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

ID PMID Title PublicationDate abstract
12379525 Assessing periarticular bone mineral density in patients with early psoriatic arthritis or 2002 Nov BACKGROUND: Periarticular osteoporosis is an early finding in the hands of patients with rheumatoid arthritis (RA), due to release of bone resorbing cytokines from the inflamed synovium. There has been disagreement as to whether periarticular bone loss occurs in psoriatic arthritis (PsA). Bone mineral density (BMD) can now be measured accurately using dual energy x ray absorptiometry (DEXA). Recently, DEXA has been used to measure periarticular BMD at predefined regions of interest (ROIs) around the joints. OBJECTIVES: Firstly, to compare periarticular BMD around the finger joints of patients with early RA or PsA. Secondly, to determine whether periarticular bone loss is related to joint inflammation and radiological erosions in RA and PsA. METHODS: Seventeen patients with RA and 15 with PsA were recruited, all with disease duration of less than five years. All finger joints were examined by one person for swelling, or tenderness, or both. Hand radiographs were scored for the presence of erosions. Periarticular BMD was measured at 10 predetermined ROIs using a Hologic QDA-4500A fan-beam densitometer. RESULTS: Patients with PsA were less likely to be positive for rheumatoid factor (RF) (13% v 94%) and more likely to be men (60% v 23%) than patients with RA. There were no other clinical differences between patients with RA or PsA. Patients with RA had significantly lower BMD at each of the ROIs than those with PsA (p<0.05). However, these differences disappeared after adjusting for age and sex. Among patients with RA, those with a higher total number of swollen and/or tender hand joints had significantly lower periarticular BMD at the metocarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. No such association was found for patients with PsA. CONCLUSIONS: In early disease, periarticular bone loss occurred both in patients with RA and those with PsA. Among patients with RA, periarticular osteoporosis was related to measures of joint inflammation. There was no association between joint inflammation and periarticular bone loss in patients with PsA, which lends support to the hypothesis that the primary site of inflammation in PsA is extrasynovial.
15530456 Autoantibodies to citrullinated proteins in rheumatoid arthritis: clinical performance and 2004 Dec Rheumatoid arthritis (RA) is a common, systemic autoimmune disease of which the exact etiology is not known. In the past 10 years, substantial progress has been made in the identification of the antigens specifically recognized by the autoantibodies of RA patients. A central factor in this respect is citrullination, a form of post-translational modification that is strongly associated with autoimmunity in RA. Here, we summarize and discuss our current knowledge on (i) autoantibody systems in RA, (ii) the occurrence of peptidylarginine deiminases and (iii) citrullinated proteins in natural and diseased environments, and (iv) genetic factors involved in RA that may influence the generation and presentation of citrullinated proteins and the resulting antibody production against these modified proteins. Citrullination of proteins may play a key role in the initiation and/or the progression of RA. The onset of citrulline-specific autoimmunity in RA is probably mediated by both environmental and genetic factors, and future studies will learn whether therapeutic intervention at the level of citrullination may provide new possibilities to treat RA.
15124244 Glucocorticoids and insulin sensitivity in rheumatoid arthritis. 2004 May OBJECTIVE: To evaluate the effects of glucocorticoids on cardiovascular (CV) risk in rheumatoid arthritis (RA). METHODS: We recorded demographic, clinical, disease outcome, and treatment variables in 92 consecutive RA patients who were not taking lipid-lowering or antidiabetic medications. Fasting blood tests were taken for determination of lipids, ultra sensitive C-reactive protein (CRP), rheumatoid factor, insulin, and glucose. Insulin sensitivity was determined using the Quantitative Insulin Sensitivity Check Index (QUICKI). RESULTS: Seventy-four (80%) patients were women, 80 Caucasian, 9 Asian, 2 of mixed ancestry and 1 Black. Their mean (95% confidence interval, CI) age, disease duration, and followup duration at our clinic were 56 (54-58), 11 (9-13) and 6 (5-6) years, respectively. Thirty-seven (40%) patients had received oral prednisone [cumulative dose 4.8 (2.0-8.5) g; duration one month to 20 years], and all patients had received pulsed (intraarticular, intramuscular, and/or intravenous) methylprednisolone [cumulative dose 2.0 (1.6-2.6) g]. Glucocorticoids were not associated with obesity, hypertension, or dyslipidemia. Having taken prednisone and high yearly frequencies of pulsed glucocorticoid administrations were associated with decreased insulin sensitivity (p < 0.05). After controlling for body mass index, ever having taken prednisone and high doses of pulsed glucocorticoids were independently associated with decreased insulin sensitivity (p < 0.05). CONCLUSION: Previous exposure to oral prednisone and high doses of pulsed glucocorticoids were associated with decreased insulin sensitivity in RA. Since decreased insulin sensitivity is an independent risk factor for CV disease, glucocorticoids may contribute to the excess CV event rates in RA.
