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

ID PMID Title PublicationDate abstract
12209509 Influence of epitopes CD44v3 and CD44v6 in the invasive behavior of fibroblast-like synovi 2002 Aug OBJECTIVE: To investigate the functional implications of CD44 splice variant expression in fibroblast-like synoviocytes (FLS) obtained from patients with rheumatoid arthritis (RA). METHODS: FLS were isolated from synovial tissue obtained from both diseased and nondiseased joints. The expression of splice variants containing exons v3 and v6 was analyzed using immunocytochemistry with exon-specific antibodies and reverse transcription-polymerase chain reaction followed by Southern blotting. The invasive capacity of the cells was studied in a transwell invasion assay. RESULTS: FLS obtained from RA joints expressed various CD44 splicing combinations containing the variant exons v3 and/or v6. These cells were highly invasive, whereas cells from normal tissues, which lacked expression of CD44 splice variants, were not. Variant exons CD44v3 and CD44v6 were instrumental in matrix invasion in vitro, with cells enriched for CD44v3 and v6 exhibiting greater invasion and antibodies that specifically recognize CD44v3 and v6 abrogating this capacity to invade. Invasive cells showed a reduced expression of CD44v7/8, and antibodies against this epitope had no significant effect on cellular infiltration of the matrix. The antibodies had no effect on cell migration into the porous section of the transwell. CONCLUSION: FLS obtained from patients with RA express CD44 splice variants and are highly invasive, whereas cells obtained from healthy tissue do not express these variants and are not invasive. Expression of the epitopes CD44v3 and CD44v6 is instrumental in the invasive capacity but not in cell migration. This finding highlights a functional implication for the expression of CD44 splice variants at the level of matrix degradation.
15146441 Skin reaction to adalimumab. 2004 May The tumor necrosis factor alpha (TNFalpha) inhibitors etanercept and infliximab have shown good clinical results in the treatment of rheumatoid arthritis and other autoimmune disorders. With these novel fusion proteins, immune-mediated side effects, among them various cutaneous reactions, have been encountered. We report herein the case of an erythema multiforme-like skin reaction to treatment with the monoclonal anti-TNFalpha antibody adalimumab in a patient with rheumatoid arthritis. The reaction occurred after the sixth injection and affected the palms and soles as well as the injection site. Discontinuation of the adalimumab therapy resulted in rapid improvement of the condition. Although this patient was receiving concomitant immunomodulatory therapy with methotrexate and leflunomide, these medications were not discontinued when the reaction developed, and no other potential pathogenetic mechanisms were identified. We believe the reaction is most likely attributable to adalimumab.
12510362 [Efficacy of leflunomide]. 2002 Dec Leflunomide(Arava) is a novel immunomodulatory drug, the primary action of which is inhibition of de-novo pyrimidine synthesis by selective inhibition of dihydro-orotate dehydrogenase. It has been shown that leflunomide is effective in treating active rheumatoid arthritis(RA) in a placebo-controlled phase II study. Subsequent multinational, randomized, controlled phase III clinical trials demonstrated that leflunomide is as effective and safe as methotrexate and sulfasalazine in treatment of RA. Frequently reported adverse effects included diarrhea, nausea and vomiting, skin rash, reversible alopecia, and transient lever enzyme elevations. However, accumulating concerns about its toxic effects, especially hepatotoxicity, have been raised recently. In addition, rheumatologists should be aware that leflunomide has a much longer half life than any other disease modifying antirheumatic drug.
12109312 [Fatal miliary tuberculosis during treatment with infliximab]. 2002 Jun 22 A 73-year-old woman was admitted to hospital with fever whilst under treatment with infliximab for rheumatoid arthritis. Despite repeated and specific testing, tuberculosis was only diagnosed post mortem. During infliximab therapy, latent tuberculosis can reactivate in subacute form with a possible fatal outcome. For infliximab therapy to be administered safely, the risk that the patient concerned is latently infected with tuberculosis has to be estimated beforehand; if necessary a prophylactic anti-tuberculosis treatment may be given.
