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ID PMID Title PublicationDate abstract
16793624 [Long-term follow-up results of synovectomy for rheumatoid knee]. 2006 Jun OBJECTIVE: To continuously observe the long-term effects of synovectomy for improving joint damage and quality-of-life in patients with the rheumatoid knee. METHODS: Twenty-one consecutive patients with rheumatoid arthritis (RA) involving 24 knees underwent open synovectomy from November 1988 to January 1997 between November 1988 and January 1997. The changes in radiographic damage were assessed with Larsen score on plain films before and 6 months after surgery with subsequent annual assessment for 8 years, and the functional recovery of the patients was also evaluated with Health Assessment Questionnaire (HAQ) at the same time. RESULTS: The radiographic joint damage and juxta-articular osteoporosis or bone erosion was ameliorated after surgery in all the patients. Larsen score began to decrease 6 months after the operation, and the best effects were achieved at one year and maintained for at least 5 years after the operation, but then followed by recurrence of joint lesions. HAQ scores were improved after the surgery with the best effects observed 6 months after the operation lasting for over 2 years. HAQ score gradually decreased 4 years after the operation till reaching the preoperative scores. CONCLUSION: Synovectomy in the patients with rheumatoid knee not only reverses progressive joint damage, but also improves juxta-articular bone erosions and the patients' quality of life. However, radiographic joint damage and functional deterioration may recur due to hyperplasia of the inflammatory synovium in the long term after operation, suggesting that the inflammatory synovium participates in local joint damage with bone erosions and systemic pathologic process of RA.
16690763 Prevalence and management of rheumatoid arthritis in the general population of Greece--the 2006 Dec OBJECTIVE: To assess the prevalence and management of rheumatoid arthritis (RA) in the general adult population of Greece. METHODS: This cross-sectional study was conducted on the total adult population (> or =19 yrs old) of seven communities (8,547 subjects), and on 2,100 out of 5,686 randomly selected subjects in two additional communities. The study, based on a standardized questionnaire and clinical evaluation and laboratory investigation when necessary, was carried out by rheumatologists who visited the target population at their homes. Diagnosis of RA was based on the American College of Rheumatology (ACR) 1987 criteria. RESULTS: A total of 8,740 subjects participated (response rate 82.1%). RA was diagnosed in 59 individuals. The prevalence of RA was 0.68% (95% CI 0.51-0.85); it was significantly higher in females than males (P< 0.0005), and increased significantly with age up to and including the 50-59-yr-old group (P< 0.002), and then decreased slightly. On their first medical visit, 19% (95% CI 9.7-30.9) of the RA patients had consulted a rheumatologist, while during the first year after disease onset, 61% (95% CI 48.6-73.4) had done so. Early consultation with a rheumatologist and disease-modifying anti-rheumatic drug (DMARD) combination therapy were negatively associated with ACR functional classes II-IV [adjusted odds ratios 0.18 (95% CI 0.04-0.85) and 0.17 (95% CI 0.04-0.72), respectively]. CONCLUSIONS: The prevalence of RA in the general adult population of Greece is similar to that in many other European countries; early consultation with a rheumatologist and DMARD combination therapy are associated with a better RA outcome.
16872514 Environmental risk factors differ between rheumatoid arthritis with and without auto-antib 2006 The aim of this study was to evaluate new and previously hypothesised non-genetic risk factors for serologic subtypes of rheumatoid arthritis (RA) defined by the presence or absence of auto-antibodies to cyclic citrullinated peptides (CCP). In a national case-control study, we included 515 patients recently diagnosed with RA according to the American College of Rheumatology 1987 classification criteria and 769 gender- and age-matched population controls. Telephone interviews provided information about non-genetic exposures, and serum samples for patients were tested for anti-CCP-antibodies. Associations between exposure variables and risk of anti-CCP-positive and anti-CCP-negative RA were evaluated using logistic regression. A series of RA subtype-specific risk factors were identified. Tobacco smoking (odds ratio [OR] = 1.65; 95% confidence interval: 1.03-2.64, for > 20 versus 0 pack-years) was selectively associated with risk of anti-CCP-positive RA, whereas alcohol consumption exhibited an inverse dose-response association with this RA subtype (OR = 1.98, 1.22-3.19, for 0 versus > 0-5 drinks per week). Furthermore, coffee consumption (OR = 2.18; 1.07-4.42, for > 10 versus 0 cups per day), ever use of oral contraceptives (OR = 1.65; 1.06-2.57) and having a first-degree relative with schizophrenia (OR = 4.18; 1.54-11.3) appeared more strongly associated with risk of anti-CCP-positive RA. Obesity was selectively associated with risk of anti-CCP-negative RA, with obese individuals being at more than 3-fold increased risk of this subtype compared with normal-weight individuals (OR = 3.45; 1.73-6.87). Age at menarche was the only examined factor that was significantly associated with both serologic subtypes of RA (p-trends = 0.01); women with menarche at age > or = 15 years had about twice the risk of either RA subtype compared with women with menarche at age < or = 12 years. Major differences in risk factor profiles suggest distinct etiologies for anti-CCP-positive and anti-CCP-negative RA.
