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ID PMID Title PublicationDate abstract
17341506 Assessing remission in clinical practice. 2007 Jun OBJECTIVE: Remission constitutes the best achievable state in patients with rheumatoid arthritis. We aimed at evaluating sustained remission in a large cohort of patients followed prospectively in clinical practice and to evaluate available instruments to define remission for their stringency in defining this state. PATIENTS AND METHODS: We analysed remission and sustained remission in 621 patients who had two consecutive and complete clinical observations; the average period between the two visits was 92 days (median; quartiles: 82; 105). Remission was evaluated according to modified ACR (mACR), 28 Joint Disease Activity Score (DAS28), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) criteria. Sustained remission was defined as remission at both consecutive visits. Patients were treated with traditional disease- modifying antirheumatic drugs, mainly methotrexate, and partly with biological agents (approximately 11%). RESULTS: Remissions at any one of the two visits were seen in 33.5% of patients by SDAI or CDAI, 42.7% by DAS28, and 38.6% by mACR criteria (P < 0.01). Sustained remission was observed in much lower proportions of patients (between 16.7 and 19.6%, dependent on the instrument). Agreement between classifications of remission by kappa-statistics was very good for SDAI vs CDAI, good for DAS28 vs SDAI or CDAI, and only moderate for mACR vs the three other scores. Residual swollen joints were observed in 15% of patients in DAS28 remission (range 1-9), 6% of patients in mACR remission (range 1-8), but only approximately 5% of patients in CDAI or SDAI remission (range 1-2) (P < 0.01). CONCLUSION: Sustained remission can be observed in 17-20% of patients in clinical practice. CDAI and SDAI remission criteria are more stringent than DAS28 and mACR criteria, since they allow for lesser residual disease activity. Consequently, smaller proportions of patients are classified as in remission by SDAI and CDAI than by DAS28 and mACR criteria. Sustained remission is an achievable goal in clinical practice even with the most stringent of the definitions studied.
16606649 Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies in rheumat 2006 Jul OBJECTIVE: To evaluate the two generations of anti-cyclic citrullinated protein (CCP) antibodies as a diagnostic marker of rheumatoid arthritis (RA) and as a predictor of future development of RA in healthy subjects and in patients with early undifferentiated arthritis. METHODS: A systematic analysis of the literature published between 1999 and February 2006 was conducted. Data were collected on the sensitivity and specificity of the two generations of anti-CCP antibodies for diagnosing RA and predicting future development of the disease. RESULTS: Among 107 studies initially identified, 68 had interpretable data and were analysed. Diagnostic properties were assessed in 58 studies: mean (SD) sensitivity was 53 (10)% (range 41-68) and 68 (15)% (range 39-94) for anti-CCP1 and anti-CCP2, respectively; mean (SD) specificity was 96 (3)% (range 90-99) and 95 (5)% (range 81-100) for anti-CCP1 and anti-CCP2, respectively. Predictive properties were assessed in 14 studies; odds ratio (95% confidence interval) of anti-CCP1 and anti-CCP2 for the future development of RA were 20 (14 to 31) and 25 (18 to 35), respectively, among patients with early undifferentiated arthritis and 64.5 (8.5 to 489) and 28 (8 to 95), respectively, among healthy subjects. CONCLUSION: Sensitivity of the second generation of anti-CCP is close to that of rheumatoid factor, with a higher specificity, for distinguishing RA from other rheumatic diseases. Moreover, anti-CCP antibodies appear to be highly predictive of the future development of RA in both healthy subjects and patients with undifferentiated arthritis.
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.
