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ID PMID Title PublicationDate abstract
21884808 Chondroitin sulfate effect on induced arthritis in rats. 2011 Nov OBJECTIVE: Rodent models of osteoarthritis and rheumatoid arthritis are useful tools to study these disease processes. Adjuvant arthritis (AAR) is a model of polyarthritis widely used for preclinical testing of antiarthritis substances. We report the effect of two different doses of highly purified chondroitin sulfate (CS) pharmaceutical grade in the AAR animal model after oral administration. DESIGN: AAR was induced by a single intradermal injection of heat-inactivated Mycobacterium butyricum in incomplete Freund's adjuvant. The experiments included healthy animals, untreated arthritic animals, arthritic animals having been administered 300 or 900 mg/kg of CS daily, 14 days before AAR induction until the end of the experiment (day 28), arthritic animals having been administered 300 or 900 mg/kg of CS daily, from day 1 until the end of the experiment. RESULTS: CS was capable of significantly reducing the severity of arthritis along with oxidative stress, a consequence of chronic inflammatory processes occurring in AAR. The CS pre-treatment regimen was effective throughout the whole subacute phase, while treatment from day 1 proved effective only in the chronic period. The effects were confirmed by improved total antioxidant status and γ-glutamyltransferase activity. CS administered under a pre-treatment regimen was also able to reduce the production of pro-inflammatory cytokines, C-reactive protein in plasma, phagocytic activity and the intracellular oxidative burst of neutrophils. CONCLUSIONS: CS proved to be effective in slowing down AAR development and in reducing disease markers, thus supporting its beneficial activity as a drug in humans.
21722401 Atlantoaxial subluxation as an early manifestation in an adolescent with undifferentiated 2011 Jul 3 INTRODUCTION: Atlantoaxial instability has been described as a manifestation of ankylosing spondylitis (juvenile and adult onset), reactive arthritis, juvenile idiopathic arthritis, and rheumatoid arthritis; however, it has rarely been reported as an early manifestation of these disorders. We present this case report to increase awareness of the condition in the hope that earlier recognition of this disease may prevent further serious injury. CASE PRESENTATION: We report the case of a 17-year-old Hispanic adolescent woman who was initially diagnosed with undifferentiated spondyloarthritis due to peripheral arthritis, enthesitis, a positive human leukocyte antigen B27 result, and inflammatory spinal pain lasting two months. Our patient experienced persistent and worsening occipitocervical pain and signs of myelopathy three months after diagnosis; consequently, we found atlantoaxial instability along with cervical spine bone erosion and pannus formation. She was treated surgically with a C1-2 posterior instrumented fusion and at six weeks post-operatively was started on tumor necrosis factor α blockade. Her occipitocervical symptoms subsided following surgery and initiation of immunomodulation. CONCLUSIONS: Our report serves to emphasize to pediatric and adult general practitioners, pediatricians, internists, family physicians, pediatric and adult rheumatologists and spine surgeons that atlantoaxial subluxation may be an early manifestation of spondyloarthritis, and that the condition is treatable by surgical intervention and immunomodulation.
21401516 Targeting the coagulation factor fibrinogen for arthritis therapy. 2011 Sep Fibrinogen is a provisional matrix protein of the coagulation system that following proteolytic cleavage by the protease thrombin polymerizes to form fibrin, the structural basis of the blood clot. Fibrin polymer formation at sites of vessel injury is critical to normal hemostasis. However, fibrin deposition within damaged tissues is also a common pathological feature of inflammatory diseases, including rheumatoid arthritis. Fibrin deposition has been readily detected along articular surfaces, within inflamed hyperplastic synovial tissue, and as a component of insoluble "rice bodies" within the synovial fluid of arthritic joints. Recent data has suggested that fibrin deposition within inflamed tissues is not simply a reflection of a disease process but rather actively contributes to disease pathogenesis. One mechanism that has been demonstrated to directly link fibrin(ogen) to the regulation of inflammation is the ability of fibrin(ogen) to serve as a ligand for cell-surface receptors, particularly integrins. Indeed, engagement of fibrin(ogen) by the leukocyte integrin receptor αMβ2 appears to be a common and fundamental event driving local inflammation. Recent studies have demonstrated that eliminating fibrin(ogen)-αMβ2 interactions can significantly limit the progression of multiple inflammatory diseases, including arthritis, without compromising the ability of fibrinogen to function in coagulation. These exciting findings have opened the door to new opportunities for targeting fibrinogen as an inflammatory mediator while leaving intact its hemostatic properties.