16821265 SLC22A4, RUNX1, and SUMO4 polymorphisms are not associated with rheumatoid arthritis: a ca 2006 Jul OBJECTIVE: To replicate the association reported in Japanese individuals of functional SLC22A4 and RUNX1 polymorphisms with rheumatoid arthritis (RA), and to test the possible role in this trait of a functional variant of the SUMO4 gene that was shown to be associated with another related autoimmune disease, type 1 diabetes (T1D). METHODS: Our study population consisted of 886 patients with RA and 987 healthy controls. All subjects were of Spanish Caucasian origin. We conducted a case-control association study with 6 single-nucleotide polymorphisms (SNP) spanning the SLC22A4 gene. SNP mapping in the RUNX1 gene associated with RA in a Japanese population and a SUMO4 polymorphism associated with T1D were also studied. RESULTS: No statistically significant differences between patients with RA and healthy controls were observed when comparing the distribution of the genotypes or alleles of any of the SLC22A4 polymorphisms tested. Similarly, no evidence of association between RA and the SLC22A4 haplotype previously reported to be associated in a Japanese population was found. With regard to the RUNX1 and SUMO4 SNP, we did not observe statistically significant differences in the distribution of genotypes or alleles between patients with RA and healthy controls. CONCLUSION: These results suggest that the SLC22A4, RUNX1, and SUMO4 polymorphisms analyzed do not confer a relevant role in susceptibility to RA in the Spanish population.
16211338 Rheumatoid lung nodulosis and osteopathy associated with leflunomide therapy. 2006 May BACKGROUND: Leflunomide (LEF) is indicated in adults for the treatment of active rheumatoid arthritis (RA). LEF inhibits dehydroorotate dehydrogenase, a key enzyme of the pyrimidine synthesis in activated lymphocytes. Among rare adverse effects, fatal interstitial lung disease has been recently reported during treatment of RA with LEF in Japan. Clinical trials outside Japan do not suggest that LEF causes an excess of pulmonary adverse effects. Development and increase of peripheral rheumatoid nodules in typical sites of RA patients following LEF therapy has been recently reported. OBJECTIVES: Two cases with new and accelerated development of rheumatoid lung nodulosis during LEF therapy were described in this study. METHODS: LEF treatment was administered to two male patients (77 and 66 years old) with long-standing active seropositive nodular RA with failure of multiple second line drugs and without lung involvement. Clinical and laboratory assessment using the American College of Rheumatology response criteria, chest computed tomography (CT), quantification of serum rheumatoid factor (RF), and monocyte count of peripheral blood along with routine laboratory follow up were performed on both patients before and during therapy. In case 1, a bone scan was performed due to sustained limbs pain. Open lung biopsy was performed in case 1 and core lung biopsy in case 2. RESULTS: Both patients achieved full clinical remission during 2 months of LEF therapy. In case 1, the first complaints were limbs pain after 10 months of treatment associated with intensive bone uptake on a bone scan consistent with hypertrophic pulmonary osteopathy. Productive cough developed after 3 months of the therapy in case 2. Initially, these complaints were not attributed to therapy. New lung disease was present on CT with cherry-like progressive cavitary nodules, predominantly involving the basal segments of the right lung. The first lung lesions were found by CT 13 months (case 1) and 7 months (case 2) after the beginning of therapy and were erroneously related to bronchiectasia in case 2. In both cases, the lung biopsy showed necrosis surrounded by epithelioid mononuclear inflammation with giant cells, consistent with rheumatoid lung node. The time that elapsed between the beginning of the first symptoms to LEF discontinuation was very long: 13 months in case 1 and 24 months in case 2. Discontinuation of LEF therapy was followed by an arrest in growth of lung nodules, resolution of limb pain, and gradual improvement of bone scan. A significant decrease of monocyte count and RF level in peripheral blood was observed during LEF therapy in both cases. CONCLUSION: For the first time, we described rheumatoid lung nodulosis as complication of successful LEF therapy for RA. Hypertrophic pulmonary osteopathy with severe limbs pain and dry cough were the first manifestations of the lung nodulosis. Monocytopenia during LEF therapy is proposed to be involved in pathogenesis of this rare complication of LEF therapy.
