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

ID PMID Title PublicationDate abstract
15022333 Magnetic resonance imaging evaluation of the effects of juvenile rheumatoid arthritis on d 2004 Mar OBJECTIVE: To examine magnetic resonance imaging-derived T2 relaxation times in the weight-bearing cartilage of the distal femur in healthy children and in children with juvenile rheumatoid arthritis (JRA). METHODS: T2 relaxation time maps were created for 39 girls (ages 4.9-10.9 years), 21 of whom were considered healthy and 18 of whom had JRA. The spatial distribution of T2 relaxation times for the distal femoral weight-bearing cartilage (including epiphyseal and articular cartilage) was mapped for each group as a whole. Average data sets for each group were then compared using paired t-tests to detect differences between the 2 populations. RESULTS: The spatial distribution of T2 relaxation time values was nearly identical in the 2 groups, with a concave curve that was highest near the subchondral bone and articular surfaces. The average T2 relaxation times were significantly higher in the girls with JRA than in the group of healthy girls (P < 0.05). CONCLUSION: The finding of an increased average T2 relaxation time in the children with JRA suggests that T2 relaxation time maps may reflect cartilage microstructure differences that occur in JRA. T2 relaxation time mapping may allow for early detection of cartilage changes and provide an objective, quantitative method of monitoring disease progression, with the long-term potential to guide therapy.
15251081 Tumor necrosis factor-alpha in psoriasis and psoriatic arthritis: a clinical, genetic, and 2004 Aug The successful introduction of anti-tumor necrosis factor (TNF) therapies in psoriasis and psoriatic arthritis has sharpened considerable interest in this chronic and frequently disabling disease. Unlike the situation in rheumatoid arthritis, where anti-TNF therapies were introduced after years of painstaking research which confirmed a key proinflammatory role for TNF, the evidence for TNF having a key role in psoriatic arthritis has lagged behind. In this paper, the emerging immunohistochemical, genetic, and clinical literature relating to TNF's role in skin and joint manifestations of this disease is reviewed and areas for future research are suggested.
12716449 Collagen-induced arthritis is exacerbated in IL-10-deficient mice. 2003 IL-10 is a potent immunoregulatory cytokine attenuating a wide range of immune effector and inflammatory responses. In the present study, we assess whether endogenous levels of IL-10 function to regulate the incidence and severity of collagen-induced arthritis. DBA/1 wildtype (WT), heterozygous (IL-10+/-) and homozygous (IL-10-/-) IL-10-deficient mice were immunized with type II collagen. Development of arthritis was monitored over time, and collagen-specific cytokine production and anticollagen antibodies were assessed. Arthritis developed progressively in mice immunized with collagen, and 100% of the WT, IL-10+/-, and IL-10-/- mice were arthritic at 35 days. However, the severity of arthritis in the IL-10-/- mice was significantly greater than that in WT or IL-1+/- animals. Disease severity was associated with reduced IFN-gamma levels and a dramatic increase in CD11b-positive macrophages. Paradoxically, both the IgG1 and IgG2a anticollagen antibody responses were also significantly reduced. These data demonstrate that IL-10 is capable of controlling disease severity through a mechanism that involves IFN-gamma. Since IL-10 levels are elevated in rheumatoid arthritis synovial fluid, these findings may have relevance to rheumatoid arthritis.
14748567 Laminoplasty for cervical myelopathy caused by subaxial lesions in rheumatoid arthritis. 2004 Jan OBJECT: Although controversy exists regarding surgical treatment for rheumatoid subaxial lesions, no detailed studies have been conducted to examine the efficacy of laminoplasty in such cases. To discuss indications for laminoplasty in rheumatoid subaxial lesions, the authors retrospectively investigated clinical and radiological outcomes in patients who underwent laminoplasty for subaxial lesions. METHODS: Thirty patients (11 men and 19 women) underwent laminoplasty for rheumatoid subaxial lesions. The patients were divided into those with mutilating-type rheumatoid arthritis (RA) and those with nonmutilating-type RA according to the number of eroding joints. As of final follow-up examination laminoplasty resulted in improvement of myelopathy in 24 patients (seven with mutilating- and 17 with nonmutilating-type RA) and transient or no improvement in six (five with mutilating- and one with nonmutilating-type RA). In the group with mutilating-type RA, significantly poorer results were displayed (p < 0.05). In most patients preoperative radiographs demonstrated vertebral slippage less than or equal to 5 mm at only one or two levels. Postlaminoplasty deterioration of subaxial subluxation and unfavorable alignment change occurred significantly more often in patients with mutilating-type RA (p < 0.05). CONCLUSIONS: Patients with nonmutilating-type RA can benefit from laminoplasty for myelopathy due to subaxial lesions.
