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ID PMID Title PublicationDate abstract
19127529 The impact of patient-perceived restricted access to anti-TNF therapy for rheumatoid arthr 2009 Sep OBJECTIVE: To explore rheumatoid arthritis (RA) patients' experience of access to anti-tumour necrosis factor (anti-TNF) therapy in the UK, and of switching therapies after an initial failure. METHODS: Patients were asked about their experience of accessing, receiving and discontinuing anti-TNF therapy in face-to-face indepth interviews, within the context of the larger study about treatment outcomes. Seventeen individuals with a diagnosis of RA and experience of receiving anti-TNF therapy were interviewed in one hospital trust in England. RESULTS: Different emotions (Theme 1) surrounded the process of accessing anti-TNF therapy: hope, desperation, apprehension, anxiety and frustration. Experience of receiving anti-TNF therapy (Theme 2) included not only positive transformation, but also fear of failure and discontinuation. The subsequent value that patients placed on anti-TNF therapy (Theme 3) included having a right to receive therapy and being lucky. These three themes were underpinned by the core category of 'willing to try anything'. Those switching therapies reported increased caution over the possibility of recurring side effects, but some suggestion of benefit. There was a perception that access to anti-TNF therapy was restricted by cost, rather than being recommended for those in clinical need. CONCLUSIONS: Anti-TNF therapies may have a sudden and dramatic impact on RA patients' lives that contrast with other available medications. However, the stress of the patient's journey through the need to 'qualify' for anti-TNF therapy, and the fear of failing or discontinuation of therapy, should not be underestimated by clinicians.
19502907 Management of patients with rheumatoid arthritis in Latin America: a consensus position pa 2009 Jun OBJECTIVE: A consensus meeting of representatives of 18 Latin-American and Caribbean countries gathered in Reñaca, Chile, for 2 days to identify problems and provide recommendations for the care of patients with rheumatoid arthritis (RA) in Latin America, a region where poverty and other health priorities make the efforts to provide effective and high quality care difficult. This report includes recommendations for health professionals, patients, and health authorities in Latin America, with an emphasis on education and therapeutic issues. METHODS: Fifty-one rheumatologists (list available only online on the JCR website) from 18 Latin-American and Caribbean countries with a special interest in RA participated in the consensus meeting. Participants were experts identified and appointed by the National Societies of Rheumatology affiliated with the Pan-American League of Associations for Rheumatology (PANLAR) and by the Grupo Latino Americano De Estudio de Artritis Reumatoide (GLADAR)-an independent group of Latin American rheumatologist researchers were also invited to the meeting. Eight topics were identified as priorities: patient, community and allied health professional education, health policy and decision making, programs for early detection and appropriate treatment of RA, role of classic disease modifying antirheumatic drugs (DMARDs), role of biologic therapy, and drug safety surveillance. To reach consensus, a survey with questions relevant to the topic of interest was sent to all participants before the meeting. During a 2 day meeting, the answers of the survey were reviewed and discussed by each group, with final recommendations on action items. RESULTS: The specific topic of the survey was answered by 86% of the participants and 68% of them answered the entire survey. It was agreed that RA and rheumatic diseases which are currently not but should be public health priorities in Latin America, because of their prevalence and impact on quality of life. CONCLUSIONS: Strategic areas identified as priorities for our region included: early diagnosis and access to care by multidisciplinary teams, creation of databases to identify infections with the use of biologic agents in RA which are relevant to Latin America, and overall efforts to improve the care of RA patients in accordance with international standards. Implementation of educational programs aimed to improve self-management for patients with RA was also considered crucial.