16881105 Frequency of osteoporosis in 187 men with rheumatoid arthritis followed in a university ho 2006 Aug OBJECTIVE: Although there is relevant information on frequency of osteoporosis in women with rheumatoid arthritis (RA), data about male patients are limited. We evaluated the frequency of osteoporosis in a group of Spanish men with RA followed in a university hospital. METHODS: From the database of our bone densitometry unit, we searched for men with RA evaluated between January 1991 and December 2004 and identified 187 patients, 156 of whom were older than 50 years. Previously recorded demographic, disease, and treatment-related variables were collected. Bone mineral density (BMD) was measured by dual x-ray absorptiometry (DEXA). Osteoporosis was defined according to the criteria of the World Health Organization (WHO), recommended for postmenopausal Caucasian women, as a T score
15286005 Association between baseline radiographic damage and improvement in physical function afte 2005 Jan OBJECTIVES: To identify factors associated with poor physical function in rheumatoid arthritis and to assess whether baseline joint damage has an impact on improvement in physical function during infliximab treatment. METHODS: 428 patients with active rheumatoid arthritis despite methotrexate treatment received methotrexate alone or with infliximab (3 mg/kg or 10 mg/kg every four or eight weeks) for 54 weeks (the ATTRACT trial). Data on clinical outcomes and physical function (assessed by the health assessment questionnaire (HAQ)) were collected. Structural damage was assessed using the van der Heijde modification of the Sharp score. Odds ratios (OR) for factors associated with severe functional disability (HAQ > or =2.0) at baseline were estimated using multiple logistic regression analyses, and baseline factors related to the change in physical function after treatment at week 54 were determined. RESULTS: Baseline radiographic scores were correlated with baseline HAQ scores. After adjustment for demographic characteristics in the logistic regression model, baseline disease activity scores, radiological joint damage, fatigue, and morning stiffness were found to be associated with severe functional disability (HAQ >2.0), with OR values of 2.00 (1.53 to 2.63), 1.82 (1.15 to 2.87), 1.19 (1.05 to 1.34), and 1.07 (1.01 to 1.13), respectively. In multiple linear regression analysis, physical disability, joint damage, and fatigue at baseline were correlated with less improvement in physical function after treatment. Infliximab treatment was associated with greater improvement in physical function. CONCLUSIONS: Greater joint damage at baseline was associated with poorer physical function at baseline and less improvement in physical function after treatment, underlining the importance of early intervention to slow the progression of joint destruction.
15716317 Clinical characteristics of an anatomical hand index measured in patients with rheumatoid 2005 May OBJECTIVES: To determine the clinical characteristics of an anatomical hand index previously reported as a potential measure of joint deformity and outcome in patients with rheumatoid arthritis. METHODS: The hand index (open hand span - closed hand span/lateral height of the hand) was measured in a cross-sectional study of 145 out-patients with rheumatoid arthritis with disease durations 0-55 yr. Subsets of patients were restudied at mean follow-ups of approximately 9 months and 4 yr. RESULTS: The hand index fell gradually with disease duration. Correlations were demonstrated with the Sharp index (r = - 0.39, P = 0.000) and to a lesser extent with disease activity score (r = - 0.28, P = 0.001). At 260 +/- 115 days the hand index worsened by 0.09 units (P = 0.09, NS). At 51.6 +/- 5.4 months the index showed a fall from 1.96 +/- 0.73 to 1.61 +/- 0.65 (P = 0.000). During the same interval the Sharp index increased from 60 +/- 68 to 80 +/- 71 (P = 0.000). CONCLUSIONS: Measurement of simple hand dimensions can demonstrate worsening of hand deformity with time in patients with rheumatoid arthritis. We suggest that more sophisticated analysis of digital hand images, as used in our original study, might yield additional information and increase the sensitivity of an anatomical hand index as an outcome measure in rheumatoid arthritis.
