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

ID PMID Title PublicationDate abstract
17729081 Work in inflammatory and degenerative joint diseases. 2007 Sep 15 This article focuses on work disability and sick leave and their cost; it also discusses the value of vocational rehabilitation programmes in rheumatic conditions such as rheumatoid arthritis, ankylosing spondylitis, hip and knee osteoarthritis. It acknowledges the importance of work not only for the worker who has one of these diseases but also for the public purse. Much can be done to improve the health of the persons and reduce their disability and its impact in the workplace which will have an important effect on their and their family's quality of life. It is important that neither rehabilitation nor vocational rehabilitation are regarded as bolt-on activities after drug treatment but are seen as an integral part of effective management. Publications dealing with return to work are relatively common in rheumatoid arthritis, less common in ankylosing spondylitis and relatively rare in osteoarthritis. Vocational rehabilitation programmes should aim to facilitate job retention or, failing that, to improve the ability to return to work. The process must be started with in the health arena and it has to be recognised that slow or poor practice in the health service can jeopardise the patient's work potential.
17502870 Construction and purification of the murine p75-murine IgG1 fusion protein. 2007 May Etanercept (Amgen Inc, Thousand Oaks, CA) is a human soluble p75 tumor necrosis factor (TNF) receptor-human-IgG1 (hup75 TNFR-huIgG1) fusion protein used in the treatment of chronic inflammatory diseases in humans, including rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. To be able to study the effects of the soluble receptor fusion protein in mouse models, including those that mimic human granulomatous infections, a murine soluble p75-TNF receptor-murine IgG1 (murine p75-murine IgG1) fusion protein had to be constructed. This article discusses the generation, large-scale production, and purification of this molecule.
16855142 Innervation of the joint and role of neuropeptides. 2006 Jun Rheumatoid arthritis is considered to represent a disease of the synovial membrane, osteoarthritis of the hyaline articular cartilage, and osteoporosis of the bone. It can be questioned to what extent this is true and to what extent these diseases could be considered to be due to extra-articular, extra-skeletal pathology related to the neuroendocrine system. Pain is the main symptom in arthritis. This is related to prostaglandin-mediated sensitization of the primary afferent nociceptive nerves. Accordingly, nonsteroidal anti-inflammatory drugs are used in symptomatic treatment, occasionally together with opioids and tricyclic antidepressants. The midline symmetry and involvement of the richly innervated, small peripheral joints in rheumatoid arthritis have raised speculation about the role of neurogenic inflammation and neuropeptides in its pathogenesis. In contrast to the free nerve endings, the role of the proprioceptive sensors is to provide information of our actual motor performance (the afferent copy of our movements) compared to the efferent motor program, which is activated by our will to move. These include proprioceptors in the skin (e.g., Meissner corpuscles), muscles (annulospiral and flower-spray endings of the muscle spindles), Golgi tendon organs, and Ruffini end organs and Pacinian corpuscles in the superficial and deep layers of the joint capsule. Elderly people may have slow reflexes, lax joints, joint incongruity, and loss of muscle power; obesity, alcohol and medicinal use, and joint pain can be combined with poor/nonexisting capacity for repair and remodeling of the musculoskeletal tissues. Impaired biomechanics contributes to increased joint tenderness, accumulation of minor trauma (secondary osteoarthritis), and falls (osteoporotic fractures). More attention needs to be paid to aging of proprioception, not only to the terminal disease target.
18028004 Tumor necrosis factor as a therapeutic target of rheumatologic disease. 2007 Nov TNF-alpha is a crucial pro-inflammatory and immunoregulatory cytokine that is central to the pathogenesis of various inflammatory and autoimmune conditions. A number of controlled trials have shown effectiveness for TNF-alpha inhibitors in several diseases, in particular rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and Crohn's disease. These agents may also be useful in additional autoimmune conditions. The introduction of TNF-alpha inhibitors has revolutionized the therapeutic approach and treatment paradigms especially for patients with rheumatoid arthritis. Despite extensive investigation, the full profile of their mechanisms of action remain incompletely understood. Optimal use of these agents requires consideration of their possible adverse effects. In addition to the presently available TNF-alpha blockers, other agents targeting this key mediator are under study. Recent advances and future directions in anti-TNF-alpha therapy are discussed in this paper.
