Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 16931026 | Five-year results of the Sigma total knee arthroplasty. | 2006 Oct | The DePuy Sigma total knee arthroplasty (TKA) was introduced in 1997 as a modification of the Press Fit Condylar Knee (PFC) TKA and has been used extensively in the United Kingdom and worldwide. It is the most commonly used TKA in England and Wales, where it accounts for 36% of all primary TKA. The PFC was well established, with reported 10-year survival rates of 93-97%, but this study reports the first 5-year clinical and radiographic follow-up data for the Sigma TKA. Over a 10-month period, 212 Sigma TKAs were performed in 180 patients. Patients were seen at a specialist nurse-led clinic 7 to 10 days before admission and at 6 months, 18 months, 3 years and 5 years after surgery. Data were recorded prospectively at each visit. Radiographs were obtained at the 5-year follow-up appointment. Of 212 knees, 178 (151 patients) were alive at 5 years. Three were lost to follow up. Six knees (3.0%) were revised, five for infection and one underwent change of polyethylene insert at 4.9 years. Five-year survival with an endpoint of revision for any reason was 97.0%; with an endpoint of revision for aseptic failure it was 99.5%. The median American Knee Society knee rating score was 93 out of 100 at 5 years compared with 25 out of 100 at admission. Of 147 radiographs, none showed radiographic loosening of either component. Seventeen (11.6%) showed radiolucent lines. Twenty-eight (19.0%) had alignment outside the range of 7+/-3 degrees valgus. These results suggest that the Sigma TKA gives acceptable clinical results after 5 years. Further follow-up studies are required to see if this performance is maintained in the long term. | |
| 18648537 | A large-scale rheumatoid arthritis genetic study identifies association at chromosome 9q33 | 2008 Jun 27 | Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease affecting both joints and extra-articular tissues. Although some genetic risk factors for RA are well-established, most notably HLA-DRB1 and PTPN22, these markers do not fully account for the observed heritability. To identify additional susceptibility loci, we carried out a multi-tiered, case-control association study, genotyping 25,966 putative functional SNPs in 475 white North American RA patients and 475 matched controls. Significant markers were genotyped in two additional, independent, white case-control sample sets (661 cases/1322 controls from North America and 596 cases/705 controls from The Netherlands) identifying a SNP, rs1953126, on chromosome 9q33.2 that was significantly associated with RA (OR(common) = 1.28, trend P(comb) = 1.45E-06). Through a comprehensive fine-scale-mapping SNP-selection procedure, 137 additional SNPs in a 668 kb region from MEGF9 to STOM on 9q33.2 were chosen for follow-up genotyping in a staged-approach. Significant single marker results (P(comb)<0.01) spanned a large 525 kb region from FBXW2 to GSN. However, a variety of analyses identified SNPs in a 70 kb region extending from the third intron of PHF19 across TRAF1 into the TRAF1-C5 intergenic region, but excluding the C5 coding region, as the most interesting (trend P(comb): 1.45E-06 --> 5.41E-09). The observed association patterns for these SNPs had heightened statistical significance and a higher degree of consistency across sample sets. In addition, the allele frequencies for these SNPs displayed reduced variability between control groups when compared to other SNPs. Lastly, in combination with the other two known genetic risk factors, HLA-DRB1 and PTPN22, the variants reported here generate more than a 45-fold RA-risk differential. | |
| 17091247 | FcgammaRII and multi-system autoimmune disease. | 2006 Dec | The FcR are a crucial link in the immune response between humoral and cellular immunity and cell-based effector systems, mediating a wide variety of physiological and biochemical responses. The FcR for IgG (FcgammaR) and in particular the most widely expressed of these, FcgammaRII, are important in regulating adaptive immunity. Disruption of their function is a key factor in the development of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), which are characterized by chronic, multi-organ inflammation. Studies of the FcgammaRII include structure/function relationships, investigation of the associations between FcR polymorphisms and human disease and animal studies using knockout or transgenic mouse models. These investigations showed that the various forms of FcgammaRII interact with immune complexes to either initiate or inhibit inflammation. In conjunction with environmental antigens and genotype, the FcgammaRII activating and inhibitory receptors determine the nature and magnitude of response to antigens. In this review, the structure and function of the FcgammaRIIs and their role in immune complex-mediated auto-immunity are discussed. | |