11845016 Cost of illness studies in rheumatic diseases. 2002 Mar Knowledge about the economic burden of rheumatic diseases has progressed during recent years. In addition to the increasing number of studies published, the Economics Working Group of the Outcome Measures in Rheumatoid Arthritis Clinical Trial (OMERACT) Conference has produced substantial work to improve methodological standards for the economic evaluation of rheumatic diseases. Some of their preliminary results are presented in this review. Recent data have confirmed two main conclusions of previous studies: the total economic burden of rheumatic diseases is often more substantial than other chronic conditions, including cardiovascular diseases and cancer; and the impact of the disability caused by musculoskeletal diseases is significant on both direct (long-term care in osteoporosis for example) and indirect costs (productivity loss in chronic patients). Besides that, cost-effectiveness studies have provided valid information to improve disease management, especially for patients with rheumatoid arthritis or chronic low back pain.
14969057 Early predictors of outcome in juvenile idiopathic arthritis. 2003 Sep The definition and management of "early arthritis" in children differ from those in adults because juvenile idiopathic arthritis (JIA) is markedly different from adult rheumatoid arthritis. Since a significant proportion of patients with JIA develop articular damage and enter adult life with persistently active disease, it is important to predict early in the disease course the long-term outcome in order to tailor treatment to the risk of disability. Over the past 3 decades a number of studies have evaluated the long-term outcome of cohorts of patients with JIA and some of them have also attempted to identify early prognostic factors. In summary, greater severity/extension of arthritis at onset, symmetric disease, precocious hip/wrist involvement, the presence of rheumatoid factor, and prolonged active disease were the best predictors of a poor outcome. Specific correlates for systemic JIA were persistent systemic features and thrombocytosis at 6 months following presentation, whereas joint symmetry and a higher erythrocyte sedimentation rate at onset were associated with a more severe course in oligoarticular JIA. However, although data is accumulating on prognostic factors in JIA, prediction of long-term outcome in the first few months remains difficult. To better define prognostic factors in future analyses, a considerable effort should be made to increase standardization among studies. Furthermore, a radiographic scoring system and a set of remission criteria specific for JIA should be developed.
19776441 PFC Modular Total Knee Replacement System - Middle Term Results. 2002 Jun 30 Background. Total knee replacement, which is now the preferred solution for severe primary osteoarthritis, rheumatoid arthritis or posttraumatic osteoarthritis, is indicated in patients of various pathological changes and deformities. Every joint requires an individual treatment.
Material and method. We performed a prospective study of 500 cemented primary PFC modular total knee replacement implanted from 1991 to 2001, involving 350 prostheses (55 bilateral) in 295 patients with diagnosis of primary osteoarthritis, rheumatoid arthritis or posttraumatic osteoarthritis. The average age of our patients was 68,3 years (range 2,2-70,4 years). A survivorship curve was constructed based on revision surgery due to aseptic loosening.
Results. According to the Knee Society Clinical rating System, the results were excellent in 288 knees, good in 45 knees, poor in 13 knees and extremely poor 4 knees. We observed posterior dislocation of the tibial component in2 cases. In one patient we had to replace the implant in a two-stage procedure because of septic loosening.
Conclusions. The PFC total knee system seems to be a prosthesis of good quality, permitting, the solution of almost any problem that may arise in both primary and revision cases. We achieved good outcomes and high patient satisfaction.
12787527 Virus-associated arthritis. 2003 Apr The occurrence of arthritis in patients who were infected by a virus has been widely observed. In some cases, the clinical appearance seems to resemble that of rheumatoid arthritis. The mechanism by which the viral infection proceeds to the arthritic manifestation is, however, still to be investigated. Several biological and immunological pathways are suggested to be involved in the pathogenesis. The representatives of such potentially 'arthritogenic' viruses include human T-cell lymphotropic virus type I (HTLV-I), which causes destructive inflammatory arthritis in model animals. Other examples are hepatitis C virus and rubella virus. Clinical and pathological features of these virus-induced forms of arthritis are discussed.
