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

ID PMID Title PublicationDate abstract
15644388 Endothelial cells, fibroblasts and vasculitis. 2005 Jul One of the most important questions in vasculitis research is not why inflammation of blood vessels occurs but why it persists, often in a site-specific manner. In this review we illustrate how stromal cells, such as fibroblasts and pericytes, might play an important role in regulating the site at which vasculitis occurs. Smooth muscle cells and fibroblasts directly influence the behaviour of overlying vascular cells, amplifying the response of the endothelium to proinflammatory agents such as TNF-alpha and allowing enhanced and inappropriate leucocyte recruitment. An abnormal local vascular stromal environment can therefore influence local endothelial function and drive the persistence of local vascular inflammation. However, such local vascular inflammation can have distant effects on the systemic vascular system, leading to widespread endothelial cell dysfunction. Vascular endothelial dysfunction is common in a range of immune-mediated inflammatory diseases, is seen in multiple vascular beds, and is reversible following the induction of disease remission. The mechanisms that drive such systemic vascular endothelial dysfunction are unclear but factors such as TNF-alpha and CRP may play a role. Persistence of such widespread endothelial dysfunction in systemic vasculitis appears to have long-term consequences, leading to the acceleration of atherosclerosis and premature ischaemic heart disease. It may also underlie the accelerated atherosclerosis seen in other immune-mediated rheumatic diseases, such as rheumatoid arthritis.
16876794 Normal acute and chronic inflammatory responses in sphingosine kinase 1 knockout mice. 2006 Aug 21 Sphingosine-1-phosophate, generated from the phosphorylation of sphingosine by sphingosine kinase enzymes, is suggested to function as an intracellular second messenger for inflammatory mediators, including formyl peptide, C5a, and Fc. More recently, a role for sphingosine kinases during inflammation has also been proposed. Here we show that sphingosine kinase 1 knockout mice exhibit normal inflammatory cell recruitment during thioglycollate-induced peritonitis and that sphingosine kinase 1-null neutrophils respond normally to formyl peptide. In the collagen-induced arthritis model of rheumatoid arthritis, sphingosine kinase 1 knockout mice developed arthritis with normal incidence and severity. Our findings show that sphingosine kinase 1 is dispensable for inflammatory responses and support the need for more extensive studies of sphingosine kinases in inflammation.
15871674 Adeno-associated virus pseudotype 5 vector improves gene transfer in arthritic joints. 2005 Apr The potential for gene delivery to joints, using recombinant adeno-associated virus (rAAV) vectors for the treatment of rheumatoid arthritis (RA), has received much attention. Different serotypes have different virion shell proteins and, as a consequence, vary in their tropism for diverse tissues. The aim of this study was to compare the transduction efficiency of different AAV serotypes encoding murine secreted alkaline phosphatase (mSEAP) or Escherichia coli beta-galactosidase for intraarticular gene delivery in an experimental model of arthritis. The vectors contained AAV2 terminal repeats flanking the reporter gene in an AAV1, AAV2, or AAV5 capsid, producing the pseudotypes rAAV-2/1, rAAV-2/2, and rAAV-2/5. Left knee joints of mice with collagen-induced arthritis were injected and transgene expression was analyzed by chemiluminescence or direct in situ staining of frozen sections. We show for the first time that intraarticular gene transfer with AAV- 2/5 was far more efficient than with the other serotypes tested. Transgene expression was detectable as early as 7 days after injection, reached a maximum at 21 days, and was stably expressed for at least 130 days, whereas AAV-2/1- and AAV-2/2-mediated expression levels were barely detectable. These findings provide a practical application for future local AAV-mediated gene therapy trials in RA.
15731905 Occurrence of haemophagocytic lymphohistiocytosis at less than 1 year of age: analysis of 2005 May We analysed data of 96 infants (under 1 year of age) with haemophagocytic lymphohistiocytosis (HLH) from the registry of an HLH study conducted during 1986-2002 in Japan. The cases were classified into five groups. The diagnosis of familial HLH (FHL) as group 1 (n = 27) was made with positive family history and/or recent molecular test for perforin and Munc13-4 mutations. Neonatal enterovirus- or herpes simplex virus-associated HLH as group 2a (n = 7), Epstein-Barr virus-associated HLH (n = 12) as group 2b, adenovirus- or cytomegalovirus-associated HLH as group 3 (n = 9) were mostly diagnosed by viral isolation or by the detection of viral genome. Juvenile rheumatoid arthritis-associated macrophage activation syndrome was classified as group 4 (n = 4) and the remaining without known triggers as group 5 (n = 37). The peak onset age was 1-2 months for group 1, 1-2 weeks for group 2a, 12 months for group 2b, none for group 3, 9 months for group 4 and 2 months for group 5. Future novel diagnostic measures are required to define the precise nature of HLH in group 5. CONCLUSION: These data may provide useful information for neonatologists/ paediatricians in the differential diagnosis of haemophagocytic lymphohistiocytosis in early infancy.