23124849 An exploratory study of the interplay between decreased concentration of tryptophan, accum 2012 Dec Tryptophan is an essential amino acid which influences a wide range of physiological processes, including mood, cognition, and immunity. In the autoimmune diseases, such as rheumatoid arthritis (RA), the induction of tryptophan catabolism may help to diminish exacerbated immune responses. In this study, using collagen-induced arthritis (CIA) in DBA/1 mice which is an animal model of RA, the endogenous activity of the kynurenine pathway in the immune system was monitored before and after onset of the disease. An increased rate of the initiation of tryptophan catabolism via the kynurenine pathway throughout CIA has been observed. However, decreased tryptophan concentration in the lymph nodes from pre-arthritic mice was not enough to prevent development of CIA. In contrast, resolution of inflammation coincided with the decreased concentration of tryptophan and accumulation of its catabolites: kynurenine, anthranilic acid, and 3-hydroxyanthranilic acid in lymph nodes but not in the spleen. In addition, the lack of the accumulation of kynurenine and its downstream metabolites in the pre-arthritic lymph nodes coincided with increased mRNA expression for genes involved in the catabolism of kynurenine (Kynureninase, kynurenine 3-monooxygenase, and 3-hydroxyanthranilate 3,4 dioxygenase). However, in the lymph nodes from mice with established CIA, mRNA expression for these genes was normalized. Hence, keeping in mind an exploratory character of the results, it can be postulated that an anti-inflammatory role of the kynurenine pathway reaches its full potential only when decreased concentration of tryptophan coincides with accumulation of kynurenines driven by metabolic regulation of gene expression on the kynurenine pathway.
22258637 Guidance on the use of adalimumab for juvenile idiopathic arthritis in Japan. 2012 Aug Adalimumab is a monoclonal antibody produced by DNA recombination technology, and is the first human monoclonal antibody against human tumor necrosis factor (TNF)-α in the world. Adalimumab binds with high affinity and specificity to soluble TNF-α and normalizes its biological action. The clinical development of adalimumab started in Europe. Adalimumab was approved for the treatment of rheumatoid arthritis (RA) in December 2002 in the United States and in September 2003 in the European Union. Since then, adalimumab has been approved for the expanded indications of psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease (CD), psoriasis (Ps), and juvenile idiopathic arthritis (JIA) in the United States and the European Union, and it is now used widely for the treatment of these diseases. In Japan, adalimumab was approved for the treatment of RA in April 2008, and its use was approved for the indications of Ps and PsA in January 2010, and for CD and AS in October 2010. In Japan, children who have been diagnosed and treated according to the "Proposal for juvenile idiopathic arthritis guidance on diagnosis and treatment for primary care pediatricians and nonpediatric rheumatologists (2007)" (published in this journal in 2007; see reference 1 in the main text), but who have responded poorly to treatment must move onto the next stage of treatment. Such treatments include biological drugs, which, however, should be used with strict adherence to the indications and exclusion criteria and should be used, for the time being, only by physicians trained in how to use them. In Japan, adalimumab was approved for the treatment of JIA in July 2011. Although this drug has brought about a revolutionary advance in the treatment of JIA, it is our task to maximize its therapeutic effects and minimize its toxic effects. The guidance presented here define the indications, exclusion criteria, usage, and evaluation criteria of adalimumab for the treatment of polyarticular JIA.