23480266 Targeted therapy in rheumatoid arthritis. 2008 Mar BACKGROUND: Rheumatoid arthritis (RA) is the most common inflammatory joint disease in adults leading to pain and disability. New drugs, called biologicals, have opened up new possibilities in the treatment of RA. OBJECTIVE: Targeting pro-inflammatory cytokines such as tumour necrosis factor-α (TNF-α) or interleukin-1 (IL-1) is well established in clinical care of RA patients. However, lack or loss of clinical response occurs in up to 25% of the patients. New strategies beyond these targets, namely blocking T cells by abatacept or B cells by rituximab (RTX), have been introduced recently. METHODS: All relevant clinical trials published in peer-reviewed journals are discussed in this article. Data from abstracts presented at congresses have not been included. CONCLUSION: TNF blocking agents have significantly improved therapy of and outcome in RA patients and, therefore, are still the first choice biologicals for the treatment of RA. Alternatively, abatacept or RTX offer new options in case of inefficacy of or contraindications against anti-TNF therapy. Forthcoming drugs, such as tocilizumab, will extend our armamentarium to treat RA effectively.
17236234 Type II collagen without adjuvant induces eosinophilic arthritis. 2007 Feb Eosinophilia is a characteristic feature of many inflammatory diseases including inflammatory bowel disease and asthma. It also occurs in a subtype of rheumatoid arthritis but the role of eosinophils has been unclear and animal models have been lacking. Here, we introduce a new mouse model to study the role of eosinophilia in arthritis. Intraperitoneal injection of type II collagen alone, without any adjuvant, was sufficient to induce chronic arthritis in a mouse with transgenic T cells specific for type II collagen. The arthritis was accompanied by infiltration of eosinophils into the synovial tissue and the disease could be blocked with neutralizing anti-IL-5 antibodies. To our knowledge, this is the first description of an eosinophilic disease form of destructive arthritis.
21857595 Assessment of autonomic function in patients with rheumatoid arthritis using spectral anal 2007 Apr OBJECTIVE: To assess the effect of rheumatoid arthritis (RA) on autonomic function of a group of RA patients in comparison with a normal control group by measuring the frequency gain response of the 2 groups. Also, to determine whether the duration of RA correlated with measures of heart rate variability signal (HRV) using an approximate entropy index (ApEn). METHODS: We evaluated 52 patients with RA, and 51 matched healthy subjects at the Arthritis Center, Johns Hopkins Hospital, Maryland, United States during 2004 and 2005. We measured breathing at different rates, and the HRV signal derived from ECG. The auto-power and cross power spectra between HRV signal and breathing signal at different breathing rates was calculated, and the frequency gain response for both groups was obtained. The ApEn, described as a measure of regularity of HRV, was calculated for both patients with RA and the healthy control subjects. RESULTS: Both frequency gain response and ApEn measure were reduced in patients with RA in comparison with the control group. The power spectra of patients with RA showed a reduced high frequency (HF) value and higher low frequency for control subjects. However, the ApEn measure was significantly reduced in longer RA duration patients. CONCLUSION: These findings suggest that the spectral analysis of HRV signal using breathing at different frequencies may detect an unbalance of the autonomic system of patients with RA, especially with increasing the sympathetic activity (higher low frequency) and reducing the parasympathetic tone (reduced frequency gain response), which can lead to sudden death in patients with RA. The ApEn may be a marker of RA stage.
