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ID PMID Title PublicationDate abstract
12746897 beta1 integrin-mediated signaling induces intercellular adhesion molecule 1 and Fas on rhe 2003 May OBJECTIVE: Rheumatoid arthritis (RA) synovial cells interact with inflammatory cells, as well as extracellular matrices, through integrins. However, the relevance of beta1 integrin to inflammatory processes in RA remains unclear. We examined the role of beta1 integrin-mediated signaling in RA. METHODS: Expression of cell-surface molecules was assessed by FACScan. Engagement of beta1 integrins was performed by crosslinking using a specific monoclonal antibody (mAb) and ligand matrices such as fibronectin or collagen. To determine the involvement of tyrosine kinases in beta1 integrin-mediated signaling, the cells were pretreated with various inhibitors of intracytoplasmic signaling or were transfected with a wild-type focal adhesion kinase (FAK) or a dominant negative truncation of the FAK expression plasmid via cationic liposome-mediated transfection. Apoptosis of synovial cells was detected by double staining with propidium iodide and annexin V. RESULTS: beta1 integrin was highly expressed on RA synovial cells. Engagement of beta1 integrins by crosslinking as well as by ligand matrices markedly up-regulated expression of intercellular adhesion molecule 1 (ICAM-1) and Fas. Up-regulation of ICAM-1 and Fas induced by beta1 integrin was mediated by the tyrosine kinase signaling pathway, especially involving FAK. Fas-mediated early apoptotic change in the cells was amplified by beta1 crosslinking. CONCLUSION: Our results suggest that interaction of beta1 integrins with extracellular matrix augments expression of ICAM-1 and Fas on RA synovial cells, as well as Fas-mediated apoptosis of synovial cells. This might lead to the spontaneous growth arrest through the Fas/Fas ligand pathway observed in RA synovitis.
15359362 Five-day food intake in elderly female outpatients with Parkinson's disease, rheumatoid ar 2004 AIM: The aim of this study was to describe and analyse the intake of food, energy and selected nutrients in elderly outpatients, i.e. women with Parkinson's disease, rheumatoid arthritis or stroke. SUBJECTS AND METHODS: Sixty-three elderly women aged 64-88 years participated in the study. For assessing dietary intake, a repeated 24-h recall and an estimated food diary for three consecutive days were used. RESULTS: The mean age was 73.4 +/- 6.6 years. Mean reported daily energy intake was 6.4 +/- 1.7 MJ, i.e. lower than reference figures for all groups. However, looking at nutrient density, only intakes of vitamin E and folate were below recommended levels. The most frequently consumed food groups were bread, coffee, milk products, buns and cookies, and spreads. CONCLUSION: The reported energy intake among the elderly female outpatients was low. This might be explained by actual low intake and/or under-reporting. However, the intake of most vitamins and minerals, i.e. nutrient density, was adequate, with the exception of vitamin E and folate intake, which was below recommended levels. Food intake showed large variation and good diet composition, and there was a tendency towards high consumption of food items that are easily prepared and eaten.
14517340 A nonredundant human protein chip for antibody screening and serum profiling. 2003 Dec There is burgeoning interest in protein microarrays, but a source of thousands of nonredundant, purified proteins was not previously available. Here we show a glass chip containing 2413 nonredundant purified human fusion proteins on a polymer surface, where densities up to 1600 proteins/cm(2) on a microscope slide can be realized. In addition, the polymer coating of the glass slide enables screening of protein interactions under nondenaturing conditions. Such screenings require only 200-microl sample volumes, illustrating their potential for high-throughput applications. Here we demonstrate two applications: the characterization of antibody binding, specificity, and cross-reactivity; and profiling the antibody repertoire in body fluids, such as serum from patients with autoimmune diseases. For the first application, we have incubated these protein chips with anti-RGSHis(6), anti-GAPDH, and anti-HSP90beta antibodies. In an initial proof of principle study for the second application, we have screened serum from alopecia and arthritis patients. With analysis of large sample numbers, identification of disease-associated proteins to generate novel diagnostic markers may be possible.