21717043 Anti-inflammatory effect of Curcuma longa (turmeric) on collagen-induced arthritis: an ana 2011 INTRODUCTION AND OBJECTIVE: Curcuma longa (CL) or turmeric is an Ayurvedic herb that has been traditionally used to treat inflammatory conditions like rheumatoid arthritis (RA). Collagen-induced arthritis (CIA) is a well established experimental auto-immune mediated polyarthritis in susceptible strains of rodents. The main aim of the study was to observe the inflammatory, macroscopic and radiological changes in the arthritic ankle joints of experimentally collagen-induced arthritis animals treated with or without CL extract. MATERIALS AND METHODS: Thirty six male Sprague-Dawley (6-8 weeks-old, 150 ± 50) rats were equally divided into six groups. The first group served as a control while the rest five groups were immunized subdermally with 150 µg collagen type-II on day-0. All rats with established CIA with arthritis score (AS) exceeding 1 were treated orally with betamethasone (0.5 mg/ml/kg body weight) and varying doses of CL extract (30, 60 and 110 mg/ml/kg body weight) using olive oil as vehicle, daily for four weeks. Arthritic scoring (AS) of the paws, measurement of erythrocyte sedimentation rate (ESR) and paw thickness and radiological scoring were performed. RESULTS: Treatment with 110 mg/ml/kg CL showed significant mean difference in the ESR (p<0.01), AS (p<0.05) and radiological scores (p<0.01) on day-28 compared to the vehicle treated group. The mean difference for the ESR, AS and radiological scores of this highest CL dose group were found to be insignificant compared to the betamethasone treated group. CONCLUSION: The administration of CL extract arrested the degenerative changes in the bone and joints of collagen-induced arthritic rats.
21106777 Acute parvovirus B19 infection causes nonspecificity frequently in Borrelia and less often 2011 Jan Several infectious agents may cause arthritis or arthropathy. For example, infection with Borrelia burgdorferi, the etiologic agent of Lyme disease, may in the late phase manifest as arthropathy. Infections with Campylobacter, Salmonella, or Yersinia may result in a postinfectious reactive arthritis. Acute infection with parvovirus B19 (B19V) may likewise initiate transient or chronic arthropathy. All these conditions may be clinically indistinguishable from rheumatoid arthritis. Here, we present evidence that acute B19V infection may elicit IgM antibodies that are polyspecific or cross-reactive with a variety of bacterial antigens. Their presence may lead to misdiagnosis and improper clinical management, exemplified here by two case descriptions. Further, among 33 subjects with proven recent B19V infection we found IgM enzyme immunoassay (EIA) positivity for Borrelia only; for Borrelia and Salmonella; for Borrelia and Campylobacter; and for Borrelia, Campylobacter, and Salmonella in 26 (78.7%), 1 (3%), 2 (6%), and 1 (3%), respectively; however, when examined by Borrelia LineBlot, all samples were negative. These antibodies persisted over 3 months in 4/13 (38%) patients tested. Likewise, in a retrospective comparison of the results of a diagnostic laboratory, 9/11 (82%) patients with confirmed acute B19V infection showed IgM antibody to Borrelia. However, none of 12 patients with confirmed borreliosis showed any serological evidence of acute B19V infection. Our study demonstrates that recent B19V infection can be misinterpreted as secondary borreliosis or enteropathogen-induced reactive arthritis. To obtain the correct diagnosis, we emphasize caution in interpretation of polyreactive IgM and exclusion of recent B19V infection in patients examined for infectious arthritis or arthropathy.
23218811 Arthritis: its prevalence, risk factors, and association with cardiovascular diseases in t 2013 Feb OBJECTIVE: Arthritis is associated with cardiovascular diseases (CVDs). However, there are limited epidemiologic studies on arthritis in a national survey study. We therefore investigated the prevalence of self-reported arthritis and its association with CVDs. METHODS: Data from 15,888 subjects aged 40 years or older in the United States National Health and Nutrition Examination Survey 1999 through 2008 were analyzed. CVD was defined as a self-reported history of heart attack, congestive heart failure, coronary heart disease, angina, or stroke. RESULTS: The overall prevalence of self-reported arthritis in subjects aged 40 years or older increased from 33.5% in 1999 through 2000 to 37.0% in 2007 through 2008 (P for trend = 0.017). Among subjects with arthritis in 1999 through 2008, 35.3% had osteoarthritis (OA), 17.9% had rheumatoid arthritis (RA), and 10.2% had other types of arthritis, but 36.6% were unaware of their type of arthritis. Compared with subjects without OA, subjects with OA had higher odds for CVDs (odds ratio [OR], 1.53; P < .001), especially angina (OR, 2.18: P < .001). Compared with subjects without RA, subjects with RA had higher odds for CVDs (adjusted OR, 2.39; P < .001), especially congestive heart failure (OR, 3.59; P < .001). CONCLUSIONS: Both RA and OA are strongly associated with CVDs in the general population. Further studies are needed to investigate their causal relationship.
