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ID PMID Title PublicationDate abstract
24605075 Potential role of bacterial infection in autoimmune diseases: a new aspect of molecular mi 2014 Feb Molecular mimicry is an attractive mechanism for triggering autoimmunity. In this review, we explore the potential role of evolutionary conserved bacterial proteins in the production of autoantibodies with focus on granulomatosis with polyangiitis (GPA) and rheumatoid arthritis (RA). Seven autoantigens characterized in GPA and RA were BLASTed against a bacterial protein database. Of the seven autoantigens, proteinase 3, type II collagen, binding immunoglobulin protein, glucose-6-phosphate isomerase, α-enolase, and heterogeneous nuclear ribonuclear protein have well-conserved bacterial orthologs. Importantly, those bacterial orthologs are also found in human-associated bacteria. The wide distribution of the highly conserved stress proteins or enzymes among the members of the normal flora and common infectious microorganisms raises a new question on how cross-reactive autoantibodies are not produced during the immune response to these bacteria in most healthy people. Understanding the mechanisms that deselect auto-reactive B cell clones during the germinal center reaction to homologous foreign antigens may provide a novel strategy to treat autoimmune diseases.
25276611 Hip Arthroscopic Synovectomy and Labral Repair in a Patient With Rheumatoid Arthritis With 2014 Aug The arthroscopic surgical procedures reported previously for a rheumatic hip joint have been primarily performed as diagnostic procedures. Only a few studies have reported the success of arthroscopic surgery in hip joint preservation. We encountered a special case in which joint remodeling was seen in a patient with rheumatoid arthritis treated with biological drugs after hip arthroscopic synovectomy and labral repair. We report the case of a 39-year-old woman with rheumatism, which was controlled with tocilizumab, prednisolone, and tacrolimus. The hip joint showed Larsen grade 3 destruction, and the Harris Hip Score was 55 points. Because of the patient's strong desire to undergo a hip preservation operation, we performed hip arthroscopic synovectomy and repair of a longitudinal labral tear. After 2.5 years, the joint space had undergone rebuilding with improvement to Larsen grade 2, and the Harris Hip Score had improved to 78 points; the patient was able to return to work with the use of 1 crutch. It is possible to perform hip arthroscopic surgery for rheumatoid arthritis with a hip preservation operation with biological drugs.
24502187 Early start and stop of biologics: has the time come? 2014 Feb 6 Despite considerable advances in the management of rheumatoid arthritis, results are still not satisfactory for all patients. The treatment goal in rheumatoid arthritis is remission, and there currently are numerous conventional and biological medications available to reach this aim. There are also different treatment strategies but with only limited comparative evidence about their efficacies. More patients now achieve remission while on treatment, but it remains elusive in the majority of patients. Treatment-free remission, the ultimate goal of therapy, is only achieved in very few patients; even when this happens, it is most likely due to the natural course of the disease rather than to any specific therapies. Modern treatment is based on the initiation of aggressive therapy as soon as the diagnosis is established, and on modifying or intensifying therapy guided by frequent assessment of disease activity. In this commentary we will discuss the current treatment paradigm as well as the possibility of an induction-maintenance regimen with biological disease-modifying antirheumatic drugs in early rheumatoid arthritis.
23522436 Autoimmune diseases and reproductive aging. 2013 Nov As the population ages, more individuals with autoimmune diseases are experiencing reproductive senescence. Understanding the impact of menopause and age-related androgen decline on disease onset and course, as well as the potential for hormonal interventions, is critically important. In men, lupus erythematosis (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS) are associated with lower androgen levels. However, the impact of age-related declines in testosterone, as well as of testosterone replacement, on disease course remains underexplored. In women, the course of all three diseases with onset after the age of menopause differs from that with onset before menopause. Early age at menopause is associated with increased disease risk, and after menopause, disease course changes in SLE and RA. Less is known about MS. This article summarizes what is known about the relationship between reproductive aging and autoimmune diseases in men and women, and highlights areas for further investigation.
