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

ID PMID Title PublicationDate abstract
15170548 Amyloid tumor in the anterior mediastinum: report of a case. 2004 A 33-year-old woman being treated for rheumatoid arthritis was referred to our hospital for investigation of a mediastinal mass. A chest computed tomography scan showed an anterior mediastinal mass, 8.5 x 7.0 cm in size, with a cystic lesion and calcification. These findings were suggestive of either a noninvasive thymoma or a mature teratoma. Therefore, we performed tumor resection and thymectomy. Histologically, the tumor consisted of diffuse deposits of massive eosinophilic amorphous material. The tumor was stained red-orange by Congo red, and the staining disappeared following potassium permanganate digestion. Based on these findings, a diagnosis of reactive amyloidosis of the amyloid A-protein-derived type was made. Amyloidosis in the mediastinum has rarely been described.
12010571 Differential expression of the angiogenic Tie receptor family in arthritic and normal syno 2002 Angiopoietins (Ang) are vascular endothelial cell-specific growth factors that play important roles principally during the later stages of angiogenesis. We have compared the distribution of the receptor tyrosine kinase (Tie) and the Ang ligands in synovial tissues from normal subjects and those with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunohistochemical analysis was used to determine the expression of Ang-1, Ang-2, Tie1 and Tie2 in synovial tissue of normal subjects and those with RA and OA. Ang-1, Ang-2, Tie1 and Tie2 mRNA and protein expression were quantified in synovial tissues and RA synovial tissue fibroblasts with real-time reverse transcription polymerase chain reaction and western blot analysis. In RA, Ang-1 positive immunostaining on lining cells, macrophages and endothelial cells was significantly higher than in OA and normal synovial tissue. The expression pattern of Ang-2 in synovial tissue was similar in RA and OA, whereas the Ang-2 expression was low in normal tissue. Synovial tissue from subjects with RA and OA showed a significant upregulation of Tie1 on lining cells, macrophages and endothelial cells compared to that from normal subjects. Tie2 was significantly upregulated in the RA and OA synovial tissue lining cells, macrophages and smooth muscle cells compared to normal synovial tissue. Generally Ang-1, Ang-2, Tie1 and Tie2 mRNA levels were higher in RA synovial tissue compared to normal and OA synovial tissues, and RA synovial tissue fibroblasts. Western blot analysis also demonstrated greater Tie1 and Tie2 protein expression in RA and OA synovial tissue compared to RA synovial tissue fibroblasts. In conclusion, the dominance of Ang-1 mRNA and protein expression over Ang-2 is in agreement with an active neovascularization in RA synovial tissue.
14597758 The TRAIL to arthritis. 2003 Nov Antigen-specific lymphocytes are involved in synovial proliferation within inflamed joints. Activated lymphocytes and synoviocytes from patients with rheumatoid arthritis express receptors that can bind TNF-related apoptosis-inducing ligand (TRAIL). A new study demonstrates that DCs pulsed with collagen and transduced with an adenovirus-based vector able to express TRAIL limit the incidence of arthritis in a model of collagen-induced arthritis and joint inflammation. These results suggest that gene-modified cell therapy represents a therapeutic option for systemic rheumatic diseases.