17202130 The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and car 2007 Apr The recent insight that inflammation contributes to the development of atherosclerosis and type 2 diabetes mellitus constitutes a major breakthrough in understanding the mechanisms underlying these conditions. In addition, it opens the way for new therapeutic approaches that might eventually decrease the prevalence of these public health problems. Tumor necrosis factor-alpha (TNF-alpha) has been shown to play a key role in these processes and thus might be a potential therapeutic target. Increased concentrations of TNF-alpha are found in acute and chronic inflammatory conditions (e.g., trauma, sepsis, infection, rheumatoid arthritis), in which a shift toward a proatherogenic lipid profile and impaired glucose tolerance occurs. Although therapeutic blockade of TNF-alpha worsens the prognosis in patients with abscesses and granulomatous infections, this strategy is highly beneficial in the case of chronic inflammatory conditions, including rheumatoid arthritis. Current investigations assessing the impact of anti-TNF agents on intermediary metabolism suggest that TNF-alpha blockade may improve insulin resistance and lipid profiles in patients with chronic inflammatory diseases.
18716941 Autoimmune disease during pregnancy and the microchimerism legacy of pregnancy. 2008 Pregnancy has both short-term effects and long-term consequences on the maternal immune system. For women who have an autoimmune disease and subsequently become pregnant, pregnancy can induce amelioration of the mother's disease, such as in rheumatoid arthritis, while exacerbating or having no effect on other autoimmune diseases like systemic lupus erythematosus. That pregnancy also leaves a long-term legacy has recently become apparent by the discovery that bi-directional cell trafficking results in persistence of fetal cells in the mother and of maternal cells in her offspring for decades after birth. The long-term persistence of a small number of cells (or DNA) from a genetically disparate individual is referred to as microchimerism. While microchimerism is common in healthy individuals and is likely to have health benefits, microchimerism has been implicated in some autoimmune diseases such as systemic sclerosis. In this paper, we will first discuss short-term effects of pregnancy on women with autoimmune disease. Pregnancy-associated changes will be reviewed for selected autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid disease. The pregnancy-induced amelioration of rheumatoid arthritis presents a window of opportunity for insights into both immunological mechanisms of fetal-maternal tolerance and pathogenic mechanisms in autoimmunity. A mechanistic hypothesis for the pregnancy-induced amelioration of rheumatoid arthritis will be described. We will then discuss the legacy of maternal-fetal cell transfer from the perspective of autoimmune diseases. Fetal and maternal microchimerism will be reviewed with a focus on systemic sclerosis (scleroderma), autoimmune thyroid disease, neonatal lupus and type I diabetes mellitus.
18780125 Failure of small joint arthrodesis from resorption around a compression screw in a patient 2008 Mar We report the unusual case of a patient with systemic lupus erythematosus (SLE)-associated arthritis mutilans. Arthritis mutilans is a variant of erosive arthritis that is more commonly reported with psoriatic and rheumatoid arthritis and not with SLE. Joint fusion has been shown to be the most effective measure to preserve bone length and prevent further erosive joint changes in arthritis mutilans. We attempted to enhance success of a thumb interphalangeal joint fusion in our patient by adding compression across the fusion with implant screws, given the difficulty of achieving solid bone fusion ordinarily. Osteolysis around the compression screw resulted in arthrodesis failure. We were finally able to achieve successful fusion with iliac crest corticocancellous bone grafts and Kirschner wire fixation. Implant athroplasty in patients with bone loss is risky as it often furthers joint instability because of bone resorption around the prosthesis. This is a point of caution regarding use of any implant (including large screws) in patients with arthritis mutilans, as osteolysis around the implant may occur.
16609821 Seronegative arthritis in patient with solitary bone plasmacytoma. 2007 Jul We report a patient with localized focus of the bone destruction due to a rare disease, solitary bone plasmacytoma (SBP). The patient suffered from arthritis, mimicking seronegative rheumatoid arthritis. To our knowledge, it is the first description of coexistence of arthritis and SBP.