12410699 Clinical and histopathological spectrum of cutaneous vasculitis in rheumatoid arthritis. 2002 Nov BACKGROUND: Cutaneous manifestations are the most frequent, and often the initial feature of extra-articular involvement in patients with rheumatoid vasculitis. OBJECTIVES: The purpose of the study was to evaluate the clinical and histological spectrum of cutaneous vasculitis and the associated systemic involvement in patients with rheumatoid vasculitis. METHODS: Among 525 patients with rheumatoid arthritis, 20 tissue specimens with histologically proven cutaneous necrotizing vasculitis from 11 patients were investigated by studying the types and levels of affected vessels and related clinical features. RESULTS: Small-vessel vasculitis identified as dermal necrotizing venulitis was found in 10 patients, clinically characterized by palpable purpura, maculopapular erythema, erythema elevatum diutinum and haemorrhagic blisters. Arteritis histologically resembling cutaneous polyarteritis nodosa, clinically characterized by subcutaneous nodules, livedo reticularis, atrophie blanche and deep ulcers was identified in four patients all with systemic complications. Coexistence of venulitis and arteritis was identified in three patients. Different cutaneous vasculitic manifestations often coexisted and recurred in the same patient. Three patients with systemic complications of mononeuritis multiplex (two of three), interstitial pulmonary fibrosis (two of three) and abdominal microaneurysms (one of three) died within 1 year of onset of the cutaneous vasculitis. Immunofluorescence demonstrated vessel wall deposition of IgM and/or complement in six of the seven patients examined. CONCLUSIONS: Features of cutaneous rheumatoid vasculitis overlapping both the characteristics of cutaneous necrotizing venulitis and cutaneous polyarteritis nodosa together with coexistence of these different type of vasculitis in the same or different lesional skin account for the associated diverse cutaneous vasculitic manifestations. Although dermal venulitis (leucocytoclastic vasculitis) was the most common presentation, the presence of leucocytoclastic vasculitis in rheumatoid patients did not necessarily indicate a favourable prognosis. Associations with mononeuritis multiplex and bowel involvement had a fatal prognosis, while patients with superficial dermal venulitis without other extra-articular involvement may follow a favourable prognosis.
15767955 [Respiratory complications of new treatments for rheumatoid arthritis]. 2004 Dec INTRODUCTION: Treatment of rheumatoid arthritis (RA) has changed with the release of more efficient disease-modifying anti-inflammatory drugs (DMARDs) and biologicals, such as methotrexate, leflunomide and TNF blockers, respectively. However they are prone to trigger potential pulmonary side effects. STATE OF KNOWLEDGES: Diffuse interstitial pneumonitis with alveolar lymphocytosis are induced by methotrexate. This drug increases also the risk of opportunistic infections (Pneumocyctis carinii) and of delayed lymphomas. Many intracellular bacterial infections, about 80 cases of diffuse pneumonitis, and rare vasculitis are attributable to leflunomide. PERSPECTIVES: The TNF blocking agents (infliximab, etanercept and adalimumab) trigger immunization and consequently, rare type I and III hypersensitivity pneumonitis, serological lupus-like reactions usually without any clinical manifestations. Indeed the risk of infection with intracellular agents remains the first concern. Several hundreds of cases of pulmonary and non pulmonary tuberculosis (TB) have been described. They present as disseminated forms, with pulmonary manifestations present in half cases; of note, other sites are atypical, namely meningitis, lymph node, and digestive involvement. Pathological diagnosis can be difficult since granulomas are sparse or absent. Therefore TB can be lethal because of delayed diagnosis and treatment. CONCLUSION: To prevent this major risk when using TNF blockers, the French agency AFFSAPS recommends to screen and treat susceptible patients such as latent tuberculosis. Specifically, antituberculous drugs have to be started three weeks before anti-TNF agents. During biological therapy, physicians must regularly look for usual and unusual symptoms of TB. When TB is diagnosed, anti -TNF agents have to be discontinued, probably definitively, and appropriate antituberculosis treatment started in order to achieve an uneventful course.