25199201 Postinfective skin contracture: a rare cause of fifth metatarsophalangeal joint subluxatio 2014 Sep 8 Dislocation or subluxation of the metatarsophalangeal joint (MTP) is common and usually follows a traumatic event. Non-traumatic causes usually include inflammatory arthritis (rheumatoid arthritis), connective tissue disorders, crowded shoewear or flexor digitorum longus tendon contracture. We present a very unusual case of subluxation of the fifth MTP joint following a postboil skin contracture. The case was treated with the release of contracture by Z-plasty. It resulted in concentric reduction of the joint and normal skin healing.
23271168 Validation of different sets of criteria for the diagnosis of Sjögren's syndrome in Japan 2013 Mar OBJECTIVE: To validate the revised Japanese Ministry of Health criteria for the diagnosis of Sjögren's syndrome (SS) (JPN) (1999), The American-European Consensus Group classification criteria for SS (AECG) (2002), and American College of Rheumatology classification criteria for SS (ACR) (2012). METHODS: The study subjects were 694 patients with SS or suspected SS who were followed-up in June 2012 at ten hospitals that form part of the Research Team for Autoimmune Diseases, The Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare (MHLW). All patients had been checked for all four criteria of the JPN (pathology, oral, ocular, anti-SS-A/SS-B antibodies). We studied the clinical diagnosis made by the physician in charge and the satisfaction of the above criteria. RESULTS: Of the 694 patients, 499 patients did not have other connective tissue diseases (CTDs). SS was diagnosed in 476 patients (primary SS in 302, secondary SS in 174), whereas non-SS was diagnosed in 218 patients (without other CTDs in 197, with other CTDs in 21) by the physician in charge. The sensitivities of JPN, AECG, and ACR in the diagnosis of all forms of SS (both primary and secondary SS) were 79.6, 78.6, and 77.5 %, respectively, with respective specificities of 90.4, 90.4, and 83.5 %. The sensitivities of the same systems in the diagnosis of primary SS were 82.1, 83.1, and 79.1 %, respectively, with specificities of 90.9, 90.9, and 84.8 %, respectively. The sensitivities of the same systems in the diagnosis of secondary SS were 75.3, 70.7, and 74.7 %, respectively, with specificities of 85.7, 85.7, and 71.4 %, respectively. CONCLUSION: The sensitivity of JPN to all forms of SS and secondary SS, the sensitivity of AECG to primary SS, and the specificities of JPN and AECG for all forms of SS, primary SS, and secondary SS were highest in the diagnosis of SS in Japanese patients. These results indicate that the JPN criteria for the diagnosis of SS in Japanese patients are superior to ACR and AECG.
24702728 Proteasome inhibitor MG132 modulates inflammatory pain by central mechanisms in adjuvant a 2017 Jan AIMS: In rheumatoid arthritis (RA), pain and inflammation are initial symptoms followed by various degrees of bone and cartilage destruction. Previously, we have shown that reversible proteasome inhibitor MG132 attenuates pain and joint inflammation in a rat model of adjuvant-arthritis. Our present study aims to study the effects of MG132 on molecular changes in the dorsal root ganglia (DRG) and in the spinal cord (SC) using the same animal model. METHODS: Arthritis was induced by heat-killed Mycobacterium butyricum in rats. The expression of substance P (SP) was analyzed by quantitative reverse transcription polymerase chain reaction and immunohistochemistry in DRG and in the SC. The nuclear factor-κB (NF-κB) DNA-binding activity in the SC was analyzed by electromobility shift assay. RESULTS: Arthritic rats treated daily with MG132 demonstrated a marked reduction of SP gene expression in the DRG and number of SP-positive cells was reduced. In the spinal cord of arthritic rats elevated SP messenger RNA levels were normalized and NF-κB-DNA-binding activity was down-regulated in arthritic rats treated with MG132. CONCLUSION: Our results indicate that proteasome inhibitor MG132 attenuates pain in adjuvant arthritis by targeting the sensory neuropeptide substance P in the peripheral and central nervous systems. These effects may be mediated through the inhibition of NF-κB activation.