18854880 [Viral genotype and HLA class II alleles influence on extra-hepatic manifestations of chro 2008 Jul OBJECTIVE: To test whether an association between HCV genotype, HLA class II alleles distribution and extra-hepatic manifestations (EHM ) can be demonstrated in a group of Italian patients with chronic HCV infection . METHODS: Sixty patients affected by HCV infection with EHM were consecutively enrolled. 163 HCV patients without EHM were tested as controls for the prevalence of HCV genotypes, while we referred to literature as to the controls for HLA distribution. HCV-RNA was quantified by a RT-PCR. HLA class II alleles typing was performed using a standard microlymphocytotoxicity assay. We used chi-square or Fisher test (p<0.05 significant). Odds Ratio (OR) was performed by 2X2 contingency table. RESULTS: HCV 2c genotype was found in 63.46% of patients compared to 19.63% of controls (p<0.0001; OR=7.11). Furthermore, it correlated with carpal tunnel syndrome (p=0.03; OR=4.5) and autoimmune thyroiditis (p=0.02; OR=9.2). On the contrary, 1b genotype protected from EHM in toto (p=0.0004; OR=0.21) and particularly from carpal tunnel syndrome (p=0.0014; OR=0.07). Moreover, 3a genotype prevented HCV people from having cryoglobulinemia (p=0.05; OR=0.11). As to HLA, DR6 seemed to facilitate EHM in HCV patients (p=0.041; OR=1.61), while DQ2 (p=0.03; OR=0.5) and DQ3 (p=0.002; OR= 0.5) may play a protective role. In addition, HLA DR3 was associated with cryoglobulinemia (p=0.02; OR=9.5). CONCLUSIONS: According to our findings, 2c genotype can be considered as a major risk factor for developing HCVrelated EHM, while 1b genotype seems to prevent their onset; there are also evidences suggesting that HLA might play a role in chronic HCV infected patients.
16322971 [Synovial disorders and loose bodies in the hip joint. Arthroscopic diagnostics and treatm 2006 Jan Synovial disorders and loose bodies are one of the most common indications for hip arthroscopy. Arthroscopic intervention has been reported for loose bodies, synovial plicae, synovial chondromatosis, pigmented villonodular synovitis (PVNS) as well as rheumatoid and septic arthritis. One major advantage in comparison to radiologic imaging is the ability to inspect, biopsy, and treat within one procedure. In contrast to an arthrotomy, hip arthroscopy avoids the potential risks of extensive surgical exposure and prolonged rehabilitation. Nevertheless, hip arthroscopy cannot be promoted as curative in all synovial disorders. In patients with loose bodies, synovial plicae, initial septic arthritis and, to a certain extent, PVNS curative therapy and "restitutio ad integrum" can be achieved. In contrast, in patients with synovial chondromatosis and rheumatoid arthritis, the goal of hip arthroscopy is to enable the correct diagnosis and to provide symptomatic relief and maintain or improve joint function. Success or failure of arthroscopic treatment depends on proper patient selection and a correct arthroscopic technique.