15895074 Inflammatory arthritis requires Foxo3a to prevent Fas ligand-induced neutrophil apoptosis. 2005 Jun In inflammatory arthridities such as rheumatoid arthritis, cognate lymphocytes have long been considered instigators of autoimmunity, but accumulating evidence indicates that innate immune cells such as neutrophils and mast cells are responsible for a vast majority of acute and ongoing inflammation; however, the molecular mechanisms that govern them remain largely unknown. Here we show that such inflammation requires the forkhead transcription factor Foxo3a: Foxo3a-deficient mice are resistant to two models of neutrophilic inflammation, immune complex-mediated inflammatory arthritis and thioglycollate-induced peritonitis. This reflects a need for Foxo3a to maintain neutrophil vitality during inflammation by suppressing Fas ligand; because Foxo3a can bind and suppress the Fasl promoter, Foxo3a-deficient neutrophils upregulate Fas ligand and undergo apoptosis in response to TNF-alpha and IL-1, and Fas ligand blockade renders Foxo3a-deficient mice susceptible to both arthritis and peritonitis. Thus, Foxo3a ensures neutrophil survival during inflammation, identifying Foxo3a as therapeutic target in inflammation.
16039459 Salvage of post-traumatic arthritis following distal radius fracture. 2005 Aug There are practical recommendations that can be drawn from the aforementioned results. Due to the minimal morbidity of the wrist denervation, patients with good but painful wrist motion following fracture of the distal radius should first be evaluated for wrist denervation unless formal resection of the dorsal interosseous nerve has clearly been included in the previous treatment. The evaluation is performed in a standardized manner before and after test infiltration of both interosseous nerves. This evaluation includes assessment of pain, strength, and working capacity. Whereas the grip strength often does not (cannot)increase more than 10% to 20%, the subjective pain relief can be remarkable, leading to higher repetition counts and increased dexterity. Inpatients with insufficient response to the anesthetic nerve blocks, other pain sources must be sought, especially on the ulnar side of the wrist. Patients with less than functional range are candidates for complete arthrodesis. A way for further evaluation with regard to the potential of partial and complete wrist arthrodesis is trial immobilization of the wrist in a light cast ora firm reinforced brace. Trial immobilization also allows anticipating the functional deficit from loss of range of wrist motion. Due to the still-unrestricted pronation and supination, ulnar-sid-ed wrist pain may persist and will need adequate follow-up adjunct treatment. Patients who have good pain relief but are not willing to completely lose their wrist motion should be evaluated fluoroscopically or receive lateral radiographs in full flexion and extension to measure their mid-carpal joint mobility and anticipate the potential residual motion after radiocarpal fusion. Patients without pain relief from test anesthesia, trial immobilization, and no apparent distal radioulnar joint pathology are poor candidates for further operative treatment.In evaluating different salvage procedures,among all diagnoses, painful arthritis following fracture of the distal radius is the most difficult to treat and yields the poorest results. Emphasis must therefore be on better initial fracture treatment and earlier secondary reconstructive interventions. The current salvage procedures must allow further improvement or alternatives must be developed. Prosthetic replacement merits serious consideration, especially when it can be adapted to the specific post-traumatic setting. This situation is not worse than rheumatoid arthritis because the clinician is dealing with healthy and strong intact bone stock, tendons, and ligaments,and most important, complete absence of a progressive disease.
17117947 Investigation of the functional variant c.-169T > C of the Fc receptor-like 3 (FCRL3) gene 2006 Dec A functional variant in the Fc receptor-like 3 (FCRL3) gene has been implicated in susceptibility to autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid disease. Investigating a large case-control sample of patients with alopecia areata (AA), we found no evidence for the involvement of FCRL3 in susceptibility to AA.
16483904 Osteoarthritis: epidemiology. 2006 Feb Osteoarthritis (OA) is the most common joint disorder in the world. In Western populations it is one of the most frequent causes of pain, loss of function and disability in adults. Radiographic evidence of OA occurs in the majority of people by 65 years of age and in about 80% of those aged over 75 years. In the US it is second only to ischaemic heart disease as a cause of work disability in men over 50 years of age, and accounts for more hospitalizations than rheumatoid arthritis (RA) each year. Despite this public health impact, OA remains an enigmatic condition to the epidemiologist. In this chapter, we will review the definition and classification of OA, its prevalence, incidence, risk factors and natural history.
