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ID PMID Title PublicationDate abstract
25940298 [Impaired apoptosis of peripheral blood CD4+T cells in patients with rheumatoid arthritis] 2015 May OBJECTIVE: To investigate the role of CD4+T cell apoptosis in the pathogenesis of rheumatoid arthritis (RA). METHODS: The study enrolled 30 RA cases and 12 normal individuals as subjects. The apoptosis level of CD4+T lymphocytes in the patients with RA and the control individuals were measured by annexin V-FITC/PI staining combined with flow cytometry. The expression levels of Fas, FasL, caspase-8, caspase-3, Bcl-2 and Bax mRNAs were detected using real-time quantitative PCR (qRT-PCR); the expressions of Fas, FasL, caspase-8, caspase-3 proteins were observed using Western blotting. The correlations between the expressions of the apoptosis-related proteins and the clinical activity parameters were analyzed. RESULTS: The apoptosis level of CD4+T lymphocytes in RA patients was significantly lower than that in the healthy controls, and it was negatively correlated with erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF). Compared with the healthy control group, the expression levels of Fas, FasL, caspase-8, caspase-3 and Bax mRNAs in CD4+T cells of the RA patients were significantly reduced, whereas Bcl-2 mRNA was significantly elevated. The expression of Fas mRNA in CD4+T cells was negatively correlated with traditional Chinese medicine symptom score, whereas Bcl-2 mRNA was positively correlated with cyclic citrullinated peptide (CCP). Compared with the control group, the expressions of Fas, FasL, caspase-8 and caspase-3 proteins in CD4+T cells in the RA patients significantly decreased. The expression level of Fas protein was positively correlated with C-reactive protein (CRP), whereas FasL was negatively correlated with the time of morning stiffness. CONCLUSION: There is a decrease in the apoptosis of peripheral blood CD4+T cells in patients with RA, which has been found related to the decreased expressions of the apoptosis-related proteins (Fas, FasL, caspase-8, caspase-3, Bax) and the increased expression of Bcl-2. The study suggests that Fas-mediated apoptosis plays a role in the development of RA.
27072115 Comparative analysis of novel autoantibody isotypes against citrullinated-inter-alpha-tryp 2016 Jun 1 The purpose of this study was to discover and validate inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) as novel biomarkers, and evaluate autoantibody isotypes against an unmodified and citrullinated ITIH3(542-556) peptide among Taiwanese female patients with rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), secondary Sjögren's syndrome in rheumatoid arthritis (RA-sSS), and healthy controls (HCs). We used concanavalin A (Con A) affinity chromatography, 1-D SDS-PAGE, and label-free nano-LC-MS/MS to screen biomarker candidates (serum-derived Con A-captured proteins) and then identify PTMs of validated biomarkers (serum proteins) using pooled serum from 7 RA-sSS female patients and 7 age-matched HCs (the discovery set). Furthermore, the protein level and autoantibody isotype analyses were further validated against individual serum from 18 HCs, 18 RA, 18 pSS, and 18 RA-sSS patients (the validation set). Con A-bound ITIH3 was identified and validated as the only differentially expressed protein, which was elevated. Additionally, 2 novel PTMs in ITIH3 were identified and included citrullination at arginine-(546) and arginine-(556), and hexosamine at tryptophan-(558). Further, concentrations of anti-citrullinatd-ITIH3(542-556) peptide autoantibodies significantly increased in patients with RA, pSS, and RA-sSS compared to HCs. Especially, autoantibody IgM against the citrullinated-ITIH3(542-556) peptide showed better diagnostic performance in discriminating both RA versus pSS and pSS versus RA-sSS. SIGNIFICANCE: By using comparative proteomic analysis of serum samples, the current study discovered and validates differentially expressed Con A-bound ITIH3 as a potential biomarker for secondary Sjögren's syndrome (SS) in rheumatoid arthritis (RA) patients and healthy controls (HCs). Besides, hexosamine and citrullination on ITIH3 were further identified. Through analyzing autoantibody isotypes against the citrullinated ITIH3 peptide, patients with RA, primary SS, and RA-secondary SS, and HCs can be further discriminated. The current strategy can be applied for identifying potential diagnostic and pathologic markers for autoimmune diseases.