22992383 Matrix metalloproteinase-dependent turnover of cartilage, synovial membrane, and connectiv 2012 Sep 20 BACKGROUND: Rheumatoid arthritis is a disease affecting the extracellular matrix of especially synovial joints. The thickness of the synovial membrane increases and surrounding tissue degrades, leading to altered collagen balance in the tissues. In this study, we investigated the altered tissue balance of cartilage, synovial membrane, and connective tissue in collagen induced arthritis (CIA) in rats. METHODS: Six newly developed ELISAs quantifying MMP-derived collagen degradation (C1M, C2M, and C3M) and formation (P1NP, P2NP, and P3NP) was used to detect cartilage turnover in rats with CIA. Moreover, CTX-II was used to detect alternative type II collagen degradation and as control of the model. 10 Lewis rats were injected with porcrine type II collagen twice with a 7 day interval and 10 rats was injected with 0.05 M acetic acid as control. The experiment ran for 26 days. RESULTS: A significant increase in the degradation of type I, II, and III collagen (C1M, C2M, and C3M, respectively) was detected on day 22 (P = 0.0068, P = 0.0068, P < 0.0001, respectively), whereas no significant difference in formation (P1NP, P2NP, and P3NP) was detected at any time point (P=0.22, P=0.53, P=0.53, respectively). The CTX-II level increased strongly from disease onset and onwards. CONCLUSION: A nearly total separation between diseased and control animals was detected with C3M, making it a good diagnostic marker. The balance of type I, II, and III collagen was significantly altered with CIA in rats, with favour of degradation of the investigated collagens. This indicates unbalanced turnover of the surrounding tissues of the synovial joints, leading to increased pain and degeneration of the synovial joints.
22764042 MRI versus conventional measures of disease activity and structural damage in evaluating t 2013 Mar OBJECTIVE: To compare the American College of Rheumatology paediatric (ACRp) response criteria and conventional radiography with MRI findings in a cohort of patients with juvenile idiopathic arthritis. METHODS: Forty consecutive patients (30 girls, 10 boys; median age 10.8 years) with arthritis of the wrist starting treatment with disease-modifying antirheumatic drugs or biological agents were recruited. At 1-year follow-up the treatment response was assessed by ACRp criteria and radiographic progression using the adapted Sharp/van der Heijde method. Wrist MRIs were evaluated using both the paediatric-MRI and the OMERACT rheumatoid arthritis MRI scores. Sensitivity to change of clinical and imaging variables was assessed by standardised response mean (SRM) and relative efficiency (RE) was used to compare SRMs. RESULTS: ACRp90 responders showed a significantly higher decrease in MRI synovitis score (median change -4) than non-responders (median change 0), ACRp30-50 responders (median change 0) and ACRp70 responders (median change -1) (p=0.0006, Kruskal-Wallis test). Non-responders showed significantly higher radiographic progression than ACRp90 responders (pB=0.016). The MRI synovitis score showed a greater responsiveness to change (SRM 1.69) compared with the majority of ACR core set of variables. MRI erosion scores were less responsive than conventional radiography in detecting destructive changes (RE <1). MRI follow-up revealed no signs of inflammation in four out of 24 wrists with clinically inactive disease. CONCLUSION: Only ACRp90 responders showed a significant decrease in synovitis and the halting of structural damage, suggesting that levels of response higher than ACRp30 are more appropriate for assessing drug efficacy. The excellent responsiveness of MRI and its ability to detect subclinical synovitis make it a promising outcome measure.