15479886 Interleukin (IL) 18 stimulates osteoclast formation through synovial T cells in rheumatoid 2004 Nov OBJECTIVE: To determine whether IL18 has any indirect effects on osteoclastogenesis mediated by T cells in RA synovium, and compare its effects with those of IL1 beta and TNF alpha. METHODS: Resting T cells were isolated from peripheral blood of healthy donors, and stimulated with 2 microg/ml phytohaemagglutinin (PHA) and 0.5 ng/ml IL2 for 24 hours. Synovial T cells were isolated from RA synovial tissue. The levels of soluble receptor activator of the NF-kappa B ligand (RANKL), osteoprotegerin (OPG), IFN gamma, M-CSF, and GM-CSF were determined by ELISA. Membrane bound RANKL expression was analysed by flow cytometry. Commercially available human osteoclast precursors were cocultured with T cells to induce osteoclast formation, which was determined with tartrate resistant acid phosphatase staining and pit formation assay. RESULTS: In PHA prestimulated T cells or RA synovial T cells, IL18, IL1 beta, or TNFalpha increased soluble RANKL production and membrane bound RANKL expression in a dose dependent manner. IL18, IL1 beta, and TNF alpha did not induce M-CSF, GM-CSF, IFN gamma, or OPG production in PHA prestimulated T cells or RA synovial T cells. IL18 increased the number of osteoclasts and bone resorption area on dentine slices in the coculture of human osteoclast precursors with PHA prestimulated T cells or RA synovial T cells; its ability was equivalent to that of IL1 beta, but less potent than that of TNF alpha. In the coculture system, OPG completely blocked osteoclast induction by IL18 or IL1 beta, and greatly inhibited induction by TNF alpha. CONCLUSION: IL18, IL1 beta, or TNF alpha can indirectly stimulate osteoclast formation through up regulation of RANKL production from T cells in RA synovitis; IL18 is as effective as IL1 beta, but less potent than TNF alpha.
12716404 Older women's perceptions of independence versus dependence in food-related work. 2003 May This qualitative study aims to explore the cultural meaning of accomplishing food-related work by older women, when disease has diminished their abilities and threatens to make them dependent. Seventy-two women with stroke, rheumatoid arthritis, and Parkinson's disease, as well as women without those diseases, were interviewed. All were living at home. Results showed that older women valued independence and feared dependence when declining ability threatened performance of food-related work. They also had strong beliefs about living a "normal life," managing by oneself as long as possible, and becoming their own masters again. To remain independent, participants used three kinds of strategies: Public Health Service Support, self-managing, and adaptation. Their beliefs about dependence included not becoming a burden, retaining self-determination, and maintaining order in life. Implications for nursing include supporting independent cooking, developing care plans with the care recipient, and demonstrating respect for the women's self-determination.
12847215 Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide 2003 Jul 15 Rheumatoid arthritis (RA) is genetically associated with MHC class II molecules that contain the shared epitope. These MHC molecules may participate in disease pathogenesis by selectively binding arthritogenic peptides for presentation to autoreactive CD4(+) T cells. The nature of the arthritogenic Ag is not known, but recent work has identified posttranslationally modified proteins containing citrulline (deiminated arginine) as specific targets of the IgG Ab response in RA patients. To understand how citrulline might evoke an autoimmune reaction, we have studied T cell responses to citrulline-containing peptides in HLA-DRB1*0401 transgenic (DR4-IE tg) mice. In this study, we demonstrate that the conversion of arginine to citrulline at the peptide side-chain position interacting with the shared epitope significantly increases peptide-MHC affinity and leads to the activation CD4(+) T cells in DR4-IE tg mice. These results reveal how DRB1 alleles with the shared epitope could initiate an autoimmune response to citrullinated self-Ags in RA patients.