16374573 Bone eburnation in rheumatic diseases: a guiding trace in today's radiological diagnosis a 2006 Mar Bone eburnation is a common anatomical trace of chronic arthropathy. However, its topographical analysis in rheumatic diseases can contribute to knowledge about the latter, by explaining today's diagnosis through radiology as well as by giving an historical perspective through paleopathology. After recalling that eburnated areas can also originate in infectious arthritis, the present analysis consists in a comparison between macroscopic and radiological observations of both osteoarthritis (OA) and rheumatoid arthritis (RA) at an advanced stage. It focuses on the human femoral head because of its demonstrative interest. Two main observations emerge from our study. The eburnated surface is less extensive in OA (where it appears to be essentially linked to the original structure of the hip) and more extensive in RA at an advanced stage (where an additional systemic factor is predominant). The size of the associated osteophytes appears to be inversely proportional to the extent of the corresponding eburnated area. In connection with the OA-RA comparison above, the contribution of the original joint structure to bone eburnation was also illustrated by acromiohumeral eburnation in shoulder OA and by the comparison with dog hip OA. It must also be noted that a femoral head bone remodeling similar on the whole to that of OA can occur in ochronotic arthropathies whose causal chondropathy is due to a genetic defect. Originating in an identified chondropathy, eburnation in ochronotic arthropathy gives us the opportunity to study an OA-type bone remodeling per se as in an experiment supplied by nature and involving a human hip. However, since RA and ochronotic arthropathy are due to a diffuse chondropathy, both may create a similar macroscopic (and thus radiological) eburnation topography.
16669473 The comprehensive evaluation of temporomandibular disorders seen in rheumatoid arthritis. 2006 Mar BACKGROUND: We studied clinical signs and symptoms of temporomandibular disorders and radiological changes in the temporomandibular joint from patients with rheumatoid arthritis (RA) compared to patients with myofascial pain dysfunction of the temporomandibular system and control patients to evaluate clinical and radiological relationships. METHODS: A cross-sectional, controlled, clinical and radiological study was planned and 99 subjects (69 patients and 30 controls) were included in the study. RESULTS: Twenty-three patients with RA (69.7 per cent) had painful temporomandibular joint. Fifty-five per cent had myofascial pain dysfunction according to the research diagnostic criteria for temporomandibular disorders (TMD). Nearly all of our patients with RA (93.9 per cent) had symptoms, and almost all of them had positive findings of TMD in high resolution computed tomography. Condylar head resorption, joint space narrowing and degeneration were statistically more prominent features in patients with rheumatoid arthritis compared with controls (p < 0.05). The pain score on active palpation correlated with the number of the mandibular subchondral cysts on high resolution computed tomography (r = 0.6, p < 0.05). CONCLUSION: Although the myofascial pain of the temporomandibular system is an important cause of pain in rheumatoid arthritis, prospective controlled studies are needed to develop effective therapeutic strategies for these patients.
18548981 Anti-tumor necrosis factor therapy: 6 year experience of a single center in northern Israe 2008 Apr BACKGROUND: Infliximab and etanercept have been included in the Israeli national list of health services since 2002 for rheumatoid arthritis and juvenile idiopathic arthritis, and since 2005 for psoriatic arthritis and ankylosing spondylitis. The regulator (Ministry of Health and health funds) mandates using fixed doses of infliximab as the first drug of choice and prohibits increased dosage. For other indications (e.g., vasculitis), anti-tumor necrosis factor therapy is given on a "compassionate" basis in severe refractory disease. OBJECTIVES: To describe our experience with anti-TNF therapy in a single tertiary referral center in northern Israel and to analyze the impact of the national health policy on the results. METHODS: We reviewed the medical records of patients who received anti-TNF therapy in our institution, and analyzed demographic data, diagnosis, clinical and laboratory features, previous and current therapies, and anti-TNF treatment duration and side effects. RESULTS: Between 2001 and 2006, 200 patients received anti-TNF therapy for rheumatoid arthritis (n = 108), juvenile idiopathic arthritis (n = 11), psoriatic arthritis (n = 37), ankylosing spondylitis (n = 29), adult Still's disease (n = 4), overlap disease (RA and scleroderma or polymyositis, n = 6), temporal arteritis (n = 1), polyarteritis nodosa (n = 1), dermatomyositis (n = 1), amyloidosis secondary to RA (n = 1) and Wegener's granulomatosis (n = 1). Forty percent of RA patients discontinued the first anti-TNF agent due to side effects or insufficient response. Higher sedimentation rate and lower or negative rheumatoid factor predicted better response to therapy among RA patients. AS and PS patients had a better safety and efficacy profile. Severe infections occurred in 2% of patients. All eight patients who presented lung involvement as part of their primary rheumatic disease remained stable or improved. A significant improvement was achieved in all six patients with overlap disease. CONCLUSION: Our daily practice data are generally in agreement with worldwide experience. The 'deviations' might be explained by the local health policy at that time. The impact of health policy and economic and administrative constraints should be taken into account when analyzing cohort daily practice data.