15454124 Palindromic rheumatism and other relapsing arthritis. 2004 Oct Patients with recurrent or relapsing arthritis are frequently seen in rheumatological practice. Besides crystal arthritis, the most frequent cause of recurrent arthritis, there are several diseases that may present clinically as intermittent mono- or polyarthritis. Palindromic rheumatism is the paradigm of this type of condition, but other diseases such as systemic autoinflammatory disorders (periodic fever syndromes), Whipple's disease, arthritis associated with hyperlipidemia, intermittent hydrarthrosis and other diseases should be taken into account in the differential diagnosis of patients with recurrent arthritis. In this chapter, we discuss recent developments in these diseases with special emphasis on palindromic rheumatism, a common condition whose close relationship with rheumatoid arthritis remains intriguing.
12825539 Degenerative sternoclavicular arthritis and hyperostosis. 2003 Apr Symptomatic arthritic involvement of the sternoclavicular joint is relatively uncommon and can be a result of distant trauma, infection, and sternocostoclavicular hyperostosis, post-menopausal arthritis, condensing osteitis of the proximal clavicle, or secondary to an underlying arthropathy. Patients with degenerative osteoarthritis due to trauma most commonly have had either an anterior or posterior dislocation, subluxation, or periarticular fracture. Medical claviculectomy with or without ligamentous stabilization is indicated only in situations of painful primary and secondary rheumatoid arthritis, or in patients with neoplastic lesions. Numerous authors have recommended surgical reconstruction but few have reported series larger than two or three cases. This article reviews a few specific arthropathy conditions about the sternoclavicular joint and discusses their nonoperative and operative management.
15196245 Joint cytokine quantification in two rodent arthritis models: kinetics of expression, corr 2004 Jul Biomarker quantification in disease tissues from animal models of rheumatoid arthritis (RA) can help to provide insights into the mechanisms of action of novel therapeutic agents. In this study we validated the kinetics of IL-1beta, TNF-alpha and IL-6 mRNA and protein expression levels in joints from DBA/1OlaHsd murine collagen-induced arthritis (CIA) and Lewis rat Streptococcal cell wall (SCW)-induced arthritis by real-time polymerase chain reaction (PCR) TaqMan and Enzyme-linked immunosorbent assay (ELISA). Prednisolone was used as a reference to investigate any correlation between clinical response and cytokine levels at selected time-points. To our knowledge this is the first report showing a close pattern of expression between mRNA and protein for IL-1beta and IL-6, but not for TNF-alpha, in these two models of RA. The kinetics of expression for these biomarkers suggested that the optimal sampling time-points to study the effect of compounds on both inflammation and cytokine levels were day 4 postonset in CIA and day 3 after i.v challenge in SCW-induced arthritis. Prednisolone reduced joint swelling through a mechanism associated with a reduction in IL-1beta and IL-6 protein and mRNA expression levels. At the investigated time points, protein levels for TNF-alpha in arthritic joints were lower than the lower limit of detection of the ELISA, whereas mRNA levels for this cytokine were reliably detected. These observations suggest that RT-PCR TaqMan is a sensitive technique that can be successfully applied to the quantification of mRNA levels in rodent joints from experimental arthritis models providing insights into mechanisms of action of novel anti-inflammatory drugs.
15336954 Combination benefit of a pyrimidylpiperazine derivative (Y-40138) and methotrexate in arth 2004 Aug 30 Anti-tumor necrosis factor-alpha (TNFalpha) antibody in combination with methotrexate dramatically decreases joint destruction in rheumatoid arthritis. The aim of this study was to examine combined treatment with N-[1-(4-([4-(pyrimidin-2-yl)piperazin-1-yl]methyl)phenyl)cyclopropyl] acetamide HCl (Y-40138) and methotrexate in rat adjuvant-induced arthritis. The increase in hindpaw volume and joint destruction was suppressed by single therapeutic administration (days 15-20) of Y-40138 (30 mg/kg, p.o.), but not by prophylactic administration (days 1-9). However, arthritic progression was suppressed by single prophylactic administration of methotrexate (0.3 mg/kg, p.o.), but not by therapeutic administration. Combined administration (days 10-20) of Y-40138 (0.3-1 mg/kg) and methotrexate (0.03 mg/kg) synergistically suppressed the increase in hindpaw volume and joint destruction. We concluded that Y-40138 in combination with methotrexate synergistically suppressed arthritic progression. These data suggest that combined treatment with Y-40138 and methotrexate may increase efficacy of therapy for rheumatoid arthritis.
