Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
19234855 Serum levels of anti-cyclic citrullinated peptide antibodies are associated with a benefic 2009 Oct This study investigated the usefulness of biomarkers indicating beneficial response to traditional herbal medicine (THM) among patients with rheumatoid arthritis (RA). We assessed 34 RA patients who received keishinieppiittokaryojutsubu (KER), one of the representative THM. The observational term was 12 months, and we calculated the disease activity score of 28 joints every 3 months and evaluated the response to KER using European League Against Rheumatism (EULAR) response criteria. Additionally, serum levels of anti-cyclic citrullinated peptide antibody (ACPA) were measured by enzyme-linked immunosorbent assay at the baseline and after 6 and 12 months of the treatment with KER. As a result, 14 (41.2%) of the 34 patients were defined as responders, 13 as non-responders and 7 as out of assessment after 6 months, respectively. Pretreatment levels of serum ACPA were lower in KER responders than in non-responders (P = 0.042), although other univariate analysis did not show any significant differences in baseline clinical measures between the two groups. Furthermore, responders to KER showed a significant decrease in the serum levels of ACPA. These findings suggest that pretreatment serum levels of ACPA are a useful predictor of a good response to treatment with KER. Furthermore, a decrease in serum levels of ACPA may be an adjunctive indicator in predicting the efficacy of this kind of treatment.
19221749 Short-term results after reversed shoulder arthroplasty (Delta III) in patients with rheum 2010 Feb The purpose of this study was to describe the outcome after reversed Delta III shoulder prosthesis in patients with rheumatoid arthritis (RA) and irreparable rotator cuff tear. Fifteen patients (17 joints) were prospectively analysed using the Constant-Murley score (CS). Comprehensive outcome measure was carried out by means of four widely used questionnaires as well as clinical and radiographic examinations at an average of 24.3 months postoperatively. The CS improved significantly from 19 to 59.5 points. The mental (MSC) and physical (PCS) component summary score of the Short Form 36 (SF-36) reached 108% and 77%, respectively, while the DASH (Disabilities of the Arm, Shoulder, and Hand) was 58% of a comparative norm population. Remaining deficits were documented by SPADI (Shoulder Pain and Disability; 54.4 points) and ASES (clinical and patient-orientated American Shoulder and Elbow Surgeons; 84.3 and 61.3 points, respectively). No radiological signs of loosening were found, but scapular notching occurred in four cases. Reversed arthroplasty provides a substantial improvement of shoulder function in patients with RA. The high incidence of notching is of concern.
19060002 Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a syst 2009 Jul OBJECTIVE: To perform a systematic literature review of the long-term safety of methotrexate (MTX) monotherapy in rheumatoid arthritis (RA). METHODS: A search was performed in Medline, Cochrane and EMBASE. Adults with RA who had received MTX monotherapy for more than 2 years were studied. RESULTS: 88 published studies were included. Over 12 years of treatment, the termination rate of MTX due to toxicity was less than for sulfasalazine, gold, d-penicillamine and higher than for hydroxychloroquine (level of evidence 2a-2b). Long-term use of MTX does not appear to be a risk factor for serious infections, including herpes zoster (2b-4), and could provide a survival benefit by reducing cardiovascular mortality (2b). The prevalence of raised liver enzymes (more than twice the upper limit of normal) is close to 13% of patients; 3.7% of patients stopped MTX permanently owing to liver toxicity (2b). Data on the risk for liver fibrosis/cirrhosis are conflicting: a meta-analysis showed an incidence of fibrosis of 2.7% after 4 years of MTX (2a). However, two other studies on sequential liver biopsies did not show evidence for developing severe damage (2b). Insufficient data are available to fully assess the risk of lymphoma and malignancies, although there is no strong evidence of increased risk (2b-4). CONCLUSION: This systematic literature search on MTX monotherapy with relatively low-dose use during at least 2 years shows favourable long-term safety.