19773407 Bone erosions at the distal ulna detected by ultrasonography are associated with structura 2009 Dec OBJECTIVES: Ultrasonography (US) is a sensitive tool for detecting erosions in patients with RA. The wrist is usually involved in the RA process, where the distal ulna with its superficial localization is easily accessible for US examination. In this longitudinal study, we wanted to examine the presence, localization and development of erosions at the distal ulna by US in patients with recent onset RA, and to analyse whether erosions at this localization are associated with joint damage in hands assessed by conventional radiography (CR) and MRI. METHODS: Seventy patients with recent onset RA (median disease duration 106 days) were examined by US of the distal ulna, in addition to hand radiography [assessed by van der Heijde-modified Sharp score (vdHSS)] and MRI of the wrist [assessed by RA MRI scoring (RAMRIS) erosion score]. Twelve months later 58 patients were re-assessed. RESULTS: US detected erosions at the distal ulna in 11% of the patients at baseline and 24% at follow-up (the majority of erosions were at the ulnar side). Logistic regression analyses showed the presence of erosions at baseline to be associated with baseline RAMRIS erosion score (P < 0.001), and at follow-up to RAMRIS erosion score (P = 0.02) and vdHSS (P = 0.008). CONCLUSIONS: A significant number of patients had US erosions at the distal ulna at baseline, with increased prevalence after 1 year. The US-detected erosions were associated with structural joint damage in hands assessed by both MRI and CR. US of the distal ulna could thus give useful clinical information.
21038107 Atlanto-axial joint of atlanto-axial subluxation patients due to rheumatoid arthritis befo 2011 May This study investigated the preoperative morphology and postoperative fusion of the atlanto-axial joint (AAJ) in patients with atlanto-axial subluxation (AAS) due to rheumatoid arthritis (RA) using computed tomography (CT). Furthermore, we examined the relationship between the preoperative morphology of AAJ and other radiographic results. Thirty patients with AAS due to RA treated by C1-2 transarticular screw fixation (TSF) were reviewed. The morphology of the AAJ was evaluated using sagittal reconstruction views on CT before and 1 year after surgery. Thereafter, the atlanto-dental interval (ADI) value at the neutral and maximal flexion position and atlanto-axial angle (AAA) at the neutral position was assessed in preoperative lateral cervical radiographs. The preoperative morphology of the AAJ on CT reconstruction views was graded as follows: Grade 1 showed maintenance of the joint space, Grade 2 showed the joint space narrowing and Grade 3 showed the destructive abnormality of subchondral bone. After surgery, the ADI value at the neutral position was assessed in lateral cervical radiographs. Furthermore, the fusion in the AAJ was investigated using CT sagittal reconstruction views taken 1 year after surgery. The preoperative CT image of the AAJ demonstrated Grade 1 in 12 cases (Group A), Grade 2 in 9 cases (Group B) and Grade 3 in 9 cases (Group C). There was no significant difference in age, gender and duration of RA among the three groups. The average ADI value at the flexion position was 11.0 mm in Group A, 12.3 mm in Group B and 12.7 mm in Group C (p>0.313). The average ADI value at the neutral position before surgery was 4.5 mm in Group A, 7.3 mm in Group B and 11.4 mm in Group C (p<0.003). The mean AAA value was 20.8° in Group A, 21.8° in Group B and 8.4° in Group C (p<0.033). The average ADI value after TSF was 1.7 mm in Group A, 2.1 mm in Group B and 3.0 mm in Group C (p>0.144). Fusion in the AAJ 1 year after surgery was demonstrated in 14 cases (46.7%; Group A, 0 case; Group B, 5 cases; Group C, 9 cases). According to the preoperative grading of the AAJ, the postoperative fusion in the AAJ was demonstrated in 0 of 32 joints (0%) in Grade 1, 7 of 18 joints (38.9%) in Grade 2 and all of 10 joints (100%) in Grade 3. In conclusion, this study showed that a destructive abnormality of subchondral bone in the AAJ induced an enlargement of the ADI and anterior inclination of the atlas in patients with AAS due to RA. The current study also showed that fusion in the AAJ was demonstrated in 14 of 30 patients after C1/2 TSF. This was easy to recognize in AAS patients whose joint destruction extended to the subchondral bone.
