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ID PMID Title PublicationDate abstract
29118439 Preventing progression from arthralgia to arthritis: targeting the right patients. 2018 Jan Early treatment is associated with improved outcomes in patients with rheumatoid arthritis (RA), suggesting that a 'window of opportunity', in which the disease is most susceptible to disease-modifying treatment, exists. Autoantibodies and markers of systemic inflammation can be present long before clinical arthritis, and maturation of the immune response seems to coincide with the development of RA. The pre-arthritis phase associated with symptoms such as as joint pain without clinical arthritis (athralgia) is now hypothesized to fall within the aforementioned window of opportunity. Consequently, disease modulation in this phase might prevent the occurrence of clinically apparent arthritis, which would result in a persistent disease course if untreated. Several ongoing proof-of-concept trials are now testing this hypothesis. This Review highlights the importance of adequate risk prediction for the correct design, execution and interpretation of results of these prevention trials, as well as considerations when translating these findings into clinical practice. The patients' perspectives are discussed, and the accuracy with which RA development can be predicted in patients presenting with arthralgia is evaluated. Currently, the best starting position for preventive studies is proposed to be the inclusion of patients with an increased risk of RA, such as those identified as fulfilling the EULAR definition of 'arthralgia suspicious for progression to RA'.
30121685 Self-reported symptoms of depression, anxiety and stress among patients with Rheumatoid Ar 2018 Aug OBJECTIVE: To determine the prevalence, correlates and independent predictors of self-reported depression, anxiety and stress in Rheumatoid arthritis (RA) patients in Hospital Melaka. METHODS: This was a cross-sectional survey using convenient sampling of 192 RA patients who attended the Rheumatology Clinic outpatient appointment, Hospital Melaka from June 2013 to December 2013. Depression, Anxiety and Stress Scale (DASS21) questionnaire was used to evaluate symptoms of depression, anxiety and stress. RA disease activity was assessed using the DAS28-ESR formula. Functional status was assessed via the Health Assessment Questionnaire Disability Index (HAQ-DI). RESULTS: Out of 189 completed questionnaires, 46%(n=86) patients reported psychological distress symptoms, and 25%(n=48) experienced more than one negative emotional states. The prevalence of depression, anxiety and stress among our patients were 23.3%(n=44), 42.3%(n=80) and 20.1%(n=38) respectively. There were significant positive correlations (p<0.05) between these psychological symptoms with disease activity, number of tender joints, general health, pain and HAQ score. Age was inversely correlated with depression, anxiety and stress. Higher number of swollen joints correlated positively with depression but not with anxiety and stress. HAQ was the only independent predictor for depression (Odds Ratio [OR]=2.07; 95%CI: 1.19 to 3.61) and anxiety (OR=1.81; 95%CI: 1.1 to 3.0) whilst pain was found to be independent predictor for stress (OR=1.04; 95%CI: 1.0 to 1.1). CONCLUSION: The incidence of depression and anxiety in our Malaysian sample of RA patient was comparable to that observed in Caucasian populations. Functional status was an independent predictor of depression and anxiety, whereas pain was an independent predictor of stress.
29742185 The Role of IL-17 in the Human Immune System and Its Blockage as a Treatment of Rheumatoid 2018 May 1 Interleukin 17 (IL-17) functions as a bridge between the innate and adaptive immunity. In addition to being a crucial defense mechanism against extracellular pathogens, it plays a significant role in inflammation, therefore considered a decisive factor in inflammatory conditions; hence the importance of its understanding for the treatment of autoimmune diseases. Animal models have demonstrated that blockage of the IL-17 receptor (IL-17R) may prevent these pathologies. For instance, there is evidence that IL-17R-deficient mice may be protected against the development of collagen-induced arthritis (CIA) and experimental autoimmune encephalitis (EAE). Furthermore; inflammatory disorders such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis (PSA), and ankylosing spondylitis (AS) have been associated with IL-17, and therapeutically targeting this inflammatory pathway could improve patients' outcomes. The discovery and subsequent studies of this interleukin have aided in the understanding of the immune system, and its potential therapeutic blockage provokes optimism for the treatment of these distressing conditions. J Drugs Dermatol. 2018;17(5):539-542.
