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

ID PMID Title PublicationDate abstract
19922017 Hand bone loss measured by digital X-ray radiogrammetry is a predictor of joint damage in 2009 Nov OBJECTIVE: The aim of this study was to evaluate whether loss of bone measured by digital X-ray radiogrammetry (DXR) of hands early in the course of rheumatoid arthritis (RA) may predict future radiographic joint damage after 1 and 2 years. METHODS: A total of 166 patients with early RA, who were part of the Better Anti-Rheumatic FarmacOTherapy (BARFOT) low-dose prednisolone study, were included. The patients had been randomized to treatment with 7.5 mg prednisolone daily or no prednisolone when they started with their first disease-modifying anti-rheumatic drug (DMARD) therapy. Radiographs of hands and feet were taken at baseline and after 1 and 2 years and assessed by the van der Heijde modified Sharp (vdH-S) score. Hand bone density (HBD) was measured on the same radiographs by DXR. Changes in HBD and hand bone loss (HBL) were calculated. HBL was defined as a change in DXR bone mineral density (DXR-BMD) during the first year by more than 0.0048 g/cm(2). RESULTS: HBL was found in 64% of the patients. Patients with HBL had radiological progression significantly more often than patients without (80% vs. 57%, p=0.012). Patients not treated with prednisolone had HBL more often than patients with this treatment (83% vs. 44%, p=0.001). In multiple regression analyses, HBL and change in DXR-BMD during the first year proved to be independent predictors of radiological progression. CONCLUSIONS: Loss of bone measured by DXR was found to be an independent predictor of radiological joint damage and may thus be an additional tool in the process of treatment decision in early RA.
19696061 Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a 2009 Oct OBJECTIVES: RA is known to be associated with a high cardiovascular (CV) risk. Longitudinal data suggest that RA disease course may have become milder over the past decades. Thus, we set out to estimate the magnitude of the overall increase in CV mortality associated with RA and to determine whether it has decreased over the past 50 years. METHODS: We performed a systematic review and a meta-analysis of literature in MEDLINE and EMBASE databases from January 1960 to November 2008. All cohort studies reporting CV mortality risk were included. We then calculated pooled standardized mortality ratios (SMRs) of CV mortality, and determined their evolution with time using meta-regression analysis. RESULTS: Seventeen studies were analysed, corresponding to a total of 91 916 patients. The overall pooled SMR was 1.6 (95% CI 1.5, 1.8; I(2) = 93%; P(het) < 0.0001). Mid-cohort year ranged from 1945 to 1995 (<1980, seven studies; 1980-90, five studies; >1990, five studies). Meta-regression analyses revealed neither any trend in SMR over time (P = 0.784) nor any relation with disease duration at the time of inclusion (P = 0.513). CONCLUSIONS: Our results show that RA is associated with a 60% increase in risk of CV death compared with general population. Despite changes in RA course over the past decades, SMR for CV death has not changed. This suggests that targeting a reduction in CV mortality should still be considered as a major issue in RA.
20234359 Ethnogenetic heterogeneity of rheumatoid arthritis-implications for pathogenesis. 2010 May Autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus are generally considered multifactorial-that is, they involve both genetic and environmental factors. Technical advances in human genetics over the past 5 years have enabled the survey of the entire human genome for disease susceptibility genes and have contributed to a greater understanding of the molecular mechanisms underlying autoimmunity. Among the genetic predisposition factors identified to date, some variants have been found to be restricted to specific ethnic groups, which might reflect migration history and the natural selection that shaped genetic variation in these populations. Other genetic factors could also have exerted different magnitudes of risk for the disease among the different populations, which might be explained by their interactions with other genetic and environmental factors. These pieces of evidence suggest that substantial heterogeneity exists in the genetics underlying autoimmunity among different ethnic populations. This Review discusses the genetic heterogeneity in autoimmunity, with a focus on rheumatoid arthritis, between Asian and European populations. In addition to the most-studied and well-characterized gene HLA-DRB1, we will also describe examples of the gene-environment interactions between PADI4 and smoking, and the gene-gene interactions between PTPN22 and FCRL3.