15140335 Evaluation of quality of life following treatment with etoricoxib in patients with arthrit 2004 May An open-label study was undertaken at multiple centers in Mexico to assess the impact of treatment with etoricoxib - a selective cyclo-oxygenase-2 (COX-2) inhibitor - on quality of life (QoL) and pain relief among patients with osteoarthritis (OA), rheumatoid arthritis (RA) or chronic low-back pain (CLBP). The study involved 191 adult patients (aged > 18 years old) who had used non-selective non-steroidal antiinflammatory drugs (NSAIDs) for the treatment of OA, RA or CLBP during the month prior to study enrolment. After discontinuation of prior therapy, patients were treated with etoricoxib 60 mg for OA and CLBP,or 90 mg for RA once daily for 2 weeks. Patient and physician questionnaires were used to collect information about drug treatments, patients' QoL (Short Form-8 Health Survey [SF8] and EQ-5D VAS), patients' pain assessment, and physicians' and patients' satisfaction with treatment at baseline and at follow-up visits. Relative to prior NSAID use, etoricoxib use was associated with improvements in all SF-8 QoL domains and component scores as well as in measures of pain and physical functioning. Current pain was reduced from 59.1 mm (0-100mm VAS) at baseline to 27.1mm at follow-up and the physical component score of the SF-8 improved from 33.3 to 46.3 (on a scale from 0 to100). At follow-up, 91% of patients were satisfied with the pain control provided by etoricoxib compared with 34% who were satisfied with the pain control provided by previous NSAIDs. Among physicians, 93% reported satisfaction with the analgesic effect, 95% with the anti-inflammatory profile, and 82% with the side-effect profile of etoricoxib relative to pre-study NSAID treatment. During etoricoxib therapy, use of concomitant medications was reduced. The results of this study are limited due to the lack of a control group, the un-blinded design, and the small number of patients. Large naturalistic trials are needed to confirm the results.
12211691 Effects of alumina and zirconium dioxide particles on arachidonic acid metabolism and proi 2002 Aug We describe a model which can be used for in vitro biocompatibility assays of biomaterials. We studied the in vitro response of human osteoarthritis or rheumatoid arthritis fibroblast-like synoviocytes to Al2O3 or ZrO2 particles by analysing the production of interleukin-1 (IL-1) and interleukin-6 (IL-6) and the metabolism of arachidonic acid via lipoxygenase and cyclo-oxygenase pathways. Our results show that, in these cells and under our experimental conditions, Al2O3 and ZrO2 did not significantly modify the synthesis of IL-1 and IL-6 or the metabolism of arachidonic acid.
12964811 Assay for cross-linked carboxyterminal telopeptide of type I collagen (ICTP) unlike CrossL 2003 Aug We compared the ability of assay for cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and CrossLaps assay to reflect increased pathological degradation of type I collagen in serum and synovial fluid samples of patients with rheumatoid arthritis (RA; n = 40). ICTP and CrossLaps concentrations were correlated with each other and with markers of collagen synthesis (PINP and PIIINP, amino terminal propeptides of type I and type III procollagens, respectively) and with markers of inflammation, i.e., C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Serum ICTP was increased in half of the RA patients, whereas CrossLaps assays were increased only occasionally. Serum ICTP correlated with the other markers of collagen metabolism as well as with CRP and ESR. Serum CrossLaps correlated only with PINP and ICTP, but not with serum PIIINP, CRP or ESR. Two patients had false-positive reactions in the CrossLaps assay due to the rheumatoid factor. The ICTP and CrossLaps antigens were clearly separate peaks in gel filtration analysis. The CrossLaps assay is able to detect the same ICTP antigen, but not vice versa. The ICTP assay reflects increased matrix metalloproteinase-mediated collagen degradation in joints in RA. In contrast, the physiological cathepsin K-mediated bone resorption measured by the CrossLaps assay was only occasionally increased.