14618371 Carpal instability in rheumatoid wrists. 2004 Jan This study was conducted to identify patterns of carpal instability in the rheumatoid wrist. One hundred patients with proven rheumatoid arthritis were randomly chosen, and posteroanterior and lateral radiographs of right wrists were taken. The most common isolated pattern was volar intercalated segmental instability, apparent in 16 wrists, while nine wrists had scapholunate dissociations. Larsen grading scores revealed a correlation between disease duration, carpal height ratio, and ulnar translocation index. In the early stages of disease, the scapholunate angle was significantly increased and the lunate rotated volarly due to loosening of the intrinsic carpal ligament. In later phases, the capitolunate angle significantly increased and the capitate rotated dorsally. Patterns of carpal instability in rheumatoid wrists seem to be complicated, involving combined laxity of the intrinsic and extrinsic carpal ligaments.
15526509 Correlation between the immunophenotypical presentation of dendritic cells and the clinica 2003 BACKGROUND: Dendritic cells (DCs) are potent antigen-presenting cells (APC) that are deeply implicated in the initiation and exacerbation of rheumatoid arthritis (RA). Active RA is associated with an activated DCs population as demonstrated by high expression of adhesion and co-stimulatory molecules. PURPOSE: To compare the expression of adhesion and co-stimulatory molecules on DCs from synovial tissue (ST) in patients (pts) with RA and the clinical status before and after treatment with disease modifying antirheumatic drugs (DMARDs). METHODS: Samples of ST were obtained from RA patients at the time of hip or knee replacement or arthroscopy. Clinical status (assessed by the American College of Rheumatology - ACR - core set and the DAS28) and co-stimulatory and adhesion molecules on DCs were evaluated before and after treatment. Immunophenotype of DCs was analyzed by two-color immunofluorescence microscopy. RESULTS: In patients with active RA we found a highly differentiated subpopulation of DCs that expressed an activated phenotype. After treatment, the expression of adhesion and co-stimulatory molecules on ST DCs was correlated with the ACR and DAS28 clinical response. CONCLUSION: Clinical outcome and the immunophenotypical presentation of ST DCs after DMARDs treatment are closely correlated in pts with RA. The co-stimulatory activity in the synovium is important in determining the course of the disease and provide new therapeutic targets for immune intervention.
15338447 Relationship between high-resolution computed tomography findings and the Stoke index in p 2005 Feb The aim of this study was to evaluate the relationship between high-resolution computed tomography (HRCT) findings and the Stoke index (SI) in patients with rheumatoid arthritis (RA). Forty RA patients (31 women, 9 men) were evaluated. All patients fulfilled the criteria proposed by the American College of Rheumatology. Clinical evaluation, haematological data, chest radiography, pulmonary function tests (PFTs) and HRCT were obtained in all patients. The SI was used to assess disease activity. In 17 (42.5%) patients, there were no signs of pulmonary involvement on HRCT; 23 (57.5%) of 40 patients had abnormal HRCT findings. Of 23 patients with HRCT abnormalities, six (two male, four female) had respiratory symptoms, four (one male, three female) had abnormalities on chest radiography and five (all female) had abnormalities on PFTs. There was no relationship between pulmonary changes observed on HRCT, clinical and laboratory disease activity parameters, chest X-ray and PFTs. There was no difference in the mean SI between patients included in the HRCT (+) and those included in the HRCT (-) groups. No significant correlations between the HRCT and the SI were seen. The main findings of this study are that HRCT can give useful information on RA-associated lung changes and that there was no relationship between the SI and the HRCT findings of patients with RA.