19178122 Statin therapy in rheumatoid arthritis: a cost-effectiveness and value-of-information anal 2009 HMG-CoA reductase inhibitors (statins) are potentially excellent candidate agents for patients with rheumatoid arthritis (RA). They reduce both cardiovascular risks and RA disease activity. To evaluate the potential long-term effects of statin therapy among patients with RA, and to determine their associated cost effectiveness by incorporating both the cardiovascular and the anti-rheumatic benefits. A Markov decision-analytic model was developed to simulate cardiovascular and RA disease profiles over time. The impact of statin therapy was estimated by adjusting the risk of coronary heart disease (CHD) events and changes in the RA Disease Activity Score (DAS28), based on the results of a randomized trial. The benefits (QALYs) and costs (in year 2005 values) were evaluated from a US payer perspective. A full uncertainty analysis, including a value-of-information (VOI) analysis, was undertaken to evaluate the importance of individual parameters. Using a 10-year time horizon, the additional cost and QALYs of statin therapy were estimated to be USD4690 and 0.44 QALYs, respectively, resulting in an incremental cost-effectiveness ratio (ICER) of USD10 650 per QALY (95% CI 1525, 156 565). The QALY gain associated with statin therapy depended more on the anti-rheumatic effects of statin therapy than on its cardiovascular prevention effect. The VOI analysis found the long-term benefit of statin therapy (i.e. >or=12 months) and the consequent impact on quality of life to be the most uncertain and, therefore, influential parameters. Our analysis indicates that the dual anti-inflammatory/cardiovascular benefits of statins could make this therapy highly cost effective in RA. However, uncertainties remain in the available data, warranting further research on refining the precise RA disease-activity benefits and health-utility changes associated with statin therapy, at least over a 12-month period.
19002558 Combining effects of polymorphism of tumor necrosis factor alpha 5'-flanking region and HL 2009 We examined whether polymorphisms upstream of the TNF-alpha gene (TNFA) were associated with the radiological progression of rheumatoid arthritis (RA). One hundred and twenty-three patients with early RA (disease duration <1 year) were enrolled in a prospective follow-up study. The laboratory findings (ESR, CRP, and RF) were evaluated every 2 months for 2 years. Radiological progression in hands/wrists and feet was evaluated every 6 months for 2 years using Larsen's score. HLA-DRB1 genotype was determined by PCR-RFLP method. The genotypes for -1031, -863, and -857 single-nucleotide polymorphisms in the upstream 5'-flanking region of TNFA were determined by a PCR-preferential homoduplex formation assay in patients with RA and 265 healthy controls. Four TNFA alleles (U01, U02, U03, and U04) were identified. The frequency of individuals with U02 was significantly higher in patients than in controls (P = 0.0025). Radiographs of hands/wrists/feet were available for 72 patients after 1 year and for 73 patients after 2 years. When the HLA-DRB1 genotype was analyzed simultaneously, patients possessing U02 without an HLA-DRB1 shared epitope (SE) (U02+SE-) showed the lowest progression of Larsen's score (12 months). There was no difference in the level of ESR, CRP, or RF at the first visit among U02+SE+, U02+SE-, U02-SE+, and U02-SE- groups. The combination of the polymorphism of the TNFA upstream promoter region and HLA-DRB1 allele was associated with radiological progression in the early stage of RA.
19432131 [Indications for and use of biologics in early rheumatoid arthritis based on the evidence] 2009 May Given the recent consensus that main goal of therapy for rheumatoid arthritis (RA) is remission, it is extensively studied how to get remission effectively and early. Initial treatment with biologics along with methotrexate (MTX) has been shown to achieve clinical remission much greater than that with MTX alone, suggesting that early intervention with biologics plus MTX should be seriously considered. In this regard, personalized strategy to start biologics in individual patients based on the disease activity and prognosis factors has been proposed. In this review, indication and use of biologics in early RA are discussed by showing the clinical studies published in the literature.