15120191 HLA-DRB1 alleles and HLA-DRB1 shared epitopes are markers for juvenile rheumatoid arthriti 2004 Apr We studied the association of human leukocyte antigen (HLA)-DRB1 and HLA-DQB1 alleles and HLA haplotypes with juvenile rheumatoid arthritis (JRA) in 65 patients and 65 controls from Colombia. The JRA subsets were distinguished on the basis of criteria established by the American College of Rheumatology. Two alleles were associated with protection, HLA-DRB1*1501 (p = 0.002) and HLA-DRB1*1402 (p = 0.01). HLA-DRB1*1602 (p = 0.0000002) was associated with susceptibility for systemic JRA and HLA-DRB1*1104 (p = 0.0002) for pauciarticular JRA. Amino acid sequences at residues 70-74 of DRB1 chain shared by HLA-DRB1 alleles (shared epitomes) were also informative. The polyarticular JRA subset revealed association with (70)QRRAA(74), which includes HLA-DRB1*04, 01, and (70)DRRAA(74), which includes DRB1*1601, 1602, 1101, and 1104. Two new findings of interest were the association of the haplotypes DRB1*1104, DQB1*0301(p = 0.0002) with pauciarticular JRA and DRB1*1602, DQB1*0301 (p = 0.0000002) association with systemic JRA. The DRB1 alleles of these two haplotypes share the epitope (70)DRRAA(74)and were associated with both the pauciarticular and the systemic subset of JRA. Our results suggest that studies of disease susceptibility in populations of admixed genetic background should take into account the contribution of different ethnic groups or nationalities in the recruitment of controls and patients studied in order to rule out genetic stratification.
12739045 Methotrexate inhibits interleukin-6 production in patients with juvenile rheumatoid arthri 2003 May OBJECTIVES: Methotrexate (MTX) is one of the most widely used disease-modifying antirheumatoid drugs in the treatment of juvenile rheumatoid arthritis (JRA). We studied its effect on the production of two proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha), by peripheral blood cells in patients with JRA. METHODS: Interleukin-6 and TNFalpha levels were measured at 0 and 4 weeks in whole blood cultures with and without lipopolysaccharide (LPS) stimulation in 19 children treated with MTX (10 mg/m(2 )per week) or placebo. Ten healthy individuals were included as healthy controls. RESULTS: Spontaneous production of IL-6 and TNFalpha by peripheral blood cells of patients with JRA was higher than in healthy controls ( P<0.01). However, IL-6 and TNFalpha production after LPS stimulation was similar in healthy controls and patients. The two groups of patients, i.e., those treated with placebo and those treated with MTX, had similar spontaneous and induced IL-6 and TNFalpha production. At 4 weeks, the drop in spontaneous IL-6 and TNFalpha production was no different in the two groups, but LPS-stimulated IL-6 production was significantly lower in the MTX-treated group than the placebo group ( P<0.05). CONCLUSION: Methotrexate reduces the production of IL-6 by activated cells, and this may be responsible for its anti-inflammatory property.