15324928 A pH-induced modification of CII increases its arthritogenic properties. 2004 Sep Immunoreactivity to collagen type II (CII) has been implicated in the pathogenesis of rheumatoid arthritis. Patients have been described to have an acidic pH in their inflamed synovial tissue. It is known that protein structures are modified by environmental pH, thus it is plausible that changes in synovial pH could affect the conformation of proteins like CII. Posttranslational modifications could alter the biophysical properties of cartilage proteins leading to autoimmunity. In this study we investigated if arthritogenicity of CII was affected by changes in pH, and if so, this could be correlated to altered protein conformation. Immunisation with CII at neutral pH induced a milder disease than did CII at acidic pH. All animals elicited a humoral response to CII, although with a significantly higher IgG1/IgG2b-ratio in the pH 7.4 group. Analysis by circular dichroism and electron microscopy indicated less fibrillation of CII at low pH as compared to neutral pH. Our results suggest that CII is more immunogenic and arthritogenic in an acidic environment than in a neutral environment. We can correlate these findings to pH-induced conformational changes of CII. Hence, self-tolerance to CII might be affected by changes in pH leading to altered and increased arthritogenicity.
15176169 Counter-regulatory balance: atopic dermatitis in patients undergoing infliximab infusion t 2004 May Atopic dermatitis has been characterized as an autoimmune or auto-allergic phenomenon in which environmental allergens resembling human proteins activate auto-reactive T-cells to release pro-inflammatory cytokines of the T-helper 2 (Th2) cytokine profile (IL-4, IL-5, IL-10, and IL-13). Infliximab is a chimeric IgG1 monoclonal antibody that blocks the effects of the inflammatory cytokine tumor necrosis factor (TNF)-alpha. Infliximab has been shown to benefit greatly patients suffering from diseases associated with a Th1 profile (IL-1, TNF-alpha, and IFN-mu), such as psoriasis, Crohn's disease and rheumatoid arthritis. Some researchers have suggested that disrupting the Th1-Th2 balance by downregulating Th1 cytokines may result in manifestations of Th2 disease. Consistent with this hypothesis, we present the cases of three patients who exhibited vivid manifestations of atopic dermatitis after the inception of infliximab induction therapy.
14971821 Leflunomide-induced acute hepatitis. 2004 Jan Leflunomide, a new immunomodulatory agent, was prescribed to a 67-year-old female patient with rheumatoid arthritis. Fifteen days later she developed diarrhoea and elevated liver enzymes. A liver biopsy showed a pattern of acute hepatitis. The patient was homozygous for the rare CYP2C9*3 allele, which determines the slowest metabolic rate for CYP2C9 enzymatic activity, that is probably involved in the metabolism of leflunomide. Liver damage subsided in few weeks. This case illustrates the risk of hepatotoxicity by leflunomide and suggests that it is possibly related to CYP2C9 polymorphism.
15154871 Filtration leukocytapheresis therapy in the treatment of rheumatoid arthritis patients res 2004 Jun Filtration leukocytapheresis (LCP) is a treatment for abnormal autoimmune states, which removes responsible leukocytes from the peripheral blood. To examine the efficacy of LCP therapy in the treatment of rheumatoid arthritis (RA), nine patients were selected, who were either resistant to methotrexate, or failed with methotrexate due to drug ineffectiveness or adverse side effects. For these patients, LCP therapy was performed once a week for five weeks. After five LCP treatments, the patients were observed for 12 weeks, to test the efficacy of the treatment. The definition of improvement given by the American College of Rheumatology (ACR core set) was used for efficacy evaluation of LCP therapy. As the result, 77.8% of the patients showed an ACR 20% response and 44.4% of the patients showed an ACR 50% response. With improvement of joint symptoms, IL-6 was significantly decreased at 8 weeks and 12 weeks after the treatment. The expression of adhesion molecules CD11a, CD11b, and CD18 on granulocytes decreased directly after the LCP treatment. No adverse side effect was monitored during the study period. These results indicates that LCP treatment is a useful treatment for RA patients who were resistant to methotrexate, or failed with methotrexate due to ineffectiveness or side effects of the drug.