19228654 Comparison of threshold cutpoints and continuous measures of anti-cyclic citrullinated pep 2009 Apr OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are strongly associated with increased risk of rheumatoid arthritis (RA).While the anti-CCP level is commonly dichotomized for clinical use, the best threshold for and utility of the titer as a continuous variable to predict development of RA are uncertain. METHODS: Using data from the Nurses' Health Study and Nurses' Health Study II longitudinal cohorts, we examined the sensitivity, specificity, and hazard of RA at various thresholds of the anti-CCP. Incident RA was confirmed using the Connective Tissue Disease Screening Questionnaire and medical record review in 93 women from among 62,437 participants with blood samples. Three controls per case were randomly chosen, matching on cohort, age, and menopausal status. Stored plasma was tested for anti-CCP antibodies with the second-generation Diastat ELISA. Five threshold values were assessed for sensitivity, specificity, and time to diagnosis of RA. Hazard of RA was assessed with conditional logistic regression models adjusting for smoking and reproductive factors. RESULTS: Using the suggested threshold of >5 U/ml for anti-CCP positivity, specificity was 100%, but sensitivity was only 28%. A threshold of >2 U/ml had a higher sensitivity (51%), and similar specificity (80%), with an odds ratio of 11.2 (95% confidence interval 4.7-26.9) for RA. Anti-CCP level as an ordinal variable was strongly associated with time to RA onset, with higher values predicting shorter time to RA onset. CONCLUSION: A lower threshold for anti-CCP positivity was more sensitive in predicting RA development. Higher ranges of the level were informative in predicting time to RA onset.
19243211 Modulation of T-cell co-stimulation in rheumatoid arthritis: clinical experience with abat 2009 Rheumatoid arthritis (RA), characterized by progressive joint destruction, deformity, disability and impaired quality of life (QOL), is a prevalent autoimmune disease affecting 1% of adults in the US. The goal of therapy in patients with RA is to arrest the disease and to achieve remission by preventing or controlling joint damage, preventing loss of function and providing pain relief, thereby improving QOL. Non-biological disease-modifying antirheumatic drugs (DMARDs) have been the mainstay of early intervention in RA, of which methotrexate has been used most frequently. However, in the long term, patients treated with non-biological DMARDs (including methotrexate) may experience joint deterioration and subclinical inflammation even after clinical remission, emphasizing the need for alternative therapies. Several biological therapies, such as anti-tumour necrosis factor (TNF)-alpha agents, have been developed in the last decade and may be used either as monotherapy or in combination with non-biological DMARDs. Although anti-TNFalpha therapy is generally associated with an improvement in symptoms of RA, some patients may experience inadequate response to or may not tolerate these agents. The new biological agent abatacept, a recombinant protein consisting of the extracellular region of the human cytotoxic T-lymphocyte-associated antigen (CTLA)-4 receptor fused to the constant fragment (Fc) region of IgG1, binds to the CD80/CD86 molecules on antigen-presenting cells and modulates T-cell activation. Clinical trials have shown that abatacept is effective in reducing disease activity, structural joint damage and improving QOL in patients with RA who had inadequate response to prior methotrexate or anti-TNFalpha therapy. Pooled analysis of these trials showed that abatacept was also generally well tolerated in these patients. Thus, abatacept therapy may be an option for the treatment of RA in patients who have had an inadequate response to prior DMARD therapy.
19822058 Comparison of cardiovascular risk in ankylosing spondylitis and rheumatoid arthritis. 2009 Jul Cardiovascular co-morbidity is now a recognised complication of chronic inflammation and an elevated acute phase response predisposes to hypertension, stroke and myocardial infarction. Dyslipidaemia is a feature of inflammatory joint diseases and is closely related to elevated CRP and Il-6 levels. Rheumatoid arthritis (RA) has an increased standardised mortality ratio largely attributable to cardiovascular risk. An increased although lesser, cardiovascular morbidity has also been observed in ankylosing spondylitis (AS) which has a similar abnormal lipid profile to that seen in RA. There is some evidence that therapeutic agents such as anti-tumour necrosis factor-alpha (TNF-alpha) drugs that down-regulate the acute phase response, also have an effect in reducing cardiovascular complications in RA and AS.
19236901 Dendritic cells in rheumatoid arthritis: Which subset should be used as a tool to induce t 2009 May Dendritic cells (DC) comprise a complex network of heterogeneous antigen-presenting cells (APC) that are critical not only to the initiation and regulation of adaptive immunity (Th1/Th2/Th17 responses), but also to the maintenance of both central and peripheral tolerance (regulatory T cells, peripheral T-cell deletion). Previous work has clearly indicated a role for DC subsets in the pathogenesis of rheumatoid arthritis (RA). Therefore, utilizing these cells as therapeutic agents could be beneficial in the treatment of RA. However, it remains unclear which DC should be used for tolerance-inducing immunotherapy: myeloid, plasmacytoid, or both? This review summarizes the data obtained thus far concerning the functional characterization of several DC subsets in human RA and accordingly explores their potential use for immunotherapy.