30365902 Use of synthetic and biologic DMARDs during pregnancy. 2019 Jan Introduction: Since most of the autoimmune diseases (AID) affect mostly women in their fertile years, and fertility is in general preserved, the use of disease-modifying antirheumatic drugs (DMARDs) during conception, pregnancy, and lactation has been a matter of concern in the treatment of women affected by AID. Areas covered: We performed a comprehensive review of the latest and most relevant research papers published in the field and discussed different aspects related to the use of synthetic and biologic DMARDs and immunosuppressants in the preconceptional period, during pregnancy and lactation in AID patients, both in males and females. Expert commentary: Active AID impose an increased risk for adverse maternal and fetal outcomes, such as preeclampsia, miscarriage, intrauterine growth restriction, prematurity, low birth weight, and stillbirth. Family planning with proper contraception and shared decision-making on the ideal time to conceive with treatment adjustment must be a rule. One of the main challenges when counseling and/or adjusting treatment of patients that are planning a pregnancy is to provide a medication that is at the same time efficacious and safe at the conceptional period and to developing the fetus.
29106059 Increased levels of neutrophil extracellular trap remnants in the serum of patients with r 2018 Feb AIMS: Neutrophil extracellular traps (NETs) comprise a unique form of non-apoptotic cell death exhibited by neutrophils, which occurs in a stepwise process termed NETosis. It has been postulated that NETosis plays an important role in the pathogenesis of autoimmune disorders. The aim of this study was to evaluate serum levels of NET remnants in patients with rheumatoid arthritis (RA), as well as potential associations between NET remnants and indicators of RA. METHODS: Serum levels of myeloperoxidase (MPO)-DNA complexes (NET remnants) were examined in 74 RA patients and 50 healthy controls using a modified enzyme-linked immunosorbent assay. Associations between the levels of these complexes and indicators of RA were then statistically evaluated. RESULTS: RA patients exhibited significantly higher levels of MPO-DNA complexes than the healthy controls, and these levels were associated with increased neutrophil counts and positivity for rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA). Among the 63 ACPA-positive RA patients examined, those with ACPA titers > 1600 U/mL showed significantly increased MPO-DNA levels. Receiver operating characteristic analysis determined that the area under the curve for all 74 RA patients was 0.798, with a sensitivity of 91.9% and a specificity of 56.0%, while that for the ACPA-negative patients was 0.891, with a sensitivity and specificity of 81.8% and 84.0%, respectively. CONCLUSIONS: The results of this study suggest that the disease status of RA is associated with increased NETosis. In particular, evaluation of serum MPO-DNA levels may comprise a useful complementary tool for discriminating RA patients from healthy individuals.
29445994 Estimation of Posturographic Trajectory Using k-Nearest Neighbors Classifier in Patients w 2018 Rheumatoid arthritis (RA) and osteoarthritis (OA) are common rheumatic diseases and account for a significant percentage of disability. Posturography is a method that assesses postural stability and quantitatively evaluates postural sways. The objective of this study was to estimate posturographic trajectories applying pattern recognition algorithms. To this end, k-nearest neighbors (k-NN) classifier was used to differentiate between healthy subjects and patients with OA and RA. The following parameters of trajectories were computed: radius of sways, developed area, total length, and two directional components of sways: length of left-right and forward-backward motions. Posturographic tests were applied with eyes open and closed, and with biofeedback control. We found that in RA, the radius of sways, the trajectory area, and the biofeedback coordination were related to the patients' condition. The trajectory dynamics in OA patients were smaller compared to those in RA patients. The smallest misclassification errors were observed after feature selection in the biofeedback test compared with the eyes open and closed tests. We conclude that the estimation of posturographic trajectory with k-NN classifier could be helpful in monitoring the condition of RA patients.