14532140 Comparison of the efficacy of the tumour necrosis factor alpha blocking agents adalimumab, 2003 Nov OBJECTIVE: To determine, using the method of adjusted indirect comparisons, whether there are differences in efficacy of tumour necrosis factor (TNF alpha) blocking agents, as measured by the rate ratios for American College of Rheumatology (ACR) 20, 50, and 70 responses, in patients with rheumatoid arthritis with an incomplete response to methotrexate. METHODS: A systematic review was performed to identify placebo controlled trials of 24-30 weeks' duration of combination therapy that used a step-up approach with the addition of TNF alpha blocking agents to methotrexate. The method of "adjusted indirect comparisons" was used to compare results across trials to determine the relative risk for an ACR20 or 50 response. RESULTS: Placebo controlled trials for adalimumab, etanercept, and infliximab provided data on ACR20 and 50 responses. Both the similarity of demographic and disease characteristics of patients at entry, and the homogeneity of response rates in the placebo groups across trials, suggested that comparing results across trials was valid. The relative risk for obtaining an ACR20 and 50 response derived from the adjusted indirect comparisons of the TNF alpha blocking agents did not significantly differ from unity. CONCLUSION: The analysis showed that the three currently marketed TNF alpha blocking agents have similarly efficacy when added to methotrexate in the treatment of patients with rheumatoid arthritis with active disease.
14566091 Quantitative assessment of angiogenesis in murine antigen-induced arthritis by intravital 2003 Sep Inhibition of angiogenesis might be a therapeutic approach to prevent joint destruction caused by the overgrowing synovial tissue during chronic joint inflammation. The aim of this study was to investigate angiogenesis in the knee joint of mice with antigen-induced arthritis (AIA) by means of intravital microscopy. In 14 mice (C57BL6/129Sv) intravital microscopic assessment was performed on day 8 after AIA induction in two groups (controls, AIA). Synovial tissue was investigated by intravital fluorescence microscopy using FITC-dextran (150 kD). Quantitative assessment of vessel density was performed according to the following categories: functional capillary density (FCD, vessels <10 microm in diameter), functional vessel density (FVD, vessels >10 microm) and FVD of vessels with angiogenic criteria (convoluted vessels, abrupt changes of diameter, vessels which are generated by sprouting and progressively pruned and remodelled). Microvessel count was performed using immunohistochemistry. There was no significant difference in FCD between the control group (337 +/- 9 cm/cm2; mean +/- SEM) and the AIA group (359 +/- 13 cm/cm2). The density of vessels larger than 10 microm diameter was significantly increased in animals with AIA (135 +/- 10 vs. 61 +/- 5 cm/cm2 in control). The density of blood vessels with angiogenic criteria was enhanced in arthritic animals (79 +/- 17 vs. 12 +/- 2 cm/cm2 in control). There was a significant increase in the microvessel count in arthritic animals (297 +/- 25 vs. 133 +/- 16 mm(-2) in control). These findings demonstrate that angiogenesis in murine AIA can be assessed quantitatively using intravital microscopy. Further studies will address antiangiogenic strategies in AIA.
15495793 The immunosuppressive effect of methotrexate in active rheumatoid arthritis patients vs. i 2004 Aug This cytometric study assesses the effects of methotrexate (MTX) on the expanded CD4+ lymphocyte population in active and nonactive rheumatoid arthritis (RA) patients. In the active patients, MTX was found to reduce the predominant CD4+ CD28+ subpopulation (by 30%), and the minor subpopulation of CD4+ CD28- (by 34%). The incidence of CD25 phenotype was downregulated by 15%. These reductions can be attributed to immunosuppression through apoptosis, which was demonstrated by MTX-induced fluorescein diacetate (FDA) hyperpolarization (an established indicator of early apoptosis). In contrast, in nonactive RA patients, the major CD4+ CD28+ subpopulation of small lymphocytes appeared to be activated by MTX, subsequently transforming into a major hyperblast population, whereas the minor CD4+ CD28- subpopulation was not affected by MTX treatment. The activation by MTX in this group of patients is evidenced by MTX-induced FDA depolarization (an indicator of early activation). Thus, MTX immunosuppressive effect on CD4+ subsets was found in active patients, whereas immunostimulation by MTX was shown in nonactive patients. The found discriminative effect of MTX may suggest a higher effectiveness of low-dose MTX therapy in active RA patients.