11779757 Screening for amyloid in subcutaneous fat tissue of Egyptian patients with rheumatoid arth 2002 Jan OBJECTIVE: To screen for amyloid and to assess associated clinical and laboratory characteristics in Egyptian patients with rheumatoid arthritis (RA). METHODS: Abdominal subcutaneous fat aspirates were consecutively collected from 112 patients (103 women, nine men) having RA for five years or more. To detect amyloid, fat smears were stained with Congo red and the concentration of amyloid A protein in fat tissue was measured. Clinical, radiological, and laboratory characteristics of the patients were assessed. RESULTS: Amyloid was detected in eight (7%) of the fat smears stained with Congo red. Compared with the Congo red stain, the sensitivity for detecting amyloid by measurement of amyloid A protein in fat tissue was 75% and the specificity was 100%. The amount of amyloid found was small for both methods. The median disease duration of the eight amyloid patients was significantly longer (17 years) than that of the non-amyloid patients (10 years). Bronchopulmonary disease and constipation were more common, whereas proteinuria and chronic renal insufficiency were not. The number of swollen joints and the number of red blood cells were significantly lower in the amyloid group. CONCLUSIONS: Quantification of amyloid A protein and staining with Congo red are strongly concordant methods of screening for amyloid in fat tissue. The prevalence of amyloid in Egyptian patients with RA is 7%. Proteinuria is not a discriminating feature, whereas long disease duration, constipation, bronchopulmonary symptoms, and a moderate to low number of red blood cells may help to identify the arthritic patients with amyloid.
15230129 [Persistence of various infective agents in blood mononuclear leukocytes in a debut of rhe 2004 AIM: To study persistence in blood mononuclear leukocytes (ML) of Herpesviridae viruses (cytomegalovirus-CMV, herpes virus of type I and II, Epstein-Barr virus-EBV, hepatitis B and C viruses, Mycoplasma arthritidis-Ma,, Mycoplasma fermentans-Mf, Ureaplasma urealiticum-U, Chlamydia trachomatis-Ct). MATERIAL AND METHODS: 56 patients with debut of rheumatoid arthritis (RA) and 30 healthy persons were examined using methods of direct and indirect immunofluorescence, polymerase chain reaction and enzyme immunoassay. RESULTS: In patients with early RA persistence of infective agents in blood ML was found high (67.9%). Persistence of the viruses was studied for 1.5-2 years. Features of the clinical course of the disease were specified for various infective agents: seronegativeness in persistence of Ma, Mf and U, high activity and frequent development of systemic manifestations of RA in persistence of Herpesviridae viruses, rapid progression of bone destruction in persistence of Ct. CONCLUSION: Carriage of Herpesviridae was associated with high activity of inflammatory process, of chlamydia--with rapid bone destruction, of mycoplsma and ureaplasma--with unchanged rate of progression. Eradication of Herpes viruses, CMV, EBV and CT is indicated.
15172050 Interleukin-18 and the treatment of rheumatoid arthritis. 2004 May Interleukin (IL)-18 is a new member of the IL-1 family of proinflammatory cytokines. Based on preclinical studies in animals, IL-18 likely plays a role in rheumatoid arthritis, and strategies to block IL-18 activity are underway in clinical trials. In one of these trials,a naturally occurring IL-18 binding protein (IL-18 BP) binds IL-18 with a high affinity and reduces disease severity in models of inflammatory diseases. IL-18 BP is not the soluble receptor for IL-18 but rather a distinct molecule, which appears to be distantly related to the IL-1 receptor type II, both structurally and functionally, and hence represents part of the IL-1 family of receptors.
12480661 Will pharmacogenetics allow better prediction of methotrexate toxicity and efficacy in pat 2003 Jan Methotrexate (MTX) remains the most commonly used disease modifying antirheumatic drug in rheumatoid arthritis (RA) because of its cost and experience in its use, despite the availability of new treatments such as leflunomide and the biological agents. However, a significant number of patients with RA either do not benefit from the drug or are unable to tolerate it. Pharmacogenetic approaches may help optimise treatment with MTX, and also other agents, in RA.
12486477 Periodontoid pannus migration into the spinal canal with reduction of rheumatoid atlantoax 2002 We report a patient with rheumatoid arthritis in whom periodontoid pannus migrated into the spinal canal with reduction of atlantoaxial subluxation. In this case, magnetic resonance imaging in the extension position was valuable for determining the therapeutic strategy.