16227151 Cytokine signal regulation and autoimmune disorders. 2005 Aug Understanding of biological activities of cytokines and exquisite mechanism to regulate their functions has facilitated the therapeutic concept to restore the disequilibrium between pro-inflammatory cytokines and anti-inflammatory cytokines or cytokine inhibitors in some autoimmune inflammatory diseases such as rheumatoid arthritis (RA) and Crohn's disease. The application of molecular biology techniques to design monoclonal antibodies, soluble receptors, or receptor antagonists as therapeutic biologic agents made it possible to regulate the cytokine signals for the treatment of the diseases refractory to conventional therapies. Japanese researchers have contributed considerably to the establishment of cytokine signal regulation in autoimmune diseases. In this article, Japanese studies of cytokine signal regulation, particularly for Interleukin-6 (IL-6) in autoimmune diseases are reviewed.
16164203 [Introduction to osteoimmunology]. 2005 Sep Since research into the bone destruction in rheumatoid arthritis led us to realize the importance of the interplay of the immune and skeletal systems, interdisciplinary research field called osteoimmunology has attracted further attention. This is partly based on the identification of a number of unexpected bone phenotypes in mice lacking immunomodulatory molecules. Accumulating evidence suggests that the immune and skeletal systems share not only cytokines but also various signaling molecules, transcription factors and membrane receptors. This emerging field will be increasingly important not only for the future strategy for rheumatic diseases but also for clinical and basic studies in all the related fields.
18958651 Silica, apoptosis, and autoimmunity. 2005 Jul 1 Relatively little is known regarding mechanisms of environmental exposures in the development of autoimmune disease. However, several environmental agents are implicated in triggering or accelerating systemic autoimmune disease, including mercury, iodine, vinyl chloride, certain pharmaceuticals, and crystalline silica. There is increasing epidemiological evidence supporting the hypothesis that occupational silica exposure is associated with a variety of systemic autoimmune diseases, including scleroderma (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), glomerulonephritis (GN) and small vessel vasculitis (SVV). However, there have been few mechanistic studies examining silica exposure and autoimmune disease initiation and progression. This review summarizes human epidemiology data linking silica exposure with systemic autoimmune disease, but focuses on possible mechanisms by which silica can lead to the development and progression of autoimmunity.
16932736 Therapy insight: The recognition and treatment of retinal manifestations of systemic vascu 2006 Aug A variety of retinal signs can occur in patients who have systemic vasculitides, or who experience complications of these diseases or their treatment. Although treatment of these retinal manifestations is usually the treatment of the systemic disease, specific treatment is occasionally indicated to preserve vision. The more prevalent of the systemic vasculitides are giant cell arteritis, polyarteritis nodosa, Wegener's granulomatosis, Churg-Strauss syndrome, relapsing polychondritis and systemic lupus erythematosus. Less frequently occurring vasculitides include Takayasu's arteritis, Goodpasture's disease, microscopic polyangiitis and Henoch-Schönlein purpura, as well as vasculitis secondary to scleroderma and rheumatoid arthritis. This article describes the pathogenesis, clinical features and treatment of retinal manifestations of systemic vasculitides.
16898092 [Aseptic necrosis of the head of the femur in patients with major rheumatic diseases of in 2005 Nov A total of 2392 patients treated at the Unit of Rheumatology, Tula Regional Hospital, in 2002 and 2003 were analyzed. Among them, there were 71 patients who were found to have aseptic necrosis of the head of the femur. A statistical analysis of clinical, laboratory, and X-ray data revealed a number of correlations. It was established that the risk factors of aseptic necrosis of the femoral heads were anemia concurrent with the high laboratory values in rheumatoid arthritis and elevated lipid levels and blood coagulative system activation in primary coxarthrosis.
16144289 Elastosis perforans serpiginosa secondary to D-penicillamine therapy with coexisting cutis 2005 Jul Elastosis perforans serpiginosa (EPS) is a rare complication of D-penicillamine therapy. EPS has been reported in patients with Wilson disease, cystinuria, and rheumatoid arthritis after many years of high-dose therapy. We report a case of D-penicillamine-induced EPS with coexisting acquired cutis laxa in a patient with cystinuria. Although both EPS and acquired cutis laxa can be associated with D-penicillamine therapy, few cases have been reported with overlapping clinical presentations, and previously only in patients with Wilson disease. We review the characteristic clinical and histologic features of EPS and discuss the potential dermatologic manifestations of D-penicillamine therapy.