12110119 Perspectives for TNF-alpha-targeting therapies. 2002 Rheumatoid arthritis (RA) is the most common chronic autoimmunopathy, clinically leading to joint destruction as a consequence of the chronic inflammatory processes. The pathogenesis of this disabling disease is not well understood, but molecular events leading to tissue inflammation with cartilage and bone destruction are now better defined. Therapy with slow-acting, disease-modifying antirheumatic drugs (DMARDs), such as low-dose methotrexate, which is generally accepted as a standard, leads to a significant amelioration of symptoms but does not stop joint destruction. Due to these disappointing treatment options and the identification of certain inflammatory mediators as therapeutic targets, novel therapeutic agents such as monoclonal antibodies, cytokine-receptor/human-immunoglobulin constructs or recombinant human proteins have been tested in RA with some success. Clinical trials testing anti-TNF-alpha agents, alone or in combination with methotrexate, have convincingly shown the feasibility and efficacy of these novel approaches to the therapy of RA. A clinical trial testing combination therapy with chimeric (mouse/human) anti-TNF-alpha monoclonal antibody infliximab and methotrexate showed, for the first time in any RA trial, that there was no median radiological progression in the groups given infliximab plus methotrexate over a 12-month observation period. Similar encouraging results might arise from trials employing other TNF-alpha-directed agents, such as the fully human monoclonal antibody D2E7, the p75 TNF-alpha-receptor/Ig construct, etanercept, or others, as discussed in this review. Combination partners other than methotrexate will be established as suitable cotreatment along with anti-TNF-alpha biologicals. Forthcoming new indications for TNF-alpha-targeted therapies are discussed.
15248223 Etanercept in Sjögren's syndrome: a twelve-week randomized, double-blind, placebo-control 2004 Jul OBJECTIVE: To assess the safety and potential efficacy of etanercept in the treatment of Sjögren's syndrome (SS). METHODS: This pilot study was a 12-week randomized, double-blind, placebo-controlled trial of etanercept, with 14 subjects in each group. Patients received 25 mg of etanercept or placebo (vehicle) by twice-weekly subcutaneous injection. Patients met the American-European Consensus Group criteria for SS. The primary outcome required at least 20% improvement from baseline values for at least 2 of the following 3 domains: subjective or objective measures of dry mouth, subjective or objective measures of dry eyes, and IgG level or erythrocyte sedimentation rate (ESR). RESULTS: Of the 14 patients taking etanercept, 11 had primary SS and 3 had SS secondary to rheumatoid arthritis. Baseline measures did not differ between the 2 groups. Three etanercept-treated patients and 1 placebo-treated patient did not complete the trial. Five etanercept-treated patients and 3 placebo-treated patients showed improvement from baseline in the primary outcome variable at 12 weeks, but the difference was not statistically significant. There were no significant differences between the groups for changes in subjective measures of oral or ocular symptoms (by visual analog scale), the IgG level, Schirmer I test result, van Bijsterveld score, or salivary flow. At 12 weeks, the ESR had decreased in the etanercept group compared with baseline (P = 0.004); however, the mean reduction was only 18.6%. CONCLUSION: We found no evidence to suggest that treatment with etanercept at a dosage of 25 mg twice weekly for 12 weeks was clinically efficacious in SS. A larger trial will be necessary to definitively address the efficacy of etanercept in the treatment of SS.
12820079 Anterior knee pain with a posterior-stabilized mobile-bearing knee prosthesis: the effect 2003 Jun Femoropatellar problems have been reported with some designs of posterior-stabilized knee prostheses with fixed bearings; we report similar findings with a posterior-stabilized mobile-bearing prosthesis. A review of 184 patients (193 knees) who underwent placement of a Rotaglide (Corin, Cirencester, UK) posterior-stabilized prosthesis with patellar resurfacing showed that only 33 knees (17%) had complete absence of femoropatellar complaints after at least 1 year of follow-up evaluation. Femoropatellar grinding was noted in the other 160 knees; 65 were asymptomatic, 78 were mildly symptomatic, and 17 were severely symptomatic. Two patients refused secondary treatment; 15 underwent arthroscopic debridement. The only abnormal finding was intra-articular fibrosis surrounding the patellar implant. After arthroscopic debridement of the fibrosis, all patients reported immediate relief of their symptoms followed by recurrence within 6 to 9 months. Inappropriate trochlear design of the femoral implant appears to be the main determinant of femoropatellar problems in these patients. Encroachment on the trochlea by a broad intercondylar box with a sharp anterior edge appears detrimental to function irrespective of the presence or absence of bearing mobility.