18795293 Bone mineral density in Indian women with rheumatoid arthritis. 2009 Feb Osteoporosis (OP) is being increasingly recognized in inflammatory rheumatic diseases like rheumatoid arthritis (RA). Ethnicity influences bone mineral density (BMD) and fracture risk. Due to paucity of data on this aspect of RA from Asian countries including India, we prospectively studied 84 premenopausal women with RA of at least 2 years duration and 247 healthy, age (within 5 years) and sex-matched controls. A significant difference in BMD between patients and controls was observed only at the femoral neck. As many as 22% patients with RA exhibited osteoporosis at least one site in contrast to 9% controls. Nearly 40% of patients exhibited osteopenia at all the three sites. Modified Sharp score, disease duration and DMARD naive period were found to correlate with low BMD. However, on multivariate analysis, only modified Sharp score was shown to be significantly associated with low BMD. Our study draws attention to the poor bone health in Asian Indian women with RA.
20812194 The L55M polymorphism of paraoxonase-1 is a risk factor for rheumatoid arthritis. 2010 Aug 31 Paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme that exhibits antioxidant and antiatherogenic activities. We examined a possible association between T172A (L55M) and T(-107)C polymorphisms and rheumatoid arthritis. These polymorphisms were determined in 88 rheumatoid arthritis patients and 78 healthy subjects, using the tetra-amplification refractory mutation system-PCR method. The prevalence of the PON1 55MM genotype was significantly greater among rheumatoid arthritis patients (17%) when compared to control subjects (5.2%) (odds ratio (OR) = 3.75; 95% confidence interval (CI) = 1.87-11.8, P = 0.025). In addition, the M allele was more frequent in rheumatoid arthritis patients (40%) than in healthy subjects (24.7%) (OR = 1.997; 95%CI = 1.243-3.210, P = 0.005). There were no significant differences in the -107C/T polymorphism in the promoter sequence of PON1 between rheumatoid arthritis and normal subjects (chi(2) = 0.861, P = 0.650). In conclusion, the PON1 55MM genotype is a risk factor for rheumatoid arthritis.
19396446 Longitudinal changes in rheumatoid arthritis after rituximab administration assessed by qu 2009 Sep We retrospectively assessed the longitudinal changes of rheumatoid arthritis under rituximab therapy by use of quantitative and dynamic contrast-enhanced 3-T magnetic resonance (MR) imaging of the metacarpophalangeal joints of 10 patients at baseline and 26 weeks (n = 10). Additional studies were available at 12 weeks (n = 9) and at 52 weeks (n = 5). Clinical activity was assessed by use of the 28-joint disease activity score (DAS28). MR imaging was used to assess volumes of synovial enhancement, osseous enhancement, and erosions and early rapid enhancement. DAS28 and serum C-reactive protein trended down over time and were significantly lower at 26 weeks. Volume of synovial enhancement and early rapid enhancement showed a significant minimum at 26 weeks and increased thereafter. The erythrocyte sedimentation rate paralleled these two trends. Osseous enhancement did not significantly change over time. Erosions showed a significant progression. Trends of DAS28 and erosions were significantly different (P = 0.0075). In conclusion, our preliminary results suggest that rituximab is associated with a decrease of the inflammatory activity of synovitis with a minimum at 26 weeks and increasing activity thereafter suggesting recurrence. Our results further suggest subclinical progression of erosions with an inverse relationship to decreasing disease activity scores. Further studies are needed to confirm these results.
20676547 General principles for treatment of early rheumatoid arthritis. 2010 May The main goals of the treatment of a patient with RA are: to reduce pain, joint swelling and constitutional symptoms such as fatigue, to improve joint function, stop progression of bone-cartilage damage , prevent disabilities and reduce morbidity and mortality. In recent years, the therapeutic concept of early RA (first 12 months of symptoms) has undergone major changes. Three aspects in particular have become the basis of the new treatment paradigm: early diagnosis, immediate beginning of Disease Modifying Antirheumatic Drugs therapy (DMARD) and strict control of the inflammatory activity. In this article, the authors review the general principles of management of patients with early RA.