15768999 [The simultaneous measurements of time-dependent laser-induced fluorescence intensity of h 2004 Feb Since the selectivity of photodynamic therapy (PDT) depends on the distribution of a photosensitizer in a tissue during the treatment, an investigation of drug distribution is a key step for performing PDT effectively. The distribution of photosensitizer absorbed in tissues is adjusted by the animal body system, so an apparatus that can measure the fluorescence intensity of photosensitizer in different tissues of the same body simultaneously is in demand. To achieve precise estimate of tissue selectivity of the photosensitizer, a spatially separated three-channel laser-induced fluorescence (LIF) detection system was set up and employed in the present study to measure the fluorescence intensity of Hematoporphyrin Monomethyl Ether (HMME) in different tissues of the same body simultaneously. The time-dependent variations in the concentrations of HMME within the skin,cartilage, normal synovium and inflammatory synovium of rabbit were monitored in vivo. The results obtained showed that the synovium has higher absorptivity of HMME thanthe skin and cartilage. The difference is distinct from the very beginning of injection. Although the quantity of HMME absorbed in the inflammatory synovium is not very high in the first 20 min, it is still 6 times higher than that in the skin and cartilage. In addition, the absorptivity of HMME is much stronger for the inflammatory synovium than that for the normal synovium. If thelaser beam irradiates outside the joint for the rheumatoid arthritis, tissues around the inflammatory synovium have less HMME, thereby causing weak PDT effect. This would help reduce the side effect of PDT. Thus we suggest that for PDT treated rheumatoid arthritis, taking the first 20 min after the injection for outside-the-joint excitation employing HMME maybe a good choice.
12847890 [Use of monoclonal antibodies to tumor necrosis factor (remicade) in rheumatoid arthritis: 2003 AIM: To study effectiveness and tolerance of monoclonal antibodies to tumor necrosis factor (the drug remicade) in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Remicade treatment results are considered for 25 RA patients receiving methotrexate the activity of which was inadequate for these patients. Remicade was infused intravenously in a dose 200 mg 4 times for 22 weeks. RESULTS: Remicade produced positive clinical and laboratory effects as early as the first infusion. The response was observed during 22 weeks of the treatment in 17 of 25 patients. Remicade tolerance was good. One patient failed the treatment because of development of collapse. CONCLUSION: Pilot results of remicade trial point to its high therapeutic potential and perspectives in rheumatology.
12235920 Serum interleukin 2 levels in patients with rheumatoid arthritis and correlation with insu 2002 Jul Interleukin 2 (IL-2), a Th1 lymphocyte-derived cytokine, is thought to play an important role in the pathogenesis of type 2 diabetes and rheumatoid arthritis (RA). The aim of our study was to evaluate changes in serum IL-2 levels and their correlation with glucose metabolism abnormalities, such as insulin resistance, in patients with RA. Thirty-six subjects with varying degrees of disease activity and 20 healthy age-, sex- and body mass index-matched control individuals were evaluated. Patients with any causes of peripheral insulin resistance were excluded. After a 12-h overnight fast, fasting insulin levels, homeostatic model assessment-insulin resistance (HOMA-IR) estimated insulin sensitivity, and serum IL-2 levels were significantly higher in all patients with RA than in the control individuals. Fasting insulin, HOMA-IR scores and IL-2 levels were correlated in the RA group. This study showed that patients with RA have altered IL-2 regulation, and that there was a significant correlation between serum IL-2 levels and insulin sensitivity.
12111629 Cervical spine disorders in patients with rheumatoid arthritis and amyloidosis. 2002 Jun The aim of this radiographic study was to ascertain the extent of inflammatory cervical spine disorders in patients with rheumatoid arthritis (RA) complicated by secondary amyloidosis (SA). The study involved 147 patients with RA and SA, whose cervical spine radiographs were available. They were treated at the Rheumatism Foundation Hospital, Heinola, during the period 1989-2000 and had had RA for a mean of 24 years. The inflammatory abnormalities of the cervical spine were studied from radiographs taken at or after the diagnosis of SA during flexion and extension. One-hundred and eleven (76%) patients had subluxations, impaction or apophyseal joint ankylosis. Atlantoaxial impaction (AAI) was seen in 76 (52%) patients and anterior atlantoaxial subluxation (AAS) in 59 (40%). Apophyseal joint ankylosis was the third most frequent finding, seen in 34 (23%) cases. A combination of AAI and apophyseal joint ankylosis was noted in 26 (18%) patients. Eight (5%) patients had undergone surgery on the cervical spine. In conclusion, inflammatory and destructive changes are frequent in the cervical spine of patients with RA and SA. Characteristic changes are AAI and AAS. RA patients with SA have more severe disease than those in epidemiological studies when cervical spine disorders are concerned.