21245814 [Assessment of erythrocyte sedimentation rate (ESR) and C- reactive protein (CRP) on rheum 2010 Oct OBJECTIVE: Rheumatoid Arthritis (RA) disease activity plays an important role in patients disability. A standardized approach to measure it was achieved by using disease activity score (DAS) based on erythrocyte sedimentation rate (ESR) and more recently C-reactive protein (CRP). In this study we will assess the role and influence of ESR and CRP in evaluating and assessing the disease activity. METHODS: This is a retrospective, longitudinal study, whose data was obtained from the national RA patient clinical database BioreportAR (following ACR criteria) under biological disease modifying anti-rheumatic drugs (BDMARDs), involving 71 patients from CHLO-Hospital Egas Moniz. The ESR and CRP of each patient were recorded from 2 separated visits. The swollen joint counts (SJC), tender joint counts (TJC), visual analog scale (VAS) for pain, patient global assessment and physician global assessment were also recorded. DAS 28-ESR, DAS 28-CRP, simplified disease activity index (SDAI) and clinical disease activity index (CDAI) were calculated. The relevant Pearson correlations were established between variables. RESULTS: A sample of 71 patients with an average age of 55 years old and an average RA duration of 9,8 years, was analysed. ESR and CRP correlated poorly between themselves (r=0,31, p<0,001) and they were shown not to be significant predictors of SJC (ESR r=0,29 p< 0,001 and CRP r=0,089 p<0,001) or TJC (ESR r=0,28 p<0,001 and CRP r=0,072 p<0,001). However DAS-ESR and DAS-CRP were highly correlated (r=0,88, p<0,001) as also as, DAS ESR-CDAI (r=0,89, p<0,001), DAS RCP-CDAI (r= 0,88 p< 0,001) and SDAI-CDAI (r=0,89 p<0,001). DAS-CRP values were lower than those in DAS-ESR, but in 84,7% of the visits disease activity status were. CONCLUSIONS: The significant correlation between DAS-ESR and DAS-CRP, indicated that it will not be necessary to perform both evaluations. DAS-CRP yielded a better activity score more often than DAS-ESR, but with 84,7% of concordance in the disease activity status, indicating that both measures are useful for assessing disease activity in RA. Furthermore the correlation between DAS scores and CDAI, and also between SDAI-CDAI may enable physicians to easily assess the disease activity without ESR or CRP values.
19822064 Analyses of similarities and differences in glucocorticoid therapy between rheumatoid arth 2009 Jul Glucocorticoids (GCs) have powerful and potent anti-inflammatory and immunomodulatory effects and are widely established in regard to the treatment of rheumatism and other diseases. In rheumatoid arthritis (RA), GCs are used systemically at several different dosages and/or local (intraarticular) therapy. They have been shown to exert strong short-term anti-inflammatory effects but also long-term positive effects on radiographic progression of the disease. In comparison, patients with ankylosing spondylitis (AS) are considered to be less responsive to GC therapy than patients with RA, although controlled studies on the effects of low-dose GCs in AS are lacking. In AS, GCs are mainly used for local therapy and occasionally for systemic pulse therapy only. The underlying mechanisms for these differences are unclear. GCs act on primary and secondary immune cells via different mechanisms of action: cytosolic GC receptor (cGCR)-mediated genomic and non-genomic effects, membrane-bound GC receptor (mGCR)-mediated non-genomic effects and - as achieved at very high concentrations - non-specific non-genomic effects. The phenomenon of GC resistance is also known in RA. Several different mechanisms may mediate this phenomenon; among them are alterations in number, binding affinity or phosphorylation status of the GCR, polymorphic changes and/or over-expression of chaperones/ co-chaperones, increased expression of inflammatory transcription factors, the multidrug resistance pump, over-expression of the GCR beta isoform, alteration in the expression of mGCR and imbalance of 11beta-hydroxysteroid dehydrogenase type 1 & 2 activity. Translation of insights on GC action and resistance obtained in RA to AS may contribute to a better understanding of the pathophysiology of both diseases.