15361394 Immune activation in the small intestine in patients with rheumatoid arthritis. 2004 Oct OBJECTIVES: To determine whether inflammation in the gut associated immune system is activated in rheumatoid arthritis (RA). The expression of chemokine receptor- (CCR4, CCR5) and cytokine- (interleukin (IL)2, IL10, interferon gamma (IFNgamma), tumour necrosis factor alpha (TNFalpha), and transforming growth factor beta (TGFbeta)) specific mRNA in intestinal biopsy samples from patients with RA was examined. METHODS: Duodenal biopsy samples from 13 patients with RA and 15 control subjects were studied. The mRNA expression of CCR4, CCR5, IL2, IL10, IFNgamma, TNFalpha, and TGFbeta in intestinal biopsy samples was demonstrated by real time quantitative reverse transcriptase-polymerase chain reaction. RESULTS: The mRNA expression of CCR4, CCR5, and IL10 in intestinal biopsy samples was increased in patients with RA in comparison with control subjects (p = 0.001, p = 0.046, p = 0.019). No difference in the expression levels of IL2, IFNgamma, TNFalpha, or TGFbeta was seen between patients with RA and controls. CONCLUSIONS: The increased intestinal mRNA expression of IL10, CCR5, and CCR4 suggests that gut associated immune cells are activated in patients with RA.
14673984 Efficacy and safety of tacrolimus in patients with rheumatoid arthritis: a double-blind tr 2003 Dec OBJECTIVE: To evaluate the efficacy and safety of tacrolimus as monotherapy in controlling the signs and symptoms of patients with rheumatoid arthritis (RA). METHODS: This was a 6-month, phase III, double-blind, multicenter study. Patients with active RA who had discontinued all disease-modifying antirheumatic drugs (DMARDs) for an appropriate washout period (at least 1 month) and who, after the washout period, had a stable joint count (at least 10 tender/painful joints and 7 swollen joints) were stratified according to DMARD intolerance or DMARD resistance, and randomized to receive a single daily oral dose of placebo, tacrolimus 2 mg, or tacrolimus 3 mg. RESULTS: A total of 464 patients received at least 1 dose of study drug. Baseline characteristics were similar among the 3 treatment groups. American College of Rheumatology 20% improvement (ACR20) success (defined as completion of 6 months of treatment and an ACR20 response at the month 6 visit) for the placebo, tacrolimus 2 mg, and tacrolimus 3 mg groups was 10.2%, 18.8% (P < 0.05 versus placebo), and 26.8% (P < 0.0005 versus placebo), respectively. At the end of treatment, the ACR20 and ACR50 response rates in the 3-mg group were 32.0% (P < 0.005 versus placebo) and 11.8% (P < 0.05 versus placebo), respectively. DMARD-intolerant patients had better ACR response rates than did DMARD-resistant patients. Although serum creatinine levels increased by >/=40% from baseline at some time during the trial in 20% and 29% of patients receiving tacrolimus 2 mg/day and 3 mg/day, respectively, the serum creatinine level remained within the normal range throughout the trial in approximately 90% of patients. CONCLUSION: Tacrolimus, at dosages of both 2 mg/day and 3 mg/day, is efficacious and safe as monotherapy for patients with active RA, but treatment with the 3-mg dose of tacrolimus resulted in generally better ACR response rates.
12944013 The sensitivity and specificity of Brucella agglutination tests. 2003 Aug Brucellosis is a systemic infectious disease caused by Gram-negative bacilli, the genus Brucella, and clinical features are diverse. Therefore, several infectious and non-infectious diseases are considered in its differential diagnosis. In this study, we aimed to determine the positivity rate of Brucella agglutination tests in the culture-positive brucellosis and in diseases mimicking brucellosis clinically.Thirty patients with culture-positive brucellosis, and 280 patients with the diseases mimicking brucellosis clinically (20 with miliary tuberculosis, 33 with malaria, 20 with typhoid fever, 20 with adult-onset Still's disease, 47 with systemic lupus erythematosus, 50 with rheumatoid arthritis, 27 with sarcoidosis, and 63 with active lymphoma) were included in the study. Brucella agglutination tests (Rose-Bengal and Wright) were studied in serum samples of these 310 patients. Both Rose-Bengal and Wright tests (the latter in a titer of 1/160 or higher) were positive in all patients with brucellosis. For the other diseases, the test was slightly positive (1/40) in one patient with malaria and another with non-Hodgkin's lymphoma, and weakly positive (1/20) in a patient with typhoid fever. It remained negative in the remaining. In conclusion, agglutination tests currently used in the diagnosis of brucellosis are very sensitive and specific. Brucellosis can be effectively excluded from the diseases having similar clinical features by the use of agglutination tests.