22833373 Rituximab in psoriatic arthritis: an exploratory evaluation. 2012 Nov BACKGROUND/OBJECTIVE: Current therapies for psoriatic arthritis (PsA) comprise synthetic drugs and tumour necrosis factor inhibitors. In contrast, other biologicals including rituximab (RTX) are available for treating rheumatoid arthritis (RA). RTX is effective in autoantibody positive RA patients, although some efficacy has been reported in seronegative individuals. RTX has not yet been assessed in PsA. Therefore, an open label study of RTX in PsA was performed. PATIENTS AND METHODS: Nine patients with PsA and 14 with RA received RTX at 1000 mg twice within 14 days and were evaluated over 6 months. RESULTS: A PsA response criteria response was attained in 56% of patients. DAS28 improved from 6.2 to 4.9 (medians) in PsA and 6.4 to 5.2 in RA, and Health Assessment Questionnaire from 1.5 to 1.0 and from 2.1 to 1.4, respectively (all p≤0.05). Disease Activity index for PSoriatic Arthritis changed from 52.0 to 32.5 (p<0.05); C reactive protein and Psoriasis Area and Severity Index did not change significantly. RTX was tolerated well. CONCLUSIONS: In this exploratory open study, RTX exhibited significant efficacy in PsA patients with long-standing disease. Thus, RTX may have efficacy in PsA warranting a randomised controlled clinical trial.
21839715 JNK1, but not JNK2, is required in two mechanistically distinct models of inflammatory art 2011 Oct The roles of the c-Jun N-terminal kinases (JNKs) in inflammatory arthritis have been investigated; however, the roles of each isotype (ie, JNK1 and JNK2) in rheumatoid arthritis and conclusions about whether inhibition of one or both is necessary for amelioration of disease are unclear. By using JNK1- or JNK2-deficient mice in the collagen-induced arthritis and the KRN T-cell receptor transgenic mouse on C57BL/6 nonobese diabetic (K/BxN) serum transfer arthritis models, we demonstrate that JNK1 deficiency results in protection from arthritis, as judged by clinical score and histological evaluation in both models of inflammatory arthritis. In contrast, abrogation of JNK2 exacerbates disease. In collagen-induced arthritis, the distinct roles of the JNK isotypes can, at least in part, be explained by altered regulation of CD86 expression in JNK1- or JNK2-deficient macrophages in response to microbial products, thereby affecting T-cell-mediated immunity. The protection from K/BxN serum-induced arthritis in Jnk1(-/-) mice can also be explained by inept macrophage function because adoptive transfer of wild-type macrophages to Jnk1(-/-) mice restored disease susceptibility. Thus, our results provide a possible explanation for the modest therapeutic effects of broad JNK inhibitors and suggest that future therapies should selectively target the JNK1 isoform.
22232948 [Spondyloarthritides--clinical features]. 2011 The spondyloarthritides are group of interrelated and overlapping arthritic conditions which primarily include ankylosing spondylitis, reactive arthritis/Reiter's disease and arthritis associated with psoriasis and inflammatory bowel disease. They are characterised by the absence of rheumatoid factor and by association with HLA-B27 antigen. The main clinical features are inflammatory back pain, spondylitis, sacroileitis, asymmetric arthritis of lower limbs, enthesitis, dactylitis, besides fatigue, uveitis, skin and mucous membrane lesions, cardiac and pulmonary involvement. Although there are similarities among the spondyloarthritides, each of them have specific characteristic that help us to distinguish them.
22415803 Multivalent structure of galectin-1-nanogold complex serves as potential therapeutics for 2012 Mar 13 Cellular behaviour is controlled by numerous processes, including intracellular signalling pathways that are triggered by the binding of ligands with cell surface receptors. Multivalent ligands have multiple copies of a recognition element that binds to receptors and influences downstream signals. Nanoparticle-ligand complexes may form multivalent structures to crosslink receptors with high avidity and specificity. After conjugation onto gold nanoparticles, galectin-1 (Au-Gal1) bound with higher affinity to Jurkat cells to promote CD45 clustering and inhibition of its phosphatase activity, resulting in enhancement of apoptosis via caspase-dependent pathways. Au-Gal1 injected intra-articularly into rats with collagen-induced arthritis (CIA) promoted apoptosis of CD4+ T cells and reduced pro-inflammatory cytokine levels in the ankle joints as well as ameliorated clinical symptoms of arthritis. These observed therapeutic effects indicate that the multivalent structure of nanoparticle-ligands can regulate the distribution of cell surface receptors and subsequent intracellular signalling, and this may provide new insights into nanoparticle applications.