20418185 Pain and functioning of rheumatoid arthritis patients based on marital status: is a distre 2010 Oct Relationships may influence adjustment to chronic pain conditions such as rheumatoid arthritis (RA). We examined how both marital status and marital adjustment were related to pain, physical disability, and psychological disability in 255 adults with RA. Among married participants (n = 158), better marital adjustment (assessed using the Locke-Wallace Marital Adjustment Scale) was correlated with less pain and physical and psychological disability (all P values < .05). Married participants were divided into distressed (n = 44) and nondistressed (n = 114) subgroups and compared with unmarried participants (n = 97). Controlling for demographics and disease severity, unmarried participants had higher affective pain (P = .009) and higher psychological disability (P = .02) than only the nondistressed married participants, but unmarried participants did not differ from distressed married participants. These findings suggest that being married in itself is not associated with better health in RA but that being in a well-adjusted or nondistressed marriage is linked with less pain and better functioning. PERSPECTIVE: This study examined relationships of marital status and marital adjustment to pain and physical and psychological disability in RA. Findings underscore the importance of considering not only marital status but also degree of marital adjustment in RA and may inform clinical interventions in this population.
19924710 Genome-wide association studies for discrete traits. 2009 Genome-wide association studies of discrete traits generally use simple methods of analysis based on chi(2) tests for contingency tables or logistic regression, at least for an initial scan of the entire genome. Nevertheless, more power might be obtained by using various methods that analyze multiple markers in combination. Methods based on sliding windows, wavelets, Bayesian shrinkage, or penalized likelihood methods, among others, were explored by various participants of Genetic Analysis Workshop 16 Group 1 to combine information across multiple markers within a region, while others used Bayesian variable selection methods for genome-wide multivariate analyses of all markers simultaneously. Imputation can be used to fill in missing markers on individual subjects within a study or in a meta-analysis of studies using different panels. Although multiple imputation theoretically should give more robust tests of association, one participant contribution found little difference between results of single and multiple imputation. Careful control of population stratification is essential, and two contributions found that previously reported associations with two genes disappeared after more precise control. Other issues considered by this group included subgroup analysis, gene-gene interactions, and the use of biomarkers.
20360188 Estimating indirect costs in primary Sjögren's syndrome. 2010 May OBJECTIVE: To estimate the indirect costs associated with primary Sjögren's syndrome (pSS) compared with rheumatoid arthritis (RA) and community controls. METHODS: Data were obtained from 84 women patients with pSS as part of a study to develop a systemic activity measure, from 87 consecutive women patients with RA attending a hospital clinic, and from 96 women community controls on a general practice list. A modified economic component of the Stanford Health Assessment Questionnaire was used to assess lost productivity. RESULTS: Using a conservative model, the estimated total annual indirect costs (95% CI) were 7677 pound sterling (5560 pound sterling, 9794 pound sterling) for pSS, 10,444 pound sterling (8206 pound sterling, 12,681 pound sterling) for RA, and 892 pound sterling (307 pound sterling, 1478 pound sterling) for controls. Using a model that maximizes the estimates, the equivalent figures were 13,502 pound sterling (9542 pound sterling, 17,463 pound sterling), 17,070 pound sterling (13,112 pound sterling, 21,028 pound sterling), and 3382 pound sterling (2187 pound sterling, 4578 pound sterling), respectively. These were all significantly greater at p < 0.001 for patient groups than for the control group. CONCLUSION: pSS is associated with significantly increased indirect costs equivalent to 69%-83% of that for patients with RA. This needs to be taken into account when evaluating the overall economic consequences of pSS.