| 18300281 | Autoimmune disease concomitance among inflammatory bowel disease patients in the United St | 2008 Jun | BACKGROUND: Recent studies suggest that inflammatory bowel disease (IBD) may share an underlying pathogenesis with other autoimmune diseases. METHODS: Two United States data sets with patient-level medical and drug claims were used to explore the occurrence of autoimmune diseases in patients with IBD, particularly Crohn's disease (CD) and ulcerative colitis (UC), with that in controls. From 2001 to 2002 IBD patients were identified using International Classification of Diseases, 9th revision, diagnosis codes in the IMS Health Integrated Administration Claims Database and the Market Scan Commercial Claims and Encounters Database. Controls were selected by matching on sex, age, Census Bureau region, and length of previous medical insurance coverage. Odds ratios (ORs) evaluated the risk relationship between IBD patients and controls within an estimated Mantel-Haenszel 95% confidence interval. Sensitivity analysis tested the case identification method used to select IBD patients. RESULTS: The risk for ankylosing spondylitis (AS) was substantially increased across both data sets: OR (95% confidence interval [CI]) of 7.8 (5.6-10.8) in IMS Health and 5.8 (3.9-8.6) in MarketScan. The risk for rheumatoid arthritis (RA) was 2.7 (2.4-3.0) and 2.1 (1.8-2.3), respectively; for multiple sclerosis (MS); the ORs were 1.5 (1.2-1.9) and 1.6 (1.2-2.1), respectively. There was no increased risk for type 1 diabetes mellitus, and the results for psoriatic arthritis (PsA) were inconsistent. The sensitivity analysis supported these findings. CONCLUSIONS: A much higher risk for RA, AS, PsA, and MS was observed in IBD patients compared with controls. Prospective epidemiologic studies are needed to confirm these findings and explore the pathogenic mechanism of this relationship. | |
| 18094540 | Analysis of risk epitopes of anti-neutrophil antibody MPO-ANCA in vasculitis in Japanese p | 2007 | Autoantibodies to myeloperoxidase (MPO) are a subset of anti-neutrophil cytoplasmic antibody (ANCA, MPO-ANCA) detected in the sera of some patients with primary systemic vasculitis. The titer of MPO-ANCA does not always reflect disease activity and this inconsistency may be attributable to differences in epitopic specificity by MPO-ANCA among various patients with vasculitis. Epitope analysis may also explain the occurrence of MPO-ANCA in different vasculitic syndromes. We screened the sera of 148 MPO-ANCA positive patients from six vasculitic syndromes: rapidly progressive gromerulonephritis (RPGN), microscopic polyangiitis (MPA), idiopathic crescentic glomerulonephritis (I-CrGN), classic polyangiitis nodosa (cPAN), Churg-Strauss syndrome (CSS), Kawasaki disease (KD); and from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The sera were collected by the Intractable Vasculitis Research Project Group in Japan. No serum showed epitopes La and Lb of light chain of MPO, and sera with 68.6% of patients showed a positive reaction to one or more epitopes in heavy chain of MPO. Analysis of binding level showed that RPGN, I-CrGN and MPA sera mainly reacted to the Ha epitope at the N-termimus of the MPO heavy chain, CSS sera reacted to Ha and the Hf epitope close to the C-terminus of the MPO heavy chain, KD reacted mainly to Hf, while SLE and RA sera reacted to all epitopes. These results suggest that MPO-ANCA recognizing specific regions of the N-terminus of the MPO H-chain confer an increased risk of vasculitis RPGN, I-CrGN, MPA and CSS. Furthermore, the epitopic specificity of MPO-ANCA differentiates vasculitic from non-vasculitic syndromes associated with MPO-ANCA positivity and differentiates in the cirtain type of vasculitis from various vasculitic syndromes. In particular, vasculitic syndromes associated with kidney involvement had similar epitopic reactivity which suggests that this pattern confers an increased risk of vasculitis. | |