12115304 Fine-needle aspiration cytology of articular and periarticular lesions. 2002 Jun 25 BACKGROUND: The cytologic diagnosis of joint and articular surface-based lesions traditionally has been accomplished by examination of fluids or effusions. Although exfoliative cytology remains an accurate diagnostic test, not all joint-based lesions will produce effusions that are amenable to this type of examination. Fine-needle aspiration (FNA) represents an excellent alternative to traditional cytologic or histologic methods of diagnosis in joint pathology. METHODS: The authors reviewed FNA materials for the period 1992-2001 from lesions of joint spaces and periarticular soft tissues. All diagnoses based on cytologic materials that were included in this study were confirmed with histologic follow-up. Cytologic and histologic materials were prepared using standard methods. RESULTS: The authors found six relatively common lesions that were amenable to diagnosis by FNA. These included rheumatoid nodule, gouty tophi, ganglion cysts, pigmented villonodular synovitis, synovial chondromatosis, and synovial sarcoma. There are potential pitfalls in discriminating gout from pseudogout and synovial chondromatosis from chondrosarcoma. CONCLUSIONS: In most instances, mass-producing lesions of the joint space or the periarticular soft tissues can be diagnosed successfully by FNA. The common lesions are easily recognizable and are cytologically distinctive.
12452942 Arthritis treatment in Hong Kong--cost analysis of celecoxib versus conventional NSAIDS, w 2002 Dec BACKGROUND: Selective cyclo-oxygenase-2 inhibitors have been reported to cause fewer gastrointestinal complications when compared with conventional, non-selective, non-steroidal anti-inflammatory drugs (NSAIDs). AIM: To analyse the cost of celecoxib (selective cyclo-oxygenase-2 inhibitor) and conventional NSAID regimens for the treatment of osteoarthritis and rheumatoid arthritis from the perspective of a public health organization in Hong Kong. METHODS: A decision tree was used to analyse the cost of celecoxib, NSAID alone, NSAID plus histamine2-receptor antagonist, NSAID plus misoprostol and NSAID plus proton pump inhibitor over 6 months. Model outcomes were no gastrointestinal toxicity, gastrointestinal discomfort, symptomatic ulcer, anaemia with occult bleeding and serious gastrointestinal complications. The clinical probabilities were estimated from clinical trials. Resource utilization for gastrointestinal events was determined locally. Sensitivity analysis was performed. RESULTS: The 6-month costs per base-case analysis were as follows: NSAID plus histamine2-receptor antagonist, 1404 HK dollars (1 US dollar = 7.8 HK dollars); celecoxib, 1545 HK dollars; NSAID alone, 1610 HK dollars; NSAID plus misoprostol, 2213 HK dollars; NSAID plus proton pump inhibitor, 2857 HK dollars. The model was sensitive to the patients' underlying gastrointestinal risk scores, daily cost of NSAID regimen, risk ratio of NSAID plus histamine2-receptor antagonist for symptomatic ulcer, daily cost of celecoxib and daily cost of histamine2-receptor antagonist. CONCLUSIONS: Celecoxib appeared to be the least costly alternative in patients with intermediate to high gastrointestinal risk for the treatment of osteoarthritis and rheumatoid arthritis in Hong Kong.
14524403 Diagnostic approach to polyarticular joint pain. 2003 Sep 15 Identifying the cause of polyarticular joint pain can be difficult because of the extensive differential diagnosis. A thorough history and a complete physical examination are essential. Six clinical factors are helpful in narrowing the possible causes: disease chronology, inflammation, distribution, extra-articular manifestations, disease course, and patient demographics. Patients with an inflammatory arthritis are more likely to have palpable synovitis and morning stiffness; if the condition is severe, they may have fever, weight loss, and fatigue. Viral infections, crystal-induced arthritis, and serum sickness reactions are common causes of acute, self-limited polyarthritis. Because chronic arthritides may present abruptly, they need to be considered in patients who present with acute polyarticular joint pain. Joint palpation can help to distinguish inflammatory synovitis from the bony hypertrophy and crepitus that typically occur with osteoarthritis. Extra-articular manifestations of rheumatologic disease may be helpful in arriving at a more specific diagnosis. Many classic rheumatologic laboratory tests are nonspecific. A complete blood count, urinalysis, and a metabolic panel may provide more useful diagnostic clues. Plain-film radiographs may demonstrate classic findings of specific rheumatologic diseases; however, radiographs can be normal or only show nonspecific changes early in the disease process.