29875354 Tenosynovitis with Rice Body Formation Due to Mycobacterium Intracellulare Infection After 2018 Jun 7 BACKGROUND Rheumatoid arthritis tenosynovitis is difficult to discriminate from non-tuberculous tenosynovitis on the basis of radiological and pathological findings. CASE REPORT A 74-year-old woman with a 4-year history of rheumatoid arthritis was referred to our hospital to undergo treatment for uncontrollable tenderness and swelling in her right third metacarpophalangeal joint, right wrist, and left knee joint. In the previous year, she underwent surgery at a local hospital for the swelling in her right metacarpophalangeal joint, the information of which was not known precisely, but the swelling subsided in due course after an operation. We treated the patient with infliximab (monthly intravenous infusions of 150 mg), but 2 months later, she complained of exacerbation of the swelling in her right third metacarpophalangeal joint and right wrist, and fluid discharge that contained Mycobacterium intracellulare. After synovectomy and aggressive debridement in the palmar side of the right wrist, she was diagnosed as having granulomatous tenosynovitis caused by the M. intracellulare infection and abundant rice body formation in the right carpal tunnel area. We considered the rice bodies inside and outside the bursa, along with a history of tenosynovitis exacerbation after initiation of infliximab therapy (tumor necrosis factor alpha inhibitor [TNFi]), to be related to the M. intracellular infection. CONCLUSIONS Tenosynovitis caused by atypical mycobacteria is uncommon and usually affects the hand or wrist. Therefore, for early diagnosis, mycobacterial infection should be considered in cases of indolent chronic granulomatous tenosynovitis, especially in RA cases that recur after TNFi therapy is started.
29538012 Multiple hit infection and autoimmunity: the dysbiotic microbiota-ACPA connection in rheum 2018 Jul PURPOSE OF REVIEW: This review highlights the most recent data obtained in this field and provides clues toward the better understanding of the close interplay between microbiota and host, leading to autoimmune diseases. RECENT FINDINGS: A well-described model of microbiota/host interaction of relevance to autoimmunity is linking anti-citrullinated peptide antibody positive rheumatoid arthritis and alterations of microbiota largely concentrating on Porphyromonas gingivalis and more recently of Aggregatibacter actinomycetemcomitans and Prevotella copri. SUMMARY: The perception of the classical link between microbial infection and development of autoimmune disease has evolved to the more recent concept of the connection between the microbiome/dysbiosis and breaking of immunological tolerance.
30191388 [Change in rheumatic hip surgery]. 2018 Dec There is a trend towards a reduction in joint-preserving hip surgery, such as synovectomy and total hip joint replacement in rheumatic patients. This is mostly due to the success of biological disease-modifying antirheumatic drugs (bDMARD) in systemic anti-rheumatic therapy. The results of hip surgery in rheumatic patients are comparable to those in non-rheumatic patients, except for prosthetic joint infections, which are higher in patients with rheumatoid arthritis. Especially in hip surgery there was a big evolution in the last few years including a broad range of minimally invasive surgical methods, such as hip arthroscopy, mini-open hip surgery and minimally invasive hip arthroplasty with bone preservation or short femoral shafts. These surgical methods also have an advantage in the treatment of typical rheumatoid pathologies and have the benefit of a rapid recovery.
30602956 Diagnostic utility of, and influence of tobacco usage and genetic predisposition on, immun 2018 Jun BACKGROUND: The immunoglobulin A isotypes of anti-cyclic citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) are associated with disease severity and progression in Caucasian rheumatoid arthritis (RA) patients, as well as with genetic predisposition and tobacco use. OBJECTIVES: To compare levels of ACPA-IgA and RF-IgA with those of ACPA-IgG and cRF in a cohort of black South African RA patients and healthy controls.To investigate the relationship between IGA autoantibodies and disease severity, genetic predisposition and tobacco use. METHODS: RF-IgA and ACPA-IgA were determined in a cohort of predominantly black South African RA patients (n=75) in relation to serodiagnostic and prognostic potential, as well as tobacco use and genetic predisposition. Healthy control subjects were included to determine sensitivity, specificity and predictive values.ACPA-IgG/IgA and RF-IgA were determined by enzyme immunoassay and hs-CRP and cRF by nephelometry. Cotinine levels were determined by ELISA. RESULTS: The frequencies of ACPA-IgA and RF-IgA were 31% and 88% respectively compared to 88% for both types of traditional autoantibody procedures. ACPA-IgA was significantly higher (p=0.007) in patients with short disease duration, while linear regression analysis revealed a positive relationship with baseline disease activity scores. Levels of ACPA-IgG and ACPA-IgA were significantly higher in tobacco users who carried the HLA shared epitope. CONCLUSION: Although lacking in serodiagnostic superiority over cRF and ACPA-IgG, inclusion of RF-IgA and ACPA-IgA in autoantibody panels may provide insights into disease pathogenesis, interactions between tobacco usage and HLA genotype in the production of potentially disease-triggering ACPA-IgA antibodies.
