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

ID PMID Title PublicationDate abstract
19208322 Renal amyloidosis in juvenile rheumatoid arthritis. 2009 Feb We report a case of a rare disorder of renal amyloidosis occurring as a complication of juvenile rheumatoid arthritis in a 16-year-old adolescent male. He presented with generalized edema and hypertension. The laboratory work-up showed nephrotic-range proteinuria and hypoalbuminemia and normal renal function despite bilateral shrunken kidneys revealed by the abdominal ultrasound. His renal biopsy showed deposition of amyloid fibrils in the form of homogenous eosinophilic material within the glomeruli demonstrating the pathognomonic apple-green birefringence by polarized light microscopy.
19822060 Juvenile idiopathic arthritis. Subgroup characteristics and comparisons between rheumatoid 2009 Jul In terms of adult-onset definitions, rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are rarely diagnosed in children. Adult RA is in most aspects similar to seropositive polyarticular arthritis in children, but AS differs in its clinical presentation according to age at onset. In general, the nomenclature and classifications of arthritis in children encompass subgroups with specific signs or laboratory tests and pathogenic mechanisms that distinguish one clinical form from the other. While one of these subgroups corresponds to RA, the one related to AS usually includes children with undifferentiated SpA and not definite AS. Thus, comparisons of RA and AS in children actually correspond to comparisons of various forms of childhood arthritis, currently classified as juvenile idiopathic arthritis (JIA) and AS in its early undifferentiated form. In this paper, we review these to finally compare the two populations.
18679135 Accelerated pulmonary nodulosis and sterile pleural effusion in a patient with psoriatic a 2009 Feb Pulmonary nodulosis and sterile pleural exudates are well-known extra-articular manifestations in rheumatoid arthritis patients with a positive rheumatoid factor. In some patients, treatment with methotrexate has been postulated as the trigger of these complications. We report a patient with psoriatic arthropathy, negative RF, negative anticyclic citrulinated peptide antibodies but positive antibodies to cardiolipin who developed massive sterile pleural empyema and multiple cavitary pulmonary nodules during methotrexate treatment. We suggest that awareness of methotrexate-induced lung and pleural complications should be extended to other than rheumatoid arthritis diseases, not necessarily accompanied by rheumatoid factor or anticyclic citrulinated peptide antibodies.
20018014 Application of imputation methods to the analysis of rheumatoid arthritis data in genome-w 2009 Dec 15 Most genetic association studies only genotype a small proportion of cataloged single-nucleotide polymorphisms (SNPs) in regions of interest. With the catalogs of high-density SNP data available (e.g., HapMap) to researchers today, it has become possible to impute genotypes at untyped SNPs. This in turn allows us to test those untyped SNPs, the motivation being to increase power in association studies. Several imputation methods and corresponding software packages have been developed for this purpose. The objective of our study is to apply three widely used imputation methods and corresponding software packages to a data from a genome-wide association study of rheumatoid arthritis from the North American Rheumatoid Arthritis Consortium in Genetic Analysis Workshop 16, to compare the performances of the three methods, to evaluate their strengths and weaknesses, and to identify additional susceptibility loci underlying rheumatoid arthritis. The software packages used in this paper included a program for Bayesian imputation-based association mapping (BIMBAM), a program for imputing unobserved genotypes in case-control association studies (IMPUTE), and a program for testing untyped alleles (TUNA). We found some untyped SNP that showed significant association with rheumatoid arthritis. Among them, a few of these were not located near any typed SNP that was found to be significant and thus may be worth further investigation.
18955284 Potential Use of Plectranthus amboinicus in the Treatment of Rheumatoid Arthritis. 2010 Mar Plectranthus amboinicus (P. amboinicus) is a folk herb that is used to treat inflammatory diseases or swelling symptoms in Taiwan. We investigated therapeutic efficacy of P. amboinicus in treating Rheumatoid Arthritis (RA) using collagen-induced arthritis animal model. Arthritis was induced in Lewis rats by immunization with bovine type II collagen. Serum anti-collagen IgG, IgM and C-reactive protein (CRP) were analyzed. To understand the inflammation condition of treated animals, production of TNF-α, IL-6 and IL-1β from peritoneal exudates cells (PEC) were also analyzed. P. amboinicus significantly inhibited the footpad swelling and arthritic symptoms in collagen-induced arthritic rats, while the serum anti-collagen IgM and CRP levels were consistently decreased. The production of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β were also decreased in the high dosage of P. amboinicus group. Here, we demonstrate the potential anti-arthritic effect of P. amboinicus for treating RA, which might confer its anti-rheumatic activity. This differs the pharmacological action mode of indomethacin.
