Browse

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

ID PMID Title PublicationDate abstract
16095005 IL-6 promoter polymorphism in patients with rheumatoid arthritis. 2005 Mar OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which cytokines play an important role. The aim of the present study was to examine the interleukin-6 (IL-6) -174 promoter polymorphism in patients with RA and its association with disease susceptibility and activity. METHODS: The study included 98 patients with RA diagnosed according to the criteria of the American College of Rheumatology. Polymerase chain reaction (PCR) amplification was used for analysis of the polymorphism at position -174 in the promoter of the IL-6 gene. RESULTS: The distribution of IL-6 genotypes in RA patients did not differ from that in control subjects. Nevertheless, in patients with a GG genotype the active form of RA was more frequently diagnosed compared with homozygous CC and GC patients. Moreover, in carriers of two G alleles the parameters of disease activity score (DAS28), erythrocyte sedimentation rate (ESR), number of swollen and tender joints] were significantly increased. CONCLUSION: We suggest that the IL-6 promoter polymorphism may be a genetic risk factor for RA activity.
15693112 B cell-directed therapy in rheumatoid arthritis--clinical experience. 2005 Feb Recent evidence has provided renewed insight into the role of B cells in the pathophysiology of rheumatoid arthritis (RA). The B cell surface antigen CD20 has been identified as an appropriate therapeutic target in the treatment of a number of immune-mediated conditions, including RA. Binding to CD20 results in depletion of B cells, with an associated improvement in symptoms, while leaving stem and plasma cells - which are devoid of this marker - unaffected. In a randomized double-blind controlled trial in patients with severe active RA who had had an inadequate response to disease modifying antirheumatic drugs (DMARD), a single short course of rituximab, an anti-CD20 chimeric monoclonal antibody, resulted in profound, long-lasting selective peripheral depletion of CD20+ B cells without compromising immunoglobulin levels, as well as significant and clinically meaningful improvements in symptoms of RA for up to 48 weeks without further treatment with rituximab. Rituximab added to existing methotrexate treatment was particularly effective and well tolerated, and provided the basis for further exploration of this promising alternative treatment approach in RA.
15989482 Effects of radiosynovectomy with p-32 colloid therapy in hemophilia and rheumatoid arthrit 2005 Jun AIM: The aim of this study was to assess the effects of treatment with our locally produced P-32 colloidal suspension on knee synovitic inflammations of hemophilic and rheumatoid arthritis (RA) patients, as well as to compare results with chemical synovectomy or corticoid intra-articular injections and evaluate the cost-benefit ratio. MATERIALS AND METHODS: Thirty-six hemophilic male patients, 4-28 years of age and sent by the Hemophilic Foundation (Buenos Aires, Argentina), were enrolled for knee radiosynovectomy (RS) with P-32 colloid (26 patients), or the antibiotic rifampicin with the cooperation of orthopaedists (10 patients). Parents' informed consent was obtained. The following procedures were performed: routine blood tests, X-ray, ultrasound, a 3-phase bone scan, plus monthly methylene diphosphonate (MDP) controls. Patients were included in this study only if several knee episodes had occurred. Exclusion criteria included bone destruction and big Baker's cyst. Twelve RA patients were included, with similar selection criteria: 6 RA patients received P-32 therapy, and the other 6 patients intra-articular corticoids. Clinical, blind evaluation (state of joint involvement, pain, motility, requirements of antihemophilic factors, corticoids, or analgesics) was registered in follow-up charts. If required, joint aspiration was carried out. Intra-articular instillation of saline plus flushing was done before the needle was withdrawn. P- 32 Bremsstrahlung emission was used in the gamma camera for early and late imaging to confirm the absence of leakage. For intra-articular chemical injections therapy, 4 MBq of Tc-99m MAA (macroaggregates) was used. Immobilization and relative rest for 72 hours followed the procedures. RESULTS: There were neither local or systemic effects, nor leakage during P-32 treatment. Intra-articular rifampicin and corticoids procedures required frequent injections. Comparison of regions of interest (ROIs) in treated knees during soft-tissue scintigraphies in pre- and post-third MDP control showed knee improvement. The follow-up evaluation demonstrated an increase in joint motion, diminished volume, and less requirement and frequency of the use of antihemophilic factors (AHF) in 80% of the radiosynovectomies (21 of 26), thus lowering health costs. Five female RA patients (5 of 6) had decreased joint swelling and pains, resulting in increased joint motion. CONCLUSIONS: Radiosynovectomy in RA showed a 3-month pain palliative effect. One intra-articular knee radiosynoviorthesis in haemophilic patients provides a more than 3- month relief of symptoms after treatment with locally produced P-32 (11 patients). This turned out to be a safe, economic alternative procedure in emerging nations where the availability of AHF is difficult and expensive.