12595629 Hydroxypyridinium collagen crosslinks in serum, urine, synovial fluid and synovial tissue 2003 Feb OBJECTIVE: To investigate the relationship between inflammation markers and content of pyridinium crosslinks in hydrolysates of synovial tissue and to specify the significance of urinary excreted pyridinoline, released primarily from collagen I and II of bone and cartilage, and deoxypyridinoline released especially from collagen I of bone and dentin, dependent on disease activity in rheumatoid arthritis (RA). METHODS: Synovial tissue and fluid from knee endoprosthesis surgery, as well as simultaneously obtained serum and urine, were collected from 12 patients with inactive RA or RA with low disease activity [iRA: C-reactive protein (CRP) <28 mg/l], 10 with active RA (aRA: CRP > or =28 mg/l) and 21 with OA. After preparation of the synovial tissue, including hydrolysis, completely released synovial pyridinoline and deoxypyridinoline crosslinks as well as those from synovial fluid, serum and urine were investigated using a gradient ion-paired reversed-phase HPLC method. Crosslink levels in synovial tissue are expressed as mol/mol collagen, assuming 300 residues of hydroxyproline per collagen molecule, also measured by HPLC. RESULTS: In the synovial tissue of aRA patients we found significantly elevated total pyridinoline concentrations and pyridinoline/deoxypyridinoline (Pyr/Dpyr) quotients compared with the iRA and OA controls, indicating an elevated crosslinking density of mature synovial tissue collagen with increased activity of RA. Pyridinoline levels and the Pyr/Dpyr ratio were correlated with those of urine and with acute-phase reactants in RA patients. Compared with serum crosslink levels, which were unrelated to disease activity, the urinary concentration of pyridinoline was increased by a factor of 2 and showed a simultaneous increase with increasing synovitis. CONCLUSION: Both crosslinking density and degradation of mature collagen from synovial tissue depend on the disease activity in RA. Urinary excretion of associated crosslinks, expressed as the Pyr/Dpyr ratio, correlates with those in synovial tissue and may be confirmed as a marker of synovial tissue collagen degradation. We suggest that increased crosslinking of mature collagen in the synovial tissue of RA is related to an inflammation-dependent regulation of collagen synthesis in activated synovial fibroblasts, in which lysyl oxidase represents the final enzymatic step for crosslinking.