20065634 Denosumab. 2009 May Denosumab is an anti-receptor activator of nuclear factor (NF)-kappaB (RANK) ligand human monoclonal antibody studied as a treatment for postmenopausal osteoporosis (PMO) and bone destruction due to rheumatoid arthritis (RA) or metastatic cancers. As of February 2009, the candidate was undergoing US Food and Drug Administration review, and might be approved by October 2009. Late phase clinical trials demonstrated that denosumab possesses a similar safety profile to bisphosphonates and that it can be either equally or more effective than bisphosphonates at preventing bone loss due to PMO, RA or cancer treatment and metastases.
20112361 Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis. 2010 Feb OBJECTIVE: To identify whether cytokines, cytokine-related factors, and chemokines are up-regulated prior to the development of rheumatoid arthritis (RA). METHODS: A nested case-control study was performed in 86 individuals who had donated blood samples before experiencing any symptoms of disease (pre-patients) and 256 matched control subjects (1:3 ratio). In 69 of the pre-patients, blood samples were also obtained at the time of the diagnosis of RA. The plasma levels of 30 cytokines, related factors, and chemokines were measured using a multiplex system. RESULTS: The levels of several of the cytokines, cytokine receptors, and chemokines were significantly increased in individuals before disease onset compared with the levels in control subjects; i.e., those representing signs of general immune activation (interleukin-1beta [IL-1beta], IL-2, IL-6, IL-1 receptor antagonist, and tumor necrosis factor), activation of Th1 cells (interferon-gamma, IL-12), Th2 cells (IL-4, eotaxin), Treg cells (IL-10), bone marrow-derived factors (IL-7, granulocyte-macrophage colony-stimulating factor, and granulocyte colony-stimulating factor), as well as chemokines (monocyte chemotactic protein 1 and macrophage inflammatory protein 1alpha). The levels were particularly increased in anti-cyclic citrullinated peptide antibody- and rheumatoid factor-positive individuals, and the concentration of most of these increased further after disease onset. The concentration of IL-17 in individuals before disease onset was significantly higher than that in patients after disease onset. Individuals in whom RA subsequently developed were discriminated from control subjects mainly by the presence of Th1 cells, Th2 cells, and Treg cell-related cytokines, while chemokines, stromal cell-derived cytokines, and angiogenic-related markers separated patients after the development of RA from individuals before the onset of RA. CONCLUSION: Individuals in whom RA later developed had significantly increased levels of several cytokines, cytokine-related factors, and chemokines representing the adaptive immune system (Th1, Th2, and Treg cell-related factors); after disease onset, the involvement and activation of the immune system was more general and widespread.
20419126 A comprehensive molecular interaction map for rheumatoid arthritis. 2010 Apr 16 BACKGROUND: Computational biology contributes to a variety of areas related to life sciences and, due to the growing impact of translational medicine--the scientific approach to medicine in tight relation with basic science--, it is becoming an important player in clinical-related areas. In this study, we use computation methods in order to improve our understanding of the complex interactions that occur between molecules related to Rheumatoid Arthritis (RA). METHODOLOGY: Due to the complexity of the disease and the numerous molecular players involved, we devised a method to construct a systemic network of interactions of the processes ongoing in patients affected by RA. The network is based on high-throughput data, refined semi-automatically with carefully curated literature-based information. This global network has then been topologically analysed, as a whole and tissue-specifically, in order to translate the experimental molecular connections into topological motifs meaningful in the identification of tissue-specific markers and targets in the diagnosis, and possibly in the therapy, of RA. SIGNIFICANCE: We find that some nodes in the network that prove to be topologically important, in particular AKT2, IL6, MAPK1 and TP53, are also known to be associated with drugs used for the treatment of RA. Importantly, based on topological consideration, we are also able to suggest CRKL as a novel potentially relevant molecule for the diagnosis or treatment of RA. This type of finding proves the potential of in silico analyses able to produce highly refined hypotheses, based on vast experimental data, to be tested further and more efficiently. As research on RA is ongoing, the present map is in fieri, despite being--at the moment--a reflection of the state of the art. For this reason we make the network freely available in the standardised and easily exportable .xml CellDesigner format at 'www.picb.ac.cn/ClinicalGenomicNTW/temp.html' and 'www.celldesigner.org'.