16728461 Detailed analysis of the cell infiltrate and the expression of mediators of synovial infla 2006 Dec BACKGROUND: The synovial tissue is a primary target of many inflammatory arthropathies, including psoriatic arthritis (PsA). Identification of proinflammatory molecules in the synovium may help to identify potentially therapeutic targets. OBJECTIVE: To investigate extensively the features of cell infiltration and expression of mediators of inflammation and joint destruction in the synovium of patients with PsA compared with patients with rheumatoid arthritis matched for disease duration and use of drugs. METHODS: Multiple synovial tissue biopsy specimens were obtained by arthroscopy from an inflamed joint in 19 patients with PsA (eight oligoarthritis, 11 polyarthritis) and 24 patients with rheumatoid arthritis. Biopsy specimens were analysed by immunohistochemistry to detect T cells, plasma cells, fibroblast-like synoviocytes, macrophages, proinflammatory cytokines, matrix metalloproteinases and tissue inhibitor metalloproteinase-1, adhesion molecules and vascular markers. Stained sections were evaluated by digital image analysis. RESULTS: The synovial infiltrate of patients with PsA and rheumatoid arthritis was comparable with regard to numbers of fibroblast-like synoviocytes and macrophages. T cell numbers were considerably lower in the synovium of patients with PsA. The number of plasma cells also tended to be lower in PsA. The expression of tumour necrosis factor alpha (TNFalpha), interleukin (IL) 1beta, IL6 and IL18 was as high in PsA as in rheumatoid arthritis. The expression of matrix metalloproteinases, adhesion molecules and vascular markers was comparable for PsA and rheumatoid arthritis. CONCLUSION: These data show increased proinflammatory cytokine expression in PsA synovium, comparable to results obtained for rheumatoid arthritis, and support the notion that, in addition to TNFalpha blockade, there may be a rationale for treatments directed at IL1beta, IL6 and IL18.
16802148 CT analysis of the axis for transarticular screw fixation of rheumatoid atlantoaxial insta 2006 Sep OBJECTIVE: To investigate the morphological characteristics of the axis of rheumatoid arthritis (RA) patients with atlantoaxial instability and to determine, by means of sagittal reconstructed computed tomography (CT), the suitability for atlantoaxial transarticular screw fixation. DESIGN AND PATIENTS: Twenty-seven patients, who had undergone reconstructed cervical spine CT scanning preoperatively and posterior atlantoaxial arthrodesis for atlantoaxial instability, were identified from a database for inclusion in this study. The isthmus height and internal height of the lateral mass of the axis were measured using digital imaging software. RESULTS: The mean isthmus height and internal height of the lateral mass of the axis in RA patients (n=14) were significantly lower than in non-RA patients (n=13) (P<0.01). A high-riding vertebral artery (VA) was present in 54% (15 joints, 9 patients) of the 28 atlantoaxial joints in the RA group and in 12% (3 joints, 2 patients) of the 26 atlantoaxial joints in the non-RA group (P<0.01). CONCLUSIONS: In RA patients, the axis showed more extensive thinning of the isthmus and lateral mass than in non-RA patients. A precise preoperative evaluation of screw trajectory using reconstruction CT imaging may be useful in atlantoaxial transarticular fixation, particularly for RA patients with atlantoaxial instability.