12594113 Does yttrium radiosynovectomy increase the risk of cancer in patients with rheumatoid arth 2003 Mar OBJECTIVE: To study the long term risk of cancer in patients with rheumatoid arthritis (RA) who have been treated with yttrium. METHODS: The medical record numbers of 1228 patients with RA who were admitted to hospital in 1979-85 were identified in the database of Jyväskylä Central Hospital. Radiosynovectomy of the knee joint was performed in a total of 143 patients using yttrium-90 silicate during the years 1970-85, while 1075 did not receive yttrium radiosynovectomy; 10 received yttrium treatment later than 1985 and were excluded from the analysis. The Finnish Cancer Registry database was used to examine whether the subjects had cancer during the follow up from 1979 until the end of 1999. RESULTS: Nine cases of cancer were found among the patients who had received yttrium, whereas the expected number based on the incidence among the population in the region was 14.9. The standardised incidence ratio of cancer was 0.6 (95% confidence interval (CI) 0.3 to 1.1) for the patients who received yttrium, and 1.1 (95% CI 0.9 to 1.3) for the patients who did not receive yttrium. CONCLUSIONS: Yttrium treatment did not increase the risk of cancer.
11956978 Carpal tunnel syndrome grading system in rheumatoid arthritis. 2002 The grading system of Hashizume and Hirooka for carpal tunnel syndrome (CTS) was modified to refine the system for surgical treatment selection for specific subsets of CTS in patients with rheumatoid arthritis (RA). The grading system uses clinical signs and symptoms of CTS, including pain indications, to identify surgical subsets of patients to facilitate treatment selection. Retrospective analysis of the system included radiographic and electromyographic findings. Twenty-nine hands of 21 adult patients with CTS in RA were graded in the current study. Eight hands with mild synovitis received conservative treatment only. Endoscopic carpal tunnel release (ECTR), using Okutsu's universal subcutaneous endoscopic system with a clear cannula, was performed in 11 hands with moderate synovitis. Open carpal tunnel release (OCTR) combined with flexor tenosynovectomy was performed in 9 hands with severe synovitis. One more hand required OCTR after ECTR when malignant RA was diagnosed. Clinical results, evaluated using Kelly's criteria, were: excellent in 19 hands, good in 5, fair in 4, and poor in the 1 patient with malignant RA. Clinical symptoms of CTS improved in all but the latter patient. Although the sample size in the current study is small, the results appear to warrant further study to determine the clinical utility of the grading system.
15225361 Role of RUNX in autoimmune diseases linking rheumatoid arthritis, psoriasis and lupus. 2004 Recent studies investigating the genetic susceptibility of systemic lupus erythematosus, rheumatoid arthritis and psoriasis have revealed a potential role for the RUNX proteins in the development of autoimmune disease. A new pathway of disease pathogenesis opens new avenues of research with thousands of questions that remain to be answered. In this review I attempt to propose how the RUNX proteins might be involved in these diseases and review current knowledge on this very interesting trio of transcription factors that was previously only suspected to be involved in cancer.
14662397 Transgenic animals in inflammatory disease models. 2003 Dec Inflammatory diseases affect a significant portion of the population worldwide and have been intensely studied for several decades. The advent of transgenic technology has allowed researchers to study individual gene contributions to the pathogenesis of these diseases. This has been done using standard inflammatory disease models in transgenic animals and by identifying novel models through the spontaneous generation of disease in the transgenic animal. Recent advances have been made in the understanding of rheumatoid arthritis, pulmonary inflammation, multiple sclerosis and inflammatory bowel disease through the use of transgenic animals in models of human inflammatory disease.