23667226 Acute encephalomyelitis with multiple herpes viral reactivations during abatacept therapy. 2013 May 9 To describe the case of a patient who had been receiving abatacept, a T-cell costimulatory molecule blocker for rheumatoid arthritis, and developed an acute encephalomyelitis associated with reactivation of the varicella zoster virus (VZV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). A 61-year-old woman receiving abatacept therapy for rheumatoid arthritis developed a disturbance of consciousness. MRI indicated multifocal parenchymal lesions in the brainstem, supratentorial areas and cervical spinal cord. Although steroid therapy significantly improved the neurological symptoms and MRI findings, the patient died of sepsis aggravated by coinfection with a fungal infection. Retrospectively, a PCR assay revealed continued systemic reactivation of VZV, EBV and CMV. Acute encephalomyelitis may be associated with VZV EBV and CMV reactivation during abatacept therapy. Clinicians must be aware of the possibility of acute encephalomyelitis associated with herpes virus reactivation during abatacept therapy for rheumatoid arthritis.
25548570 Pain mystery score beliefs: a comparison of fibromyalgia and rheumatoid arthritis. 2014 Objectives. To compare the mysteriousness scores of the Pain Beliefs and Perceptions Inventory in fibromyalgia. Methods. Two cohorts of patients, one with fibromyalgia (FM) and one with rheumatoid arthritis (RA), completed the Mystery Scale component of the Pain Beliefs and Perceptions Inventory to determine whether subjects in the two diagnostic groups had significantly different scores on the Mystery Scale. Results. A total of 126 subjects (64 FM, 62 RA) completed all questionnaires. The FM group had a greater percentage of female subjects, more severe pain, more severe anxiety, more severe depression, and a higher perceived injustice score. When the RA and FM group scores for the Mystery Scale were adjusted for age, sex, pain severity, HADS scores, and perceived injustice scores, the FM group still had a higher Mystery Scale score. Discussion. Fibromyalgia is associated with a higher level of perception of mysteriousness in the Pain Beliefs and Perceptions Inventory than is seen with rheumatoid arthritis. This difference appears to be independent of levels of pain, depression, anxiety, and perceived injustice. This sense of mysteriousness may reflect a lack of understanding of pain in fibromyalgia as previously reported and may be an area to be addressed in therapy.
24031147 Etanercept Promotes Bone Formation via Suppression of Dickkopf-1 Expression in Rats with C 2013 Mar BACKGROUND: Various clinical reports suggest etanercept (ETN) has some efficacy in bone formation in rheumatoid arthritis (RA). To examine this effect, we investigated the gene expression of cytokines relevant to osteoblast/osteoclast differentiation, and evaluated histomorphometric findings in mature rats with collagen-induced arthritis (CIA). METHODS: Total RNA was extracted from knee joints with CIA after ETN or placebo administration. Subsequently, realtime-PCR was carried out to quantify the mRNAs encoding Wnt-1, Dickkopf-1 (DKK-1), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegelin (OPG) and TNF (tumor necrosis factor)-alpha. In histomorphometric analysis, the infiltrating pannus volume and pannus surface, and the following items in contact with pannus surface were measured: osteoclast number, osteoid surface, osteoid volume and labeling surface. These were evaluated in the distal femur with CIA with or without ETN administration. RESULTS: TNF-alpha, RANKL and OPG mRNA expressions, linked to osteoclastogenesis, were not significantly different with or without ETN administration. ETN administration significantly increased Wnt-1 mRNA expression, the osteoblast promoter, and decreased DKK-1 mRNA expression, the Wnt signal inhibitor. In histomorphometric analysis, pannus volume, pannus surface and osteoclast number, parameters of bone destruction, were not significantly different among groups. Osteoid volume, osteoid surface and labeling surface, parameters of bone formation, increased significantly with ETN administration. CONCLUSION: Our results suggest that ETN suppresses DDK-1 expression, and, as a result, Wnt expression is promoted and osteoblastogenesis becomes more active, independent of the regulation of osteoclast activity. Marked bone formation is attributed to the fact that ETN directly promotes osteoblastogenesis, not as a result of suppressing osteoclastogenesis.