19570223 Antibodies to cyclic citrullinated protein and erythrocyte sedimentation rate predict hand 2009 INTRODUCTION: Radiographic progression in rheumatoid arthritis (RA) has in several studies been shown to be predicted by serological markers widely used in daily clinical practice. The objective of this longitudinal study was to examine if these serological markers also predict hand bone mineral density (BMD) loss in patients with RA of short disease duration. METHODS: 163 patients with RA of short disease duration (2.4 years) were included and followed longitudinally. Antibodies to cyclic citrullinated protein (anti-CCP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were analysed from baseline blood-samples. Hand BMD was measured by digital X-ray radiogrammetry (DXR) based on hand and wrist radiographs obtained at baseline and 1, 2 and 5-year follow-up. RESULTS: During the study period, DXR-BMD decreased by median (inter quartile range) 1.7% (4.1 to 0.4), 2.8% (5.3 to 0.9) and 5.6% (11.7 to 2.3) after 1, 2 and 5 years, respectively. Elevated baseline anti-CCP, RF, ESR and CRP levels were in univariate linear regression analyses consistently associated with DXR-BMD change at all time-points. Anti-CCP and ESR were independently associated with hand DXR-BMD in multivariate linear regression analyses. Elevated anti-CCP levels were consistent and independent predictors of loss in cortical hand bone during the study period, with the odds ratios (95% confidence interval) 2.2 (1.0 to 4.5), 2.6 (1.1 to 6.2) and 4.9 (1.4 to 16.7) for the 1, 2, and 5-year follow-up periods, respectively. CONCLUSIONS: Anti-CCP and ESR were found to be independent predictors of early localised BMD loss. This finding adds to the understanding of anti-CCP and ESR as important predictors of bone involvement in RA.
18633125 Influence of peptidylarginine deiminase type 4 genotype and shared epitope on clinical cha 2009 Jun BACKGROUND: Recent evidence suggests that distinction of subsets of rheumatoid arthritis (RA) depending on anti-cyclic citrullinated peptide antibody (anti-CCP) status may be helpful in distinguishing distinct aetiopathologies and in predicting the course of disease. HLA-DRB1 shared epitope (SE) and peptidylarginine deiminase type 4 (PADI4) genotype, both of which have been implicated in anti-CCP generation, are assumed to be associated with RA. OBJECTIVES: To elucidate whether PADI4 affects the clinical characteristics of RA, and whether it would modulate the effect of anti-CCPs on clinical course. The combined effect of SE and PADI4 on autoantibody profile was also analysed. METHODS: 373 patients with RA were studied. SE, padi4_94C>T, rheumatoid factor, anti-CCPs and antinuclear antibodies (ANAs) were determined. Disease severity was characterised by cumulative therapy intensity classified into ordinal categories (CTI-1 to CTI-3) and by Steinbrocker score. RESULTS: CTI was significantly associated with disease duration, erosive disease, disease activity score (DAS) 28 and anti-CCPs. The association of anti-CCPs with CTI was considerably influenced by padi4_94C>T genotype (C/C: OR(adj) = 0.93, p(adj) = 0.92; C/T: OR(adj) = 2.92, p(adj) = 0.093; T/T: OR(adj) = 15.3, p(adj) = 0.002). Carriage of padi4_94T exhibited a significant trend towards higher Steinbrocker scores in univariate and multivariate analyses. An association of padi4_94C>T with ANAs was observed, with noteworthy differences depending on SE status (SE-: OR(adj) = 6.20, p(adj)<0.04; SE+: OR(adj) = 0.36, p(adj) = 0.02) and significant heterogeneity between the two SE strata (p = 0.006). CONCLUSIONS: PADI4 genotype in combination with anti-CCPs and SE modulates clinical and serological characteristics of RA.