19917174 A systematic review on the optimum management of the use of methotrexate in rheumatoid art 2009 Sep OBJECTIVE: To examine the use of metho-trexate (MTX) in rheumatoid arthritis (RA) patients during the perioperative period. METHODS: Systematic review of studies retrieved by a sensitive search strategy in Medline (1961-July 2007), Embase (1961-July 2007), Cochrane Library (up to July 2007), and from the abstracts of the ACR (2005, 2006) and EULAR (2005-2007) annual scientific meetings. SELECTION CRITERIA: (population) studies had to include patients with RA undergoing surgery; (intervention and control) studies had to test continuing MTX versus stopping MTX; and (outcomes), studies had to report complications within a year after the surgery including infections, wound morbidity, surgery complications, and RA flares. Only randomized controlled trials (RCT) or high quality cohort studies with a control group were included. RESULTS: Patients from the four included studies were mostly women with mean ages around 60. All of them underwent elective orthopaedic surgery and were taking MTX doses mainly from 5 mg/week to 10 mg/week. By order of level of evidence, we found two RCTs, in which continuing on MTX was not associated with increasing risk of surgery complications, but it was statistically associated with less RA flares. In a prospective cohort study, four infections were observed in the MTX group while none were observed in the control group. No disease flare was reported in any group. A retrospective study showed that patients on MTX reported fewer cases of wound morbitity (p=0.038), RA flares (p=0.050), and no differences related to infections compared to those who stopped MTX. CONCLUSIONS: Continuing with low doses of MTX seems to be a safe option during the perioperative period in RA patients without relevant comorbidities and/or risk factors of infections, undergoing elective orthopaedic surgery, while maintaining disease control.
20232184 Successes achieved and challenges ahead in translating biomarkers into clinical applicatio 2010 Sep Biomarkers are important tools for identifying and stratifying diseases, predicting their progression and determining the effectiveness, safety, and doses of therapeutic interventions. This is important for common chronic diseases such as diabetic nephropathy, osteoporosis, and rheumatoid arthritis which affect large numbers of patients worldwide. This article summarizes the current knowledge of established and novel biomarkers for each of these diseases as presented at the 2008 AAPS/ACCP joint symposium "Success Achieved and Challenges Ahead in Translating Biomarkers into Clinical Applications," in Atlanta, Georgia. The advantages and disadvantages of various proteomic, metabolomic, genomic, and imaging biomarkers are discussed in relation to disease diagnosis and stratification, prognosis, drug development, and potential clinical applications. The use of biomarkers as a means to determine therapeutic interventions is also considered. In addition, we show that biomarkers may be useful for adapting therapies for individual needs by allowing the selection of patients who are most likely to respond or react adversely to a particular treatment. They may also be used to determine whether the development of a novel therapy is worth pursuing by informing crucial go/no go decisions around safety and efficacy. Indeed, regulatory bodies now suggest that effective integration of biomarkers into clinical drug development programs is likely to promote the development of novel therapeutics and more personalized medicine.
20731815 The relationship between the presence of anti-cyclic citrullinated peptide antibodies and 2010 Aug 23 BACKGROUND: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific for RA, but are not detectable in all RA patients. The aim of this study was to establish whether the clinical phenotypes of anti-CCP positive and negative disease are distinct at the earliest clinically apparent phase of disease. METHODS: Patients were recruited from the Birmingham early inflammatory arthritis clinic. Participants were included in the current study if they presented within 3 months of symptom onset and fulfilled 1987 ACR criteria for RA at some point during an 18 month follow-up. Data were collected on demographic variables, joint symptoms and tender (n = 68) and swollen (n = 66) joint counts. CRP, ESR, rheumatoid factor and anti-CCP2 status were measured. RESULTS: 92 patients were included (48 anti-CCP positive). The anti-CCP positive and negative groups were comparable in terms of demographic variables, inflammatory markers, joint counts and 1987 ACR classification criteria, except that more anti-CCP positive patients were rheumatoid factor positive (83.3% vs. 11.4%, p < 0.01). There was no significant difference in the pattern of joint involvement, except for an increased prevalence of knee joint swelling in anti-CCP positive patients (42.9% vs. 22.2%, p = 0.03). CONCLUSIONS: Patients with and without anti-CCP antibodies present in a similar way, even within three months of clinically apparent disease that eventually develops into RA.