26028339 Early biomarkers of joint damage in rheumatoid and psoriatic arthritis. 2015 Jun 1 Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate biomarkers in rheumatoid and psoriatic arthritis, evaluated the evidence for their potential as biomarkers of bone (joint) damage, and outlined how mass spectrometry-based targeted and multiplexed measurement of candidate biomarker proteins is likely to accelerate their clinical validation and the development of clinical diagnostic tests.
27463825 Ultrasound-guided synovial biopsy of the wrist does not alter subsequent clinical or ultra 2016 Sep OBJECTIVES: Ultrasound-guided synovial biopsy (UGSB) is a minimally-invasive procedure capable of retrieving good quality tissue from small and large joints. The use of UGSB in prospective clinical trials poses a dilemma as to whether biopsied joints may be later included in core data sets for clinical or imagining response, as the procedure itself may alter disease activity assessment. In this study, we examine the impact of UGSB of the wrist on subsequent clinical and ultrasound (US) assessments in a cohort of rheumatoid arthritis (RA) patients prior to initiation of anti-TNF-alpha therapy. METHODS: Patients had active disease (DAS>5.1) involving their wrist. Both wrists were scanned and the most inflamed one underwent an UGSB. Ultrasonographic and clinical assessments were repeated at the patients' subsequent visit, without any changes in disease-modifying treatment between visits. US images were scored semi-quantitatively and quantitatively for synovial thickness (ST) and power Doppler (PD). Mixed-effects model and paired-Wilcoxon signed rank test were used to assess the effect of UGSB on these scores. RESULTS: Twenty-nine patients were enrolled. No significant difference in mean ST (p=0.32) or PD (p=0.21) was demonstrated pre- and post-biopsy (mean time 14.7 days). Similar results were obtained using quantitative measures. The DAS-28 and its components did not change significantly post-biopsy. CONCLUSIONS: In this population, UGSB of the wrist did not significantly alter subsequent clinical or US assessments, indicating that a wrist joint, which has undergone UGSB, may be incorporated into an US dataset or clinical outcome assessment tools, such as the DAS-28, without prejudice.
26758815 Emergence of liposome as targeted magic bullet for inflammatory disorders: current state o 2016 Nov Inflammatory diseases are considered to be highly dreadful ones responsible for higher mortality in the developed countries. This includes cancer, psoriasis, rheumatoid arthritis, and inflammatory bowel disease. The tremendous strides in the area of drug development to find newer molecules like non-steroidal and steroidal agents and immunosuppressant agents delivered by conventional formulation. These therapy have enhances the life expectancy of patient, but it provide the therapeutic benefits only to a limited extent. Recent advancement in liposomes based nanomedicines has led to the possibility of improves the efficacy and safety of the pharmacotherapy of inflammatory disorders. Of late, liposomes have been highly explored as one of the promising systems for delivering numerous anti-inflammatory drugs for attaining enhanced therapeutic outcomes. Over the conventional carriers, liposomal systems have numerous drug delivery merits including advantages in both passive and active targeting of drug molecules to the inflammatory lesions. The current review article, therefore, endeavors to provide a bird's eye view account on the success of liposome-based therapeutic systems in the management of dreadful inflammatory disorders along with updated knowledge to pharmaceutical scientists in the field.
26526669 The development of a questionnaire to evaluate rheumatoid arthritis patient's knowledge ab 2016 Mar AIMS AND OBJECTIVES: Assess knowledge concerning methotrexate in rheumatoid arthritis patients by means of a questionnaire. BACKGROUND: Methotrexate is the standard drug for rheumatoid arthritis treatment. It has potentially serious side effects that can be largely prevented by making sure that patients are well informed and comply with prescription guidelines. DESIGN: Cross-sectional survey. METHODS: A questionnaire on methotrexate (mode of action, administration, drug interactions), side effects, monitoring and lifestyle implications was offered to all the rheumatoid arthritis patients treated with the drug seen between March and September 2013 in a large hospital in France. RESULTS: One hundred and eighty-three patients (143 women), mean age 60 (13·5) years, with a median disease duration of 12 years [7-20] and treated with methotrexate for eight years [5-13] took part. Methotrexate was identified as a disease-modifying antirheumatic drug by 78% of the patients. The weekly administration method was well assimilated (97%); 67% indicated that the rationale for folic acid was to reduce treatment toxicity. Only 21% knew that trimethoprim was contraindicated. Half were aware of the haematologic risk and 36% were aware of the risk of hypersensitivity pneumonitis. There was knowledge concerning laboratory testing (80%), but 54% thought they were only being monitored for rheumatoid arthritis activity. Only 13% of the men, but 90% of the women, of childbearing age knew that contraception was essential, and 75% indicated that alcohol consumption should be limited. A low knowledge score correlated significantly with age and low educational level. It was independent of sex, duration of treatment for rheumatoid arthritis. CONCLUSIONS: Rheumatoid arthritis patient's knowledge concerning methotrexate is poor, particularly for the most serious side effects (haematologic and hypersensitivity pneumonitis), interactions with trimethoprim, and in men, the need for contraception. RELEVANCE TO CLINICAL PRACTICE: Patient knowledge concerning methotrexate should be regularly checked and supported using the different therapeutic education tools available, especially when patients are older people and have had limited schooling.