| 17848581 | Pharmacologic inhibition of tpl2 blocks inflammatory responses in primary human monocytes, | 2007 Nov 16 | Tumor necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine that controls the initiation and progression of inflammatory diseases such as rheumatoid arthritis. Tpl2 is a MAPKKK in the MAPK (i.e. ERK) pathway, and the Tpl2-MEK-ERK signaling pathway is activated by the pro-inflammatory mediators TNFalpha, interleukin (IL)-1beta, and bacterial endotoxin (lipopolysaccharide (LPS)). Moreover, Tpl2 is required for TNFalpha expression. Thus, pharmacologic inhibition of Tpl2 should be a valid approach to therapeutic intervention in the pathogenesis of rheumatoid arthritis and other inflammatory diseases in humans. We have developed a series of highly selective and potent Tpl2 inhibitors, and in the present study we have used these inhibitors to demonstrate that the catalytic activity of Tpl2 is required for the LPS-induced activation of MEK and ERK in primary human monocytes. These inhibitors selectively target Tpl2 in these cells, and they block LPS- and IL-1beta-induced TNFalpha production in both primary human monocytes and human blood. In rheumatoid arthritis fibroblast-like synoviocytes these inhibitors block ERK activation, cyclooxygenase-2 expression, and the production of IL-6, IL-8, and prostaglandin E(2), and the matrix metalloproteinases MMP-1 and MMP-3. Taken together, our results show that inhibition of Tpl2 in primary human cell types can decrease the production of TNFalpha and other pro-inflammatory mediators during inflammatory events, and they further support the notion that Tpl2 is an appropriate therapeutic target for rheumatoid arthritis and other human inflammatory diseases. | |
| 17660179 | Effects and mechanisms of catechin for adjuvant arthritis in rats. | 2007 May | The present study was carried out to investigate the effects of catechin on adjuvant arthritis (AA) in the rat and its possible mechanisms of action. AA was induced by metatarsal footpad injection with complete Freund's adjuvant in male Sprague-Dawley rats. The secondary inflammatory reaction was evaluated through assessment of hind paw swelling, polyarthritis index, and pain response. Proliferation of synoviocytes and the activity of interleukin-1 were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tumor necrosis factor-alpha, prostaglandin E(2) (PGE(2)), and cyclic adenosine monophosphate levels in synoviocytes were measured by radioimmunoassay. The PGE(2) receptor, EP(2), was analyzed by Western blot analysis. Intragastric administration of catechin (60 and 120 mg/kg) significantly suppressed secondary inflammatory paw swelling, pain response, and polyarthritis index. It also inhibited production of interleukin-1, tumor necrosis factor-alpha, and PGE(2) and increased cyclic adenosine monophosphate levels in rats with AA. In the immunoblot analysis, catechin could upregulate expression of EP(2) in the synoviocytes of rats with AA. The results showed that catechin reduced secondary inflammation in rats with AA; this outcome reflects its ability to mediate cAMP levels, upregulate expression of EP(2), and inhibit secretion of proinflammatory cytokines in rats with AA. | |
| 18409343 | [Effectiveness evaluation of knee joint 90Y radiosynovectomy]. | 2007 | INTRODUCTION: Chronic knee synovitis with effusion, because of the special role of knee joint is an important therapeutic problem. This leads to searching for new treatment modalities. One of them is radiosynovectomy based on anti-proliferative and anti-inflammatory activity of ionizing radiation. It is made using 90Y mainly (high energy of beta [electrons] radiation [2.2 MeV], large average penetration in soft tissues [3.6 mm] and long physical half-life [2.7 days]). MATERIAL AND METHOD: Analyzed material is comprised of 30 patients (33 treatments) suffering from proliferative synovitis of knee joint treated by radiosynovectomy using intra-articular injection of 6 mCi 90Y. In 20 cases the reason of disease was non-specific reactive arthritis, in 5 rheumatoid arthritis, in 3 villonodular synovitis, in 3 psoriasis and in 2 ulcerative colitis. Symptoms duration varied from 3 to 144 months (mean 43). A knee circumference at the treatment day varied from 33.5 cm to 49 cm (mean 41). The operation was based on knee biopsy, evacuation of exudate and delivery of 6 mCi of colloid 90Y. Follow up ranged up to 14 months (mean 4.4). Patients were examined 2 weeks, 1, 3, 6 and 12 months after treatment. During examination a knee circumference was measured, a knee mobility, temperature and patella floating symptom were examined. Pain in treated region was assessed and amount of exudate was measured. RESULTS: A knee circumference and exudate amount enlarged during following controls, and compared between the treatment day and the last control did not differ significantly (41 vs. 41.6 cm and 43 vs. 42.5 ml respectively) but number of biopsies decreased. A percentage