11838840 Effect of direct angiogenesis inhibition in rheumatoid arthritis using a soluble vascular 2002 Feb OBJECTIVE: We evaluated the effect of direct angiogenesis inhibition in synovium of patients with rheumatoid arthritis (RA), using a soluble vascular endothelial growth factor receptor 1 (VEGFR1) chimeric protein. METHODS: Dispased cells from active RA synovial tissues were cocultured on OP9 stromal cells. Control synovial tissues were obtained from patients with injury of the anterior cruciate ligament. Chimeric protein (30 microg/ml) of the extracellular domain of VEGFR1 fused to the Fc portion of human IgG1 (VEGFR1-Fc) was added to culture medium. After 10 days, the cells were stained with anti-CD31 antibody and anti-Tie-2 antibody. RESULTS: Endothelial cells from patients with active RA had high angiogenic growth capacity compared with controls. Proliferation of these endothelial cells was strongly suppressed by VEGFR1-Fc. Quantitative analysis revealed that VEGFR1-Fc inhibited angiogenesis in a dose dependent manner. CONCLUSION: VEGFR1-Fc is able to suppress angiogenesis in rheumatoid synovium, suggesting that direct inhibition of angiogenesis activity could serve as a novel therapeutic strategy to prevent progressive synovial hyperplasia and inflammatory reactions in active RA.
11925908 [Dynamics of matrix metalloproteinase (MMP)-13 in the patients with rheumatoid arthritis]. 2002 Feb OBJECTIVE: Matrix metalloproteinase (MMP) is a novel proteolytic enzyme that plays an important role in joint destruction in rheumatoid arthritis (RA). To elucidate the dynamics of MMPs in serum and synovial fluid, we measured the concentration and activity of MMP-1, -9, -13 in serum and synovial fluid of RA patients. Among them especially we focused on newly defined MMP-13 and compared with MMP-1 and MMP-9. METHODS: Serum, synovial fluid and synovial, and pannus tissues used in this study were obtained from RA patients. To compare the dynamics of each enzymic protein, we performed the following procedures: Firstly, we measured concentration of MMP-1, -9, -13 by using ELISA kit. Secondly, the activity of MMP-1, -9, -13 were also measured by using the MMP activity assay system. Then we obtained the activity ratio of each MMP from calculation of activity/concentration. We also examined the expression of MMP-13 in synovial tissues by immunohistochemical and in situ hybridization studies. RESULT: Concentration and activity levels of MMP-1, -9, -13 were significantly higher in RA serum and synovial fluid than in OA. Activity ratio of MMP-1, MMP-9 MMP-13 were 3.60 +/- 1.56, 1.03 +/- 1.75, 35.30 +/- 24.28 (ODA450/ng) in RA serum and 1.60 +/- 2.02, 3.97 +/- 14.83, 14.25 +/- 15.04 (ODA450/ng) in synovial fluid. In synovial and pannus tissues. MMP-13 positive cells were diffusely demonstrated by immunohistochemical and in situ hybridization studies. They were synovial lining cells, endothelial cells, fibroblasts, monocytes, osteoblasts, and chondrocytes. CONCLUSION: MMP-13 positive cells were diffusely presented in joint regions including synovial and pannus tissues. Although the concentration of MMP-13 was not so high, its activity ratio was elevated in serum and synovial fluid in the patients with rheumatoid arthritis.
