predictive value for SpA was accomplished when absence and presence of increased thickness, hypoechogenicity and enthesophytes were scored as 0 and 1; absence and presence of PD and erosions were scored as 0 and 4. Belgrade Ultrasound Enthesitis Score (BUSES) represents a cumulative score of derived enthesitis lesion scores at examined entheses. Independent-samples t-test was used for BUSES comparison between pts with and without SpA. Validity of BUSES for SpA diagnosis was evaluated by sensitivity and specificity. Cut-off point was chosen as the smallest value with specificity of at least 90%. The reliability was analysed by intra-class-correlation coefficient (ICC). RESULTS: BUSES was 9.9 ± 12.4 (mean ± SD) in SpA pts and 3.1 ± 4.2 in pts without SpA (p<0.001). BUSES cut-off point ≥ 7 achieved excellent specificity (90.2%) and fair sensitivity (47.4%). ICC was 0.99. CONCLUSIONS: BUSES is highly specific, valid and reliable to identify patients with SpA.
26420629 Risk of low bone mineral density in patients with rheumatoid arthritis treated with biolog 2015 Sep 30 BACKGROUND: Osteoporosis is a complication of rheumatoid arthritis (RA). We identified risk factors for osteoporosis during treatment with biologics. METHODS: Femoral neck bone mineral density (BMD) was measured in 186 patients with biologics-treated RA. We compared the characteristics of those with BMD ≥70% of young adult mean (YAM) and those with BMD <70% of YAM, and undertook multivariable logistic regression analysis to identify risk factors for bone loss. RESULTS: Mean age and disease duration, the proportion of females, scores in the Modified Health Assessment Questionnaire and history of vertebral fracture were significantly greater in the BMD <70% of YAM group, but body mass index (BMI) was significantly lower in the BMD <70% of YAM group. There was no significant difference between the groups in terms of other biomarkers of RA activity, the proportion treated with methylprednisolone, or the duration or choice of biologics. The proportions of patients treated with anti-osteoporosis drugs and parathyroid hormone were significantly higher in the BMD <70% of YAM group. In the multivariable analysis, advanced age, female, longer disease duration, history of past thoracic or lumbar vertebral fracture, higher Steinbrocker classification and lower BMI were significant factors for BMD <70% of YAM. DISCUSSION: We identified risk factors for bone loss in patients with RA treated with biologics. Before suppression of disease activity by biologics, bone loss might already be advanced. CONCLUSIONS: We recommend that patients with RA who possess these risk factors be considered for earlier and more intense treatment to prevent bone loss, as well as addressing RA disease progression.
27137184 SOCS3 revisited: a broad regulator of disease, now ready for therapeutic use? 2016 Sep Since their discovery, SOCS have been characterised as regulatory cornerstones of intracellular signalling. While classically controlling the JAK/STAT pathway, their inhibitory effects are documented across several cascades, underpinning their essential role in homeostatic maintenance and disease. After 20 years of extensive research, SOCS3 has emerged as arguably the most important family member, through its regulation of both cytokine- and pathogen-induced cascades. In fact, low expression of SOCS3 is associated with autoimmunity and oncogenesis, while high expression is linked to diabetes and pathogenic immune evasion. The induction of SOCS3 by both viruses and bacteria and its impact upon inflammatory disorders, underscores this protein's increasing clinical potential. Therefore, with the aim of highlighting SOCS3 as a therapeutic target for future development, this review revisits its multi-faceted immune regulatory functions and summarises its role in a broad ranges of diseases.
26082314 15-hydroxyprostaglandin dehydrogenase is upregulated by hydroxychloroquine in rheumatoid a 2015 Sep 15-Hydroxyprostaglandin dehydrogenase (HPGD) is the key enzyme responsible for the metabolic inactivation of prostaglandin E2 (PGE2) catabolism. PGE2 is one of the predominant catabolic factors involved in rheumatoid arthritis (RA). However, the expression and regulation of HPGD in RA fibroblast‑like synoviocyte (FLS) remain to be elucidated. Disease‑modifying anti‑rheumatic drugs (DMARDs) are the most important anti‑arthritic drugs, which reduce the effect of joint injury. The aim of the present study was to assess the expression of HPGD in RA tissues and cells, and normal synovial tissues and cells. The effect of the most popular DMARDs, hydroxychloroquine, on the expression of HPGD in RA‑FLS was also investigated. Western blotting and immunohistochemical analysis demonstrated that the expression levels of HPGD in human synovium were lower in RA synovium compared with the normal and OA synovium. In RA‑FLS, the expression of HPGD was increased following treatment with several DMARDs, including sulfasalazine, methotrexate, and hydroxychloroquine. Hydroxychloroquine (10 µM) treatment induced the phosphorylation of ERK, SAPK/JNK and p38. Hydroxychloroquine induced a decrease in the release of PGE2, which was restored by mitogen‑activated protein (MAP) kinase pathway inhibitors. Hydroxychloroquine may therefore, affect the pathogenesis of RA through the MAP kinase pathway by regulating the expression of HPGD.
27045818 Relation among anti-rheumatic drug therapy, CD14(+)CD16(+) blood monocytes and disease act 2016 May Circulating human monocytes, a functionally and phenotypically heterogeneous population, are emerging as fundamental cell types in rheumatoid arthritis (RA). The aim of this pilot study was to assess the correlation, if any, among anti-rheumatic drug therapy, circulating CD14(+)CD16(+) monocytes and validated clinical scales (e.g., DAS28 score and ultrasonography US7 score) of disease severity in RA. Thirty consecutive RA patients, either naïve or under disease-modifying anti-rheumatic drugs (DMARDs) or biological therapy, and 10 age-matched healthy volunteers, were enrolled. Monocytes were prepared from heparinized blood samples; surface expression of CD14 and CD16 was determined by flow cytometry. RA patients presented a significantly higher percentage of CD14(+)CD16(+) monocytes, as compared to healthy subjects. There was a good correlation between DAS28 clinical score and the ultrasound composite score US7 (r=0.66), as well as between both scores and the percentage of CD14(+)CD16(+) monocytes (r=0.43 and 0.47, respectively). Naïve RA patients had the highest expression (19.2±3.2%) of CD14(+)CD16(+) monocytes and elevated DAS28 score; patients on DMARDs presented a 7-fold increased expression of CD14(+)CD16(+) monocytes, relatively to healthy volunteers (2.1±1.4%), and an intermediate disease severity. The RA patients treated with biological therapy had a low percentage of CD14(+)CD16(+) monocytes (5.1±3.6%; p<0.01 vs naïve and DMARDs groups), similar to the one detected in healthy controls, and reduced US7 and DAS28 scores. Interestingly, for the same DAS28 score, monocytes isolated from RA patients on biological therapy had a lower CD16 expression than patients on DMARDs. Therefore, CD14(+)CD16(+) circulating blood monocytes may represent an appropriate biomarker to assess RA disease activity along with DAS28 and US7 scores. Together, these three parameters may represent a better indicator for evaluating therapy efficacy.