12138686 [Infliximab combined with methotrexate in the treatment of rheumatoid arthritis]. 2002 Jul Infliximab is a chimeric anti-tumor necrosis factor alpha (anti-TNF-alpha) monoclonal IgG1 antibody successfully used for the treatment of active rheumatoid arthritis (RA) not completely controlled with methotrexate or other disease modifying anti-rheumatic drugs. We evaluated both clinical efficacy and safety of infliximab in 63 patients with persistently active RA (Disease activity score > or = 3.7). All the patients received infliximab (3 mg/Kg) at week 0, 2, 6 and then every 5 weeks in combination with methotrexate (7.5-10 mg/week) in an open label study. At week 14th, ACR 20% response criteria have been fulfilled by 43 (91.4%) out of 47 patients, 31 (72%) of them achieving also an ACR 50% and 9 (21%) an ACR 70% response. At the time of this report 33 patients touched 22 weeks of treatment: ACR 20% response was achieved in 95%, while ACR 50% and ACR 70% were respectively found in 78% and 39% of the cases. Only 1 case of bronchopulmonary mycosis and 2 of mild urticaria were observed. The initiation of infliximab therapy in patients with active RA resulted in a rapid and sustained improvement of articular manifestations and quality of life. Even though, major adverse events were rare, clinicians should be aware of this possibility.
12715722 [Interleukin-1 receptor antagonists in the treatment rheumatoid arthritis]. 2002 Interleukin-1 (IL-1) is one of the main inflammatory mediators associated with development of rheumatoid arthritis (RA). Deficiency in secretion of the natural IL-1 antagonist was found in RA patients, and enhanced joint inflammation. This finding was confirmed by numerous studies using the animal model of the disease. Two randomized, multicenter clinical trials with anakinra, a recombinant IL-1 receptor antagonist (rHHHuIL-1Ra), revealed that application of anakinra with or without methotrexate induces remission (ACR 20) in 38-71% of patients with RA. Induction of remission was dose and treatment-time-dependent. The present paper reviews theoretical application of rHuIL-1Ra in patients with RA and summarizes results of published clinical trials of the drug.
15248211 Lymphotoxin beta-mediated stimulation of synoviocytes in rheumatoid arthritis. 2004 Jul OBJECTIVE: Lymphotoxin beta (LTbeta), a cytokine produced by T cells and B cells, plays a central role in the normal development of lymph nodes and is critical in the formation of ectopic germinal center reactions in rheumatoid synovitis. Because resident fibroblast-like synoviocytes (FLS) express receptors for LTbeta, we examined the consequences of FLS activation by LTbeta. METHODS: FLS from patients with rheumatoid arthritis were isolated and examined for the expression of LTbeta receptor. FLS were incubated with LTalpha1beta2 and assayed for the production of cytokines and chemokines and the up-regulation of adhesion molecules. RESULTS: Exposure of FLS to recombinant LTalpha1beta2 resulted in the production of multiple inflammatory cytokines and metalloproteinases, implicating FLS as amplifiers of the inflammatory process in the inflamed joint. Additionally, LTalpha1beta2 was found to up-regulate the expression of cell adhesion molecules, rendering FLS to efficient adhesion substrates for T cells. LTalpha1beta2 also induced production of the chemokines CCL2 and CCL5, which elicited transmigration activity of T cells. Upon stimulation with LTalpha1beta2, FLS did not acquire characteristics of follicular dendritic cells. CONCLUSION: These data document that FLS are involved in multiple stages of the inflammatory process, including the recruitment and retention of lymphocytes in the synovial microenvironment. We propose that the heterotypic interaction between LTbeta-producing lymphocytes and responding FLS contributes to the establishment of complex lymphoid microstructures, and that this may be one element that defines susceptibility of the synovial membrane to lymphoid organogenesis.