19342955 Anticytokine therapy in non-rheumatoid arthritis indications in 2009. 2009 May PURPOSE OF REVIEW: To review the current uses of antitumor necrosis factor alpha (TNFalpha) therapies for non-rheumatoid arthritis inflammatory joint diseases. Emphasis is given to important questions regarding long-term use of anti-TNFalpha therapies. RECENT FINDINGS: TNFalpha blockade is one of the anticytokine therapies with major impact in the treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and juvenile idiopathic arthritis among the inflammatory joint diseases. As a result of the impressive response to TNFalpha inhibitors, new agents continue to be developed and a few are currently being tested in phase III trials. The evaluation of a potential relationship between inflammation and structural damage in ankylosing spondylitis has been an important focus of recent studies and will likely result in a better understanding and use of anti-TNFalpha therapy. Other aspects of treatment such as long-term safety and selection of patients who will likely have a major response have been evaluated in recent studies and will continue to be important topics in future research. SUMMARY: As TNFalpha inhibitors have been a major advance in the treatment of a number of inflammatory joint diseases and have been widely available in clinical practice, future research will need to continuously assess longitudinal efficacy and safety.
21346905 Detection of Viral Citrullinated Peptide Antibodies Directed Against EBV or VCP: In Early 2010 Jul AIM: Study was undertaken to analyze the frequency of anti-viral citrullinated peptide (anti-VCP) antibodies in sera from patients with early rheumatoid arthritis (ERA). MATERIALS AND METHODS: Viral citrullinated peptide (VCP) and Epstein-Barr nuclear antigen (EBNA-1) peptide were commercially prepared and antibodies to these were determined in 25 patients of ERA, 40 disease control patients constituting 25 rheumatoid arthritis (RA), 7 systemic lupus erythematosus (SLE), 2 scleroderma, 1 spondyloarthritis (SpA), 1 juvenile rheumatoid arthritis (JRA), 1 osteoarthritis (OA), 1 psoriatic arthritis (PsA), 1 undifferentiated arthritis (UA), and 1 gout and 25 healthy controls (HCs) were taken for comparison. In-house ELISA was established for both the antibodies while cyclic citrullinated peptide (CCP) antibody was detected by commercial ELISA kit. RESULTS: Significant increase in VCP antibody by ERA and disease controls than healthy normal was observed. VCP IgM antibody was significantly increased in RA patients than HC. The presence of VCP antibody signifies a good marker for ERA. We observed significant difference in the VCP IgG and IgM antibody when compared to EBNA-1. In-house ELISA established for EBNA-1 and VCP antibodies showed low sensitivity but 96% specificity. CONCLUSIONS: We observed that sera from early RA patients reacted to the deiminated protein encoded by Epstain Barr Virus (EBV). Thus a possible role of virus in inducing an anti-citrullinated peptide antibody (ACPA) response reveals viral etiology in this disease.
20161980 Safety of etanercept in elderly subjects with rheumatoid arthritis. 2010 Feb 4 OBJECTIVE: To report side effects seen in a clinical cohort of patients aged >65 years with rheumatoid arthritis (RA) treated with the tumor necrosis factor-alpha TNF-alpha blocker etanercept and to compare the side effects rate with patients aged 65 years and 62 (40 females, 22 males) aged <65 years. In the patients aged >65 years, the safety profile (defined as rate of side effects) of etanercept was similar to that in patients aged 0.05) and the survival curves between the groups were similar (P > 0.05). CONCLUSIONS: In our three-year experience, the anti-TNFalpha agent etanercept has been well tolerated and safe in elderly patients. The risk of side effects in these patients was no greater than in subjects aged
20689780 Regression of macular edema secondary to branch retinal vein occlusion during anti-TNF-alp 2010 Jul 30 A patient with macular edema secondary to a branch retinal vein occlusion (BRVO) was treated with intravenous injections of infliximab, an antitumor necrosis factor (TNF)-alpha antibody, for her rheumatoid arthritis (RA). Before the injection, the thickness of the right fovea, determined by optical coherent tomography, was 629 mum and the best-corrected visual acuity (BCVA) was 20/50. After eight injections of infliximab and 10 months after the first injection, her foveal thickness was decreased to 293 mum and the visual acuity improved to 20/20. There was no recurrence of macular edema during the infliximab injections. However, the infliximab injection was stopped because the patient developed pneumonia. Eight months after stopping the infliximab injection, her foveal thickness increased to 494 mum. To treat the RA, her orthopedists began weekly subcutaneous injections of etanercept, a fusion protein of a section of the TNF receptor and immunoglobulin. Five months later, the foveal thickness had decreased to 260 mum, and the visual acuity remained at 20/25(+). Because TNF-alpha is known to break down the blood-retinal barrier, the improvements in our case suggest that TNF-alpha plays a role in the pathogenesis of macular edema in some patients with BRVO.