15940756 Familial seropositive rheumatoid arthritis in North American Native families: effects of s 2005 Jun OBJECTIVE: A number of North American native (NAN) populations have high prevalence rates of both rheumatoid arthritis (RA) and the shared epitope (SE). We examined the phenotype and familial incidence of RA in a NAN population, and investigated how the SE and cytokine genes may affect disease risk within affected families. METHODS: NAN patients with seropositive RA or polyarthritis rheumatoid factor (RF) positive juvenile idiopathic arthritis (JIA) were identified from clinical databases. Patients were recruited consecutively as they presented for clinic visits. Family pedigrees were constructed and consenting relatives were interviewed and examined. The risk of RA within families was calculated by multiple logistic regression. Input variables were the SE and cytokine genotypes. Probands and affected relatives were entered as the affected group, and unaffected relatives within families as the unaffected group. Results were confirmed among unrelated subjects, i.e., unrelated patients and unaffected relatives of other probands. RESULTS: The familial prevalence of RA was 0.50 (95% confidence intervals 0.30, 0.70) among 28 families studied. The interleukin 10 (IL-10) promoter -1082 G/A genotype decreased the odds of RA relative to the A/A genotype in affected families (OR 0.247, 95% CI 0.081, 0.751; p = 0.014) and among unrelated subjects (OR 0.203, 95% CI 0.064, 0.640; p = 0.006). The G/G genotype yielded an OR of 0.093 (95% 0.013, 0.676; p = 0.019) among unrelated subjects. The SE had no effect in these calculations. CONCLUSION: There was a high familial prevalence of RA in this NAN cohort. In susceptible NAN families, the risk of RA was reduced by IL-10 genotypes, whereas the SE did not affect risk. Study of healthy NAN controls is required to determine if these conclusions apply to this NAN population as a whole.
17100402 Role of apheresis in rheumatoid arthritis. 2006 Apheresis, a therapeutic procedure that has been available for decades, has recently been added to the long-term management of rheumatoid arthritis (RA). It is a procedure whereby blood is removed from the body and divided into its various components. With the development of specific instrumentation, it has become possible to target the specific cellular or humoral components to be removed or altered. RA is a destructive, chronic progressive disease with high morbidity and significant mortality if it is not treated. Recently, combinations of disease-modifying pharmacotherapeutic agents have successfully been brought to bear on this serious disease. This approach of combining potent anti-inflammatory, disease-modifying antirheumatic drugs (DMARDs), chemotherapy and biologicals continues with some success but not without significant dangers of severe adverse toxicity, including the risks of sepsis, immunopathology and malignancy. In the setting of RA, various apheresis procedures, with and without these combination modalities, have been tested with variable success. This article reviews that experience as an overall approach to better, safer RA disease management.
17031485 Poor relationship between joint swelling detected on physical examination and effusion dia 2007 Jun The purpose of this study was to assess the relationship between swelling detected on physical examination and effusion diagnosed by ultrasonography (US) in glenohumeral (GH) joints in patients with rheumatoid arthritis (RA). Fifty consecutive patients with RA entered the study and 20 healthy control persons formed a control group. Altogether 100 GH joints of the RA patients and 40 of the controls were evaluated. The clinical assessments were carried out by one doctor and the US investigations by another, and they were blinded to each other's results. The clinical examination and US gave similar results in 70 GH joints, whereas they differed in the remaining 30 GH joints. The kappa coefficient between these investigations was 0.202, showing poor agreement. These results showed poor agreement between the clinical assessment of swelling and effusion detected by US in GH joints. Therefore, US may considerably improve the accuracy of diagnosis of effusion in GH joints, which usually means synovitis in patients with RA.