24024675 Discontinued drugs for pulmonary, allergy, gastrointestinal, arthritis (2012). 2013 Nov INTRODUCTION: Various compounds are developed to interfere with pathogenic pathways involved in inflammation processes. Some of them are able to enter the clinical development for different diseases with a common pathogenic denominator such as, for example, rheumatoid arthritis and chronic obstructive pulmonary disease (COPD), based on the preclinical evidence, but not all these molecules prove to be efficacious while tested in different phases of clinical development. AREAS COVERED: This review discusses about the drugs that were discontinued from further development for pulmonary, allergy, gastrointestinal and arthritis diseases EXPERT OPINION: Most of the drugs discontinued during 2012 were compounds with anti-inflammatory activity which were mostly designed to treat arthritis/rheumatoid arthritis. Some of these molecules were also intended for COPD. Many of them failed the late phases of the clinical development.
23875127 A simple set of validation steps identifies and removes false results in a sandwich enzyme 2013 Dec Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are chronic diseases characterized by activation of the immune system and production of antibodies. Thus, rheumatoid factor, anti-animal IgG antibodies and heterophilic antibodies in plasma samples from arthritis patients can interfere with immunoassays such as sandwich enzyme-linked immunosorbent assay (ELISA) systems often used in arthritis research. However, standard methodologies on how to test for false results caused by these antibodies are lacking. The objective of this study was to design a simple set of steps to validate a sandwich ELISA before using it for measuring analytes in plasma from arthritis patients. An interleukin-24 (IL-24) sandwich ELISA system was prepared with a monoclonal mouse capture antibody and a polyclonal goat detection antibody and tested for interference by rheumatoid factor, anti-animal IgG antibodies and heterophilic antibodies. Plasma samples from 23 patients with RA and SpA were used. No differences were found between plasma samples measured in wells coated with anti-IL-24 specific antibody and in wells coated with isotype control antibody (false positive results), and recombinant human IL-24 was not recovered in spiked samples (false negative results). This interference was removed after preincubating the plasma samples from patients with arthritis with goat or bovine IgG, suggesting that anti-animal IgG antibodies found in the plasma of the arthritis patients caused the false results. Additional testing showed that the signal-to-noise ratio could be increased by titration of the capture and detection antibodies and by using the ELAST amplification system. Finally, the calculated concentration of IL-24 was increased in ethylenediaminetetraacetic acid (EDTA) plasma compared to heparin plasma and serum and decreased with repetitive freeze/thaw cycles of the samples illustrating how sample handling could additionally contribute to the variations reported by different laboratories in measurement of the same analyte. This study proposes a simple set of validation steps to evaluate and optimize a sandwich ELISA before using it for measuring analytes in plasma from arthritis patients. Anti-animal IgG antibodies are also present in healthy individuals, suggesting that validation of ELISA systems for measuring non-arthritis samples could also be improved by this simple set of validation steps.
25013736 Marked multiple tendinitis at the onset of rheumatoid arthritis in a patient with heterozy 2014 A 59-year-old woman who had been diagnosed with heterozygous familial hypercholesterolemia developed rheumatoid arthritis (RA). She presented with marked tendinitis of the Achilles tendons, patellar tendons, and finger extensor tendons at the onset of RA. Ultrasonographic examination revealed that tendon lesions were predominantly tendinitis rather than paratenonitis, and that the tendinitis was of the noninsertional variety, rather than the insertional variety. Preexisting tendon xanthomas might have contributed to the unusually dominant noninsertional tendinitis of multiple tendons.
24982573 Sudden flare of rheumatoid arthritis associated with newly diagnosed atrial flutter. 2014 Jul We present an 89-year-old woman with newly diagnosed atrial flutter associated with a flare of her rheumatoid arthritis (RA). She had a history of diet-controlled type 2 diabetes mellitus, hypertension, and RA and presented with lightheadedness and worsening hand pain. She was found to be in new atrial flutter with rapid ventricular response and to have an active RA flare. In addition to adequate atrial flutter rate control, her RA flare was managed by adding hydroxychloroquine and doubling her existing methotrexate dose.