21523217 Rheumatoid arthritis and the role of oral bacteria. 2010 Dec 21 Rheumatoid arthritis (RA) and periodontal disease (PD) have shown similar physiopathologic mechanisms such as chronic inflammation with adjacent bone resorption in an immunogenetically susceptible host; however, PD has a well-recognized bacterial etiology while the cause of RA is unclear. Some reports have indicated that an infectious agent in a susceptible host could be one possible trigger factor for RA, and it has been suggested that oral microorganisms, specialty periodontal bacteria could be the infectious agent (mainly Porphyromonas gingivalis). It has been reported that PD is more frequent and more severe in patients with RA, suggesting a positive association between both diseases. There have been reports regarding the detection of antibodies against periodontal bacteria while other studies have identified periodontal bacterial DNA in serum and synovial fluid of RA patients and have explored the possible pathways of transport of periodontal bacterial DNA. In conclusion, there is no question that RA and PD have pathologic features in common and there is strong evidence of an association between both diseases, but further studies, including experimental models, are needed to demonstrate the arthritogenicity of oral microorganisms.
26192426 Aortoesophageal fistula following nasogastric tube placement. 2009 Aug A 78-year-old woman was admitted to our hospital because of fresh cerebral infarction. She had been diagnosed as having rheumatoid arthritis, but had not been treated for 50 years. She could not take in sufficient food. Upper gastrointestinal endoscopy revealed no esophageal or gastric lesions, but the procedure was difficult because of her stiff neck from severe rheumatoid degenerative changes of the cervical spine. A nasogastric (NG) tube was placed, and enteral nutrition was initiated. On the 15th day from initiation of enteral nutrition, she presented hematemesis, and suddenly went into a state of shock and died. An autopsy revealed two esophageal ulcers, one of which penetrated into the descending thoracic aorta. The patient was diagnosed with hemorrhagic shock due to aortoesophageal fistula. We suspect that the NG tube compressed the esophageal wall, and ischemia caused the ulcers.
22096355 Current perspectives on the role of IL-17 in autoimmune disease. 2010 Until recently, autoimmune diseases had been categorized as either Th1- or Th2-mediated diseases. However, the discovery of a novel subset of helper T cells producing interleukin (IL)-17, ie, Th17 cells, changed this paradigm. Currently, IL-17 and Th17 cells are implicated in many autoimmune diseases, such as rheumatoid arthritis, psoriasis, multiple sclerosis, and inflammatory bowel diseases. Such conclusions were initially drawn from observations in animal models of autoimmune diseases, and accumulating data from clinical research also support the involvement of IL-17 in human diseases as well. Reagents targeting Th17-related molecules have been under clinical investigation for some diseases but have not always been effective in controlling disease activity. Consistent with this, it has become evident that there are substantial differences in the development of Th17 cells and in the way they function in autoimmune diseases between humans and experimental animals. Thus, further investigation is needed before we can draw any conclusions about the importance of IL-17 and Th17 cells in human autoimmune diseases.
20017995 A principal-components-based clustering method to identify multiple variants associated wi 2009 Dec 15 Multivariate techniques are an important area of investigation for studying contributions of multiple genetic variants to disease onset and pathology. We analyzed the Genetic Analysis Workshop 16 North American Rheumatoid Arthritis Consortium (NARAC) data using a principal-components analysis (PCA) with an orthoblique rotation to identify specific subsets of single-nucleotide polymorphisms (SNP) in the major histocompatibility complex (MHC) region associated with rheumatoid arthritis (RA) and rheumatoid factor IgM (RFUW), and compared this method with a traditional PC approach. Using the orthoblique PC-based clustering method, we identified new clusters of SNPs across the MHC region associated with RA and RFUW, and replicated known SNP cluster associations with RA, such as those in the HLA-DRB region.