15465226 Long-term assessment of Swanson implant arthroplasty in the proximal interphalangeal joint 2004 Sep PURPOSE: The purpose of this study was to evaluate the clinical results of Swanson silicone implant arthroplasty of the proximal interphalangeal (PIP) joint, specifically evaluating clinical results with long-term assessment. METHODS: A retrospective review of 70 silicone implants of the PIP joint in 48 patients was performed with an average follow-up period of 6.5 years (range, 3-20 y). Clinical assessment included motion, stability, and alignment. Radiographic assessment included implant fracture, deformity, and cystic bone resorption. The pathology consisted of degenerative joint disease in 14, posttraumatic arthritis (TA) in 11, rheumatoid arthritis (RA) in 13, and idiopathic arthritis (IA) associated with collagen disease in 12 patients. Swan neck and boutonniere deformities were assessed separately. Statistical analysis of preoperative risk factors was compared with the postoperative assessment of pain, motion, and function (return to work). RESULTS: There was no significant change in the active range of motion (ROM) before and after PIP arthroplasty (26 degrees vs 30 degrees ). Correction of swan neck and boutonniere deformities was difficult, usually leading to poor results. There was improvement in maximum active extension before surgery lacking 32 degrees to after surgery lacking 18 degrees . From a statistical standpoint rheumatoid joint involvement with PIP arthroplasty had poorer results than degenerative or posttraumatic arthritis with respect to pain relief and ROM. Pain relief was present in 70% of replaced PIP joints with residual pain and loss of strength in 30%. Radiographic analysis showed abnormal bone formation (cystic changes) in 45%. There were 11 implant fractures and 9 joints that required revision surgery. CONCLUSIONS: Silicone replacement of the PIP joint is effective in providing relief of pain from arthritis but does not provide improvement in motion or correction of deformity. It provided a poorer outcome in rheumatoid disease in comparison with degenerative, posttraumatic, or idiopathic arthritis.
24387119 Antibodies to type II collagen and their association with HLA DR1 alleles in Japanese pati 2003 Mar Abstract To investigate whether immunological responses to type II collagen (CII) play an important role in the pathogenesis of rheumatoid arthritis (RA), the presence of anti-CII antibodies was examined by enzyme immunoassay in 130 Japanese patients with RA, 10 systemic lupus erythematosus (SLE) patients, and 30 healthy subjects. In addition, the HLA-DRB1 genes of 40 RA patients were determined, and their association with positive findings of anti-CII antibodies was examined. A significantly high frequency of positive findings of anti-CII antibodies was detected in sera from RA patients (19%, P < 0.05) in comparison with that in sera from healthy subjects (3%). High frequencies of DRB1 *0405 and 0101 alleles were observed in the 40 RA patients examined (40.0% and 30.0%, respectively). Patients with DRB1 *0101 had a significantly higher rate of positive findings of anti-CII antibodies than those without DRB1 *0101 (66.7% and 28.6%, respectively, P < 0.05). No such association was observed for DRB1 *0405. From these findings, we suggest that immunological responses to CII may play an important role in the development of arthritis in some RA patients.
15557201 Tracking of proinflammatory collagen-specific T cells in early and late collagen-induced a 2004 Dec 1 Rheumatoid arthritis is a chronic inflammatory disease associated with certain HLA-DR4 subtypes. The target autoantigen(s) is unknown, but type II collagen (CII) is a candidate, with a single immunodominant DR4-restricted 261-273 T cell epitope (CII(261-273)). In the present study, we have prepared HLA-DR4:CII(261-273) tetramers and analyzed peripheral blood, lymph node, and synovial fluid cells from DR4-transgenic mice with early and late collagen-induced arthritis to draw a fuller picture of the role of CII-reactive Th cells in disease development. Their frequencies increased approximately 20-fold in blood 1-2 wk postimmunization, and even more in acutely arthritic joints. Our data strongly suggest that CII-specific Th cells are necessary, but not sufficient for collagen-induced arthritis. The CII-specific Th cells displayed an activated proinflammatory Th1 phenotype, and their expansion correlated with onset and severity of arthritis and also with anti-CII Ab levels. Surprisingly, shortly after the first clinical signs of arthritis, activated HLA-DR4:CII tetramer(+) cells became undetectable in the synovial fluid and rare in the blood, but persisted in lymph nodes. Consequently, future human studies should focus on patients with early arthritis, and on their synovial cells, to re-evaluate the occurrence and pathogenic importance of CII-specific or other Th cells in rheumatoid arthritis.