of patients with impaired knee mobility also did not change (59% vs. 58%). Probably, it was caused by resignation from control examination when symptoms disappeared. A percentage of patients without pain relief decreased from 43.5% 2 weeks after treatment to 20% one year later and a patient percentage with complete pain relief increased from 8.5% to 60%. A patient percentage with increased knee temperature and with floating patella decreased significantly (54 vs. 25% and 83 vs. 48% respectively). CONCLUSIONS: Obtained results do not allow to form univocal conclusions regarding effectiveness of 90Y radiosynovectomy. The decreasing biopsies number, decreasing percentage of patient with increased knee temperature and with floating patella; increased percentage of patients with analgetic effect and with total pain relief show a necessity of renewed evaluation of this treatment modality on the base of bigger patients number and longer and more precise observation. | |
| 18209062 | The soluble leukocyte-associated Ig-like receptor (LAIR)-2 antagonizes the collagen/LAIR-1 | 2008 Feb 1 | Leukocyte-associated Ig-like receptor (LAIR)-1 is a collagen-receptor that inhibits immune cell function upon collagen binding. Next to LAIR-1, the human genome encodes LAIR-2, a putative soluble homolog. In this study we show, for the first time, that the LAIR-2 gene is broadly transcribed in human PBMC, mirroring the expression profile of LAIR-1. LAIR-2 protein is expressed as a soluble receptor exhibiting high affinity for various collagen molecules to which it binds in a hydroxyproline-dependent manner. In vitro stimulation of PBMC induces secretion of LAIR-2. We detect high amounts of LAIR-2 in urine of pregnant women, indicating that the soluble receptor is indeed produced in vivo and can be cleared from the body via urine. Furthermore, LAIR-2 levels are increased in synovial fluid of patients with rheumatoid arthritis as compared with osteoarthritis patients. We hypothesize that soluble LAIR-2 may function as a natural competitor for LAIR-1, thereby regulating its inhibitory potential. Indeed, LAIR-2 prevents binding of human LAIR-1 to collagens and LAIR-1 cross-linking in vitro, suggesting that the protein has an immunoregulatory function in vivo. Hence, we reveal a novel mechanism of immune regulation by a soluble LAIR receptor regulating the inhibitory potential of the membrane-bound LAIR-1 via competition for ligands. | |
| 18260301 | [Adult-onset Still's disease following severe sore throat and fever. Case report]. | 2008 Jan | Adult-onset Still's disease (AOSD) is characterized by fever, rash, and joint pain and may lead to chronic arthritis. The cause of AOSD is unknown, and it is rare. In children, Still's Disease is called systemic juvenile rheumatoid arthritis. We encountered a patient with adult-onset Still's disease following a severe sore throat and fever. The patient was a 17-year-old woman who consulted our hospital because of a sore throat and fever. She was admitted and treated with antibiotics, but the fever persisted. Laboratory parameters of inflammatory activity increased at an accelerated rate, and after ruling out sepsis, EBV-associated disease, and malignant lymphoma, a diagnosis of AOSD was made. Steroid therapy was very effective. When acute pharyngitis is observed in association with significant changes in laboratory parameters despite mild local symptoms, or when pharyngitis is observed in association with joint pain, continuous fever, and a rash, it is important to consider AOSI). | |
| 17713029 | Therapeutic potential of cannabinoid-based drugs. | 2007 | Cannabinoid-based drugs modeled on cannabinoids originally isolated from marijuana are now known to significantly impact the functioning of the endocannabinoid system of mammals. This system operates not only in the brain but also in organs and tissues in the periphery including the immune system. Natural and synthetic cannabinoids are tricyclic terpenes, whereas the endogenous physiological ligands are eicosanoids. Several receptors for these compounds have been extensively described, CB1 and CB2, and are G protein-coupled receptors; however, cannabinoid-based drugs are also demonstrated to function independently of these receptors. Cannabinoids regulate many physiological functions and their impact on immunity is generally antiinflammatory as powerful modulators of the cytokine cascade. This anti-inflammatory potency has led to the testing of these drugs in chronic inflammatory laboratory paradigms and even in some human diseases. Psychoactive and nonpsychoactive cannabinoid-based drugs such as Delta9-tetrahydrocannabinol, cannabidiol, HU-211, and ajulemic acid have been tested and found moderately effective in clinical trials of multiple sclerosis, traumatic brain injury, arthritis, and neuropathic pain. Furthermore, although clinical trials are not yet reported, preclinical data with cannabinoid-based drugs suggest efficacy in other inflammatory diseases such as inflammatory bowel disease, Alzheimer's disease, atherosclerosis, and osteoporosis. | |