19433470 Invasive fungal infections in patients with systemic lupus erythematosus: experience from 2009 Jun The purpose of study was to determine the nature, outcomes and associated risk factors of invasive fungal infection (IFI) in patients with systemic lupus erythematosus (SLE), and compare the incidence of IFI in patients with rheumatoid arthritis (RA). A total of 1155 patients with SLE and 2004 patients with RA were retrospectively reviewed between 1992 and 2007. Twelve cases of IFI patients were identified in SLE patients (6 Aspergillus spp.; 5 Cryptococcus spp.; 1 Candida spp.). The incidence of IFI was significantly higher in patients with SLE than RA (1.04 vs. 0.15%). Among 12 patients with SLE, 10 had high Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores (>or=8). The most commonly involved organ was the lung (n = 6), followed by the meninges (n = 4). Most of SLE patients with IFI (91.7%) had taken steroids prior to IFI. Three SLE patients resulted in death. Notably, these patients were all infected with Aspergillus spp. The mortality was associated with the presence of leukopenia, high anti-DNA antibodies and high SLEDAI. Collectively, IFI is more common in patients with SLE than in patients with RA. High disease activity in patients with SLE might contribute to increased risk of IFI. In addition, mortality was associated with aspergillus infection, leukopenia and high anti-DNA antibodies.
20727426 All you wanted to know about anti-CCP but were afraid to ask. 2010 Dec The most specific biomarker associated with the diagnosis of rheumatoid arthritis (RA) is autoantibodies to citrullinated peptides/proteins (ACPA). Though recognized as an important marker of progressive erosive disease its use has been hampered by doubt about what is a positive versus a negative reaction in the several assays that have become available commercially. This review intends to indicate that the CCP2 assay has the highest specificity and sensitivity in stratified studies that encompass sera from RA patients and non-RA inflammatory controls compared to other ACPA tests. Still, larger and strictly stratified studies are highly warranted to substantiate this conclusion.
20945622 Comparison of seronegative and seropositive rheumatoid arthritis with regard to some clini 2009 The aim of this study is to establish a scientific comparative analysis between seronegative and seropositive rheumatoid arthritis (RA), with regard to some clinical characteristics. The studied group consisted of RA seronegative patients with titters lower then 1:64 defined by Rose-Waaler test, while the control group consisted of RA seropositive patients with titters of 1:64 or higher. Examinees all belonged to the 2nd and 3rd functional classes according to ARA criteria, were between 25-60 years of age (Xb = 49.96), with disease duration between 1-27 years (Xbox = 6.41). In the disease onset most frequently affected joints were metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joint of the hands, almost equally represented with regard to sero-status and sex. During the examination seropositive patients showed a higher presence of inflamation of peripheral joints of hand and foot, but only the presence of PIP of the hands was statistically significant (chi2 = 15.63, p < 0.01). Knees, talocrural joints and elbows were more frequently affected in seropositive patients, whereas humeroscapular, coxofemoral and sacroiliacal joints were more frequently affected in seronegative patients, but without significant statistical difference with regard to sero-status. The presence of affected PIP of the hands (chi2 = 9.96, p < 0.01) and knees (chi2 = 4.17, p < 0.05) with regard to sex was statistically significant in seropositive female patients, as well as the presence of atacked PIP of the hands (chi2 = 6.08, p < 0.05), and cervical vertebrae (chi2 = 6.00, p < 0.05) in seropositive male patients. There were some differences between groups with regard to sex in metatarsophalangealjoints (MTP), PIP of the foot, and other joints, but without any statistical significance. In both subsets statistically significant domination was found in affected second (chi2 = 20.85, p < 0.01) and third (chi2 = 15.70, p < 0.01) fingers of the PIP level of hands and third finger (chi2 = 6.52, p < 0.05) of the MCP level. The mentioned parameters did not show a significant statistical difference with regard to sero-status and sex. Majority of patients had 1-4 deformities. Seropositive group had prevalent knee contractures, e.g. the eversion of the foot, while seronegative group had more "swan neck" deformities. The mentioned parameters did not show a significant statistical difference with regard to sero-status and sex. Longer duration of the disease resulted in an increased number of deformities, and this difference was statistically significant (t = 5.92, p < 0.01). Linear correlation between these two parameters resulted as high positive in general (r = 0.49, p < 0.01) and for groups separately, but without significant statistical difference with regard to sero-status. Duration of the disease with regard to the type of deformities was different in both subsets: in case of the longer duration of the disease "buttonhole" was prevalent with statistically significant difference in seropositive patients (t = 2.10, p < 0.05), whereas "fibular deviation" was prevalent in seronegative patients (t = 2.64, p < 0.01).