26758436 A population-based study on the association between rheumatoid arthritis and voice problem 2016 Jul The objective of this study was to investigate whether rheumatoid arthritis increases the frequency of organic laryngeal lesions and the subjective voice complaint rate in those with no organic laryngeal lesion. We performed a cross-sectional study using the data from 19,368 participants (418 rheumatoid arthritis patients and 18,950 controls) of the 2008-2011 Korea National Health and Nutrition Examination Survey. The associations between rheumatoid arthritis and organic laryngeal lesions/subjective voice complaints were analyzed using simple/multiple logistic regression analysis with complex sample adjusting for confounding factors, including age, sex, smoking status, stress level, and body mass index, which could provoke voice problems. Vocal nodules, vocal polyp, and vocal palsy were not associated with rheumatoid arthritis in a multiple regression analysis, and only laryngitis showed a positive association (adjusted odds ratio, 1.59; 95 % confidence interval, 1.01-2.52; P = 0.047). Rheumatoid arthritis was associated with subjective voice discomfort in a simple regression analysis, but not in a multiple regression analysis. Participants with rheumatoid arthritis were older, more often female, and had higher stress levels than those without rheumatoid arthritis. These factors were associated with subjective voice complaints in both simple and multiple regression analyses. Rheumatoid arthritis was not associated with organic laryngeal diseases except laryngitis. Rheumatoid arthritis did not increase the odds ratio for subjective voice complaints. Voice problems in participants with rheumatoid arthritis originated from the characteristics of the rheumatoid arthritis group (higher mean age, female sex, and stress level) rather than rheumatoid arthritis itself.
27932870 Evaluation of quality of life in chronic, progressing rheumatic diseases based on the exam 2016 BACKGROUND: Rheumatic diseases, irrespective of etiology and clinical course, influence different areas of a patient's life. Adapting to disability and limitations caused by an illness is very difficult for many patients. The main goal of a therapeutic procedure should be improvement of health-related quality of life (QoL). OBJECTIVE: Evaluation of the factors that influence the QoL that are conditioned by the state of health of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). METHODS: The study group consisted of 198 patients diagnosed with OA, according to the American College of Rheumatology criteria (1988), and 100 patients diagnosed with RA, according to the American College of Rheumatology criteria (2010). A diagnostic survey using visual analog scale of pain, health assessment questionnaire disability index, and 36-item short form health survey were used in this study. RESULTS: The average age of patients with OA was 59.16 (±15.87) years and patients with RA was 55.22 (±14.87) years. The average duration of illness examined for OA was 5.5 (±4.32) years, whereas for RA, it was slightly more at 6.8 (±5.21) years. Overall the QoL in both study groups was of medium level. Among patients with OA and RA, lower evaluation of QoL was mainly affected by age (OA - physical sphere [PCS] r(s) =-0.177, P<0.012; MCS r(s) =-0.185, P=0.008; RA - PCS r(s) =-0.234, P=0.019; MCS r(s) =-0.208, P=0.038), the level of physical disability (OA - PCS r(p) =-0.532, P<0.001; MCS r(s) =-0.467, P<0.001; RA - PCS r(p) =-0.326, P<0.001; MCS r(s) =-0.229, P<0.001), and pain (OA - PCS r(p) =-0.425, P<0.001; mental sphere/mental functioning (MCS) r(s) =-0.359, P<0.001; RA - PCS r(p) =-0.313, P<0.001; MCS r(p) =-0.128, P<0.001). CONCLUSION: Patients with OA, despite their average older age, had a higher evaluated QoL than patients with RA. Overall QoL in terms of mental functioning in both rheumatic diseases was assessed at a higher level than in the area of physical functioning.