| 17037405 | [Gastropleural fistula due to perforated gastric ulcer]. | 2006 Sep | A 65-year-old woman, who had been taking non-steroidal anti-inflammatory drugs (NSAIDs), prednisolone and methotrexate for rheumatiod arthritis, was admitted to our hospital with a sudden onset of left-back and chest pain and breathlessness. A chest radiograph and computed tomography revealed a left-side pneumothorax and pleural effusion. Chest tube was inserted for drainage and the fluid was formed to contain food residuum. Contrast radiography demonstrated escape of soluble contrast medium into the left pleural space. A thoracotomy and transdiaphragmatic revealed a gastropleural fistula. It was repaired and the gastric origin was resected. Pathologic evaluation revealed evidence of chronic peptic ulceration, but no malignant change. Gastropleural fistula due to peptic ulcer without esophageal herniation, malignancy, or traumatic injury is extremely unusual. The cause of the focal adhesion of the gastric ulcer and diaphragm, fistula formation was not certain but was probably related to the ingestion of NSAIDs in combination with prednisolone and other immunosuppressive agents. Although gastropleural fistula is rare, the prognosis in such patients related to early diagnosis and surgical intervention, emphasizing the importance of including this condition when making a differential diagnosis. | |
| 17053321 | Effects of insulin-like growth factor I on transforming growth factor beta1 induced chondr | 2006 | The aim of this study was to demonstrate the induction of chondrogenesis by transforming growth factor (TGF)-beta1 from synovium-derived mesenchymal stem cells in a three-dimensional polyglycolic acid (PGA) scaffold, and to evaluate the effects of insulin-like growth factor (IGF)-I on TGF-beta1-induced chondrogenesis. Adult human synovial membranes were obtained from the knees of patients with osteoarthritis or rheumatoid arthritis. Cells were expanded in monolayers, seeded onto a PGA scaffold, and cultured for 4 or 8 weeks in chondrogenic medium containing TGF-beta1 with or without IGF-I. As a control, the cells were cultured in chondrogenic medium without TGF-beta1. The glycosaminoglycan content was quantified using dimethylmethylene blue dye-binding assay, and the DNA content was measured fluorometrically. Histological examination was also performed using safranin-O staining. The expression of mRNA for aggrecan and collagen type II was confirmed by RT-PCR. After 4 weeks of cultivation with TGF-beta1, the cells differentiated to a chondrocytic phenotype, and these chondrogeneses were more potent when cultured for 8 weeks. The combination of IGF-I and TGF-beta1 produced higher amounts of glycosaminoglycan than TGF-beta1 alone at 8 weeks. In conclusions, chondrogenesis from human synovium-derived mesenchymal cells was identified, and IGF-I plays a role in maintaining the extracellular matrix in combination with TGF-beta1. | |
| 16944142 | ACL reconstruction and the implication of its tibial attachment for stability of the joint | 2007 Aug | The planar topography of the anterior cruciate ligament (ACL) insertion was investigated and correlated to the use of the double-bundle/double tibial tunnel ACL reconstruction technique within the ACL tibial insertion area. The anteroposterior and mediolateral length of the tibial ACL attachment and the distances of the tibial insertion area from the anterior and posterior tibial borders were measured and the stability of the joint was tested using the double-bundle/double tibial tunnel ACL reconstruction technique. The anteroposterior length, 19.54 mm in men and 17.36 mm in women, of the ACL insertion, averaged approximately 40% of the total intercondylar anteroposterior dimension of the plateau. This broad distribution of insertion fibres ensures ligament tension and hence joint stability. The reported anteroposterior broad insertion of ACL fibres to the tibia is not sufficiently reproduced by the use of one or more bundles having a common tibial tunnel for the ACL reconstruction. In our view, this might be better achieved with two different bundles, with separate tunnels, and independent tensioning in different knee angles. This technique might achieve better results in human knee stability as opposed to other reported techniques. | |