20863444 Associations between the genetic polymorphisms of MTHFR and outcomes of methotrexate treat 2010 Sep OBJECTIVES: To determine whether 5, 10-methylenetetrahydrofolate reductase (MTHFR) rs1801133C/T, rs1801131A/C, rs2274976A/G, rs2066462C/T genetic polymorphisms are associated with clinical response and adverse effects (AEs) of methotrexate (MTX) treatment in Chinese Han patients with rheumatoid arthritis (RA). METHODS: One hundred and ten RA patients defined by the American College of Rheumatology (ACR) 1987 revised criteria were involved in this study. All patients were treated with low-dose MTX (10-15 mg/week) without concomitant uses of other DMARDs. Clinical response (using ACR20 criteria) and AEs were evaluated at 0, 4, 12, 16 and 24 weeks. The genotypes of MTHFR rs1801133C/T, rs1801131A/C, rs2274976A/G and rs2066462C/T were detected by real-time fluorescent quantitative PCR. RESULTS: The allele frequency of rs1801131C in the clinical response group was higher than in the non-response group (21.0% vs. 8.1%, p<0.05), and the patients with CC or AC genotype had greater clinical response than those with AA genotype. The allele frequencies of rs1801133T and rs2274976A were higher in the group with AEs than that without AEs (56.4% vs. 37.5% and 14.9% vs. 4.2%, respectively, both p<0.05). The patients with CT or TT genotype in rs1801133 had higher risks of AEs than those with CC genotype. CONCLUSIONS: While rs1801131A/C genetic polymorphism is associated with the clinical response, rs1801133C/T and rs2274976A/G genetic polymorphisms are associated with MTX-related AEs in the treatment of RA. This suggests individualisation is necessary to achieve optimal outcomes in MTX therapy of RA.
20419463 Cerebral tuberculoma in a patient receiving anti-TNF alpha (adalimumab) treatment. 2010 Oct We report a case of a cerebral tuberculoma in a 60-year-old woman with rheumatoid arthritis while receiving the anti-tumor necrosis factor alpha monoclonal antibody, adalimumab (Humira), for active disease. MR brain imaging for dyspraxia revealed a left parietal ring-enhancing lesion, which on resection was shown to be a necrotizing granuloma. There were no associated pulmonary lesions, and the patient was systemically well. Sputum and urine cultures were negative for tuberculosis. The patient was treated with anti-tuberculous medications and made an excellent recovery. We consider this to be the first documented case of tuberculosis involving the central nervous system occurring in the setting of adalimumab treatment.
20662559 Serum uric acid and self-reported rheumatoid arthritis in a multiethnic adult female popul 2010 Sep OBJECTIVE: Studies suggest that serum uric acid (SUA) is significantly associated with cardiovascular disease (CVD) mortality among women and blacks. CVD rates are higher among patients with rheumatoid arthritis (RA) than the normal population. The objective of this study was to determine if there was an association between SUA levels and self-reported RA in a multiethnic female population in the United States. METHODS: This cross-sectional study was conducted using data for 7374 women above 20 years of age in the Third National Health and Nutrition Examination Survey. Multiple and logistic regression methods were used to determine an association between SUA levels and self-reported RA. RESULTS: Women self-reporting RA had significantly higher SUA levels (p < 0.0001) compared to women not self-reporting RA, also when adjusted for age and race (p < 0.0001). In a regression analysis, significant predictors of SUA levels were: self-reporting RA, race/ethnicity, being married, smoking, use of alcohol, high body mass index, high C-Reactive protein, elevated diastolic or systolic blood pressure, and increased glomerular filtration rate. Education and age were removed from the model. The model explained 24.0% of the variability seen in SUA levels (F = 208.62, p < 0.0001) in this multiethnic female population. When the analyses were repeated stratified by race, self-reporting RA was retained in the model as associated with SUA in white and Mexican American, but not in black women. CONCLUSION: Despite the limitations imposed by self-reporting of RA on self-administered questionnaires and in-person interviews, practitioners should be aware that women self-reporting RA are at risk of having high SUA levels as well as more traditional CVD risk factors. These women should be offered appropriate preventive interventions related to their increased risk for CVD events.