16468045 Manifestation of rheumatoid arthritis in a patient with hereditary haemochromatosis. 2006 Aug Articular symptoms are frequent manifestations of hereditary haemochromatosis. The clinical signs of the arthropathy of haemochromatosis are not specific and difficult to identify in case of co-incidence of haemochromatosis with Heberden's and Bouchard's osteoarthritis or rheumatoid arthritis (RA). Here the manifestation of RA in a patient is reported who was successfully treated for haemochromatosis. Six months after terminating phlebotomy, the patient presented again suffering from impressive swelling of all MCP joints, showing strong synovitis in ultrasound, and from morning stiffness longer than 1 h. ESR, CRP, IgM rheumatoid factor, and anti-cyclic citrullinated peptide antibodies were markedly elevated. Based on these findings the diagnosis of RA was made. Therefore, the high prevalence of RA and haemochromatosis in the general population underlines the usefulness of a screening for HFE gene mutations in RA patients with an atypical course of the disease as well as in patients with undifferentiated arthritis.
15751062 A novel ultrasonographic synovitis scoring system suitable for analyzing finger joint infl 2005 Mar OBJECTIVE: To develop an ultrasonographic (US) synovitis scoring system suitable for evaluation of finger joint inflammation in patients with active rheumatoid arthritis (RA) and to compare semiquantitative US scoring with quantitative US measurements. METHODS: US was performed at the palmar and dorsal sides of the second through fifth metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints in 10 healthy subjects and in the clinically more affected hand in 46 RA patients. Ten patients additionally underwent magnetic resonance imaging (MRI). Synovitis was measured, standardized, and scored according to a semiquantitative method. The 2 methods (semiquantitative US scoring, quantitative US) were compared and statistical cutoffs were identified using receiver operating characteristic (ROC) curve analysis. MRI results were compared with semiquantitative US scoring and quantitative US results. The optimal US scoring method from 6 joint combinations was identified (ROC curve analysis). RESULTS: Synovitis was most frequently detected in the palmar proximal area (86% of affected joints). We found no significant differences between individual PIP joints or between individual MCP joints, indicating that all fingers within each of these joint groups should be treated equally for statistical calculations, although each joint group as a whole should be treated separately. The optimal cutoff point to distinguish between "health" and "pathology" was 0.6 mm both for MCP joints (sensitivity 94%, specificity 89%) and for PIP joints (sensitivity 90%, specificity 88%). There was no significant difference between semiquantitative US scores and quantitative US measurements. The best results for joint combinations were achieved using the "sum of 4 fingers" (second through fifth MCP and PIP joints) and "sum of 3 fingers" (second through fourth MCP and PIP joints) methods. Comparison of MRI results with semiquantitative US scores revealed high concordance. CONCLUSION: US evaluation of finger joint synovitis can be considerably simplified by focusing on the palmar side and by applying semiquantitative grading instead of quantitative measurements. For evaluation of treatment efficacy based on synovitis in RA patients, we recommend using the "sum of 3 fingers" method in longitudinal trials.
16287593 Value of dual-energy x-ray absorptiometry as a diagnostic and assessment tool in early rhe 2005 Nov New research has revealed common pathophysiologic and cellular mechanisms behind the development of osteoporosis and joint damage in rheumatoid arthritis (RA). Because osteoporosis is a direct consequence of the inflammatory disease process, bone mass measurements in principle could be an outcome marker of inflammation, of damage, and of response to therapeutic intervention. Several devices have been developed for quantitative bone mass assessment including dual energy x-ray absorptiometry (DXA), which is considered the reference standard. This article based on current data and understanding discusses the use of DXA as a diagnostic and assessment tool especially in early RA.