19015211 Validation of a prediction rule for development of rheumatoid arthritis in patients with e 2009 Sep OBJECTIVE: To validate a model which predicts progression from undifferentiated arthritis (UA) to RA, in a Canadian UA cohort. METHODS: The prediction rule, comprising variables which are scored from 0 to 13, with higher scores reflecting an increased risk of RA, was applied to baseline characteristics of all patients with UA. Progression to RA was determined at 6 months. RESULTS: 105 patients were identified. By 6 months, 80 (76%) had developed RA while 25 (24%) had developed another diagnosis. Number of tender and swollen joints, rheumatoid factor positivity, anti-cyclic citrullinated peptide positivity, poor functional status and high disease activity were associated with development of RA (p<0.01). Median prediction score was 8.0 for progressors, 5.0 for non-progressors. With these cut-off points, 18 (72%) patients with scores < or =5 did not develop RA, while 35 (97%) with scores > or =8 did develop RA. CONCLUSIONS: High scores in our cohort predicted those who progressed to RA by 6 months. Baseline scores > or =8 corresponded with higher rates of progression.
20447316 Green tea polyphenol epigallocatechin 3-gallate in arthritis: progress and promise. 2010 Green tea's active ingredient, epigallocatechin 3-gallate (EGCG), has gained significant attention among scientists and has been one of the leading plant-derived molecules studied for its potential health benefits. In the present review I summarize the findings from some of the most significant preclinical studies with EGCG in arthritic diseases. The review also addresses the limitations of the dose, pharmacokinetics, and bioavailability of EGCG in experimental animals and findings related to the EGCG-drug interaction. Although these findings provide scientific evidence of the anti-rheumatic activity of EGCG, further preclinical studies are warranted before phase clinical trials could be initiated with confidence for patients with joint diseases.
19570596 [Contribution of ultrasonography in inflammatory rheumatic disorders (rheumatoid arthritis 2010 Jan Ultrasonography may be very useful for the positive and differential diagnosis of inflammatory rheumatic disorders (rheumatoid arthritis [RA], polymyalgia rheumatica [PMR] and spondylarthropathies) and if necessary, for the treatment response evaluation (RA). Later in the course of the disease, ultrasonography may help in diagnosing some peripheral complications (tendinous ruptures, synovial cysts, superficial bursitis...) and is useful to guide corticosteroid injections (RA, spondylarthropathies). This article addresses the main ultrasonographic features of inflammatory rheumatic disorders and the role of ultrasonography relative to other imaging modalities (especially magnetic resonance [MR] imaging).
21067530 Applying science in practice: the optimization of biological therapy in rheumatoid arthrit 2010 Most authorities recommend starting biological agents upon failure of at least one disease-modifying agent in patients with rheumatoid arthritis. However, owing to the absence of head-to-head studies, there is little guidance about which biological to select. Still, the practicing clinician has to decide. This review explores the application of published evidence to practice, discussing the goals of treatment, the (in) ability to predict individual responses to therapy, and the potential value of indirect comparisons. We suggest that cycling of biological agents, until remission is achieved or until the most effective agent for that individual patient is determined, deserves consideration in the current stage of knowledge.
19337948 Perceived work ability, quality of life, and fatigue in patients with rheumatoid arthritis 2009 OBJECTIVE: The objective of this exploratory study was to evaluate the effects and costs of a 6-month course of tumour necrosis factor (TNF) inhibitors on work ability, quality of life, and fatigue in patients with rheumatoid arthritis (RA). METHODS: In this prospective single-arm intervention study 59 consecutive patients of working age with established RA were recruited from an outpatient clinic in Amsterdam, the Netherlands. All patients received fortnightly subcutaneous injections of 40 mg adalimumab. The three outcomes at baseline and 6 months were: perceived work ability [Work Ability Index (WAI)], quality of life [Rheumatoid Arthritis Quality of Life instrument (RAQoL)], and fatigue [Checklist Individual Strength (CIS), Need for Recovery (NFR) scale]. Cost data of the preceding 6 months were collected using a self-administered patient questionnaire at baseline and follow-up. RESULTS: At 6 months, all outcomes showed a statistically significant improvement in mean scores from baseline, ranging from 10.0% (WAI), to 11.7% (RAQoL), to 15% (NFR) (subgroup paid work, n = 26). The total mean costs showed a twofold increase in mean costs per week per patient [difference EUR 169, 95% confidence interval (CI) EUR 113-226]. CONCLUSIONS: In this short-term exploratory evaluation, a 6-month course of TNF inhibitors improved work ability and quality of life, and reduced fatigue in patients with established RA. These effects are associated with an increase in total healthcare costs, attributable to the costs of TNF inhibitors. Randomized controlled trials with a longer follow-up are needed to show a long-term effect on work disability and the potential cost-effectiveness of TNF inhibitors.