20140758 Methotrexate treatment in rheumatoid arthritis: management in clinical remission, common i 2010 Jun This work was performed as part of the Portuguese participation in the 3E Initiative 2007-2008, dedicated to the use of methotrexate (MTX) in rheumatic conditions. Three questions raised by Portuguese rheumatologists and considered relevant to clinical practice remained out of the selection of a set of ten key questions formulated to further establish multinational recommendations on the use of MTX in rheumatic diseases. The authors collected and analyzed all the evidence available by using a systematic literature search methodology and selection criteria concerning the following issues in rheumatoid arthritis (RA): (1) the management of MTX after clinical remission; (2) the management of MTX during infections and (3) the screening and treatment of tuberculosis in patients on MTX treatment. A total of 1,862 references were identified, of which 163 were selected for detailed analysis and 12 included in the final review. The evidence was appraised according to the Oxford Centre for Evidence-based Medicine (EBM) levels of evidence. Although with limited evidence, the authors concluded that: (1) extending the interval for MTX therapy may be a valid alternative regimen in a subset of RA patients in clinical remission (EBM level 2b); (2) MTX may be safe during some common infections in RA patients (EBM level 3b/4); (3) screening and treatment of TB in patients on MTX should be similar to the general population (EBM level 4). The evidence available to support clinical decisions in this area is very limited in number and quality. There is a need for further research and while that is unavailable, practical decisions have to rely on experience and expert opinion.
20375422 omega-3 Fatty acids infusions as adjuvant therapy in rheumatoid arthritis. 2010 Mar BACKGROUND: The present study investigated the efficacy and safety of parenteral omega-3 fatty acids (omega-3 FA) in patients with active rheumatoid arthritis (RA). METHODS: We performed a double-blind, randomized, placebo-controlled study in 23 patients with moderate to severe RA. Patients received either 0.2 g of fish oil emulsion/kg (active) or 0.9% saline (placebo) infusion intravenously for 14 consecutive days, followed by 20 weeks of 0.05 g of fish oil/kg (active) or paraffin wax (placebo) ingested orally as capsules. A decrease in swollen and tender joint counts was the primary efficacy measure. RESULTS: At baseline, both swollen and tender joint counts were not significantly different between patients in the treatment and placebo groups. Twenty patients completed the infusion portion of the study, and 13 completed the oral portion. Swollen joint count was significantly lower in the omega-3 FA group compared with the placebo group after 1 week of infusion (P = .002) as well as after 2 weeks of infusion (P = .046). Tender joint count also tended to be lower in the omega-3 FA group, although this did not reach statistical significance. Both swollen and tender joint counts were significantly lower in the omega-3 FA group compared with the placebo group during and at the end of oral treatment. CONCLUSION: Our pilot study indicates that parenteral omega-3 FAs are well tolerated and improve clinical symptoms of RA. Subsequent oral administration of omega-3 FAs may prolong the beneficial effects of the infusion therapy. These results warrant validation in larger multicenter studies.
19772785 Prevalence of low hemoglobin levels and associations with other disease parameters in rheu 2009 Jul OBJECTIVE: To estimate the prevalence of low hemoglobin (Hb) levels in a large US cohort of patients with rheumatoid arthritis (RA) and examine the relationship between Hb levels and RA severity, associated comorbidities, and quality-of-life parameters by cross-sectional analysis of data from the Consortium of Rheumatology Researchers of North America (CORRONA) registry. METHODS: The study population comprised patients with RA >18 years of age and clinical information recorded in the CORRONA registry between October 1, 2001 and February 1, 2007. Patients were separated into low (Hb <13 g/dl for men; <12 g/dl for women) and normal Hb groups (Hb >13 g/dl for men; >12 g/dl for women). Hb levels were calculated from recorded hematocrit values. RESULTS: Of the 10,397 study patients, 1734 (16.7%) had low Hb levels and 8663 (83.3%) had normal Hb levels. More patients in the low Hb group had a history of comorbid cardiovascular disease, diabetes, and gastrointestinal disease. The low Hb group exhibited greater disease severity and activity (p<0.05) as reported by patients and rheumatologists. In multivariate analyses, RA severity ([odds ratio] OR 1.24; 95% confidence interval [CI]: 1.07-1.44) and ESR (OR 1.04; 95% CI: 1.03-1.05), and comorbid bleeding ulcers (OR 2.04; 95% CI: 1.01-4.12) were predictive of low Hb levels. CONCLUSION: Despite changes in treatment paradigms, low Hb levels remain prevalent in RA patients. This analysis suggests that low Hb levels may be associated with RA disease severity and the presence of certain comorbidities.