16840502 Prediction models for rheumatoid arthritis during diagnostic investigation: evaluation of 2007 Mar OBJECTIVES: To calculate the probabilities for rheumatoid arthritis in a consecutive cohort of patients during diagnostic investigation. Different logistic regression models evaluating the value of human leucocyte antigen (HLA)-shared epitope determination and testing for rheumatoid factor and anti-citrullinated protein/peptide antibodies (ACPA) were fitted. METHODS: 1003 consecutive patients were included in the study, presenting a new diagnostic problem for which rheumatoid arthritis was included in the differential diagnosis. All patients were tested for ACPA, rheumatoid factor and HLA-shared epitope. RESULTS: After 1 year, diagnoses were established: 153 patients had definite rheumatoid arthritis and 629 patients had rheumatoid arthritis excluded. Rheumatoid factor, used as a continuous marker, is useful in evaluating the probability for rheumatoid arthritis. Combined rheumatoid factor and shared epitope testing may provide additional predictive information, but combined ACPA and rheumatoid factor testing is superior. The redundancy of shared epitope testing in a model that includes ACPA testing can be explained by the high association between ACPA and shared epitope both in patients with rheumatoid arthritis and in those with non-rheumatoid arthritis. The value of rheumatoid factor testing increased if patients presented with at least one swollen joint at baseline. CONCLUSION: Valid probabilities for rheumatoid arthritis during routine diagnostic investigation were calculated, and showed that the potential additional value of shared epitope testing disappears when ACPA testing is available. Combined rheumatoid factor and ACPA testing is useful, especially when rheumatoid factor is considered as a continuous parameter reflecting an increasing probability for rheumatoid arthritis at higher rheumatoid factor titres. The value of (continuous) rheumatoid factor testing increases when the a priori chance is higher.
18500442 Costs and outcomes of total hip and knee joint replacement for rheumatoid arthritis. 2008 Oct The objective of the study was to ascertain costs and outcomes of total joint replacement surgery for rheumatoid arthritis (RA) in Australia from the patients' perspective and to explore whether costs were affected by health status pre- or postsurgery. RA patients, scheduled for primary unilateral total knee replacement (TKR) or total hip replacement (THR) surgery at five Sydney hospitals, were approached. Preoperatively, patients retrospectively recorded expenses incurred over the previous 3 months and the health assessment questionnaire (HAQ). Postoperatively, patients completed detailed prospective cost diaries, short form (SF) 36, and HAQ every 3 months during the first postoperative year. In addition, patients were asked to complete a visual analogue measure for pain at 12 months postsurgery. Arthritis-specific cost information included prescription and nonprescription medication, visits to health professionals, tests, special equipment, alterations to the house, and use of private or community services. Thirty-one TKR and 11 THR patients provided cost data for the first postoperative year. Out-of-pocket costs and service utilization decreased over the first postoperative year for both TKR and THR patients. In addition, there was an improvement in the health status as measured by SF-36 but not the HAQ at 3 and 12 months postoperatively. The small sample size of this analysis is reflective of the current national trends of RA joint replacement surgery. Despite the low incidence of RA joint replacement surgery, it was substantiated that patients consider the positive impact on health outcomes and costs important. The generic SF-36 detected improvements in the health status of these RA patients, while total HAQ scores failed to do so. HAQ was found to be insensitive in reflecting improvements following lower limb replacement surgery. Patient out-of-pocket costs significantly decreased postoperatively; however, these costs remain substantial compared to osteoarthritis total joint replacement patients.
16540548 Citrullination is an inflammation-dependent process. 2006 Sep OBJECTIVES: To study the presence of citrullinated proteins in inflammatory conditions and in clinically non-affected tissues of controls. METHODS: Synovial biopsy specimens from 19 patients with rheumatoid arthritis and 10 healthy controls were investigated by immunohistochemistry. Additionally, muscle tissue from 5 patients with polymyositis and from 7 healthy controls, intestinal tissue from macroscopically affected and non-affected areas from 10 patients with inflammatory bowel disease (IBD) and tonsil tissues from 4 chronically inflamed tonsils were studied. RESULTS: Citrullinated proteins were present in all synovial biopsy specimens from patients with rheumatoid arthritis, whereas only three of 10 healthy synovial biopsy specimens showed scarce amounts of citrullination. Citrullination was also present in all myositis-affected muscles, whereas it was absent in the muscle tissues of controls. All tonsil biopsy specimens studied were positive for citrulline. Even though more frequently detected in the macroscopically affected colonic areas, no marked difference was observed in the pattern or extent of citrullination between the macroscopically affected and non-affected intestinal IBD tissues. CONCLUSION: Citrullination is present in a wide range of inflammatory tissues, suggesting that this process is inflammation dependent rather than disease dependent.