28129845 The lymphatic vasculature revisited-new developments in the zebrafish. 2017 The lymphatic system is lined by endothelial cells and part of the vasculature. It is essential for tissue fluid homeostasis, absorption of dietary fats, and immune surveillance in vertebrates. Misregulation of lymphatic vessel formation and dysfunction of the lymphatic system have been indicated in a number of pathological conditions including lymphedema formation, obesity or chronic inflammatory diseases such as rheumatoid arthritis. In zebrafish, lymphatics were discovered about 10years ago, and the underlying molecular pathways involved in its development have since been studied in detail. Due to its superior live cell imaging possibilities and the broad tool kit for forward and reverse genetics, the zebrafish has become an important model organism to study the development of the lymphatic system during early embryonic development. In the current review, we will focus on the key players during zebrafish lymphangiogenesis and compare the roles of these genes to their mammalian counterparts. In particular, we will focus on novel findings that shed new light on the molecular mechanisms of lymphatic cell fate specification, as well as sprouting and migration of lymphatic precursor cells.
26598284 Use of a temporary supramalleolar orthosis to manage foot pain in a patient with rheumatoi 2016 Jun BACKGROUND: Rheumatoid arthritis is a chronic inflammatory condition characterized by joint pain, stiffness, and functional disability. Approximately 90% of patients will report symptoms in the foot or ankle during the course of their disease. CASE DESCRIPTION: A case of a 40-year-old woman with a 12-year history of rheumatoid arthritis referred to outpatient physical therapy with a chief complaint of pain in the lateral rearfoot and forefoot is presented. At the time of the initial examination, the patient reported persistent pain ranging from 3 to 9/10, aggravated when standing and walking during activities of daily living. Treatment consisted of the fabrication of a supramalleolar orthosis that incorporated an in-shoe foot orthosis to address functional limitations and abnormal foot and ankle posture. A home exercise program was prescribed to address potential balance deficits and strength loss following the application of the orthosis. OUTCOMES: Clinically significant improvements were seen in pain, gait speed, and on the Foot Function Index following the implementation of the orthotic device. The patient returned to standing and walking with minimal symptom limitations. DISCUSSION: This case report highlights the short-term clinical outcomes when using a supramalleolar orthosis in conjunction with an in-shoe foot orthosis to manage lateral rearfoot and forefoot pain in a patient with rheumatoid arthritis.
27151711 Rheumatoid nodules and quality of life in rheumatoid arthritis females - complex assessmen 2016 Rheumatoid arthritis (RA) represents the most commonly diagnosed arthropathy that affect many tissue types and organs, characterized by a clinical, functional and therapeutic pathogenic complexity and it affects especially diarthroidal joints. Rheumatoid nodules (RNs) are one of the most frequent extra-articular manifestations of RA, and usually reflect an advanced stage of the disease and a poor prognosis. The complexity of histological, clinical and functional aspects in RA has a real impact on the quality of life in all patients diagnosed with this disorder. Our prospective study presents the RNs involvement in the rehabilitation program performed in order to enhance the quality of life in the 25 RA female patients. We made a complex assessment and realized a correlation between pain, disability and histological aspect of RN, before and after the rehabilitation program. Also, we evaluated the clinical and functional effectiveness of a complex rehabilitation program and changes in impairment and activity limitation in women with RA and RNs. The immunohistological complexity of RNs reflects the intensity of the inflammatory-immune process and completes the assessment of RA patients with RNs. It allows for medical assistance quantification, even for patients that have a poor evolution prognosis.