20583112 Measuring fatigue in rheumatoid arthritis: a cross-sectional study to evaluate the Bristol 2010 Nov OBJECTIVE: Current patient-reported outcome measures of fatigue in rheumatoid arthritis (RA) have limitations, providing only a global perspective. This study constructed a questionnaire (the Bristol RA Fatigue Multi-Dimensional Questionnaire [BRAF-MDQ]) from 45 preliminary questions derived from analysis of patient interviews and surveys and explored its structure for fatigue dimensions. The BRAF-MDQ and short BRAF numerical rating scales (NRS) and visual analog scales (VAS) for severity, effect, and ability to cope with fatigue were evaluated for validity. METHODS: Two hundred twenty-nine RA patients with fatigue (VAS score ≥5 of 10) completed preliminary BRAF and comparator fatigue scales. Iterative analyses informed item removal or retention in the BRAF-MDQ and identification of subscales (using Cronbach's alpha for internal consistency and factor analysis to identify dimensions). The BRAF-MDQ and short scales were tested in relation to potentially associated variables for criterion and construct validity (Spearman's correlation). RESULTS: The 20-item BRAF-MDQ had good internal consistency (Cronbach's α = 0.932), criterion validity (correlation with other fatigue scales: r = 0.643-0.813), and construct validity (correlations with disability, mood, helplessness, and pain: r = 0.340-0.627). Factor analysis showed 4 distinct dimensions (physical fatigue, living with fatigue, cognition fatigue, and emotional fatigue), which correlated well with the RA Multidimensional Assessment of Fatigue scale (r = 0.548-0.834). The BRAF VAS and NRS showed similar criterion and construct validity. CONCLUSION: The BRAF instruments include standardized NRS and VAS for fatigue severity, effect, and coping, are RA specific, and have evidence to support validity. The BRAF-MDQ uniquely measures 4 separate dimensions, which may facilitate development of individually-tailored fatigue management programs.
20682660 Elevated serum interleukin 33 is associated with autoantibody production in patients with 2010 Oct OBJECTIVE: Interleukin 33 (IL-33) is a novel cytokine involved in joint inflammation in animal models. We analyzed the expression of IL-33 in the serum and synovial fluid of patients with rheumatoid arthritis (RA) and investigated its possible pathophysiological importance. METHODS: The concentration of IL-33 was measured by ELISA in the serum of 223 patients with RA and 159 controls. Anticyclic citrullinated peptide, rheumatoid factor (RF)-IgA, and RF-IgG were tested by ELISA. Antikeratin antibody and antiperinuclear factor were tested by indirect immunofluorescence assay. Erythrocyte sedimentation rate, C-reactive protein, and immunoglobulins were measured by standard laboratory techniques. The association of IL-33 level with clinical and serologic features of RA was analyzed. We tested the change of IL-33 level following tumor necrosis factor (TNF-α) blockade therapy in 40 patients with RA. RESULTS: In contrast to almost no detectable IL-33 in osteoarthritis and healthy serum, IL-33 could be detected in 94 out of the 223 RA cases (42.2%). Serum IL-33 concentration was significantly higher in patients with RA than in control groups. The level of serum IL-33 decreased after anti-TNF treatment. The level of serum IL-33 was correlated with the production of IgM and RA-related autoantibodies including RF and anticitrullinated protein antibodies. However, no correlation was found between IL-33 concentration and acute-phase inflammation reactant or the score of the Disease Activity Index, suggesting a complex or indirect character of the link between IL-33 and the inflammation in RA. CONCLUSION: The level of IL-33 is abnormally elevated in RA serum. The elevation of serum IL-33 was at least partly attributed to excessive TNF-α in RA. IL-33 might be involved in the regulation of autoantibody production in RA.