16859117 [Effect of bizhongxiao decoction on the expression of 2-dimensional polyacrylamide gel ele 2006 Jun OBJECTIVE: To explore the effect of bizhongxiao decoction (BZXD) on the protein maps of BZXD-treated synovitis of collagen-induced arthritis (CIA) in rats in 2-dimensional gel electrophoresis (2-DE), and to provide new clues for illuminating the active mechanism of BZXD in treating the rheumatoid arthritis (RA). METHODS: Seventy SD rats were randomly divided into nor- mal group, model group and BZXD group. The experimental arthritis rat model was established by subcutaneouly injecting Type II collagen and complete Freunds adjuvant. The total proteins of synovial tissue of rat joints in the normal group, model group and BZXD group were seperated by 2-DE respectively. The gels of the 3 groups were stained by Coomassie brilliant blue. Electron pictures were obtained by scanning the gels, and then the differential proteins among the normal group, model group and BZXD group were examined by comparing the spots density volume in the gels. The electrophoregrams of the gels were analyzed in Pdquest software. RESULTS: The incidence of arthritis in the rats was approximately 88%. The 2-DE maps of rat synovial tissue in the normal group, model group and BZXD group were well duplicated. The average protein spots in the normal group, model group and BZXD group were 947 +/- 39, 994 +/- 41, and 1031 +/- 52, and the match rates were 92%, 91%, and 94.2% respectively. The average deviations of spot position were (0.896 +/- 0.217) mm in isoelectric focusing (IEF) and (1.102 +/- 0.104) mm in sodiumdo-decylsufate-polyacrylamide gel electrophoresis (SDS-PAGE), respectively. Three hundred twenty-eight differential proteins were observed between the model group and BZXD group, of which 174 were up-regulated, 147 were down-regulated in the BZXD group, and 7 proteins were expressed only in the model group. One hundred ninty-three differential proteins were displayed between the model group and the normal group, of which 123 proteins were up-regulated and 70 were down-regulated in the model group. CONCLUSION: 2-DE protein expression profiles of synovial tissue in CIA rats are established, and many differential proteins are discovered. Further analysis on the differential proteins may serve as a new method to study the moleculer mechanism of BZXD in treating the rheumatoid arthritis.
17430790 [When does an autoimmune disease begin? Importance of the early diagnosis]. 2007 Apr 8 In autoimmune diseases, such as type I diabetes mellitus, systemic autoimmune diseases and the early phase of rheumatoid arthritis, before the development of a definitive disease, clinical and laboratory alterations can be observed. Being aware of these symptoms is crucial both for family practitioners and specialists, handling autoimmune and early arthritis patients. The early recognition and prognosticating of the disease and sending the patient immediately to a specialist will lead to the exponential improvement of the patient's life expectancies and will also help to avoid complications. The need for special diagnostics, care and treatment made the development of national immunological and rheumatological centers imperative, where sufficient experience and professional knowledge helps the proper medical attendance.
16979539 Skin disorders with arthritis. 2006 Aug Many inflammatory, metabolic and infectious diseases affect the skin and joints. Most of these, such as rheumatoid arthritis and systemic lupus erythaematosus, are considered to be rheumatic conditions with secondary skin involvement. However, several primary cutaneous diseases are associated with arthritis and may even present with joint symptoms prior to cutaneous lesions. Common skin disorders, such as acne and psoriasis, have well-known musculoskeletal manifestations. Other less common conditions, such as dermatomyositis, multicentric reticulohistiocytosis, pyoderma gangrenosum, Sweet's syndrome and various cutaneous vasculitides, also have frequent joint involvement. This review will discuss the clinical presentation, both cutaneous and musculoskeletal, diagnosis and management of these disorders.
17577322 Usefulness of mouse models to study the pathogenesis of Sjögren's syndrome. 2007 Jul Sjögren's syndrome (SS) is an autoimmune disorder characterized by ocular and oral dryness as well as systemic manifestations. The immunopathogenesis of SS is complex with different intricate factors. Because of the delay in the appearance of symptoms and due to ethical issues it is very difficult to study the wide array of factors intervening in the pathogenesis of SS in human patients. To circumvent this problem, different animal models have been elaborated for studying the different subsets of the aspects of the physiopathology of this disease. In this review, we focus on the mouse models that have been established to deepen our insight into the immunopathogenesis of SS.