25812536 Are there racial disparities in utilization and outcomes after total elbow arthroplasty? 2015 Sep The aim of the study was to assess racial disparities in utilization rates and outcomes after primary total elbow arthroplasty (TEA). We used the National Inpatient Sample from 1998 to 2010, a US national database. Patient characteristics, comorbidity and outcomes after TEA were assessed over time and differences by race studied over the study period. Cochran-Armitage test was used for time trends and logistic regression for the comparison of outcomes by race. In 1998, TEA utilization rate was 0.38/100,000 in Whites and 0.24/100,000 in Blacks (p = 0.002); in 2010, it was 0.91 and 0.59/100,000, respectively (p < 0.0001). White-Black disparity in TEA utilization was significant across 13 years (p = 0.03). Compared with White patients, Black patients undergoing TEA were younger (61.9 vs. 52 years; p < 0.0001), less likely to be female (70.6 vs. 61.4 %; p = 0.0007) and more likely to have rheumatoid arthritis as the underlying diagnosis (13.0 vs. 17.2 %; p = 0.036). Mortality was rare, 0.26 % in Blacks and 0.32 % in Whites (p = 0.83). Discharge to an inpatient facility was higher in White versus Black patients in unadjusted analyses (16.8 vs. 10.4 %; p = 0.003), but in analyses adjusted for age, sex, Deyo-Charlson index and the underlying diagnosis, the differences were no longer significant (p = 0.79). The length of hospital stay greater than the median stay was noted in 29.8 % Whites versus 31.2 % Blacks, respectively (p = 0.61). There was no evidence of White-Black disparity in hospital length of stay in 1998-2000 (p = 0.66) or 2009-2010 (p = 0.59) periods. In this study, we found persisting racial disparities in TEA utilization rates. No White-Black disparities were noted in TEA outcomes, except slight differences in discharge disposition.
27342772 High prevalence of tenosynovial inflammation before onset of rheumatoid arthritis and its 2016 Oct OBJECTIVE: To define the anatomic distribution of the earliest inflammatory and structural changes in individuals with anti-citrullinated protein antibody (ACPA+) positivity but no signs of arthritis. METHODS: ACPA+ individuals (N = 20) and healthy controls (N = 13) received simultaneous gadolinium-enhanced magnetic resonance imaging (MRI) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the hands. MRI sequences were scored for synovitis, osteitis, and bone erosions according to the RAMRIS method as well as for presence, localization, and extent of tenosynovitis. Bone erosions were validated by HR-pQCT scanning and related to the inflammatory changes found in the MRI. RESULTS: Tenosynovitis was the most prevalent inflammatory pathology, affecting 80% of ACPA+ individuals but none of the controls. Tenosynovitis at two or more anatomical sites was associated with later development of RA. Synovitis (65%) and osteitis (35%) were present in ACPA+ individuals as well, but at a lower frequency than tenosynovitis. MRI bone erosions were found in 65% of the individuals and additionally confirmed by HR-pQCT. Presence of MRI osteitis was the inflammatory pathology most strongly associated with bone erosions. CONCLUSION: Tenosynovitis is highly prevalent in ACPA+ individuals without arthritis and associated with later development of RA. Small erosions, often linked to osteitis, are also found in ACPA+ individuals without arthritis.
25359382 Methotrexate in combination with other DMARDs is not superior to methotrexate alone for re 2015 Jan OBJECTIVES: To compare the efficacy and safety of intensive combination strategies with glucocorticoids (GCs) in the first 16 weeks (W) of early rheumatoid arthritis (eRA) treatment, focusing on high-risk patients, in the Care in early RA trial. METHODS: 400 disease-modifying antirheumatic drugs (DMARD)-naive patients with eRA were recruited and stratified into high risk or low risk according to classical prognostic markers. High-risk patients (n=290) were randomised to 1/3 treatment strategies: combination therapy for early rheumatoid arthritis (COBRA) Classic (methotrexate (MTX)+ sulfasalazine+60 mg prednisone tapered to 7.5 mg daily from W7), COBRA Slim (MTX+30 mg prednisone tapered to 5 mg from W6) and COBRA Avant-Garde (MTX+leflunomide+30 mg prednisone tapered to 5 mg from W6). Treatment modifications to target low-disease activity were mandatory from W8, if desirable and feasible according to the rheumatologist. The primary outcome was remission (28 joint disease activity score calculated with C-reactive protein <2.6) at W16 (intention-to-treat analysis). Secondary endpoints were good European League Against Rheumatism response, clinically meaningful health assessment questionnaire (HAQ) response and HAQ equal to zero. Adverse events (AEs) were registered. RESULTS: Data from 98 Classic, 98 Slim and 94 Avant-Garde patients were analysed. At W16, remission was reached in 70.4% Classic, 73.6% Slim and 68.1% Avant-Garde patients (p=0.713). Likewise, no significant differences were shown in other secondary endpoints. However, therapy-related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in 69.1% of Avant-Garde patients (p=0.006). CONCLUSIONS: For high-risk eRA, MTX associated with a moderate step-down dose of GCs was as effective in inducing remission at W16 as DMARD combination therapies with moderate or high step-down GC doses and it showed a more favourable short-term safety profile. EUDRACT NUMBER: 2008-007225-39.