25199416 Surgical management of the juvenile idiopathic arthritis patient with multiple joint invol 2014 Oct Juvenile idiopathic arthritis (JIA) is recognized as a heterogenous group of disorders in which the common factor is persistent arthritis in at least 1 joint occurring before the age of 16 years. Although conservative management with nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs can be effective, approximately 10% of JIA patients have end-stage degenerative changes requiring total hip arthroplasties (THAs) and total knee arthroplasties (TKAs). This article discusses the overall epidemiology, coordination of care, and medical and surgical management of JIA patients undergoing THA and TKA.
24410427 Disease of the year: juvenile idiopathic arthritis-associated uveitis--classification and 2014 Feb Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease and the most common systemic association of uveitis in children. JIA is subdivided into seven clinically more homogeneous subtypes, using the International League of Associations for Rheumatology (ILAR) classification system: systemic arthritis, oligoarthritis, rheumatoid factor (RF)-negative polyarthritis, RF-positive polyarthritis, psoriatic arthritis, enthesitis-related arthritis, and undifferentiated arthritis. Uveitis is very rare in patients with systemic onset JIA and in patients with juvenile-onset rheumatoid arthritis. Patients with early-onset antinuclear antibody (ANA)-positive oligoarticular JIA have the highest risk of developing chronic iridocyclitis. Ocular involvement in enthesitis-related arthritis is characterized by recurrent acute symptomatic iridocyclitis. The diagnosis and differential diagnosis of JIA are based on history, physical examination, and laboratory investigations, including complete blood count, acute-phase reactants, ANA, RF, HLA-B27, and musculoskeletal imaging studies. Recent studies have revealed distinct gene expression profiles that may be useful in the diagnosis, classification, and follow-up of JIA patients.
23643672 Suppression of murine collagen-induced arthritis by vaccination of synovial vascular endot 2013 Jun 21 AIMS: Endothelial cells (ECs) lining the lumina of blood vessels are involved in leukocyte extravasation underlying inflammatory states, such as rheumatoid arthritis (RA). The rheumatoid pannus, the site of inflammation and joint destruction in the rheumatoid synovium, relies on the development of neovascular vessels to sustain its growth. We studied a method to selectively target and destroy new synovial blood vessels by vaccination with synovial EC. MAIN METHODS: Collagen-induced arthritis (CIA) mice were vaccinated with tumor necrosis factor (TNF)-alpha-stimulated EC (TNF-EC) antigen with an incomplete adjuvant. TNF-EC was used as a model of EC in synovial tissue on RA. KEY FINDINGS: Arthritis was significantly decreased in TNF-EC vaccinated mice compared with non-vaccinated mice based on the arthritis score. Moreover, the TNF-EC vaccine suppressed bone erosion, hyperplasia of the synovium and expression of neovascular vessel as shown by hematoxylin-eosin staining, X-ray analysis and immunohistochemical. SIGNIFICANCE: Vaccine therapy against vascular EC in synovial tissue may provide a novel approach to the treatment of RA.
24385944 CP-690550 Treatment Ameliorates Established Disease and Provides Long-Term Therapeutic Eff 2013 Dec Although pathogenesis of human rheumatoid arthritis (RA) remains unclear, arthritogenic T cells and downstream signaling mediators have been shown to play critical roles. An increasing numbers of therapeutic options have been added for the effective control of RA. Nevertheless, there is still a category of patients that fails treatment and suffers from progressive disease. The recently developed immunosuppressant CP-690550, a small molecule JAK kinase inhibitor, has been implicated as an important candidate treatment modality for autoimmune arthritis. In this study, we evaluated the therapeutic effect of CP-690550 on established arthritis using an SKG arthritis model, a pathophysiologically relevant animal model for human RA. CP-690550 treatment revealed remarkable long-term suppressive effects on SKG arthritis when administered to the well-advanced disease (clinical score 3.5~4.0). The treatment effect lasted at least 3 more weeks after cessation of drug infusion, and suppression of disease was correlated with the reduced pro-inflammatory cytokines, including IL-17, IFN-γ, and IL-6 and increased level of immunoregulatory IL-10.