18436208 Alterations in corneal sensitivity and nerve morphology in patients with primary Sjögren' 2008 Jun The aim of the study was to assess subjective symptoms and objective clinical signs of dry eye in relation to corneal nerve morphology and sensitivity in primary Sjögren's syndrome. Twenty eyes of 20 primary Sjögren's syndrome patients and ten eyes of 10 healthy age- and sex-matched controls were included in the study. Ocular surface disease index (OSDI) questionnaire and visual analog scales were used to assess subjective symptoms. The mechanical sensitivity of the central cornea was measured using a modified Belmonte non-contact esthesiometer followed by an analysis of corneal nerve morphology using scanning slit confocal microscopy (ConfoScan 3). OSDI symptom scores were high in primary Sjögren's syndrome patients, compared with controls. Accordingly, the mean corneal detection threshold was low in patients implicating corneal mechanical hypersensitivity (54.5+/-40.1ml/min vs. 85.0+/-24.6ml/min, P=0.036). However, nerve densities were similar, and no correlation was present between corneal sensitivity and nerve density. In contrast, alterations in nerve morphology were found; stromal nerves appeared thicker, and nerve growth cone-like structures were seen in 20% of patients, often associated with dendritic antigen-presenting cells. Sjögren's syndrome patients presented with corneal mechanical hypersensitivity, although corneal nerve density did not differ from controls. However, alterations in corneal nerve morphology (nerve sprouting and thickened stromal nerves) and an increased amount of antigen-presenting cells, implicating the role of inflammation, were observed. These observations offer an explanation for the corneal mechanical hypersensitivity, or even hyperalgesia often observed in these patients. We hypothesize that patients with primary Sjögren's syndrome dry eye suffer from neuropathic corneal mechanical hypersensitivity induced by ocular surface inflammation.
19127798 Sjögren-like syndrome after bone marrow transplantation. 2008 Nov OBJECTIVE: To study the incidence of dry eye in Sjögren-like syndrome, graft-versus-host disease (GVHD) in hematological patients undergoing bone marrow transplantation (BMT). MATERIAL AND METHOD: Prospective, cross-sectional study in twenty-six patients that were planned for BMT (group I). Twenty-nine patients undergoing BMT before study were classified as group II no GVHD (9), and group III with GVHD (20). Thirty-two normal subjects were controls. All subjects were examined by slit lamp biomicroscopy and had their tear samples analyzed about tear osmolarity. They were also evaluated for aqueous tear production by phenol red thread test, Schirmer test without anesthesia, tear film stability by tear break-up time (TBUT), and rose bengal staining 2 weeks before BMT (for group I) as well as 6 weeks, 3 months, and 6 months after BMT. The patients with GVHD were followed up 1 month later. Main outcome measures were amount of tear production, tear film stability, and dry eye symptoms. RESULTS: Average aqueous tear production in group III was less than control and group II (p < 0.001). Mean TBUT in group III was faster than control (p < 0.001) and group I before BMT (p = 0.001). Mean score of rose bengal staining in group III was more than control and group I before BMT (p < 0.001). Keratoconjunctivitis sicca and red eye developed in 27.5%, and 20% of group III, with incidence of dry eye by Schirmer test without anesthesia (67.5%). This compares with group II having incidence of dry eye of 16.7%. However, 42.3% of group I before BMT had dry eye compared with 9.4% in the controls (p < 0.001). CONCLUSION: Trend of dry eye in patients with BMT and GVHD were higher than no-GVHD group. Doctors should be aware of ocular symptoms and signs of dry eye in patients with BMT and follow-up for proper management.
18984416 Role of nuclear scintigraphy in the characterization and management of the salivary compon 2008 Nov The American-European Consensus Group, in its classification criteria of Sjögren's syndrome (SS), consigns dynamic salivary scintigraphy to providing objective evidence of xerostomia, a secondary role. In the current SS therapeutic environment, scintigraphy's ability to differentiate parenchymal damage from neuropathic or other derangements of the salivary apparatus may prove more valuable than its role as a diagnostic modality. The procedure itself is highly process-dependent and its discriminatory power task-dependent. A multiplicity of data collection protocols and interpretative approaches tends to corrode the validity of its diagnostic information. Salivary scintigraphy's clinical utility might be extended by standardization of its test protocol and uniformity in its interpretative algorithms.