20670388 Functional genomics and rheumatoid arthritis: where have we been and where should we go? 2010 Jul 28 Studies in model organisms and humans have begun to reveal the complexity of the transcriptome. In addition to serving as passive templates from which genes are translated, RNA molecules are active, functional elements of the cell whose products can detect, interact with, and modify other transcripts. Gene expression profiling is the method most commonly used thus far to enrich our understanding of the molecular basis of rheumatoid arthritis in adults and juvenile idiopathic arthritis in children. The feasibility of this approach for patient classification (for example, active versus inactive disease, disease subsets) and improving prognosis (for example, response to therapy) has been demonstrated over the past 7 years. Mechanistic understanding of disease-related differences in gene expression must be interpreted in the context of interactions with transcriptional regulatory molecules and epigenetic alterations of the genome. Ongoing work regarding such functional complexities in the human genome will likely bring both insight and surprise to our understanding of rheumatoid arthritis.
20067026 [Effects of Gaultheria yunnanensis on adjuvant arthritis in rats]. 2009 Oct OBJECTIVE: Gaultheria yunnanensis. are used widespreadly in the south of China to treat rheumatoid arthritis. The aim of this study was to provide an experimental basis for G. yunnanensis to therapy rheumatoid arthritis. METHOD: We prepared water extracts, ethanol extracts, n-butanol extracts, ethyl acetate extracts and the rest of ethanol extracts from G. yunnanensis. Then, the n-butanol extracts were applied to macroporous resin and eluted with water, 30% ethanol, and 95% ethanol. Rheumatoid arthritis was induced by Freund's complete adjuvant injected into right postpedes in Wistar rats which was utilized to elucidate the anti-inflammatory effect of different extracted liquid of G. yunnanensis. Rats were intragastric injected (ig) with extracts as experimental group or normal saline as control group. RESULT: Freund's complete adjuvant induced arthritis was successfully established: paw edema were increased after Freund's complete adjuvant injection, peaked at 2 or 3 day, then decreased, the paw edema were increased again at 7 or 8 day, and persisted 15 d. Water extracts, n-butanol extracts or ethyl acetate extracts could a significantlly decrease the paw edema as compared with the control group (P < 0.05, P < 0.01). The effect of n-butanol extracts was the most powerful. Further, n-butanol extracts eluant with water and 30% ethanol decreased the paw edema. The activity of extracts eluant with 30% ethanol was stronger than that of eluant with water. CONCLUSION: G. yunnanensis displays considerable effects against Freund s complete adjuvant induced arthritis in rats, which is in concordance with clinical practice. n-Butanol extracts and both of the eluants with water and 30% ethanol produce a significant decrease in the paw edema. 30% ethanol eluants show a stronger activity than others. The effects against rheumatoid arthritis of different parts of G. yunnanensis differ in degree. It is deserved to explore the potential mechanisms of anti-inflammtion of the G. yunnanensis, especially the n-butanol extracts eluant with 30% ethanol.
26189904 Perforation of rectal diverticulum with amyloidosis secondary to rheumatoid arthritis: cas 2010 Feb We report a case of perforation of a rectal diverticulum with amyloidosis secondary to rheumatoid arthritis (RA), and review the clinicopathologic features in 21 Japanese amyloidosis patients with colorectal perforation. A 62-year-old woman with amyloidosis secondary to RA suddenly complained of abdominal pain. Computed tomography (CT) showed ascites and free air in the abdominal cavity, and many diverticula with calculi in the sigmoid colon. Emergent surgery was performed for acute peritonitis. We observed the perforation, 5 mm in diameter, of a diverticulum in the upper rectum, and many diverticula located in the upper rectum and sigmoid colon. Anterior resection of the rectum combined with sigmoidectomy was performed. The resected specimen showed many diverticula including fecaliths, approximately 7 mm in size. Histopathologically, many inflammatory cells had infiltrated around the perforation. On Congo red staining, amyloid deposits were observed in or around the small blood vessels of the lamina propria mucosa and submucosa of the rectum. Although colorectal perforation with amyloidosis secondary to RA is rare, this complication was associated with poor prognosis. Furthermore, in patients with amyloidosis, we should be careful regarding the management of colorectal diverticula.
21794645 [Management of problematic clinical situations in rheumatoid arthritis patients. Surgery]. 2009 Apr Even though clinical management and treatment of rheumatoid arthritis patients has improved, orthopedic surgery is now a common situation in daily clinical practice. Usually, the rheumatologist is who manages the anti-rheumatic treatment in the perioperative period and decisions are not always supported by scientific information of suitable quality.