15561738 The inhibition of antithrombin by peptidylarginine deiminase 4 may contribute to pathogene 2005 Mar OBJECTIVE: The gene for peptidylarginine deiminase 4 (PADI4) has been found to be closely associated with rheumatoid arthritis (RA). Peptidylarginine deiminase (PADI) catalyses the post-translational modification of peptidylarginine to citrulline, a reaction known as citrullination. PADI extracted from rabbit muscle has been reported to citrullinate antithrombin, a principal plasma inhibitor of thrombin. Thrombin is known to induce angiogenesis, fibrin formation and inflammation, the primary events of the RA joint. Here, we investigate whether human PADI4 can inhibit antithrombin by catalysing antithrombin citrullination and how the enzyme is involved in RA pathogenesis. METHODS: Antithrombin was incubated with recombinant PADI4 protein, and the inactivation of antithrombin was determined by reduction of its thrombin-inhibiting activity. Citrullination of antithrombin was detected by western blotting and enzyme-linked immunosorbent assay (ELISA). In addition, the citrullination level, activity and concentration of antithrombin in RA plasma were investigated by sandwich ELISA. RESULTS: Incubation of antithrombin with PADI4 resulted in loss of thrombin-inhibitory activity and in citrullination of antithrombin. RA plasma showed higher levels of citrullinated antithrombin than controls with non-arthritis disease and healthy individuals. CONCLUSION: The results indicate that PADI4 could inactivate antithrombin through citrullination. The abnormal expression or activation of PADI4 in RA synovium is suggested to be responsible for the high level of citrullinated antithrombin in RA plasma. Local inhibition of antithrombin activity in RA synovium might lead to the excessive angiogenesis, fibrin deposition and inflammation of the tissue.
17009228 Pharmacogenomic and metabolic biomarkers in the folate pathway and their association with 2006 Oct OBJECTIVE: To evaluate the contribution of metabolites (methotrexate [MTX] and folate polyglutamate [PG] levels) and pharmacogenetic biomarkers in the folate pathway to the effects of MTX in patients with rheumatoid arthritis not previously treated with this antifolate. METHODS: Forty-eight MTX-naive adult patients were enrolled in a prospective longitudinal study. MTX therapy was initiated at 7.5 mg/week and was increased every 4-6 weeks until a therapeutic response was achieved. Response was assessed using the Disease Activity Score in 28 joints (DAS28). Red blood cell (RBC) MTX and folate PG levels were measured with 9 common polymorphisms in the folate pathway. Statistical analyses consisted of generalized linear models and multivariate regressions. RESULTS: After 6 months of therapy, the median weekly MTX dosage was 17.5 mg and the median decrease in the DAS28 was 2.0. There was a large interpatient variability in RBC MTXPG levels (median 35 nmoles/liter [interquartile range 28-51] at month 6). Patients with a lesser decrease in the DAS28 (fewer improvements) had lower RBC MTXPG levels (P < 0.05) despite the higher MTX dose administered (P < 0.05). RBC folate PG levels decreased significantly during treatment, and a lesser decrease in RBC folate PGs was associated with a lesser decrease in the DAS28 (P < 0.05). Primary side effects were gastrointestinal and neurologic in nature. Risk genotypes associated with toxicity were in gamma-glutamyl hydrolase (-401CC), 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (347GG), methylenetetrahydrofolate reductase (1298AC/CC), methionine synthase (2756AA), and methionine synthase reductase (66GG). CONCLUSION: RBC MTXPG levels are a useful means by which to monitor therapy. The genetic associations presented generate hypotheses, and confirmation in independent cohorts is warranted.
15895889 The development of bone mineral density and the occurrence of osteoporosis from 15 to 20 y 2005 Mar OBJECTIVE: To ascertain the occurrence of osteoporosis and the development of central bone mineral density (BMD) in long-term rheumatoid arthritis (RA) METHODS: BMD of the lumbar spine (L2-L4) and the femoral neck were measured by dual-energy X-ray absorptiometry in a cohort of 59 patients (49 women and 10 men) with rheumatoid factor-positive RA followed up for 20 years. BMD measurements were obtained at the 15- and 20-year follow-up visits. RESULTS: At the 15-year check-up the mean age was 61 (SD 13)for men and 54 (SD 11) years for women. Bone densitometry of these patients revealed decreased BMD at both lumbar spine and femoral neck, the mean T-scores being -1.1 [95%CI: -1.6 to -0.6] and -1.3 [95%CI: -1.6 to -1], respectively). Eighteen (31 %) patients thus had osteoporosis (BMD T -score < or = -2.5) and 32 (54%) patients were osteopenic (BMD T-score -1.0 to -2.5). However, when compared with reference values, the decreases in central bone mineral in this patient group were of low degree; the mean Z-score -0.2 [95%CI: -0.7 to 0.2] at the lumbar spine and -0.5 [95%CI: -0.8 to -0.3] at the femoral neck, respectively. After the subsequent five years the mean Z-score increased 0.45 [95%CI: 0.32 to 0.58] at the lumbar spine and the mean T-score decreased -0.20 [95%CI: -0.32 to -0.08] at the femoral neck. ESR, Larsen score, gender and cumulative dose of prednisolone during the 5 year follow-up and HAQ-index were used as explanatory parameters of BMD change between the 15- and 20-year follow-ups. None of these parameters explained the BMD change. CONCLUSION: We conclude that in long-term RA central bone densities seemed to be only moderately decreased after 15 years from eruption of RA. No essential change in central BMD was found after the consecutive 5 years.