20727150 A towards-multidimensional screening approach to predict candidate genes of rheumatoid art 2010 Aug 20 BACKGROUND: According to the Genetic Analysis Workshops (GAW), hundreds of thousands of SNPs have been tested for association with rheumatoid arthritis. Traditional genome-wide association studies (GWAS) have been developed to identify susceptibility genes using a "most significant SNPs/genes" model. However, many minor- or modest-risk genes are likely to be missed after adjustment of multiple testing. This screening process uses a strict selection of statistical thresholds that aim to identify susceptibility genes based only on statistical model, without considering multi-dimensional biological similarities in sequence arrangement, crystal structure, or functional categories/biological pathways between candidate and known disease genes. METHODS: Multidimensional screening approaches combined with traditional statistical genetics methods can consider multiple biological backgrounds of genetic mutation, structural, and functional annotations. Here we introduce a newly developed multidimensional screening approach for rheumatoid arthritis candidate genes that considers all SNPs with nominal evidence of Bayesian association (BFLn > 0), and structural and functional similarities of corresponding genes or proteins. RESULTS: Our multidimensional screening approach extracted all risk genes (BFLn > 0) by odd ratios of hypothesis H1 to H0, and determined whether a particular group of genes shared underlying biological similarities with known disease genes. Using this method, we found 6614 risk SNPs in our Bayesian screen result set. Finally, we identified 146 likely causal genes for rheumatoid arthritis, including CD4, FGFR1, and KDR, which have been reported as high risk factors by recent studies. We must denote that 790 (96.1%) of genes identified by GWAS could not easily be classified into related functional categories or biological processes associated with the disease, while our candidate genes shared underlying biological similarities (e.g. were in the same pathway or GO term) and contributed to disease etiology, but where common variations in each of these genes make modest contributions to disease risk. We also found 6141 risk SNPs that were too minor to be detected by conventional approaches, and associations between 58 candidate genes and rheumatoid arthritis were verified by literature retrieved from the NCBI PubMed module. CONCLUSIONS: Our proposed approach to the analysis of GAW16 data for rheumatoid arthritis was based on an underlying biological similarities-based method applied to candidate and known disease genes. Application of our method could identify likely causal candidate disease genes of rheumatoid arthritis, and could yield biological insights that not detected when focusing only on genes that give the strongest evidence by multiple testing. We hope that our proposed method complements the "most significant SNPs/genes" model, and provides additional insights into the pathogenesis of rheumatoid arthritis and other diseases, when searching datasets for hundreds of genetic variances.
19547976 The positivity of rheumatoid factor and anti-cyclic citrullinated peptide antibody in nona 2010 Feb Chronic hepatitis C virus (HCV) has extrahepatic autoimmune properties and a variety of autoantibodies were found in patients with HCV. Patients with HCV infection may have rheumatic symptoms and signs, and 50-70% of the cases may contain rheumatoid factor (RF). The increased prevalence of RF in patients with HCV infection diminishes the diagnostic specificity of serum RF for rheumatoid arthritis (RA) in patients with HCV. Therefore, the presence of RF mostly does not help in distinguishing between RA and HCV-associated rheumatic symptoms. In this study, we studied whether cyclic citrullinated peptide (CCP) antibody, a highly specific biomarker for RA in the general population, was useful for the diagnosis of RA in nonarthritic patients with HCV (hepatitis C virus). Blood samples from 39 patients with chronic HCV infection, 87 normal sera from volunteer blood donors and 108 blood samples from patients with rheumatoid arthritis, from the rheumatology clinic, were taken. RF was measured using the Dade-Behring nephelometer and antibodies to CCP were measured with ELISA. According to statistical analysis, the sensitivity, specificity and positive predictive value of the anti-CCP test was superior to the RF test. Cyclic citrullinated peptide antibody is a more useful test than RF among patients with chronic HCV infection without arthritis.