| 17024157 | Acromegaly diagnosed in a young woman presenting with headache and arthritis. | 2006 Oct | BACKGROUND: A 38-year-old woman presented with severe headaches to her primary-care physician. The patient had been diagnosed with rheumatoid arthritis and had begun having headache 4 years previously. An MRI scan revealed an 11-12 mm pituitary tumor. Her physical examination was unremarkable for the classic acral or facial changes characteristic of acromegaly, and she was referred for neuroendocrine consultation for a presumed nonfunctioning adenoma. INVESTIGATIONS: MRI of the pituitary, and laboratory investigations that included measurement of serum insulin-like growth factor 1 (IGF1) and prolactin levels. DIAGNOSIS: In view of the elevated level of IGF1 and presence of a pituitary adenoma, the patient was diagnosed with acromegaly caused by a pituitary adenoma that secretes growth hormone. MANAGEMENT: The patient underwent trans-sphenoidal surgery, which resulted in resolution of joint pain and headache, eradication of the tumor mass, normal IGF1 levels, and appropriate suppression of growth hormone (confirmed by oral glucose tolerance test postoperatively). | |
| 16505706 | Clinical correlation with the PA/plasmin system in septic arthritis of the knee. | 2006 Jun | Substantially more gelatinases appear in effusions of septic arthritis than in effusions of aseptic arthritis. We hypothesized there is greater plasminogen activator/plasmin activity in effusions of septic arthritis than aseptic arthritis. We examined the antigenic values of urokinase-type plasminogen activator and plasminogen activator inhibitor Type-1, cell counts, and levels of matrix metalloproteinase-2 and metalloproteinase-9 in 135 knee effusions from 80 patients with septic arthritis, rheumatoid arthritis, gouty arthritis, and osteoarthritis. Urokinase-type plasminogen activator and plasminogen activator inhibitor Type-1 antigenic values in effusions of septic arthritis were greater than those in effusions of aseptic arthritis. The increases of urokinase-type plasminogen activator and plasminogen activator inhibitor Type-1 antigenic values in effusions were associated with increased levels of prometalloproteinase-9 and the appearance of activated metalloproteinase-2. Antigenic values of urokinase-type plasminogen activator also correlated with the appearance of activated metalloproteinase-9. High plasminogen activator/plasmin activity, prometalloproteinase-9 levels, and the presence of activated metalloproteinase-2 and metalloproteinase-9 in effusions from replaced knees should increase suspicion of infection regardless of neutrophil counts. Joint aspiration reduces bacteria counts, endotoxins, proinflammatory cytokines, and matrix metalloproteinase. It also decreases the plasminogen activator/plasmin activity in effusions that may play a part in extracellular matrix destruction. LEVEL OF EVIDENCE: Diagnostic study, Level III (study of nonconsecutive patients without consistently applied reference "gold" standard). See the Guidelines for Authors for a complete description of levels of evidence. | |
| 18826638 | Epitope spreading to citrullinated antigens in mouse models of autoimmune arthritis and de | 2008 | INTRODUCTION: Anti-citrullinated protein antibodies have a diagnostic role in rheumatoid arthritis (RA); however, little is known about their origins and contribution to pathogenesis. Citrullination is the post-translational conversion of arginine to citrulline by peptidyl arginine deiminase, and increased citrullination of proteins is observed in the joint tissue in RA and in brain tissue in multiple sclerosis (MS). METHODS: We applied synovial and myelin protein arrays to examine epitope spreading of B cell responses to citrullinated epitopes in both the collagen-induced arthritis (CIA) model for RA and the experimental autoimmune encephalomyelitis (EAE) model for MS. Synovial and myelin protein arrays contain a spectrum of proteins and peptides, including native and citrullinated forms, representing candidate autoantigens in RA and MS, respectively. We applied these arrays to characterise the specificity of autoantibodies in serial serum samples derived from mice with acute and chronic stages of CIA and EAE. RESULTS: In samples from pre-disease CIA and acute-disease EAE, we observed autoantibody targeting of the immunising antigen and responses to a limited set of citrullinated epitopes. Over the course of diseases, the autoantibody responses expanded to target multiple citrullinated epitopes in both CIA and EAE. Using immunoblotting and mass spectrometry analysis, we identified citrullination of multiple polypeptides in CIA joint and EAE brain tissue that have not previously been described as citrullinated. CONCLUSIONS: Our results suggest that anti-citrulline antibody responses develop in the early stages of CIA and EAE, and that autoimmune inflammation results in citrullination of joint proteins in CIA and brain proteins in EAE, thereby creating neoantigens that become additional targets in epitope spreading of autoimmune responses. | |