17056470 Application of biomarkers in the clinical development of new drugs for chondroprotection i 2006 Nov Emerging evidence supports the concept that biochemical markers are clinically useful non-invasive diagnostic tools for the monitoring of changes in cartilage turnover in patients with destructive joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). Epidemiological studies demonstrated that measurements of different degradation products of proteins in the extracellular matrix of hyaline cartilage in urine or serum samples are (1) increased in OA or RA patients compared with healthy individuals, (2) correlate with disease activity, and (3) are predictive for the rate of changes in radiographic measures of cartilage loss. The present review provides an updated list of available biomarkers and summarize the research data arguing for their clinical utility. In addition, it addresses the question whether or not the monitoring of biomarkers during different treatment modalities could be a useful approach to characterize the chondro-protective effects of approved and candidate drugs. Finally, it briefly reviews the in vitro/ex vivo experimental settings - isolated chondrocyte cultures and articular cartilage explants - that can assist in the verification of novel markers, but also studies assessing direct effects of drug candidates on chondrocytes. Collectively, biomarkers may acquire a function as established efficacy parameters in the clinical development of novel chondro-protective agents.
15988600 Catalase and PPARgamma2 genotype and risk of rheumatoid arthritis in Koreans. 2006 Mar Catalase (CAT) and peroxisome proliferator activated receptor-gamma2 (PPARgamma2) are important regulators of oxidative stress and inflammation, and may contribute to the development of rheumatoid arthritis (RA). We investigated the association between CAT and PPARgamma2 genotypes and risk and severity of RA using 474 cases and 400 controls. Genotyping for the -262C-->T polymorphism of CAT and the Pro12Ala polymorphism of PPARgamma2 was performed by PCR-RFLP analysis. Severity of RA was assessed by the anatomical stage according to Steinbrocker, and a Korean language version of a Health Assessment Questionnaire (KHAQ). No association was observed between CAT and PPARgamma2 genotypes and risk of RA. Our results suggest that genetic polymorphisms of CAT and PPARgamma2 do not play a significant role in the susceptibility to RA among Koreans.
16646030 Association of the IL4R single-nucleotide polymorphism I50V with rapidly erosive rheumatoi 2006 May OBJECTIVE: To examine whether single-nucleotide polymorphisms (SNPs) of the interleukin-4 receptor gene IL4R influence susceptibility to, or radiographic progression in, rheumatoid arthritis (RA). METHODS: The contribution of 2 SNPs (I50V and Q551R) in the coding region of IL4R to RA susceptibility was analyzed by allele-specific polymerase chain reaction in a case-control study of 471 RA patients and 371 healthy controls. Patients with available radiographs of the hands and feet obtained 2 years after disease onset (n = 302) were stratified retrospectively according to radiologic outcome into an erosive and a nonerosive group to evaluate the association between IL4R SNPs and disease progression. RESULTS: No differences in the genotype and allele frequencies of the I50V or Q551R SNPs were identified between the RA patients and healthy controls. In contrast, significant differences in the distribution of I50V IL4R SNP genotypes between patients with erosive and nonerosive disease were observed (chi2 = 15.68, P = 0.0004). Bone erosions at 2 years after disease onset were present in 68.1% of patients homozygous for the V50 allele compared with 37.0% of patients homozygous for the I50 allele (odds ratio 3.86, P < 0.0001). This association was independent of individual factors previously associated with severe disease, such as rheumatoid factor or the HLA-DR shared epitope. On a cellular level, the V50 allele conferred significantly reduced responsiveness to interleukin-4, providing a possible mechanism for the association of the I50V IL4R polymorphism with early erosions in RA. CONCLUSION: Our data identify the I50V IL4R SNP as a novel genetic marker in RA, showing high predictive value for early joint destruction.