23273793 MRI and ultrasonography for diagnosis and monitoring of psoriatic arthritis. 2012 Dec Imaging techniques such as magnetic resonance imaging (MRI) and ultrasound (US) have been increasingly used in psoriatic arthritis (PsA) providing additional clues to the pathogenesis of this peripheral, axial and dermatologic disease. This has improved our understanding of the disease and can be used to aid diagnosis and then to follow outcomes of treatment. Both imaging modalities have highlighted the differing involvement of PsA when compared with rheumatoid arthritis (RA) with a significant burden of entheseal disease, flexor tenosynovitis (occurring alone or as part of dactylitis) and other extra-capsular inflammatory changes. MRI scanning has also highlighted the link between the nail and the distal interphalangeal (DIP) joint confirming previous clinical observations. Imaging studies in psoriasis patients have discovered a high level of subclinical inflammatory change but the clinical importance of such findings has not yet been defined. The potential use of MRI and US to monitor treatment outcomes has encouraged research in this field. In MRI, the PsA MRI Score (PsAMRIS) has been developed with promising initial validation. In US, work is ongoing with the OMERACT group to define key pathologies and to develop scoring systems. A few scoring systems are available for enthesitis scoring using US which are further being developed and refined. Further improvements in technologies in both of these fields offer exciting possibilities for future research. New MRI techniques offer the chance to image previously 'dark' structures such as tendons which is key in spondyloarthritides (SpA). Sonoelastography may also improve our understanding of tendon involvement in SpA. Whole-body multi-joint MRI allows a 'snapshot' of inflammation in PsA including joints, entheses and spinal involvement. Three-dimensional US should improve reliability and comparability of US scoring reducing inter-operator variability. The latest machines offer real-time fusion imaging employing US machines with an in-built virtual navigator system linked to previous MRI acquisitions. All of these new techniques should aid our understanding of PsA and our ability to objectively measure response to therapy.
21345239 Alpha-1 antitrypsin protein and gene therapies decrease autoimmunity and delay arthritis d 2011 Feb 24 BACKGROUND: Alpha-1 antitrypsin (AAT) is a multi-functional protein that has anti-inflammatory and tissue protective properties. We previously reported that human AAT (hAAT) gene therapy prevented autoimmune diabetes in non-obese diabetic (NOD) mice and suppressed arthritis development in combination with doxycycline in mice. In the present study we investigated the feasibility of hAAT monotherapy for the treatment of chronic arthritis in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). METHODS: DBA/1 mice were immunized with bovine type II collagen (bCII) to induce arthritis. These mice were pretreated either with hAAT protein or with recombinant adeno-associated virus vector expressing hAAT (rAAV-hAAT). Control groups received saline injections. Arthritis development was evaluated by prevalence of arthritis and arthritic index. Serum levels of B-cell activating factor of the TNF-α family (BAFF), antibodies against both bovine (bCII) and mouse collagen II (mCII) were tested by ELISA. RESULTS: Human AAT protein therapy as well as recombinant adeno-associated virus (rAAV8)-mediated hAAT gene therapy significantly delayed onset and ameliorated disease development of arthritis in CIA mouse model. Importantly, hAAT therapies significantly reduced serum levels of BAFF and autoantibodies against bCII and mCII, suggesting that the effects are mediated via B-cells, at least partially. CONCLUSION: These results present a new drug for arthritis therapy. Human AAT protein and gene therapies are able to ameliorate and delay arthritis development and reduce autoimmunity, indicating promising potential of these therapies as a new treatment strategy for RA.