11838844 Improvement in diagnosis of rheumatoid arthritis using dual indirect immunofluorescence an 2002 Feb OBJECTIVE: To determine the clinical usefulness of measuring antistratum corneum (ASC) and antifilaggrin autoantibodies (AFA) to discriminate between rheumatoid arthritis (RA) and other rheumatic or autoimmune diseases, using an indirect immunofluorescence (IIF) assay, along with a complementary immunoblotting technique (IB) when IIF detection of ASC was negative. METHODS: Sera from 346 patients were studied: 189 sera from patients with RA seen in the same clinic, 92 from patients with non-RA rheumatic diseases, 24 from nonrheumatic autoimmune diseases, and 41 from healthy blood donors. ASC and AFA were detected using IIF and IB, respectively. RESULTS: ASC detection using IIF showed a specificity of 97.5% for RA with 44.4% sensitivity. When both IIF and IB techniques were used, sensitivity for RA increased significantly (up to 53.4%; p < 0.01) with no decrease in specificity (p < 0.01). CONCLUSION: These data confirm the usefulness of 2 different techniques performed simultaneously for detecting ASC/AFA, and the usefulness of these biological markers for discriminating between RA and other rheumatic diseases in clinical practice.
12374044 [Use of cyclosporin A in patients with severe, active, treatment-resistant rheumatoid arth 2002 Jul BACKGROUND: Rheumatoid arthritis (RA) is a multisystemic and chronic disease whose etiology still remains to know. RA and their complications implicate a huge cost, calculated in 1% of total national internal product in US. OBJECTIVE: To evaluate the use of cyclosporine A in RA patients refractory to conventional treatment. MATERIAL AND METHODS: Several improvement variables were used, such as Ritchie index, modified Sharp radiological scale, functional status, HAQ index, analog scale of pain, and PCR. 13 female were included with a mean age of 44 years (range 30-50), with a mean of RA evolution of 6 years (range 0.5-22); each patient received an initial dosage of 2.5 mg/day by oral microemulsion of cyclosporine A, with increasing dosage of 0.5 mg/kg/day, adjusting by seric values of creatinine. RESULTS: RA patients were evaluated, initially and after three and six months. Data were analyzed using Mann-Whitney U and Kruskal Wallis tests. In three months evaluation there was an improvement in functional status (p = 0.009). In six months evaluation there was an improvement in painful joints (p = 0.006), functional status (p = 0.007) and general comfort sensation (p = 0.014). CONCLUSION: The cyclosporine use is considered an effective therapy, like disease modifier in RA refractory patients to conventional treatment in at least six months of the treatment.
11824966 Tumor necrosis factor-alpha gene polymorphism in severe and mild-moderate rheumatoid arthr 2002 Jan OBJECTIVE: To examine whether severe rheumatoid arthritis (RA) carries a -238 or +489 tumor necrosis factor-alpha (TNF-alpha) genotype different from mild-moderate RA. METHODS: We investigated 163 patients (66 with severe disease) and 67 healthy blood donor controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Patients with severe RA (all active disease despite disease modifying antirheumatic drug combination therapy) disclosed the -238 GG genotype in 100% of cases versus 92.8% of the mild-moderates and 92.5% of controls (OR 11.7, Cl 0.6-216, p = 0.03). The +489 AA genotype was seen less often in patients than in controls (OR 4.2. CI 0.97-18.4, p = 0.045), and the contribution to this trend appeared predominant in the anti-TNF treated subgroup. CONCLUSION: The -238 AG genotype was absent in severe RA; in contrast, patients with mild-moderate RA disclosed the same frequency as controls. Thus -238 GG homozygosity is associated with severe RA. The +489 AA genotype might instead protect against worse outcome in RA.
14969052 Autoantibodies in early arthritis: advances in diagnosis and prognostication. 2003 Sep Several excellent reviews have recently been published on the significance of autoantibodies in rheumatoid arthritis (RA) (1-4). Here we: (i) review selected longitudinal studies examining the predictive utility of autoantibodies in early arthritis and early RA cohorts; (ii) assess the relevance of autoantibodies as an independent parameter for prediction and prognostication of RA; and (iii) describe the potential of multiplex autoantibody assays, including miniaturized, high-throughput microarray technology, to improve diagnosis and prognostication in recent-onset synovitis/early arthritis patients.
12474726 [Diagnosis and treatment of rheumatoid arthritis]. 2002 The paper describes the typical clinical features of rheumatoid arthritis and principles of its treatment. It includes an overview of the universally accepted diagnostic criteria and discusses the diagnostic value of laboratory and instrumental investigations. The significance of correct diagnosis in an early stage of the disease is emphasized with regard to the difficulties related to differential diagnosis. Appropriate evaluation of the inflammatory activity of rheumatoid arthritis and of the functional state of the patient is discussed. Contemporary principles of complex and individual treatment of rheumatoid arthritis, depending on the course of disease are presented, placing special emphasis on the importance of disease--modifying treatment. Possible side effects of NSAIDs and glucocorticosteroids and methods of their prevention are discussed, as well as indications for new biological medications.