15526815 Role of KL-6 in evaluating the disease severity of rheumatoid lung disease: comparison wit 2004 Nov OBJECTIVE: To determine the role of KL-6 (Krebs von den Lungen-6) in evaluating the disease severity of pulmonary lesions in rheumatoid arthritis (RA) compared with high resolution computed tomography (HRCT) findings. METHODS: Fifty serum KL-6 levels and HRCT images were prospectively obtained from 47 RA patients. Eight HRCT findings were classified into five grades. Patients were also divided into two groups according to the KL-6 threshold level and HRCT findings were evaluated. RESULTS: There was a positive correlation between the serum KL-6 level and the total CT score (r = 0.83). Reticular opacity most closely related to the serum KL-6 levels (r = 0.84). In the high KL-6 group (n = 10), the average CTscore was markedly increased (64.6 points) and severe honeycombing expanded into the whole lung. One case revealed diffuse ground glass opacity. In 12 of 40 cases in the normal KL-6 group, CT scores mildly increased compared with the other cases (over 20 points). The predominant finding of these cases could be classified into four types: (1) narrow spread honeycombing; (2) subtle fibrosis; (3) airway diseases; and (4) dense consolidation. CONCLUSION: KL-6 is a useful marker to detect severe RA lung disease. It is also useful to distinguish non-fibrosis from fibrosis predominant cases. However, it sometimes could not detect early stage RA lung disease.
12416946 Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stabl 2002 Nov 5 BACKGROUND: Disease-modifying antirheumatic drugs may confer greater benefits when combined with the antimetabolite methotrexate. OBJECTIVE: To evaluate the efficacy and safety of leflunomide versus placebo when added to ongoing, stable-dose methotrexate therapy in patients with persistently active rheumatoid arthritis. DESIGN: 24-week, multicenter, randomized, double-blind, placebo-controlled trial. SETTING: 20 centers in the United States and Canada. PATIENTS: Patients with persistent rheumatoid arthritis, as defined by American College of Rheumatology (ACR) criteria, despite receiving methotrexate for at least 6 months. INTERVENTION: Leflunomide or matching placebo added to existing methotrexate therapy. MEASUREMENTS: The primary efficacy variable was the rate of achievement of 20% improvement in ACR criteria (ACR20) at the end of the study. The Health Assessment Questionnaire Disability Index was assessed at each visit, and the Medical Outcomes Study 36-Item Short Form was completed as an end point analysis. RESULTS: In the leflunomide and placebo groups, 46.2% and 19.5% of patients, respectively, met ACR20 criteria at 24 weeks (P < 0.001). Clinical improvement was demonstrated by statistically significant mean changes in individual components of the ACR20 response criteria. Discontinuation rates were similar in both treatment groups (23.1% in the leflunomide group and 24.8% in the placebo group), as were the overall incidences of adverse events (89.2% vs. 89.5%, respectively). Adverse events were predominantly mild or moderate. CONCLUSIONS: Combination therapy with leflunomide and methotrexate provides statistically significant clinical benefit in patients with active rheumatoid arthritis who are receiving methotrexate therapy. Leflunomide plus methotrexate is generally well tolerated and can be used safely with appropriate liver enzyme and hematologic monitoring.
11914999 Opportunistic infections in patients with and patients without Acquired Immunodeficiency S 2002 Apr 15 In the next decade, longer survival of patients with cancer and more-aggressive therapies applied to common conditions, such as asthma and rheumatoid arthritis, will result in a larger population with significant immune system defects. Many in this population will be at risk for opportunistic infections, which are familiar to doctors who have treated people infected with human immunodeficiency virus (HIV). However, the epidemiology, presentation, and outcome of these infections in patients with an immune system defect, other than that caused by HIV infection, may be different than those encountered in patients with acquired immunodeficiency syndrome. Reviewed are 4 common opportunistic infections: Pneumocystis carinii pneumonia, cryptococcosis, atypical mycobacterial infection, and cytomegalovirus infection. Emphasized are the important differences among these groups at risk.