17891451 The effect of blockade of tumor necrosis factor alpha on VLA-1+ T-cells in rheumatoid arth 2007 Nov The alpha1beta1 integrin, very late antigen (VLA)-1, characterizes collagen adherent interferon (IFN) gamma producing memory T cells in inflamed synovium. We now report that the mean percentage of VLA-1+ T cells is significantly lower among peripheral blood mononuclear cells of rheumatoid patients responsive to antitumor necrosis factor (TNF) alpha therapy than of those with active disease not receiving therapy. Neutralization of TNFalpha during in vitro polyclonal activation of VLA-1- T cells reduced differentiation to expression of VLA-1 and inhibited secretion of IFNgamma, but did not affect integrin expression on in vivo differentiated VLA-1+ T cells. Moreover, synovial fluids of patients relapsing during and after therapy were enriched in VLA-1+ T cells and lines derived from VLA-1+ T cells in peripheral blood of treated patients retained collagen binding and secreted IFN gamma. Thus, whereas therapy decreases VLA-1+ T cells in rheumatoid arthritis patients, a subset is resistant and contributes to residual and recurring inflammation.
18484089 Vitamin K and rheumatoid arthritis. 2008 Jun Vitamin K2 [menaquinone-4 (MK-4)] has been reported to induce apoptosis in hepatocellular carcinoma, leukemia, and MDS cell lines. The effects of MK-4 on the development of arthritis have never been addressed so far. In this study, we investigated the effect of MK-4 upon the proliferation of rheumatoid synovial cells and the development of arthritis in collagen-induced arthritis (CIA). We analyzed the effect of MK-4 on the proliferation of fibroblast-like synoviocytes (FLSs) using the 3-(4,5-demethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The proapoptotic effect of MK-4 upon FLS was investigated with annexin V staining and DNA fragmentation and caspase 3/7 assays. Moreover, we analyzed the effect of MK-4 on the development of CIA in female dark agouti rats. Our results indicated that MK-4 inhibited the proliferation of FLS and the development of CIA in a dose-dependent manner. We concluded that MK-4 may represent a new agent for the treatment of RA in the setting of combination therapy with other disease-modifying antirheumatic drugs.
17030656 Intraepidermal nerve fiber densities in chronic inflammatory autoimmune diseases. 2006 Oct BACKGROUND: Some patients with systemic lupus erythematosus have selective loss of small-diameter nerve fibers, while larger nerve fibers are unaffected. OBJECTIVE: To determine intraepidermal nerve fiber densities in patients with different chronic inflammatory autoimmune diseases. DESIGN: Cross-sectional study. SETTING: Stavanger University Hospital, Stavanger, and Haukeland University Hospital, Haukeland, Norway. PATIENTS: Sixty patients with systemic lupus erythematosus (SLE) (mean +/- SD age, 43.2 +/- 13.5 years), 61 patients with primary Sjögren syndrome (age, 57.1 +/- 14.7 years), and 52 patients with rheumatoid arthritis (age, 57.4 +/- 12.3 years) were compared with 106 healthy subjects (age, 49.0 +/- 19.6 years). INTERVENTIONS: Skin biopsy specimens. MAIN OUTCOME MEASURES: To evaluate small-diameter nerve fiber loss, intraepidermal nerve fiber densities were measured in skin punch biopsy specimens obtained from the distal part of the leg. RESULTS: The mean +/- SD densities were 7.5 +/- 3.8 fibers/mm in patients with SLE, 9.2 +/- 3.8 fibers/mm in primary Sjögren syndrome, and 10.9 +/- 5.4 fibers/mm in rheumatoid arthritis vs 12.4 +/- 4.6 fibers/mm in healthy subjects. Densities were significantly less in patients with SLE vs patients with rheumatoid arthritis and vs healthy subjects (P<.001 for both), as well as in patients with primary Sjögren syndrome vs healthy subjects (P<.001). Eight patients (13%) with SLE, 2 patients (3%) with primary Sjögren syndrome, and 2 patients (4%) with rheumatoid arthritis had densities below the lower reference limit of 3.4 fibers/mm, consistent with small-diameter nerve fiber neuropathy. CONCLUSION: The degree of loss of small-diameter nerve fibers differs among patients with these chronic inflammatory autoimmune diseases, likely reflecting differences in pathogenesis and organ affinity of the individual disease entities.