19129282 Characterisation of severe obliterative bronchiolitis in rheumatoid arthritis. 2009 May The characteristics of patients with rheumatoid arthritis (RA) who develop obliterative bronchiolitis characterised by severe airflow obstruction have been hitherto poorly investigated. A retrospective study of 25 patients with RA and functional evidence of obliterative bronchiolitis (forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) <50% and/or residual volume (RV)/total lung capacity (TLC) >140% predicted) was conducted. Patients (mean+/-SD age 64+/-11 yrs) included 17 never-smokers and eight ex-smokers (10.5+/-5.4 pack-yrs). The diagnosis of RA preceded respiratory symptoms in 88% of cases. Dyspnoea on exertion was present in all patients and bronchorrhea in 44%. High-resolution computed tomography findings included: bronchial wall thickening (96%), bronchiectasis (40%), mosaic pattern (40%), centrilobular emphysema (56%), and reticular and/or ground-glass opacities (32%). Pulmonary function tests showed: FEV(1) 41+/-12% pred, FEV(1)/FVC 49+/-14%, FVC 70+/-20% pred, RV 148+/-68% pred and RV/TLC 142+/-34% pred. Lung biopsy, available in nine patients, demonstrated constrictive, follicular and mixed bronchiolitis. Patients were followed for 48.2+/-49 months. Treatment was poorly effective. Chronic respiratory failure occurred in 40% of patients, and four patients died. Obliterative bronchiolitis associated with rheumatoid arthritis is a severe and under-recognised condition leading to respiratory failure and death in a high proportion of patients.
20521332 The Work Instability Scale for rheumatoid arthritis predicts arthritis-related work transi 2010 Nov OBJECTIVE: Among people with arthritis, the need for work transitions may signal a risk for more adverse work outcomes in the future, such as permanent work loss. Our aim was to evaluate the ability of the Work Instability Scale for Rheumatoid Arthritis (RA-WIS) to predict arthritis-related work transitions within a 12-month period. METHODS: Workers with osteoarthritis or rheumatoid arthritis (n = 250) from 3 clinical sites participated in self-administered surveys that assessed the impact of health on employment at multiple time points over 12 months. Multivariable logistic regressions were conducted to assess the ability of the RA-WIS (range 0-23, where 23 = highest work instability) to predict 4 types of work transition: reductions in work hours, disability leaves of absence, changes in job/occupation, or temporary unemployment, assembled as a composite outcome. Covariates assessed include age, sex, education, marital status, income, pain intensity, disease duration, and the Health Assessment Questionnaire. Areas under the receiver operating characteristic curves (AUROCCs) were also assessed to further examine the predictive ability of the RA-WIS and to determine optimal cut points for predicting specific work transitions. RESULTS: After 12 months, 21.7% (n = 50 of 230) of the participants had indicated at least one arthritis-related work transition. Higher baseline RA-WIS was predictive of such an outcome (relative risk [RR] 1.05 [95% confidence interval (95% CI) 1.00-1.11]), particularly at >17 (RR 2.30 [95% CI 1.11-4.77]). The RA-WIS cut point of >13 was found to be most accurate for prediction (AUROCC 0.68 [95% CI 0.58-0.78]). CONCLUSION: The RA-WIS demonstrated the ability to predict arthritis-related work transitions within a short timeframe, and could be a promising measurement candidate for risk prognostication where work disability outcomes are of concern.
20192992 Gene discovery in rheumatoid arthritis highlights the CD40/NF-kappaB signaling pathway in 2010 Jan During the past several years, substantial progress has been made in the identification of genetic variants that predispose to rheumatoid arthritis (RA) and other autoimmune disorders. Progress in this area has been facilitated by the availability of new technology that allows for a much more comprehensive screen of the genome than was possible before, in conjunction with large samples of RA patients with well-characterized disease. Recent RA genetic studies have identified genes with important functions related to intracellular signaling mechanisms, transcription factors, cytokines, membrane receptors, costimulatory molecules, and enzymes. In particular, recent discoveries highlight the importance of the CD40/NF-kappaB signaling pathway in RA, based on genetic association with several genes relevant to this pathway, including CD40, TRAF1, TNFAIP3, and REL. Progress in the identification of genes that contribute to RA is proceeding at a very rapid pace. These genetic discoveries shed light on underlying disease mechanisms in RA and provide targets for the development of novel diagnostic and therapeutic tools for future use in this chronic inflammatory disorder.