12100036 Defective expression and tyrosine phosphorylation of the T cell receptor zeta chain in per 2002 Jul We have reported that tyrosine phosphorylation and expression of the T cell receptor zeta chain (TCR zeta) was decreased in two systemic lupus erythematosus (SLE) patients with an abnormal TCR zeta lacking exon-7. To examine further the TCR zeta defect and any possible relationship with specific clinical features, we studied the expression of TCR zeta in peripheral blood T cells from 44 patients with SLE, 53 with other rheumatic diseases (30 rheumatoid arthritis (RA), 11 systemic sclerosis (SSc) and 12 primary Sjögren's syndrome(SjS)) and 39 healthy individuals. Flow cytometric analysis demonstrated a significant decrease in the expression of TCR zeta in SLE (P < 0.001), but not in the other rheumatic diseases. Immunoprecipitation experiments confirmed that the expression of TCR zeta in SLE T cells was decreased dramatically (normal: 111.4 +/- 22.6%, SLE: 51.6 +/- 37.4%, P < 0.0001). The decrease in TCR zeta did not correlate with disease activity, or with the dose of prednisolone (PSL). There were, however, three SLE patients in whom the level of TCR zeta expression normalized after treatment, suggesting that mechanisms responsible for the TCR zeta defect appear to be heterogeneous. These results confirm the defective expression and altered tyrosine phosphorylation of TCR zeta in a large proportion of SLE patients, suggesting that it may play an important role in T cell dysfunction in SLE.
12593126 Approach to imaging the patient with neck pain. 2003 Jan Neck pain is a common complaint of patients seeking care in the outpatient setting, and the cases seen vary widely in severity and cause. A careful history and physical exam, followed by appropriate imaging studies, are essential for the orderly work-up and management of neck pain in the ambulatory patient. Available imaging studies include plain film radiography, computed tomography (CT), magnetic resonance, and CT myelography. The general considerations necessary to select the appropriate imaging study are discussed for a broad spectrum of common disorders.
15168143 The prevalence of subclinical amyloidosis in Polish patients with rheumatoid arthritis. 2004 Jun The aims of this study were to determine the proportion of rheumatoid arthritis (RA) patients attending hospital in whom amyloid deposits were present in abdominal fat aspiration (AFA) samples, and to assess possible risk factors for amyloid development in RA. One -hundred and twenty-one patients (16 males, 105 females) with RA referred to the Department of Rheumatology in Wroclaw between 1996 and 2001 were studied regardless of RA duration or laboratory findings. Abdominal subcutaneous fine-needle aspiration was performed, and samples of adipose tissue stained with alkaline Congo red then examined by polarized light microscopy. The presence or absence of amyloid fat deposits (AFD) was determined according to whether typical apple-green birefringence was observed. Amyloid deposits were found in 35 (29%) patients. Amyloidosis was significantly more common in males and in patients with longer disease duration. Patients with AFD had previously undergone less treatment with disease-modifying antirheumatic drugs (DMARDs) than those without AFD, and significantly fewer patients with AFD had previously taken methotrexate than those without AFD (25% vs 45%; p<0.01). Renal involvement was found in 12 of 35 patients with AFD (34%). Using the AFA technique, amyloid deposits were found commonly in RA patients, particularly in males with longer disease duration and in patients not treated intensively with DMARDs, especially methotrexate. AFA has potential useful application as a method for detecting amyloidosis before the overt occurrence of renal or other pathology related to amyloid deposits.
12810434 Cortisol elimination from plasma in premenopausal women with rheumatoid arthritis. 2003 Jul OBJECTIVE: To test the hypothesis that cortisol elimination from plasma can contribute to relatively low cortisol in premenopausal women with rheumatoid arthritis (RA). METHODS: Twelve premenopausal female patients with RA (39.8 (1.8) years) and nine healthy control women matched for age and body mass index (42 (3.3) years) were enrolled in the study. None of the patients had previously been receiving treatment with glucocorticoids. After dexamethasone suppression (2 mg by mouth) the evening before the study, 20 mg of hydrocortisone was given. Blood and saliva samples were drawn six hours after injection of hydrocortisone. Plasma and salivary cortisol were measured. RESULTS: Dexamethasone administration suppressed plasma cortisol concentrations to an almost undetectable level in all subjects, except one with RA. In this subject, a raised concentration of plasma cortisol was verified by repeated analysis despite the fact that cortisol concentration in the saliva sample measured simultaneously was not raised. No significant difference in the disappearance curve of cortisol in plasma or in salivary cortisol levels was found between the patients with RA and the healthy controls. CONCLUSIONS: The profile of disappearance of total cortisol from plasma, and salivary cortisol levels during the elimination phase after its intravenous administration, are unchanged in premenopausal women with RA. Alterations in cortisol clearance are not likely to have a role in cortisol availability in patients with RA.