27708875 Mental health status can reflect disease activity in rheumatoid arthritis. 2014 Jun OBJECTIVE: A significant number of patients with rheumatoid arthritis (RA) link the start of illness with psychological trauma or severe stress. Impaired mental health (IMH), defined as depression and anxiety with psychoneuroimmunological factors, can play a significant role in RA. The main objective of this research was to investigate the mutual correlation of IMH and RA activity, estimated by the laboratory and clinical parameters in RA patients. MATERIAL AND METHODS: An open clinical prospective study that lasted for 6 months was designed. There were 72 patients included, 58 women and 14 men, aged 34 to 80 years and screened for mental health status. The study population was randomized following the Brief Symptoms Inventory (BSI) scale, comprised of 53 questions with a range from 0 (no symptoms) to 4 (severe). This mental test was done only once during the study. Following the results from the BSI scale, RA patients were divided into mentally stable and mentally unstable patients to investigate the influence of RA activity on mental health. The following laboratory and clinical parameters were analyzed: sex, age, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide (anti-CCP) antibody, and disease activity score (DAS28). All RA patients did not express extra-articular manifestations or Sjögren's syndrome. The chi-square test, ANOVA, Pearson's coefficient, and IBM Statistics - SPSS v19 were used. RESULTS: From a total of 72 RA patients, there were 44 mentally stable and 28 mentally unstable patients. All patients had either moderate or severe active disease. The only significant correlation of IMH and activity of RA was found in CRP and DAS28, but no significance was observed in ESR, RF, and anti-CCP. The DAS28 showed high disease activity with an average of 5.3 and CRP of 20.9 mg/L in patients with unstable mental health compared to stable mental health patients, where RA was associated with a moderate DAS average value of 4.35 and CRP of 14.1 mg/L. Depression and anxiety were found in all 28 (39%) RA patients. CONCLUSION: Mentally unstable RA patients correlate more with severe disease activity, while mentally stable patients express moderate disease activity.
25279018 Serum Adenosine Deaminase Level is High But Not Related with Disease Activity Parameters i 2014 Serum adenosine deaminase (ADA) has been previously proposed to predict disease activity in patients with rheumatoid arthritis (RA). The aim of this study was to investigate the level of serum ADA, and the relationship between ADA and disease activity markers, in a group of patients with RA. A hundred and 10 patients with a diagnosis of RA were recruited from outpatient clinic of Rheumatology Unit. Demographic properties comprising age, gender, disease duration and drugs were recorded. Disease activity based on disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) and DAS28- C reactive protein (CRP,) ESR, CRP levels, as well as pain by visual analog scale and rheumatoid factor (RF) were recorded. Serum ADA levels (IU/L) were determined in all RA patients and in 55 age and sex similar healthy control subjects. Ninety-six female and 14 male RA patients with a mean age of 54.32±11.51, and with a mean disease duration of 11.5±9.13 years were included to the study. The control group comprised of 48 female and 7 male healthy subjects. 35.5% of the patients were on methotrexate (MTX) and 64.5% of patients were on combined DMARDs or combined MTX and anti-TNF therapies. The mean serum ADA level was statistically higher in RA patients than in control subjects (27.01±10.6 IU/L vs 21.8 ±9.9 IU/L). The mean values of ESR (23.2±14.8 mm/h), CRP (1.71±1.11mg/dL), pain by VAS (37.2±27.1), DAS28-ESR (2.72±0.77), DAS28 CRP (1.37±0.5) were not correlated with ADA levels (p>0.05). Our results have shown that serum ADA levels are higher in RA patients than in controls but were not related with any of the disease activity markers. We conclude that ADA in the serum may not be a reliable biochemical marker to predict disease activity in patients with RA.