17068069 Diagnostic quality and scoring of synovitis, tenosynovitis and erosions in low-field MRI o 2007 Apr OBJECTIVE: To compare dedicated low-field MRI (lfMRI) with conventional MRI (cMRI) in the detection and scoring of synovitis, tenosynovitis and erosions in patients with rheumatoid arthritis. PATIENTS AND METHODS: The wrist and finger joints of 17 patients with rheumatoid arthritis (median (range) disease duration 8 years (7-12); Disease Activity Score 3.3 (2.6-4.5)) were examined by 0.2 T lfMRI and 1.5 TcMRI. The protocols comprised coronal spin-echo and three-dimensional gradient-echo sequences before and after contrast medium administration. Synovitis of the metacarpophalangeal and proximal interphalangeal joints 2-5 and the wrist joints was scored according to Outcome Measures in Rheumatology recommendations. Tenosynovitis and erosions were scored using 4-point and 6-point scales, respectively. The results were analysed by calculating kappa values and performing McNemar's test intra-individually on a joint-by-joint basis. RESULTS: Agreement between the two MRI techniques was good to excellent for synovitis and erosions, and moderate for tenosynovitis. Of the 306 joints evaluated, 245 and 200 joints showed synovitis in lfMRI and cMRI, respectively. Scoring of synovitis of the finger joints yielded kappa values from 0.69 to 0.94. Of the 68 flexor tendons evaluated, tenosynovitis was diagnosed by lfMRI in 24 and by cMRI in 33 instances. Of the 391 bones evaluated, 154 and 139 showed erosions in lfMRI and cMRI, respectively. kappa values for erosion scores were between 0.65 and 1. CONCLUSION: Dedicated, lfMRI shows high agreement with cMRI in diagnosing and scoring synovitis, tenosynovitis and erosions in rheumatoid arthritis when using standardised scoring systems.
16778412 Bucillamine-induced pemphigus vulgaris in a patient with rheumatoid arthritis and polymyos 2006 Jun Bucillamine is a disease modifying anti-rheumatic drug, structurally similar to D-penicillamine. Although D-penicillamine-induced pemphigus has been not infrequently demonstrated, pemphigus associated with bucillamine was rarely reported. We describe a patient complicating pemphigus vulgaris after bucillamine treatment in rheumatoid arthritis (RA) and polymyositis (PM) overlap syndrome. PM and RA overlap syndrome was diagnosed three years ago and bucillamine was administrated for 20 months. Skin lesions including erythematous flaccid blisters on her chest, axillae, and back were occurred and were compatible with pemphigus vulgaris by typical pathology. Withdrawal from bucillamine and prednisolone treatment made rapid improvement of pemphigus lesions.
16511933 Pulmonary complications of infliximab therapy in patients with rheumatoid arthritis. 2006 Mar We describe 5 patients with rheumatoid arthritis (RA) who developed pulmonary complications following infliximab therapy; 4 patients had preexisting usual interstitial pneumonia. As the pathophysiology of the pulmonary insult is unknown, we advise caution in the use of anti-tumor necrosis factor-alpha therapy in patients with RA with underlying lung disease of sufficient severity to withhold methotrexate treatment.