16439441 Racial or ethnic differences in allele frequencies of single-nucleotide polymorphisms in t 2006 Sep BACKGROUND: The anti-folate drug methotrexate (MTX) is commonly used to treat rheumatoid arthritis. OBJECTIVE: To determine the allele frequencies of five common coding single-nucleotide polymorphisms (SNPs) in the methylenetetrahydrofolate reductase (MTHFR) gene in African-Americans and Caucasians with rheumatoid arthritis and controls to assess whether there are differences in allele frequencies among these ethnic or racial groups and whether these SNPs differentially affect the efficacy or toxicity of MTX. METHODS: Allele frequencies in the 677, 1298 and 3 additional SNPs in the MTHFR coding region in 223 (193 Caucasians and 30 African-Americans) patients with rheumatoid arthritis who previously participated in one of two prospective clinical trials were characterised, and genotypes were correlated with the efficacy and toxicity of MTX. Another 308 subjects with rheumatoid arthritis who participated in observational studies, one group predominantly Caucasian and the other African-American, as well as 103 normal controls (53 African-Americans and 50 Caucasians) were used to characterise allele frequencies of these SNPs and their associated haplotypes. RESULTS: Significantly different allele frequencies were seen in three of the five SNPs and haplotype frequencies between Caucasians and African-Americans. Allele frequencies were similar between patients with rheumatoid arthritis and controls of the same racial or ethnic group. Frequencies of the rs4846051C, 677T and 1298C alleles were 0.33, 0.11 and 0.13, respectively, among African-Americans with rheumatoid arthritis. Among Caucasians with rheumatoid arthritis, these allele frequencies were 0.08 (p<0.001 compared with African-Americans with rheumatoid arthritis), 0.30 (p = 0.002) and 0.34 (p<0.001), respectively. There was no association between SNP alleles or haplotypes and response to MTX as measured by the mean change in the 28-joint Disease Activity Score from baseline values. In Caucasians, the 1298 A (major) allele was associated with a significant increase in MTX-related adverse events characteristic of a recessive genetic effect (odds ratio 15.86, 95% confidence interval 1.51 to 167.01; p = 0.021), confirming previous reports. There was an association between scores of MTX toxicity and the rs4846051 C allele, and haplotypes containing this allele, in African-Americans, but not in Caucasians. CONCLUSIONS: : These results, although preliminary, highlight racial or ethnic differences in frequencies of common MTHFR SNPs. The MTHFR 1298 A and the rs4846051 C alleles were associated with MTX-related adverse events in Caucasians and African-Americans, respectively, but these findings should be replicated in larger studies. The rs4846051 SNP, which is far more common in African-Americans than in Caucasians, can also be proved to be a useful ancestry informative marker in future studies on genetic admixture.
16997147 New therapeutics that treat rheumatoid arthritis by blocking T-cell activation. 2006 Oct Despite the recent introduction of several new biological products, there remains a significant unmet medical need in rheumatoid arthritis. A focus on the aberrant activation of autoimmune T cells, which is integral to pathogenesis, is a promising approach involved in several of these new therapies. In choosing a molecular target for the modification of T-cell function, it is argued in this article, that within co-stimulatory pathways, CD80 could have a more compelling rationale than CD86. Data are presented showing that CD80-mediated T-cell activation can be inhibited using a small-molecule antagonist, which offers the potential to prevent the inflammatory process leading to joint destruction.