26209789 Depressive symptoms predict future simple disease activity index scores and simple disease 2015 Dec OBJECTIVE: To determine whether depressive symptoms assessed in treated patients with early inflammatory polyarthritis (EPA) influence disease activity during follow-up. METHODS: Consecutively recruited EPA patients were actively treated to remission. Simple disease activity index (SDAI) and Center for Epidemiologic Studies Depression Scale (CES-D) scores were calculated at inclusion and up to 42 months into disease. SDAI scores were log-transformed to compute univariate and multivariate linear regressions. Parametric interval-censored Kaplan-Meier and survival regressions using Weibull distribution were used to assess time to and predictors of SDAI remission. RESULTS: A total of 275 EPA patients were recruited at a median of 4 months into disease. In multivariate linear regression models, accounting for baseline demographic, clinical, serological and functional variables and 12-month inflammation markers, CES-D scores at 12 months into disease were correlated (r(2) = 0.14) with subsequent SDAI scores. Patients with 12-month high CES-D (≥19; suggestive of depression) had a lower proportion of SDAI remission (31.3% vs 84.3%; P < 0.001) and reached SDAI remission less rapidly [hazard ratio = 0.25 (95% CI 0.12, 0.53); P < 0.001]. CONCLUSION: Each follow-up SDAI correlated significantly with 12-month depressive symptoms, a median of 7 months after initiation of treatment. CES-D scores suggestive of depression at 12 months were strongly correlated with delay and failure to reach remission later on. Depressive symptoms in treated EPA patients represent important clinical issues with long-term association with disease activity. Interventions to alleviate persistent depressive symptoms in treated EPA warrant careful evaluation of their potential to improve disease remission rates.
26286095 Adaptation to an autoimmune disorder: Does mental flexibility impact illness-related self- 2016 OBJECTIVE: To examine whether mental flexibility moderates the relationship between illness representations of control and coping behaviour in individuals suffering from rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). DESIGN: Recently, diagnosed RA (N = 80) and SLE (N = 75) patients completed questionnaires about illness representations of personal and treatment control and four coping behaviours: instrumental coping, adherence to medical advice, palliative coping and wishful thinking. Mental flexibility was assessed with the Trail Making Test Part B (TMT-B), while visuomotor processing speed, as a confounder, was assessed with the Trail Making Test Part A (TMT-A). Moderated mediation models were tested within a bootstrapped multiple regression framework. RESULTS: TMT-A scores had no statistically significant moderation effects on the relation between representations and coping behaviour. Conversely, in those participants with SLE, TMT-B scores moderated the relation of personal control to wishful thinking and palliative coping, as well as the relation of treatment control to both wishful thinking and palliative coping. All significant effects were restricted to the SLE group. CONCLUSION: Interactions between neurocognitive factors and the process of illness adaptation may emerge early during the course of SLE. The present findings highlight the role of cognitive functioning as an integral part of the illness-related self-regulation mechanism.
26683152 Mechanisms involved in triggering rheumatoid arthritis. 2016 Jan Rheumatoid arthritis (RA) is a chronic inflammatory syndrome with a strong autoimmune component. The autoantigens in RA are neither tissue nor organ-specific, but comprise a broad collection of post-translational modified proteins, such as citrullinated proteins. These modifications are likely to be triggered by innate stimuli. In genetically susceptible hosts, they can lead to a more substantiated secondary autoimmune reaction targeting the joints and precipitating the clinical onset of RA. Both innate and adaptive mechanisms will then closely interplay to promote chronic joint inflammation in the several absence of appropriate treatment. This scenario, is shared with other autoimmune diseases where potentially pathogenic immune responses are present already before disease onset. Better understanding of these processes will allow both earlier diagnosis of RA and identification of those healthy individuals that are at risk of developing disease, opening possibilities for disease prevention. In this review, we discuss the iterative processes of innate and adaptive immunity responsible for the (longitudinal) development of immune reactions that may contribute to the development of RA.