18381795 Cyclooxygenase-2 polymorphisms and risk of rheumatoid arthritis in Koreans. 2008 May OBJECTIVE: To determine the association of single-nucleotide polymorphisms (SNP) in the cyclooxygenase-2 (COX-2) gene with the risk and radiologic severity of rheumatoid arthritis (RA) in Koreans. METHODS: Sequencing of the COX-2 gene using a DNA analyzer revealed genetic variants in 24 Korean DNA samples. A total of 1201 Korean patients with RA and 973 controls were genotyped using the TaqMan method. HLA-DRB1 was genotyped by polymerase chain reaction and sequence-specific oligonucleotide probe hybridization techniques. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) and the corresponding probability values for each SNP site and haplotype. RESULTS: Direct sequencing identified 23 SNP of COX-2 gene, from which 2 common SNP (-1329A-->G and 6365T-->C) were selected based on the linkage disequilibrium status among SNP and minor allele frequencies. The -899G-->C SNP was also studied because it is reportedly associated with the risk of RA. The -1329A-->G SNP was not significantly associated with the risk of RA. However, the risk of RA was significantly lower in the presence of the C allele for 6365T-->C (OR 0.50, 95% CI 0.29-0.85, in a recessive model, and OR 0.80, 95% CI 0.67-0.97, in a codominant model). The C allele for -899G-->C was also associated with a significantly lower risk of RA (OR 0.67, 95% CI 0.48-0.95, in a codominant model). The radiologic severity of RA was not associated with COX-2 polymorphisms. CONCLUSION: Our study revealed a possible protective influence of the C allele for 6365T-->C and for -899G-->C in RA.
18821679 Reactivation of rheumatoid arthritis after pregnancy: increased phagocyte and recurring ly 2008 Oct OBJECTIVE: Pregnancy is associated with reduced disease activity in rheumatoid arthritis (RA) and frequently with disease exacerbation after delivery. This study was undertaken to generate a systematic overview of the molecular mechanisms related to disease remission and postpartum reactivation. METHODS: Transcriptomes of peripheral blood mononuclear cells (PBMCs) were generated from RA patients and healthy women by transcription profiling during the third trimester and 24 weeks after delivery. For functional interpretation, signatures of highly purified immune cells as well as Kyoto Encyclopedia of Genes and Genomes pathway annotations were used as a reference. RESULTS: Only minor differences in gene expression in PBMCs during pregnancy were found between RA patients and controls. In contrast, RA postpartum profiles presented the most dominant changes. Systematic comparison with expression signatures of monocytes, T cells, and B cells in healthy donors revealed reduced lymphocyte and elevated monocyte gene activity during pregnancy in patients with RA and in controls. Monocyte activity decreased after delivery in controls but persisted in RA patients. Furthermore, analysis of 32 immunologically relevant cellular pathways demonstrated a significant additional activation of genes related to adhesion, migration, defense of pathogens, and cell activation, including Notch, phosphatidylinositol, mTOR, Wnt, and MAPK signaling, in RA patients postpartum. CONCLUSION: Our findings indicate that innate immune functions play an important role in postpartum reactivation of arthritis. However, this may depend not only on the monocyte itself, but also on the recurrence of lymphocyte functions postpartum and thus on a critical interaction between both arms of the immune system.
18807543 [Administration of monoclonal antibodies to B-lymphocytes (rituximab) in rheumatoid arthri 2008 AIM: To assess efficacy and tolerance to anti-B-cell drug rituximab in therapy of rheumatoid arthritis (RA) by the data of RF register of this drug. MATERIAL AND METHODS: Rituximab was studied in 42 patients with high RA activity. 37 patients received rituximab according to a conventional scheme: 2 intravenous 1000 mg infusions with a 2-week interval. The rest patients received 2 intravenous 500 mg infusions. The response was evaluated by DAS28 index. RESULTS: Rituximab administration resulted in almost complete elimination of B-cells from peripheral blood. This produced a significant positive effect manifesting with reduction in the number of inflamed and painful joints. This trend was evident to observation week 8 reaching maximum to week 24. Clinical response correlated with decline of inflammation as shown by ESR and CRP. According to DAS28 index, good and satisfactory results were registered in 8 weeks in 62% patients, in 16 weeks--in 86%, in 24 weeks--in 100%. Rituximab tolerance was good. CONCLUSION: Effective treatment with rituximab for rheumatoid arthritis opened a new perspective in antirheumatic biological therapy and demonstrated an important role of B-cells in the disease development. This drug is recommended for wide use in the treatment of severe rheumatoid arthritis resistant to prior therapy including TNF-alpha blockers.