15814578 Genetic and genomic studies of PADI4 in rheumatoid arthritis. 2005 Jul OBJECTIVES: Strong genetic association of rheumatoid arthritis (RA) with PADI4 (peptidyl arginine deiminase) has previously been described in Japanese, although this was not confirmed in a subsequent study in the UK. We therefore undertook a further study of genetic association between PADI4 and RA in UK Caucasians and also studied expression of PADI4 in the peripheral blood of patients with RA. METHODS: Seven single-nucleotide polymorphisms (SNP) were genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism in 111 RA cases and controls. A marker significantly associated with RA (PADI4_100, rs#2240339) in this first data set (P = 0.03) was then tested for association in a larger group of 439 RA patients and 428 controls. PADI4 transcription was also assessed by real-time quantitative PCR using RNA extracted from peripheral blood mononuclear cells from 13 RA patients and 11 healthy controls. RESULTS: A single SNP was weakly associated with RA (P = 0.03) in the initial case-control study, a single SNP (PADI4_100) and a two marker haplotype of that SNP and the neighbouring SNP (PADI4_104) were significantly associated with RA (P = 0.02 and P = 0.03 respectively). PADI4_100 was not associated with RA in a second sample set. PADI4 expression was four times greater in cases than controls (P = 0.004), but expression levels did not correlate with the levels of markers of inflammation. CONCLUSION: PADI4 is significantly overexpressed in the blood of RA patients but genetic variation within PADI4 is not a major risk factor for RA in Caucasians.
16881357 [Activity of genetically programmed cell death of lymphocytes in rheumatoid arthritis]. 2006 AIM: To study activity of genetically programmed cell death (PCD) of lymphocytes in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: Lymphocytes from 30 RA patients including 14 patients with RA history up to 2 years, and 12 healthy donors were studied for activity of caspase 4, 6, 8 usingfluorescence and caspase substrates 30, 60, 120, 150 and 180 min after start of the reaction and number of 1-2-thread serration of DNA with fluorescence of two DNA-tropic stains--EtBr and 4,6-DAPY Correlation was also studied between lymphocyte activity and RA activity, x-ray stage, duration, level of TNF-alpha. The trend in PCD activity of lymphocytes in immunosuppressive therapy was analysed. RESULTS: The activity of lymphocytic caspases in RA patients was low compared to healthy donors. A negative correlation was found between RA activity and activity of caspase 8 and 6. In RA therapy with methotrexate, sulphasalasine, glucocorticosteroids the activity of caspases and number of 1-thread serrations of DNA were subnormal. CONCLUSION: RA is associated with lymphocyte PCD disorders which may be involved in RA pathogenesis, in formation of clones of potentially autoaggressive lymphocytes, in particular. This process is not normalized by current methods of RA treatment causing unsatisfactory outcomes of RA therapy.
16152730 Analysis of mucin composition in gastric juices of chronic rheumatic patients with upper g 2005 Aug Assessment of the mucin subclasses in the gastric juices of severe chronic rheumatoid arthritis (RA) patients was compared with non-RA cases which received the eradication treatment of Helicobacter pylori (H. pylori). Gastric juice samples were obtained from 8 RA patients (5 for H. pylori-negative and 3 for H. pylori-positive) and 5 control subjects in which we confirmed the successful eradication of H. pylori. The gastric luminal mucins were extracted and isolated by the ethanol precipitation method. These mucin solutions were digested with chymotrypsin, dialyzed, lyophilized, and redissolved. The obtained specimen was applied to an ion exchange column containing DEAE-Sepharose CL-6B and eluted with a discontinuous salt gradient in three salt steps. The gastric luminal mucins were divided into three fractions based on the distinctive sialic acid content. The proportion of acidic mucin rich in sialic acid from the gastric juice of RA patients without the H. pylori infection was significantly lower than those RA patients with H. pylori or the control subjects. A decrease in the acidic mucin content after eradication of H. pylori was commonly observed in all the control subjects. Our investigation raises the possibility that the gastric mucosae of RA patients have resistance against H. pylori infection. And the analysis of the composition in the gastric luminal mucin may be a very useful tool for the evaluation of gastric homeostasis in RA patients.
16786783 [Atherosclerosis and rheumatoid arthritis]. 2005 There is growing evidence that patients with rheumatoid arthritis (RA) are at higher risk of cardiovascular diseases (CVD) including myocardial infarction and stroke. Recent analysis indicate that CVD is the most common cause of death in RA; however research on traditional risk factors such as smoking, hypertension or elevated cholesterol level has shown mixed results. There are many convincing suggestions that RA-specific factors associated with systemic inflammation may play a critical role in endothelial cell damage and accelerated development of atherosclerosis. Since atherosclerosis is currently recognized as a chronic inflammatory condition that can be converted into an acute clinical event by plaque rupture and thrombosis--the interplay between inflammatory mediators including cytokines (TNF-alpha, IL-1, IL-6), C-reactive protein, blood coagulation factors and vessel wall cells attracts much attention. Their pivotal role in the pathogenesis of both diseases, RA and atherosclerosis has been presented and discussed in our review.