20100792 Synovial fluid proteomic fingerprint: S100A8, S100A9 and S100A12 proteins discriminate rhe 2010 Apr OBJECTIVE: We investigated SF and serum proteomic fingerprints of patients suffering from RA, OA and other miscellaneous inflammatory arthritides (MIAs) in order to identify RA-specific biomarkers. METHODS: SF profiles of 65 patients and serum profiles of 31 patients were studied by surface-enhanced laser desorption and ionization-time-of-flight-mass spectrometry technology. The most discriminating RA biomarkers were identified by matrix-assisted laser desorption ionization-time of flight and their overexpression was confirmed by western blotting and ELISA. RESULTS: Three biomarkers of 10 839, 10 445 and 13 338 Da, characterized as S100A8, S100A12 and S100A9 proteins, were the most up-regulated proteins in RA SF. Their expression was about 10-fold higher in RA SF vs OA SF. S100A8 exhibited a sensitivity of 82% and a specificity of 69% in discriminating RA from other MIAs, whereas S100A12 displayed a sensitivity of 79% and a specificity of 64%. Three peptides of 3351, 3423 and 3465 Da, corresponding to the alpha-defensins-1, -2 and -3, were also shown to differentiate RA from other MIAs with weaker sensitivity and specificity. Levels of S100A12, S100A8 and S100A9 were statistically correlated with the neutrophil count in MIA SF but not in the SF of RA patients. S100A8, S100A9, S100A12 and alpha-defensin expression in serum was not different in the three populations. CONCLUSION: The most enhanced proteins in RA SF, the S100A8, S100A9 and S00A12 proteins, distinguished RA from MIA with high accuracy. Possible implication of resident cells in this increase may play a role in RA physiopathology.
20483042 T cell signal transducer and activator of transcription (STAT) 4 and 6 are affected by ada 2010 Mar OBJECTIVES: TNF-alpha inhibition therapy affects the systemic immune response in rheumatoid arthritis by influencing T cell subtypes (Th1, Th2, Treg), but its effect on the intracellular signal transduction in T cells remains largely unexplored. Here we studied the activation of Th1-associated signalling molecule STAT4 and Th2-associated STAT6 in CD4+ T cells. METHODS: Eight rheumatoid arthritis patients were studied before and after 12 weeks of adalimumab therapy and compared to 8 healthy individuals. Peripheral blood mononuclear cells (PBMC) were analysed flow cytometrically either directly after isolation or after 24 hours of anti-CD3/anti-CD28 stimulation, to determine spontaneous and IL-4/IL-12-induced STAT4 and STAT6 phosphorylation in CD4+ T cells. Cytokine production by stimulated PBMC was measured in the supernatant using a cytometric bead array. Non-parametric statistical tests were applied. RESULTS: After adalimumab therapy, phospho-STAT6 increased, both in freshly isolated and anti-CD3/anti-CD28-stimulated CD4+ T cells. The STAT6 response to brief IL-4 stimulation did not change. In healthy individuals and adalimumab-treated patients, anti-CD3/anti-CD28 induced the phosphorylation of STAT4, but not in untreated patients. IFN-gamma production in untreated patients was significantly lower than in healthy individuals or adalimumab-treated patients. In contrast, the production of IL-4, IL-6 and IL-12 was not influenced. CONCLUSIONS: Adalimumab therapy increases Th2-associated STAT6 phosphorylation and restores the activation-induced STAT4 phosphorylation to the levels in healthy individuals. This advocates against a pro-inflammatory effect of Th1-associated STAT4 and might provide an explanation for the influence of TNF inhibition therapy on the systemic T cell response in rheumatoid arthritis.