16287917 Anti-CCP antibodies measured at disease onset help identify seronegative rheumatoid arthri 2006 Apr OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been identified as highly specific for rheumatoid arthritis (RA). Studies suggest an association with radiographic outcome. The aims of this study were to assess the diagnostic and prognostic utility of the second-generation anti-CCP(2) test in a large cohort of early RA patients compared with connective tissue disease (CTD) controls. METHODS: One hundred and eighty-two patients with RA and 121 patients with CTD were recruited. All RA patients had less than 24 months of symptoms and had CRP, rheumatoid factor (RF), HLA typing (SE) and anti-CCP(2) antibodies measured at baseline. Function was assessed using the Health Assessment Questionnaire (HAQ) and X-rays performed at 0, 12 and 24 months. RESULTS: The anti-CCP(2) antibody test demonstrated a specificity of 91% and sensitivity of 81% for RA when compared with controls. In RF-negative patients, specificity was 92% and sensitivity 60%. Baseline demographics of the RA cohort showed mean age 57 yr, mean symptom duration 7 months, 63% RF-positive patients, 72% SE-positive, 81% CCP-positive and 21% erosive. The only predictor of change in Larsen score from 0 to 24 months in the cohort was the presence of the shared epitope (P<0.05) and in the RF-negative subgroup it was CCP(2) antibody titre >100 (P<0.05). Baseline HAQ was the only significant predictor of HAQ at 24 months, but in the RF-negative subgroup CCP(2) antibody titre >100 predicted a poor functional response at 24 months (P<0.05). CONCLUSIONS: This study confirms the diagnostic utility of anti-CCP(2) antibodies in early RA, particularly in seronegative patients, in whom anti-CCP(2) positivity also conferred prognostic utility for radiographic and functional outcomes.
16277691 The impact of HLA-DRB1 genes on extra-articular disease manifestations in rheumatoid arthr 2005 The objective of this study was to examine HLA-DRB1 and HLA-DQB1 genotypes in patients with severe extra-articular rheumatoid arthritis (ExRA) and to compare them with the genotypes of rheumatoid arthritis (RA) patients without extra-articular manifestations. Patients with severe ExRA were recruited from a large research database of patients with RA, from two cohorts of prevalent RA cases, and from a regional multicenter early RA cohort. Cases with ExRA manifestations (n = 159) were classified according to predefined criteria. Controls (n = 178) with RA but no ExRA were selected from the same sources. Cases and controls were matched for duration of RA and for clinical center. PCR based HLA-DRB1 and HLA-DQB1 genotyping was performed using the Biotest SSP kit, with additional sequencing in order to distinguish DRB1*04 subtypes. Associations between alleles and disease phenotypes were tested using multiple simulations of random distributions of alleles. There was no difference in global distribution of HLA-DRB1 and HLA-DQB1 alleles between patients with ExRA and controls. DRB1*0401 (P = 0.003) and 0401/0401 homozygosity (P = 0.002) were more frequent in Felty's syndrome than in controls. The presence of two HLA-DRB1*04 alleles encoding the shared epitope (SE) was associated with ExRA (overall odds ratio 1.79, 95% confidence interval 1.04-3.08) and with rheumatoid vasculitis (odds ratio 2.44, 95% confidence interval 1.22-4.89). In this large sample of patients with ExRA, Felty's syndrome was the only manifestation that was clearly associated with HLA-DRB1*0401. Other ExRA manifestations were not associated with individual alleles but with DRB1*04 SE double dose genotypes. This confirms that SE genes contribute to RA disease severity and ExRA. Other genetic and environmental factors may have a more specific impact on individual ExRA manifestations.
16911768 Is there an association between anti-TNF monoclonal antibody therapy in rheumatoid arthrit 2006 A recent meta-analysis of randomized clinical trials reported by Bongartz and coworkers raised concerns about an increased rate of malignancy and serious infection in rheumatoid arthritis patients treated with anti-tumour necrosis factor monoclonal antibodies. This commentary discusses some of the methodological issues in their analysis and urges caution in interpreting the results.