17075187 [Anti-interleukin-6 receptor antibody therapy--from bedside to bench]. 2006 Oct Recent progress in immunology, utilizing molecular biology techniques, has elucidated the molecular mechanism of immune system. In the treatment of autoimmune diseases, molecular targeting therapies utilizing biologics such as monoclonal antibodies are now available. However, exact causes of the most autoimmune diseases are not known and there remain many issues which should be resolved. Interleukin-6 (IL-6) is a cytokine which regulates immune response and inflammation. Deregulated overproduction of IL-6 is involved in the immune-inflammatory diseases such as Castleman's disease and rheumatoid arthritis. A humanized anti-IL-6 receptor antibody tocilizumab has been proven to be therapeutically effective for the diseases. Simultaneously, we have learned new biological activities from the translational research. In this review, a study from bedside to bench is to be discussed.
15929613 [HLA-DRB1 alleles and rheumatoid arthritis in northern Italy: lack of correlation with dis 2005 Mar We studied HLA-DRB1 alleles in 101 patients with rheumatoid arthritis (RA) and 229 normal subjects by polymerase chain reaction and sequence-specific oligonuclotide hybridization. We observed a statistically significant association between HLA-DR4 and RA (p = 0,0088). This association was not observed for the DR1 status. No particular DR4 suballeles were preferentially expressed in patients. Allele *0102 was more frequent in RA patients (p = 0.0084), while *0103 in controls (p = 0.000047). No difference was observed for the presence of early erosions and extra-articular features in patients with no, one or two RA associated alleles and among share epitope positive and negative patients.
16510817 Arthroscopic and open synovectomy of the elbow in rheumatoid arthritis. 2006 Mar BACKGROUND: Synovectomy has been advocated for early treatment of the rheumatoid elbow. It has not been determined whether arthroscopic or open synovectomy is better and whether a preoperative arc of flexion of >90 degrees is an important prognostic factor. METHODS: Arthroscopic or open synovectomy was performed in fifty-eight elbows in fifty-three patients with rheumatoid arthritis and radiographic changes in the joint of Larsen grade 2 or less. Clinical symptoms, recurrent synovitis, postoperative complications, and radiographic changes were assessed ten to eighteen years (average, thirteen years) postoperatively. RESULTS: Eleven (48%) of twenty-three elbows in which arthroscopic synovectomy had been performed and sixteen (70%) of twenty-three elbows in which open synovectomy had been performed were mildly or not painful at the latest follow-up evaluation. However, no significant difference was detected between the overall clinical results of arthroscopic synovectomy and those of open synovectomy. In elbows with a preoperative arc of flexion of <90 degrees , the clinical results of the two procedures were comparable. In elbows with a preoperative arc of flexion of <90 degrees , arthroscopic synovectomy provided significantly (p < 0.05) better function than open surgery after mid-term follow-up, and motion and function continued to be better in those patients at the most recent follow-up evaluation. Recurrent synovitis was observed in six elbows that had arthroscopic synovectomy and in three that had open synovectomy, and the Larsen grade increased in both groups. Three elbows with a preoperative arc of flexion of <90 degrees underwent a total elbow arthroplasty to treat ankylosis after open synovectomy. Surgical complications were uncommon and not severe. CONCLUSIONS: Arthroscopic synovectomy of the elbow is a reliable procedure. One of the most favorable indications for either arthroscopic or open synovectomy is a preoperative arc of elbow flexion of >/=90 degrees in patients with early rheumatoid arthritis.