29447492 Physiotherapists' management of challenging situations in guiding people with rheumatoid a 2019 Jan OBJECTIVES: To explore strategies used by physiotherapists (PTs) in guiding people with rheumatoid arthritis to health-enhancing physical activity (HEPA) in a group setting during a 1-year intervention study. METHODS: Exploratory design with qualitative video analysis performed in three steps. Eleven female PTs were video recorded while leading support group sessions aiming at facilitating HEPA (twice-weekly exercise sessions at public gyms and 150 weekly minutes of moderately intense aerobic physical activity). RESULTS: Three categories of challenging situations emerged. They occurred when the HEPA intervention participants reported barriers to performing physical activity, when they neglected to use the planning tool for physical activity as intended in the program, and when they received negative results from physical capacity tests. PTs used different strategies to manage these challenges, with main focus either on information-giving, corresponding to a traditional health professional approach, or utilizing group resources by organizing participation. CONCLUSIONS: This study provides detailed descriptions of PTs' clinical behavior in video-recorded sessions. The results imply that motivated PTs can, despite their biomedical and practitioner-focused training, learn to adapt their communication strategies to different situations, altering between traditional information-giving and utilizing group resources by organizing participation.
29966420 Development of a Janus Kinase Inhibitor Prodrug for the Treatment of Rheumatoid Arthritis. 2018 Aug 6 While highly efficacious in treating rheumatoid arthritis (RA), the approved Janus kinase (JAK) inhibitor, Tofacitinib (Tofa, CP-690 550), has dose-dependent toxicities that limit its clinical application. In this study, we have examined whether a prodrug design that targets arthritic joints would enhance Tofa's therapeutic efficacy, which may provide an opportunity for future development of safer Tofa dosing regimens. A prodrug of Tofa (P-Tofa) was synthesized by conjugating the drug to the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer via an acid cleavable carbamate linker. The therapeutic efficacy of a single dose of P-Tofa was compared to the dose-equivalent daily oral administration of Tofa in an adjuvant-induced arthritis (AA) rat model. Saline treated AA rats and age-matched healthy rats were used as controls. Observational analyses support the superior and sustained efficacy of a single dose P-Tofa treatment compared to the dose-equivalent daily Tofa administration in ameliorating joint inflammation. Micro-CT and histological analyses demonstrated that the P-Tofa treatment provided a structural preservation of the joints better than that of the dose-equivalent Tofa. Optical imaging, immunohistochemistry, and fluorescence-activated cell sorting analyses attribute P-Tofa's superior therapeutic efficacy to its passive targeting to arthritic joints and inflammatory cell-mediated sequestration. In vitro cell culture studies reveal that the P-Tofa treatment produced sustained the inhibition of JAK/STAT6 signaling in IL-4-treated murine bone marrow macrophages, consistent with a gradual subcellular release of Tofa. Collectively, a HPMA-based nanoscale prodrug of P-Tofa has the potential to enhance the therapeutic efficacy and widen the therapeutic window of Tofa therapy in RA.