12682785 Seroprevalence of Borrelia burgdorferi in patients with Behçet's disease. 2003 Nov OBJECTIVE: Turkey is one of the countries where Behçet's disease is most prevalent. Although its pathogenesis is not defined clearly, infectious agents are thought to play a role in the etiology. In one study of a group of uveitis patients, including those with Behçet's disease, increased seropositivity to B. burgdorferi was reported by enzyme-linked immunosorbent assay (ELISA). The seroprevalence of B. burgdorferi has been found to be as high as 36% in some rural areas of Turkey, although Lyme disease caused by B. burgdorferi is quite rare. In this study, we investigated the seroreactivity to B. burgdorferi antigens in patients with Behçet's disease and compared it with that of healthy and disease controls. MATERIALS AND METHODS: This study was conducted in Izmir in western Turkey. B. burgdorferi immunoglobulin (Ig)M and IgG antibodies were tested by ELISA in the sera of patients with Behçet's disease ( n=30), rheumatoid arthritis patients as disease controls ( n=31), and healthy controls ( n=31). Positive results were confirmed by Western blotting. RESULTS: The difference in B. burgdorferi seropositivity between the groups was not significant by any method. Seroreactivity to B. burgdorferi antigens by ELISA was detected in 26.7% of the patients with Behçet's disease, 35.5% of those with rheumatoid arthritis, and 19.4% of the healthy controls. Immunoblots were positive in 13.3% of the Behçet's disease patients, 22.6% of the rheumatoid arthritis patients, and 12.9% of healthy controls. CONCLUSION: These results suggest no association between Behçet's disease and B. burgdorferi infection.
12681200 [Incidence and characteristics of tuberculosis in patients with autoimmune rheumatic disea 2003 Apr OBJECTIVE: To describe the incidence and characteristics of the infection caused by Mycobacterium tuberculosis in patients with autoimmune diseases. PATIENTS AND METHODS: Searching in the database of the department at our institution, all new cases of tuberculosis from 1991 to 2000 were identified in patients with autoimmune diseases; the total follow-up time was calculated as the difference between first and last visits. Time with immunosuppressive drug therapy was obtained for patients with rheumatoid arthritis from a database oriented to the longitudinal follow-up of these patients. The incidence density was calculated as the quotient between the absolute frequency of cases and the sum of individual periods at risk for each subgroup. RESULTS: Fifteen cases of tuberculosis were identified from 3,634 risk patients followed for an accumulated period of 9,795 years (overall incidence 153 per 100,000 patients-year). Fourteen patients were receiving disease-modifying drugs and eleven were receiving corticosteroids at diagnosis. The location of tuberculosis infection was the lung for 33.3% of cases. The incidence by drugs in patients with rheumatoid arthritis was 143 per 100,000 patients-year with methotrexate, 2,703 per 100,000 patients-year with azathioprin, 7,692 per 1,000 patients-year with cyclophosphamide, and 4,878 per 100,000 patients-year for anti-TNFalpha. CONCLUSIONS: Compared with the general population, the incidence density of tuberculosis is increasing in our population, with a higher frequency of extrapulmonary involvement. The incidence density is variable among patients with rheumatoid arthritis depending upon the used drugs.
24383998 Frequency of broncho-bronchiolar disease in rheumatoid arthritis: an examination by high-r 2002 Dec Abstract To assess the frequency of pulmonary changes in patients with rheumatoid arthritis (RA), we evaluated a subject group (all outpatients with RA visiting the hospital during a period of three consecutive days) by plain chest radiographs (CRs) and high-resolution computed tomography (HRCT). The study population consisted of 186 patients (32 men, 154 women; mean age 59.8 years), including 6 smokers or exsmokers. Chest radiography was performed on all patients. Seventy (Group A) patients demonstrated abnormal findings and 116 (Group B) did not. HRCT scans were performed on 69 of Group A and 54 of Group B. HRCT demonstrated centrilobular micronodules (n = 29; 23.6%), septal lines (n = 24; 19.5%), subpleural curvilinear shadows (n = 24; 19.5%), bronchiectasis (n = 21; 17.1%), dependent opacity (n = 14; 11.4%), nodules (n = 12; 9.8%), and honeycombing (n = 11; 8.9%). Ten (34%) of the patients with centrilobular micronodules also had bronchiectasis. The most frequent disorder was broncho-bronchiolar disease. Contrary to the CRs finding of no abnormality, HRCT detected pulmonary pathological findings in 40 of 54 patients (74.1%). Pulmonary diseases may be frequently latent, and HRCT is useful in evaluating them in patients with RA.