25630523 The presence of FCGR2B promoter or transmembrane region variant alleles leads to reduced s 2015 Aug The inhibitory FcγRIIB plays an important role for the peripheral B cell tolerance and plasma cell homeostasis, and any malfunctioning is predicted to result in humoral autoimmunity. An association between rheumatoid arthritis (RA) and FCGR2B promoter and TM region variant alleles, both of which result in a reduced functionality, is only insufficiently elucidated. We here set out to investigate the impact of these variants on disease progression in European RA patients. One hundred and five ACPA-positive RA patients were genotyped for the FCGR2B -386G>C promoter and the 695T>C transmembrane region variants. Moreover, serum titers for IL-6, TNFα, CTX-1 and ACPAs were measured and peripheral blood T cell and B cell populations analyzed for expression of the activation markers CTLA-4 and CD86. The presence of an FCGR2B variant allele results in reduced serum IL-6, a trend toward later disease onset and reduced requirement for biological treatment, but does not seem to aggravate RA. Likewise, the presence of the TM region variant allele is associated with a lower activation state of the Tregs and of naïve and memory B cells. The observation of a malfunctioning FcγRIIb not aggravating RA is counterintuitive at first. However, the etiology of RA is linked to inflammatory episodes, and the lack of B cell inhibition may support an accelerated antibody-mediated clearance of the disease initiating and perpetuating agents. It would thereby shorten inflammatory episodes, postpone the onset of disease and result in a less severe course of RA in carriers of FCGR2B variant alleles.
27277474 Guizhi-Shaoyao-Zhimu decoction attenuates rheumatoid arthritis partially by reversing infl 2016 Jun 8 BACKGROUND: Guizhi-Shaoyao-Zhimu decoction (GSZD) has been extensively used for rheumatoid arthritis (RA) therapy. Marked therapeutic efficacy of GSZD acting on RA has been demonstrated in several long-term clinical trials without any significant side effects. However, its pharmacological mechanisms remain unclear due to a lack of appropriate scientific methodology. METHODS: GSZD's mechanisms of action were investigated using an integrative approach that combined drug target prediction, network analysis, and experimental validation. RESULTS: A total of 77 putative targets were identified for 165 assessed chemical components of GSZD. After calculating the topological features of the nodes and edges in the created drug-target network, we identified a candidate GSZD-targeted signal axis that contained interactions between two putative GSZD targets [histone deacetylase 1 (HDAC1) and heat shock protein 90 kDa alpha, class A member 1 (HSP90AA1)] and three known RA-related targets [NFKB2; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta (IKBKB); and tumor necrosis factor-alpha (TNF-α)]. This signal axis could connect different functional modules that are significantly associated with various RA-related signaling pathways, including T/B cell receptor, Toll-like receptor, NF-kappa B and TNF pathways, as well as osteoclast differentiation. Furthermore, the therapeutic effects and putative molecular mechanisms of GSZD's actions on RA were experimentally validated in vitro and in vivo. CONCLUSIONS: GSZD may partially attenuate RA by reversing inflammation-immune system imbalance and regulating the HDAC1-HSP90AA1-NFKB2-IKBKB-TNF-α signaling axis.
25611418 Long-term results of shoulder hemiarthroplasty in patients with rheumatoid arthritis. 2015 Jan Rheumatoid arthritis affecting the shoulder is typically associated with destruction of the glenohumeral joint and rotator cuff impairment, which can result in severe glenoid erosion. Following hemiarthroplasty, severe glenoid erosion has also frequently been observed. The authors' aim was to retrospectively evaluate the outcome of cemented shoulder hemiarthroplasty in patients with rheumatoid arthritis. The authors performed 45 cemented hemiarthroplasties in 36 patients with rheumatoid arthritis involving the shoulder as well as associated rotator cuff compromise between 1995 and 2008. All patients were analyzed radiologically and clinically using patient-reported outcome measures. Mean±SD visual analog pain scale score was 3±2. Mean±SD Constant score was 55±16. Mean±SD validated Dutch version of the Disabilities of the Arm Shoulder and Hand (DASH) score was 42±19. No radiograph showed loosening of the implant at follow-up. One patient needed an arthrotomy and capsulotomy because of persistent pain and limited range of motion. Tissue cultures taken during this second operation were negative for infection. No major revision surgery was necessary within the follow-up period. Cemented hemiarthroplasty is a viable treatment option for glenohumeral arthritis in patients with rheumatoid arthritis. Long-term results show acceptable results and low complication rates in this case series for this specific group. A randomized, controlled trial comparing hemiarthroplasty, total shoulder arthroplasty, and reverse shoulder arthroplasty is necessary to draw definite conclusions in this specific patient population.