29669391 Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Developmen 2018 Sep OBJECTIVE: Rheumatoid arthritis (RA) is a chronic and degenerative autoimmune joint disease that leads to disability, reduced quality of life, and increased mortality. Although several synthetic and biologic disease-modifying antirheumatic drugs are available, there is still a medical need for novel drugs that control disease progression. As only 10% of experimental drug candidates for treatment of RA that enter phase I trials are eventually registered by the Food and Drug Administration, there is an immediate need for translational tools to facilitate early decision-making in drug development. In this study, we aimed to determine if the inability of fostamatinib (a small molecule inhibitor of Syk) to demonstrate sufficient efficacy in phase III of a previous clinical study could have been predicted earlier in the development process. METHODS: Biomarkers of bone, cartilage, and interstitial matrix turnover (C-telopeptide of type I collagen [CTX-I], matrix metalloproteinase-derived types I, II, and III collagen neoepitopes [C1M, C2M, and C3M]) were measured in 450 serum samples from the Oral Syk Inhibition in Rheumatoid Arthritis 1 study (OSKIRA-1, a phase III clinical study of the efficacy of fostamatinib in RA) at baseline and follow-up. Additionally, the same biomarkers were subsequently measured in conditioned media from osteoclast, cartilage, and synovial membrane cultured with the active metabolite of fostamatinib, R406, to assess the level of suppression induced by the drug. RESULTS: In OSKIRA-1 serum samples and osteoclast and cartilage cultures, fostamatinib suppressed the levels of CTX-I and C2M. In OSKIRA-1 serum samples and synovial membrane cultures, fostamatinib did not mediate any clinical or preclinical effect on either C1M or C3M, which have previously been associated with disease response and efficacy. CONCLUSION: These data demonstrate that translational biomarkers are a potential tool for early assessment and decision-making in drug development for RA treatment.
29175592 Role of extracellular vesicles in rheumatoid arthritis. 2018 Jan Cell-derived extracellular vesicles (EVs) are involved in the pathogenesis of rheumatoid arthritis (RA), playing important roles in antigen presentation, inflammation, angiogenesis, cell-cell signal communication, thrombosis, and articular cartilage extracellular matrix degradation. Understanding the pathogenic mechanism of RA is important for developing therapies. The pathogenic indicators of RA, such as submicron-sized EVs, represent promising biomarkers for evaluating RA activity. This review summarizes the recent advances in understanding the pathogenesis of RA, and sheds light on the pathogenic as well as anti-inflammatory or immunosuppressive roles of EVs. We suggest that EVs could be harnessed as tools for drug delivery or targets for RA therapies.
29496419 Rheumatoid factor testing in Spanish primary care: A population-based cohort study includi 2019 Nov OBJECTIVE: Rheumatoid factor (RF) testing is used in primary care in the diagnosis of rheumatoid arthritis (RA); however a positive RF may occur without RA. Incorrect use of RF testing may lead to increased costs and delayed diagnoses. The aim was to assess the performance of RF as a test for RA and to estimate the costs associated with its use in a primary care setting. MATERIAL AND METHODS: A retrospective cohort study using the Information System for the Development of Research in Primary Care database (contains primary care records and laboratory results of >80% of the Catalonian population, Spain). Participants were patients ≥18 years with ≥1 RF test performed between 01/01/2006 and 31/12/2011, without a pre-existing diagnosis of RA. Outcome measures were an incident diagnosis of RA within 1 year of testing, and the cost of testing per case of RA. RESULTS: 495,434/4,796,498 (10.3%) patients were tested at least once. 107,362 (21.7%) of those tested were sero-positive of which 2768 (2.6%) were diagnosed with RA within 1 year as were 1141/388,072 (0.3%) sero-negative participants. The sensitivity of RF was 70.8% (95% CI 69.4-72.2), specificity 78.7% (78.6-78.8), and positive and negative predictive values 2.6% (2.5-2.7) and 99.7% (99.6-99.7) respectively. Approximately €3,963,472 was spent, with a cost of €1432 per true positive case. CONCLUSIONS: Although 10% of patients were tested for RF, most did not have RA. Limiting testing to patients with a higher pre-test probability would significantly reduce the cost of testing.