20952476 Prognostic factors of radiological damage in rheumatoid arthritis: a 10-year retrospective 2011 Jan OBJECTIVE: to describe the longterm clinical and radiological outcomes in rheumatoid arthritis (RA) in a cohort in northwestern Greece; and to investigate predictive factors of radiological damage at the 10-year followup in patients with RA. METHODS: we studied the disease course and outcome of 144 patients with RA and radiographs of the hands and wrists available at baseline and at 10 years. Baseline measurements and time-averaged measures of swollen joint count (SJC) and inflammatory markers [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)] were tested in univariate analysis, and then those presenting a statistically significant association with either Larsen score at 10 years or annual progression rate were included in 2 logistic regression models in order to determine relevant independent prognostic factors. RESULTS: a significant clinical improvement was noted, associated with a decrease of inflammatory markers along the timepoints. Larsen score and the number of erosive joints were increased. In the univariate analysis, both final Larsen score at 10 years and accelerated annual radiological progression rate were significantly associated with baseline radiographic measurements (Larsen score and number of erosive joints), the presence of autoantibodies [anticyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor of IgA and IgM isotype], disease duration, and time-averaged measures of ESR, CRP, and SJC. In the logistic regression analysis, the baseline Larsen score, anti-CCP antibodies, and time-averaged CRP presented significant and independent associations with Larsen score at 10 years. An accelerated annual radiological progression rate was also predicted by baseline Larsen score and time-averaged measures of SJC and CRP. CONCLUSION: despite clinical improvement, the radiologic progression of RA continues over time, because of the underlying inflammatory process. Baseline radiographic damage, anti-CCP antibodies, and time-averaged CRP constitute the main predictive factors of poor radiologic outcome in the long term.
18413439 Acute cold stress in rheumatoid arthritis inadequately activates stress responses and indu 2009 Apr OBJECTIVE: Acute stress in patients with rheumatoid arthritis (RA) should stimulate a strong stress response. After cryotherapy, we expected to observe an increase of hormones of the adrenal gland and the sympathetic nervous system. METHODS: A total of 55 patients with RA were recruited for whole-body cryotherapy at -110 degrees C and -60 degrees C, and local cold therapy between -20 degrees C and -30 degrees C for 7 days. We measured plasma levels of steroid hormones, neuropeptide Y (sympathetic marker), and interleukin (IL)6 daily before and after cryotherapy. RESULTS: In both therapy groups with/without glucocorticoids (GC), hormone and IL6 levels at baseline and 5 h after cold stress did not change over 7 days of cryotherapy. In patients without GC, plasma levels of cortisol and androstenedione were highest after -110 degrees C cold stress followed by -60 degrees C or local cold stress. The opposite was found in patients under GC therapy, in whom, unexpectedly, -110 degrees C cold stress elicited the smallest responses. In patients without GC, adrenal cortisol production increased relative to other adrenal steroids, and again the opposite was seen under GC therapy with a loss of cortisol and an increase of dehydroepiandrosterone. Importantly, there was no sympathetic stress response in both groups. Patients without GC and -110 degrees C cold stress demonstrated higher plasma IL6 compared to the other treatment groups (not observed under GC), but they showed the best clinical response. CONCLUSIONS: We detected an inadequate stress response in patients with GC. It is further shown that the sympathetic stress response was inadequate in patients with/without GC. Paradoxically, plasma levels of IL6 increased under strong cold stress in patients without GC. These findings confirm dysfunctional stress axes in RA.
19933369 Effect of tumor necrosis factor-related apoptosis-inducing ligand on the reduction of join 2010 Mar This study focused on the potential therapeutic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on collagen-induced arthritis (CIA) and on the elucidation of the mechanisms involved. DBA/1J mice with established CIA were treated with various amount of recombinant soluble human TRAIL. The effects of TRAIL on the development and severity of CIA in this DBA/1J mouse model were assessed clinically and histologically, and a detailed investigation was conducted on proinflammatory cytokine and anticollagen-specific antibody levels. Cellular immunity was evaluated by investigating the proliferative responses and cytokine release profiles of splenocytes after TRAIL treatment. TRAIL treatment significantly reduced the severity and incidence of CIA, joint swelling, erythema, and edema. Histologic evaluations revealed that inflammatory cell infiltration, cartilage destruction, and bone erosion were significantly reduced in joints of TRAIL-treated mice with dose-dependent manner. TRAIL treatment also strongly decreased and/or normalized the productions of proinflammatory cytokines and of anti-collagen-specific antibodies in the sera of CIA mice. Furthermore, in vitro studies with primary splenocytes showed the cytotoxic effect of TRAIL on activated lymphocytes, with reduction of inflammatory cytokine release. These findings show that TRAIL administration is an effective anti-inflammatory treatment that prevents the development and progression of CIA in DBA/1J mice, and they suggest that TRAIL might be considered a potential treatment for human RA.