14871534 Measurement of antibodies to collagen II by inhibition of collagen fibril formation in vit 2004 Feb 1 Antibodies to type II collagen (collagen II) are pathogenic in experimental collagen-induced arthritis (CIA) and possibly also in rheumatoid arthritis (RA). Hitherto, results of assays for anti-collagen II have proven to be inconsistent. We tested whether mouse monoclonal antibodies (mAbs) to collagen II inhibit the natural self-assembly of soluble triple-stranded collagen II monomers to form insoluble polymeric fibrils. A spectrophotometric assay of self-assembly was based on change in absorbance at 313 nm, observed over 0-60 min after neutralisation and warming of a solution of monomeric collagen II. Two mAbs to collagen II (CII-CI and M2.139) strongly inhibited self-assembly of collagen II but not collagen I, whereas another antibody, CII-F4, and an irrelevant control mAb did not. Notably, CII-CI and M2.139, but not CII-F4, induce arthritis on passive transfer to naïve mice. The arthritogenic effects of mAbs CII-CI and M2.139 in vivo, and inhibition of collagen II self-assembly in vitro, may be attributable to interference with critical epitopes at sites essential for the stabilisation of the mature polymeric collagen II fibril, and, hence, the integrity of the entire cartilage matrix. This assay for inhibition of self-assembly of collagen II could be developed for routine measurement of anti-collagen II in body fluids as a marker of early RA, and perhaps also to distinguish populations of antibodies to collagen II that either have or lack the capacity to perpetuate arthritis.
12556201 Targeting monocyte chemoattractant protein-1 signalling in disease. 2003 Feb Monocyte chemoattractant protein-1 (MCP-1) has been implicated in many inflammatory and autoimmune diseases. The G-protein-coupled receptor CCR-2B is probably the most important MCP-1 receptor in vivo, and loss of MCP-1 effector function alone is sufficient to impair monocytic trafficking in inflammation models. MCP-1 signalling appears to be a relevant target, especially in rheumatoid arthritis (RA). In RA patients, MCP-1 is produced by synovial cells and infiltrating monocytes, plasma MCP-1 concentrations correlate with swollen joint count, and elevated serum MCP-1 concentrations were found in juvenile RA in patients with active disease. Modulation of MCP-1 signalling in experimental RA showed beneficial effects on inflammation and joint destruction. With respect to chronic neuroinflammation, a critical role for MCP-1 has been established in animal models for multiple sclerosis. In acute neuroinflammation, experimental evidence for a detrimental role of MCP-1 in stroke and excitotoxic injury has been found. Several selective small molecular weight CCR-2B antagonists and MCP-1-blocking antibodies have been described. The proof for the validity of targeting MCP-1 signalling in disease, however, has yet to be established in clinical trials.
12457358 The role of matrix metalloproteinases in rheumatoid tendon disease. 2002 Nov In rheumatoid arthritis (RA) invasive tenosynovitis is associated with an increase in tendon rupture, although little is known about the mechanisms involved. We obtained specimens of noninvasive encapsulating tenosynovium, invasive tenosynovium, and wrist joint synovium from 28 rheumatoid patients. In vitro production of the matrix metalloproteinase (MMP) enzymes, MMP-8 and -9, and total collagenase activity were measured. Invasive tenosynovium produced highest levels of the collagenase MMP-8 and displayed significantly greater ability to degrade collagen type I than encapsulating tenosynovium. Levels of the gelatinase enzyme MMP-9 were similar in all groups. These results show that invasive tenosynovium is more destructive than encapsulating tenosynovium at a molecular level, providing an explanation for the increased tendon rupture associated with invasive tenosynovitis in RA.