11985485 Infliximab: an updated review of its use in Crohn's disease and rheumatoid arthritis. 2002 Infliximab is a chimeric monoclonal antibody that binds to tumour necrosis factor-alpha (TNFalpha) and neutralises its effects. TNFalpha plays an important role in the development of both Crohn's disease and rheumatoid arthritis. In a large, double-blind, randomised study involving patients with active, refractory Crohn's disease, significantly more recipients of intravenous infliximab, compared with placebo, achieved a clinical response after 4 weeks' follow-up. Moreover, infliximab administration was associated with a rapid improvement in endoscopic and histological findings in clinical trials involving patients with active, refractory Crohn's disease. The results of the A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-Term Treatment Regimen (ACCENT) I study showed that maintenance infliximab therapy prolonged response and remission in patients with moderate to severe Crohn's disease. In patients with enterocutaneous fistulae associated with Crohn's disease who were involved in a double-blind, randomised study, significantly more patients who received multiple infusions of infliximab, compared with placebo, experienced a > or=50% reduction from baseline in the number of draining fistulae at > or =2 consecutive study visits. In patients with active rheumatoid arthritis refractory to treatment with methotrexate who were enrolled in a large, double-blind, randomised study [the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) study], American College of Rheumatology (ACR) 20, 50 and 70% response rates were seen in significantly more patients who received multiple infusions of infliximab plus methotrexate, compared with methotrexate plus placebo, after 30 and 54 weeks' treatment. Moreover, the ACR 20% response rate was maintained after 102 weeks' treatment. In addition, significantly less radiographic progression was seen in infliximab plus methotrexate, compared with methotrexate plus placebo, recipients after 54 weeks' treatment. Infliximab therapy was also associated with improvements in health-related quality of life in patients with Crohn's disease or rheumatoid arthritis. Infliximab was generally well tolerated in clinical trials with the most common adverse events including upper respiratory tract infection, headache, nausea, coughing, sinusitis and diarrhoea. Infliximab therapy may be associated with an increased risk of reactivation of tuberculosis in patients with latent disease. In conclusion, infliximab is an important treatment option in patients with active Crohn's disease who have not responded to conventional therapy and in patients with Crohn's disease who have fistulae. Moreover, infliximab plus methotrexate is effective in patients with active rheumatoid arthritis who have not responded adequately to traditional disease-modifying antirheumatic drugs, in terms of reducing symptoms and signs, improving physical function and delaying the progression of structural damage.
15636315 Biologics in rheumatoid arthritis. 2004 Mar Rheumatoid arthritis (RA) is a chronic progressive disease of the joints associated with significant morbidity, deformity, and impaired quality of life. A satisfactory remission of disease is seldom achieved, so therapy is aimed at controlling joint damage and pain with preservation of joint mobility. Until recently, NSAIDs, followed by DMARDs, was considered the treatment of choice. However, many patients fail to gain a satisfactory response to DMARDs or response declines over time. Biologics such as IL-1 receptor antagonist (anakinra), and anti TNF-alpha agents (Etanercept, Infliximab, and Adalimumab) are now available. The anti TNF and IL-1 therapies exert their anti-inflammatory action by neutralizing the activities of TNF-alpha and IL-1 respectively. In contrast to older DMARDs, these agents have rapid onset of action with fewer side effects and have pronounced disease reducing activity in patients who have previously been treated with other DMARDs, when administered as monotherapy or in combination with methotrexate. They have been shown to be at least as effective as methotrexate in reducing clinical disease activity and reducing radiographic progression. Biological agents are generally well tolerated, although their long-term safety needs to be determined. Some concerns have been raised that anti TNF-alpha therapy can increase the risk of serious infections, since TNF-alpha plays an important role in host defense. In light of limitations of cost and lack of long-term safety and efficacy data, newer agents for the time being are used as second- or third-line agents in patients with active RA. The dilemma is that which patients with RA are most suitable for such therapy, since it is still not possible to accurately predict which patient with RA will develop severe disease. One alternative approach may be to limit the use in patients who can afford it, and who are at high risk of radiographic progression and disability.
15334459 Induction of remission of severe and refractory rheumatoid arthritis by allogeneic mixed c 2004 Aug This report describes the first allogeneic hematopoietic stem cell transplantation (HSCT) performed for the indication of rheumatoid arthritis (RA). We used nonmyeloablative allogeneic HSCT to treat a 52-year-old woman who had treatment-refractory RA and a poor prognosis (24 swollen and 38 involved joints). She was treated with fludarabine, cyclophosphamide, CAMPATH-1H, and CD34-selected HSCT (8 million CD34+ donor cells/kg); the donor was the patient's HLA-matched, rheumatoid factor-negative sister. One year post-HSCT, the patient has had no infection except dermatomal varicella-zoster virus infection and no acute or chronic graft-versus-host disease (GVHD). Her RA has remained in remission with no immunosuppressive or immunomodulatory medications. The patient is a mixed chimera, with 55% donor T (CD3+) cells and 70% donor myeloid (CD33+) cells. This is the first published report of allogeneic HSCT performed for the indication of RA. Mixed chimerism has resulted in marked amelioration of RA, without GVHD.