30042400 Evaluating the bromodomain protein BRD1 as a therapeutic target in rheumatoid arthritis. 2018 Jul 24 Targeting epigenetic reader proteins by small molecule inhibitors represents a new therapeutic concept in autoimmune diseases such as rheumatoid arthritis (RA). Although inhibitors targeting bromodomain protein 1 (BRD1) are in development, the function of BRD1 has hardly been studied. We investigated the therapeutic potential of BRD1 inhibition in joint-resident cells in RA, synovial fibroblasts (SF) and macrophages. The proliferation of SF was decreased upon BRD1 silencing, accompanied by the downregulation of genes involved in cell cycle regulation. Silencing of BRD1 in SF decreased the basal expression of MMP1 but increased TNF-α- and LPS-induced levels of MMP3, IL6 and IL8. In monocyte-derived macrophages (MDM), silencing of BRD1 decreased the LPS-induced expression of TNF-α, but did not significantly affect basal and the TNF-α- and LPS-induced expression of IL6 and IL8. Our data point to a cell type- and a stimulus-specific function of BRD1. Inhibiting BRD1 could have potential beneficial effects in RA via decreasing the proliferation of SF. Anti-inflammatory effects were limited and only observed in MDM.
29842946 Combination of anti-citrullinated protein antibodies and rheumatoid factor is associated w 2018 Oct The development of rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPAs) can be observed years prior to clinical diagnosis of rheumatoid arthritis (RA). Nevertheless, the interaction between these two autoantibodies and their combined effect on development of RA is unclear. We measured RF, cytokines, and ACPA subtypes in serial pre-clinical serum samples collected from 83 US veterans who all developed RA. Levels of cytokines and ACPAs were compared between the following groups: anti-cyclic citrullinated peptide (anti-CCP)-/RF- (double negative), anti-CCP+/RF-, anti-CCP-/RF+, or anti-CCP+/RF+ (double-positive). The double-positive subgroup had significantly higher levels of 20 inflammatory cytokines and 29 ACPA reactivities, and the shortest interval, 1.3 years, between the preclinical sample timepoint and diagnosis of RA. Thus, the combined presence of ACPAs and RF is associated with a more rapid progression to RA, suggesting that anti-CCP+/RF+ individuals have a more advanced preclinical disease state and that the onset of RA may be imminent.
30341880 Myopericytoma-An Alternate Cause of Persistent Knee Pain in Rheumatoid Arthritis. 2018 Mar Rheumatoid Arthritis can present with consistent pain over peripheral joints. The manner of presentation of a subcutaneous tumour such as Myopericytoma may be very similar to that of an inflamed joint leading to the high frequency of it being overlooked and inadequately treated. Knowing the radiological and pathological differences will direct us in the right road to timely and adequate treatment.
29737076 [The Detection of Micro RNA346 Gene Polymorphism by Capillary Electrophoresis]. 2018 Mar OBJECTIVE: To develop a method for the detection of micro RNA346 gene polymorphism by capillary electrophoresis (CE). METHODS: The genome DNA was extracted with the kit of blood/cell/tissue genome DNA extraction,then micro RNA346 gene was amplified by PCR,digested by BciT130â… restriction enzyme and detected by CE. The conditions for CE separation were optimized. Samples from rheumatoid arthritis patients and healthy persons were detected under the optimal conditions. RESULTS: Under the optimized experimental conditions of CE (sieving medium mass concentration was 10 g/L and the separation voltage was 12 kV),the detection of the digested products of microRNA346 gene could be completed within 25 min. The intra-day relative standard deviation (RSD) of the method was 0.43%-0.63% and inter-day RSD was 1.49%-1.56%.Samples from 96 rheumatoid arthritis patients and 43 healthy persons were analyzed by the proposed method. The results showed that only micro RNA346â… type was detected but micro RNA346 â…¡ type wasn't. CONCLUSION: This method is easy to operate,and has the advantages of high efficiency,fast speed,less sample consumption and high automation level. This method is suitable for the determination of RNA gene polymorphism of mirco RNA.
30693002 Autoantibodies in the Pathogenesis, Diagnosis, and Prognosis of Juvenile Idiopathic Arthri 2018 Autoantibody production occurs in juvenile idiopathic arthritis (JIA) and numerous other autoimmune diseases. In some conditions, the autoantibodies are clearly pathogenic, whereas in others the roles are less defined. Here we review various autoantibodies associated with JIA, with a particular focus on antinuclear antibodies and antibodies recognizing citrullinated self-antigens. We explore potential mechanisms that lead to the development of autoantibodies and the use of autoantibody testing in diagnosis and prognosis. Finally, we compare and contrast JIA-associated autoantibodies with those found in adults with rheumatoid arthritis (RA).