11954883 Effects of needle-arthroscopic lavage with different volumes of fluid on knee synovitis in 2002 Feb To determine the appropriate volume of physiological fluid needed to effectively reduce synovitis and to determine the indications for intra-articular lavage of knee joints with rheumatoid arthritis (RA), intraarticular lavage with different volumes of physiological fluid via needle arthroscopy were performed on 102 rheumatoid knees in 98 patients (25 males, 77 females) with an average age of 46 years at the time of operation. Intra-articular lavage of a knee joint with 5 or 10 l of physiological fluid gave better clinical results than did intra-articular lavage with 0.5-1.5 l. There was no difference between the beneficial effects of intraarticular lavage using 5 1 or 10 l of fluid. The preoperative conditions (CRP, frequency of the susceptible factors of HLA-DRB1 alleles, radiological change in the knee joint) and the intraoperative chondroscopic assessments were correlated with clinical improvement. Our study demonstrated that intra-articular lavage with 5 l of physiological fluid performed using needle arthroscopy was beneficial. The following points at least should be checked before performing intra-articular lavage: (1) CRP is not elevated to a high level (> or =5 mg/dl), (2) the patient does not have susceptible factors in both HLA-DRB1 alleles, (3) the grade of rheumatoid knee is below Larsen II in preoperative X-ray findings, and (4) the degree of cartilage damage is not more than grade 3 in arthroscopic findings.
14989428 Safety of anakinra, a recombinant interleukin-1 receptor antagonist (r-metHuIL-1ra), in pa 2002 Sep Anakinra is a recombinant human interleukin-1 receptor antagonist (IL-1ra) recently approved by the FDA as a new therapy for patients with rheumatoid arthritis. Four clinical trials have been completed which have demonstrated that anakinra is an effective anti-rheumatic therapy either used alone or in combination with methotrexate. The most frequent adverse events reported in the clinical trials are injection-site reactions which are generally mild to moderate and rapidly resolve. A large, prospective safety study which allowed a wide-variety of comorbid conditions and concomitant medications demonstrated that anakinra therapy is a well-tolerated treatment for rheumatoid arthritis in the patient population seen by the practicing rheumatologist. Unlike therapies designed to affect TNF-alpha, there have not yet been reports of the development of tuberculosis or other fungal infections, demylinating syndromes or worsening of congestive heart failure. The safety profile of etanercept and infliximab were similar to that of anakinra in the phase I-phase III clinical trials. Unlike anakinra, these medications were not studied in the usual rheumatoid arthritis population which includes a number of patients with a wide variety of co-morbid disease and utilizing a number of concomitant anti-rheumatic medications. Post approval, several safety concerns, including patients at risk for serious infection and the emergence of latent tuberculosis and other opportunistic infections have emerged with the use of anti TNF therapy.
15022316 Lack of association of the HLA-DRB1 shared epitope with rheumatoid nodules: an individual 2004 Mar OBJECTIVE: The objective of this individual patient data (IPD) meta-analysis was to examine the relationship of rheumatoid nodules to the HLA-DRB1 shared epitope (SE) and to individual SE genotypes. METHODS: English-language studies that enrolled adult non-Hispanic Caucasian patients with rheumatoid arthritis (RA) were identified by searches of Medline and Embase, and by manual searches of medical journals. All authors were contacted for IPD. Meta-analysis was performed to assess the association of SE presence, dose, and genotype with rheumatoid nodules. Meta-analyses adjusted for disease duration and cumulative meta-analyses were also performed to assess the influence of RA duration and year of study publication on the results. RESULTS: A total of 24 studies and 3,272 patients were available for analysis. IPD were obtained for 22 of the studies. There was a nonsignificant association between the presence of the SE (i.e., 1 or 2 alleles versus 0 alleles) and rheumatoid nodules (summary odds ratio [OR] 1.3, 95% confidence interval [95% CI] 0.97-1.6). Analysis by SE genotype, however, demonstrated a weak relationship with inheritance of a single DRB1*0401 SE allele (OR 1.4, 95% CI 1.1-1.8). No other genotypes achieved statistical significance in the adjusted or unadjusted analyses. CONCLUSION: The presence of the HLA-DRB1 SE does not appear to significantly increase the risk of rheumatoid nodules among Caucasian patients with RA. Analysis by DRB1 SE genotype was uninformative, suggesting only a potential (and at most modest) role of the DRB1*0401 SE allele. Results from this IPD meta-analysis implicate other genetic, stochastic, and/or environmental factors in the susceptibility to rheumatoid nodules.