15574347 Citrullinated proteins in rheumatoid arthritis. 2005 Jan 1 Citrullinated proteins that are produced by enzymatic deimination of arginine residues in proteins by peptidylarginine deiminases (PADIs) are of particular interest in the pathogenesis of rheumatoid arthritis (RA). First, peptidylarginine deiminase type 4 (PADI4) gene, which codes one of the PADI enzyme isotypes, has a genetic variant that increases susceptibility to RA. The RA-susceptible variant of PADI4 seems to increase the risk of RA by increasing its enzymatic activity. Second, this post-translational protein modification unfolds proteins by loss of a positive charge in arginine residues, with a subsequent change in antigenicity of the self-proteins. Third, these citrullinated proteins are recognized by anti-citrullinated peptide antibodies that are the most RA-specific autoantibodies. Finally, the expression of the PADI enzyme, citrullination of proteins, and production of anti-citrullinated protein antibodies occur in synovium. These data suggest that citrullination of proteins by PADI is related to alteration of antigenicity of peptides and very closely linked to pathogenesis of RA autoimmunity.
16327849 [Rheumatoid arthritis--a risk factor of ischemic heart disease]. 2005 Dec 1 BACKGROUND: Traditional treatment of rheumatoid arthritis has been directed against joint damage, not against increased cardiovascular morbidity. METHODS: The article is based on a search in Medline, bibliography of relevant articles, abstracts from congresses of rheumatology, and discussions with experts. RESULTS AND INTERPRETATION: Rheumatoid arthritis is an independent predictor for coronary artery disease, the main cause of premature mortality in rheumatoid patients. Cardiovascular prophylaxis in rheumatoid arthritis should be prioritised. Treatments of traditional cardiovascular risk factors and of inflammation both seem to be important in reducing cardiovascular morbidity. Insight in accelerated atherosclerosis in inflammatory rheumatic diseases may improve our understanding of the pathogenesis of atherosclerosis generally.
15666033 Cytidine deaminase in polymyalgia rheumatica and elderly onset rheumatoid arthritis. 2005 Sep Serum cytidine deaminase (CD) as a marker of inflammatory disease was assessed in 44 patients and 47 controls to differentiate polymyalgia rheumatica (PMR) from elderly onset rheumatoid arthritis (EORA). The patients were divided into four groups: PMR with and without synovitis and seropositive and seronegative EORA. No statistically significant differences were found when serum CD levels of seropositive EORA patients were compared with serum CD of PMR patients without synovitis, neither when serum CD levels of all PMR patients were compared with a seronegative EORA group, nor when serum CD levels of PMR patients with synovitis were compared with those with EORA. Nevertheless, statistically significant differences were detected between EORA's serum CD levels and the control group (p=0.023). This difference was 10% when comparing CD levels of PMR patients with the control group (p=0.070). We did not demonstrate that serum CD levels could be a useful tool to differentiate PMR from EORA, but these findings could nevertheless reflect the presence of an inflammatory disease.
16341335 A radiological study of the rheumatoid hand in black South Africans. 2005 Oct OBJECTIVE: To determine wrist and hand involvement in black South African patients with rheumatoid arthritis. METHODS: Larsen scoring of the wrist and hand was done in 75 patients. The mean finger score was 9.67 (range 0 - 100) on the left hand and 10.3 (range 0 - 100) on the right. Scores for the wrists were 2.5 (range 0 - 5) for the left and 2.7 (range 0 - 5) for the right. CONCLUSION: Finger and thumb involvement were considerably less in the South African black population than in other series consisting mainly of white patients.
16164222 [The treatment of rheumatoid arthritis with NF-kappaB inhibitors]. 2005 Sep The nuclear factor kappaB (NF-kappaB) participates in the expression of a wide variety of genes that are involved in the regulation of host immune and inflammatory responses. In rheumatoid arthritis, the activation of NF-kappaB has been detected in synovium and lymphocytes, and induction of arthritis in mice produced strong NF-kappaB transcriptional activity in the affected joints. These evidences suggest that NF-kappaB is an interesting therapeutic target in rheumatoid arthritis. In this review, we are going to review briefly the signaling pathway that leads to NF-kappaB activation and then discuss the possibility that the inhibition of NF-kappaB might provide novel treatment to inhibit bone destruction in rheumatoid arthritis.