23044922 Nordihydroguaiaretic acid inhibition of NFATc1 suppresses osteoclastogenesis and arthritis 2012 Dec Nordihydroguaiaretic acid (NDGA) is known to have prominent anticancer activity against several cancers, and is also known to be an inhibitor of 5-lipoxygenase (5-LO). In this study, we investigated the regulatory function of NDGA on inflammatory bone destruction mediated by osteoclasts. NDGA markedly inhibited receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced formation of osteoclasts in cultures of murine osteoclast precursor cell line RAW-D cells and primary bone marrow-derived macrophages culture systems. The inhibitory effect of NDGA on osteoclastogenesis did not arise from the inhibition of 5-LO activity. NDGA did not affect MAPKs, such as p38, JNK, and NF-κB, but significantly inhibited the induction of NFATc1, a key transcription factor for osteoclastogenesis. NDGA also suppressed activation of ERK in osteoclast precursors. RANKL-induced calcium oscillation observed in osteoclast precursors was completely diminished by the addition of NDGA. In mature osteoclasts, RANKL-induced nuclear translocation of NFATc1 was clearly inhibited by NDGA treatment. Finally, in vivo studies demonstrated that administration of NDGA significantly reduced severe bone destruction and osteoclast recruitment in the ankle joint of rats with adjuvant-induced arthritis. These results indicate the potential utility of NDGA as a therapeutic agent for ameliorating inflammatory bone destruction in rheumatoid arthritis.
22155016 Autoantibodies in patients with chronic hepatitis C virus infection: pitfalls for the diag 2012 Jul Hepatitis C virus infection (HCV) is one of the best mimes in medicine. About 40-70% of patients suffering from this disorder develop at least one extra-hepatic disorder that can have a rheumatic nature (arthralgias, arthritis, vasculitis and sicca syndrome) and must be differentiated from the primitive rheumatic diseases. In addition, HCV infection can also alter the laboratory tests. Several alterations of first line laboratory tests can be usually found in both chronic HCV infection and chronic inflammatory rheumatic disorders. In the present review we analyze the interference of HCV in tests more specifically used in rheumatology: rheumatoid factor and other autoantibodies (ANA, anti-ENA, ANCA, anti-DNA, antiphospholipid, anti-CCP). In patients suffering from HCV infection, the diagnosis of connective tissue diseases (CTD) or rheumatoid arthritis (RA) should be made only when the detected symptoms or laboratory data are not inducible by HCV, otherwise only a diagnosis of "possible CTD" or "possible RA" should be considered.
21787353 Genetic relationships between A20/TNFAIP3, chronic inflammation and autoimmune disease. 2011 Aug A20 [also known as TNFAIP3 (tumour necrosis factor α-induced protein 3)] restricts and terminates inflammatory responses through modulation of the ubiquitination status of central components in NF-κB (nuclear factor κB), IRF3 (interferon regulatory factor 3) and apoptosis signalling cascades. The phenotype of mice with full or conditional A20 deletion illustrates that A20 expression is essential to prevent chronic inflammation and autoimmune pathology. In addition, polymorphisms within the A20 genomic locus have been associated with multiple inflammatory and autoimmune disorders, including SLE (systemic lupus erythaematosis), RA (rheumatoid arthritis), Crohn's disease and psoriasis. A20 has also been implicated as a tumour suppressor in several subsets of B-cell lymphomas. The present review outlines recent findings that illustrate the effect of A20 defects in disease pathogenesis and summarizes the identified A20 polymorphisms associated with different immunopathologies.
23129076 Common variable immunodeficiency presenting with persistent parvovirus B19 infection. 2012 Dec Parvovirus B19 infection in healthy hosts is self-limited, but persistent infection has been described in patients with cellular immune defects. A 6-year-old boy presented with a 6-month history of weight loss and malaise and a 1-month history of fever and polyarticular arthritis. Parvovirus DNA was detected in plasma at 10 300 copies/mL. Levels of immunoglobulin (Ig)G, IgA, IgM, IgG-1, and IgG-2 were low, and antibody responses to vaccine antigens were impaired. HIV antibody and DNA polymerase chain reaction were negative, and the patient had normal immunophenotype, mitogen stimulation response, CD40 ligand and inducible costimulator expression, transmembrane activator and CAML interactor sequencing, genomic analysis, and fluorescent in situ hybridization for deletions at 22q11.2. Common variable immunodeficiency was diagnosed and replacement therapy with immune globulin intravenous was initiated. The parvovirus DNA level declined by half over 3 months and was undetectable at 15 months. Constitutional symptoms improved but arthritis persisted and eosinophilic fasciitis eventually developed. This case demonstrates that persistent parvovirus infection may be a presenting feature of humoral immune deficiency and can mimic juvenile rheumatoid arthritis. The infection may respond to immune globulin intravenous therapy.