15996871 Oxidative activation of antioxidant defence. 2005 Aug Living cells maintain a delicate balance between oxidizing and reducing species, and many disorders such as rheumatoid arthritis and Alzheimer's disease have been associated with a disturbed intracellular 'redox equilibrium'. The past few years have witnessed accelerated research into how natural redox responses and antioxidant defence systems are activated and how they restore a healthy redox balance. To function properly, many of these processes rely on a powerful sulfur redox chemistry, which is best exemplified by the complex, newly emerging cysteine-based redox regulation of the glutathione and thioredoxin pathways. Other redox systems based on oxidatively activated amino acid side chains in proteins are also becoming increasingly important, but are still barely understood or explored.
15859395 A catastrophic case of skin gangrene. 2005 Jan We describe the case of a 70-year-old male with the catastrophic antiphospholipid syndrome admitted for skin gangrene of the fingers. The initial diagnosis was antiphospholipid antibody syndrome in a patient with rheumatoid arthritis and a history of deep vein thrombosis of the lower limbs. Liver involvement, the characteristic skin gangrene, pneumonia and worsening severe renal failure were determinant to make the final diagnosis of catastrophic antiphospholipid syndrome that led the patient to death.
15831260 Joint replacement in the hallux metatarsophalangeal joint. 2005 Mar Joint replacement of the hallux metatarsophalangeal joint has not enjoyed the same success as hip and knee arthroplasties. Silastic implants have achieved a high patient satisfactory rate but have caused many complications, including silicone synovitis and lymph node inflammation. Metal and polyethylene hemiarthroplasties and total toe replacements seem to be more promising although results are preliminary. Problems with these implants seem to be related to soft tissue instability of the joint; patients who have hallux rigidus have more success than patients who have hallux valgus or rheumatoid arthritis. Severe complications can be treated with removal and synovectomy or arthrodesis, depending on the length and alignment of the foot, as well as the functional demands of the patients. It would be beneficial to have more data on these implants so that improvements can be made in design and patient selection.
16093819 Autoimmunity and interstitial lung disease. 2005 Sep PURPOSE OF REVIEW: The pathogenesis of idiopathic pulmonary fibrosis as well as that of several other interstitial lung diseases is poorly understood. The role of autoimmunity in interstitial lung diseases associated with connective tissue disorders such as systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis as well as the vasculitides is well established. There is at least some evidence in the literature that supports the role of autoimmunity as one of the mechanisms of alveolar injury responsible for idiopathic pulmonary fibrosis. This review is an attempt to summarize the studies on this subject. RECENT FINDINGS: Repeated extraneous insults and exposures are considered to be responsible for recurrent alveolar injury, inflammation, dysregulated tissue repair, and fibroproliferation resulting in pulmonary fibrosis. The presence of autoantibodies in the sera of patients with idiopathic pulmonary fibrosis has been demonstrated in a few studies. Several autoantibodies, including anti-Sm antibodies, antibodies to U1 ribonucleoproteins, and antibodies to U3 ribonucleoproteins, have been demonstrated in connective tissue disorders, many of which are associated with interstitial lung involvement. Autoimmunity has been also suggested as a possible mechanism of rejection caused by bronchiolitis obliterans after lung transplantation. SUMMARY: It might seem that the role of autoimmunity in interstitial lung disease has been underestimated or even underinvestigated. The subject requires further investigation, especially with regard to the problems of lung allograft rejection due to bronchiolitis obliterans of nonalloimmunity origin and the failure of patients with idiopathic pulmonary fibrosis to respond to most forms of currently available therapy.
18751843 Haglund's syndrome: diagnosis and treatment using sonography. 2006 Feb Haglund's syndrome is a cause of retrocalcaneal pain. The clinical diagnosis of Haglund's syndrome is often confusing as the clinical picture may mimic other causes of hindfoot pain such as isolated retrocalcaneal bursitis or hindfoot involvement from more systemic arthropathies such as Reiter's syndrome or rheumatoid arthritis. With the increasing frequency of employing sonography as a diagnostic tool in the evaluation of foot and ankle pathology, recognition of the sonographic appearance of Haglund's complex is important. We report a case of Haglund's syndrome diagnosed and treated with sonography.
15941837 Problem of the atherothrombotic potential of non-steroidal anti-inflammatory drugs. 2006 Jan Treatment of pain in rheumatoid arthritis must take into account the gastrointestinal and cardiovascular risk of individual patients. Adequate results are not yet available, and until they are, treatment recommendations must take into account, not only the more favourable gastrointestinal risk profile of selective COX-2 inhibitors, but also the potential atherothrombotic risk of any NSAID or selective COX-2 inhibitor treatment.