21163125 Clinical and prognostic characteristics of 573 cases of primary Sjögren's syndrome. 2010 Nov BACKGROUND: Primary Sjögren's syndrome (pSS) is one of the autoimmune diseases with high incidence. There were several clinical investigations in Caucasian but seldom in Chinese. The aim of this study was to compare the difference of clinical manifestations, immunological features and prognosis of pSS between Caucasian and Chinese pSS patients. METHODS: Five hundred and seventy-three patients who fulfilled the 2002 international classification (criteria) for pSS from Peking Union Medical College Hospital between 1985 and 2006 were screened retrospectively and compared with other populations. RESULTS: (1) The study consisted of 524 (91%) female and 49 (9%) male patients (female: male = 10.7:1). Mean age at the onset of the disease was (39.0 ± 13.7) years and in 169 (29.5%) patients the disease onset occurred before the age of 30 years. The average duration from disease onset to pSS diagnosis was 48 months (range, 1 - 552 months). It had been shortened during the recent five years. (2) Dry mouth (84.5%) and dry eyes (70.0%) were the most common symptoms, significantly lower than foreign patients (P = 0.000). Two hundred and seventy-two (47.5%) patients presented with rampant caries, 160 (27.9%) with parotidomegaly. The positivity of xerostomia, xerophthalmia and salivary gland biopsy were 91.9%, 94.8% and 90.7%, respectively. (3) Systemic involvement occurred in 91.4% patients. Compared with studies done outside China, higher prevalence of fever 41.0%, myositis 4.9%, pericardial effusion 14.8%, pulmonary involvement 42.3%, renal involvement 33.5%, thyroid involvement 32.7%, pancrease involvement 5.6% (P < 0.01) and lower prevalence of fatigue, lymphadenectasis and Raynaud's phenomenon (P < 0.01) were seen. (4) Risk factors of death include pulmonary artery hypertension, liver damage and interstitial lung disease. CONCLUSIONS: Chinese pSS differs significantly from the non-Chinese cases in terms of the age of onset, systemic involvement, autoantibodies and proportional mortality rate. Lung and liver damage were found to be the highest risk factors of the disease prognosis.
22870451 The role of interleukin 6 in the pathophysiology of rheumatoid arthritis. 2010 Oct Interleukin 6 (IL-6) is a pleiotropic cytokine with a pivotal role in the pathophysiology of rheumatoid arthritis (RA). It is found in abundance in the synovial fluid and serum of patients with RA and the level correlates with the disease activity and joint destruction. IL-6 can promote synovitis and joint destruction by stimulating neutrophil migration, osteoclast maturation and vascular endothelial growth factor (VEGF)-stimulated pannus proliferation. IL-6 may also be mediating many of the systematic manifestations of RA including inducing the acute-phase reaction [including C-reactive protein (CRP)], anaemia through hecipidin production, fatigue via the hypothalamic-pituitary-adrenal (HPA) axis) and osteoporosis from its effect on osteoclasts. In addition, IL-6 may contribute to the induction and maintenance of the autoimmune process through B-cell maturation and TH-17 differentiation. All of the above makes IL-6 blockade a desirable therapeutic option in the treatment of RA. Following successful animal studies, a humanized anti-interleukin-6 receptor (anti-IL-6R) monoclonal antibody, tocilizumab (TCZ), entered into clinical trials and it has been shown to be an effective treatment in several large phase III clinical trials in RA with rapid and sustained improvement in disease activity, reducing radiographic joint damage and improving physical function.
20018070 Rheumatoid arthritis-associated gene-gene interaction network for rheumatoid arthritis can 2009 Dec 15 Rheumatoid arthritis (RA, MIM 180300) is a chronic and complex autoimmune disease. Using the North American Rheumatoid Arthritis Consortium (NARAC) data set provided in Genetic Analysis Workshop 16 (GAW16), we used the genotype-trait distortion (GTD) scores and proposed analysis procedures to capture the gene-gene interaction effects of multiple susceptibility gene regions on RA. In this paper, we focused on 27 RA candidate gene regions (531 SNPs) based on a literature search. Statistical significance was evaluated using 1000 permutations. HLADRB1 was found to have strong marginal association with RA. We identified 14 significant interactions (p < 0.01), which were aggregated into an association network among 12 selected candidate genes PADI4, FCGR3, TNFRSF1B, ITGAV, BTLA, SLC22A4, IL3, VEGF, TNF, NFKBIL1, TRAF1-C5, and MIF. Based on our and other contributors' findings during the GAW16 conference, we further studied 24 candidate regions with 336 SNPs. We found 23 significant interactions (p-value < 0.01), nine interactions in addition to our initial findings, and the association network was extended to include candidate genes HLA-A, HLA-B, HLA-C, CTLA4, and IL6. As we will discuss in this paper, the reported possible interactions between genes may suggest potential biological activities of RA.