| 17440592 | [GITR/GITRL expression in peripheral blood of rheumatoid arthritis]. | 2007 Apr 18 | OBJECTIVE: To explore the expression of GITR/GITRL in rheumatoid arthritis(RA) and its correlation with clinical features of the disease. METHODS: Fifty three RA patients, 35 osteoarthritis (OA) patients and 35 healthy volunteers were included in the study. The real-time-fluorescence quantitative PCR method was used to analyze the expression level of GITR/GITRL mRNA. Using fluorescence-activated cell sorting(FACS), the expression of GITR on CD4+CD25+ T cells in peripheral blood monouuclear cells (PBMC) was detected. The levels of Anti-CCP antibody, C-reactive protein(CRP), erythrocyte sedimentation rate(ESR) and rheumatoid factor (RF) of the RA patients were measured at the same time. RESULTS: It was shown that the level of GITR/GITRL mRNA and the percentage of GITR+ T cells in the CD4+CD25+ T cell subpopulation[12.38+/-5.72/16.41+/-10.16,(28.12+/-16.85)%] were significantly higher than those of the OA group [9.59+/-5.87/12.09+/-7.53,(21.01+/-14.42)%,P<0.05] and control group [8.75+/-3.78/11.99+/-8.42,(19.98+/- 9.40)%,P<0.05]. The expression of GITR/GITRL from RA patients was positively associated with the level of DAS28 and ESR (r=0.361,r=0.427,P<0.01). CONCLUSION: The GITR/GITRL expression of RA patients was higher than that of other groups which may play an important role in the development of RA. | |
| 16896990 | Serious infections under treatment with TNF-alpha antagonists compared to traditional DMAR | 2006 Nov | Biological treatments aiming to neutralize TNF-alpha (tumour necrosis factor alpha) (infliximab, adalimumab and etanercept) are increasingly used to treat rheumatoid arthritis (RA). Although increased frequency has not been observed in randomized clinical trials with TNF-alpha antagonist agents, postmarketing surveillance suggests that infections might be serious consequences of these therapies. Our aim was to compare infections in patients with RA under treatment with disease-modifying antirheumatic drugs (DMARDs) and TNF-alpha antagonists in a university outpatient rheumatology clinic in Turkey. A total of 130 RA patients treated with DMARDs and 48 treated with TNF-alpha antagonists were analysed for the incidence of infections. Patients taking TNF-alpha antagonists were also reviewed for infections before these therapies. The incidence of serious infections was 7/100 patient-years before TNF-alpha antagonists and 8.6/100 patient-years in DMARDs group. The incidence rose to 17/100 patient-years during therapy with TNF-alpha antagonists. In patients with RA on routine follow-up, treatment with TNF-alpha antagonists seems to carry an increased risk of infections compared to traditional DMARDs. | |
| 17965424 | Gastrointestinal tolerability of etoricoxib in rheumatoid arthritis patients: results of t | 2008 Mar | OBJECTIVE: A randomised, double-blind study to compare the gastrointestinal (GI) tolerability, safety and efficacy of etoricoxib and diclofenac in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A total of 4086 patients (mean age 60.8 years) diagnosed with RA were enrolled and received etoricoxib 90 mg daily (n = 2032) or diclofenac 75 mg twice daily (n = 2054). Use of gastroprotective agents and low-dose aspirin was allowed. The prespecified primary end point consisted of the cumulative rate of patient discontinuations due to clinical and laboratory GI adverse experiences (AEs). General safety was also assessed, including adjudicated thrombotic cardiovascular event data. Efficacy was evaluated using the Patient Global Assessment of Disease Status (PGADS; 0-4 point scale). RESULTS: Mean (SD; maximum) duration of treatment was 19.3 (10.3; 32.9) and 19.1 (10.4; 33.1) months in the etoricoxib and diclofenac groups, respectively. The cumulative discontinuation rate due to GI AEs was significantly lower with etoricoxib than diclofenac (5.2 vs 8.5 events per 100 patient-years, respectively; hazard ratio 0.62 (95% CI: 0.47, 0.81; p |