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ID PMID Title PublicationDate abstract
12939814 [Correlation between tumor necrosis factor alpha and matrix metalloproteinases levels in s 2003 May Tumour necrosis factor alpha (TNF-alpha) and matrix metalloproteinases (MMPs) play an important role in the pathogenesis of rheumatoid arthritis (RA). The present study was conducted to investigate whether the serum level of TNF-alpha is correlated with MMPs and tissue inhibitors of metalloproteinases (TIMPs) in RA patients. Serum concentrations of TNF-alpha, interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9), TIMP-1 and TIMP-2 were measured by ELISA in 34 patients with RA. We found the TNF-alpha to correlate with MMP-1, MMP-3, MMP-9 and total measured MMPs serum concentrations (p < 0.05 for all comparisons). Furthermore, serum TNF-alpha, MMP-1 MMP-3, MMP-9 and TIMP-1 levels correlated with markers of disease activity such as the erythrocyte sedimentation rate, C reactive protein level and the number of swollen joints. No associations were observed between TNF-alpha and TIMPs serum concentrations. Our results support the concept of the regulation of the MMPs synthesis by cytokines such as TNF-alpha. We conclude that the measurement of the serum TNF-alpha, MMPs and TIMP-1 concentrations may be useful in the assessment of RA activity.
12175730 Soluble HLA-DR levels in serum are associated with therapy and genetic factors in rheumato 2002 Sep As rheumatoid arthritis (RA) is an HLA-DR associated autoimmune disease and soluble HLA-DR (sHLA-DR) molecules have the capacity to regulate the immune response, we studied the sHLA-DR levels in RA patients in view of therapy modalities and clinical and biologic parameters of disease activity. For this sHLA-DR concentrations from 87 RA patients were determined by a sensitive enzyme-linked immunoabsorbent assay (ELISA) format. There was a weak but significant correlation between sHLA-DR levels and disease activity (r 0.186 to 0.287, p < 0.004 to < 0.001). The mean serum sHLA were not significantly different between groups with or without corticosteroids, or undergoing therapy with different disease modifying antirheumatic drugs. However, patients treated with a combination of methotrexate and prednisolone have lower sHLA-DR (206 +/- 21 ng/ml, n = 34) compared with the mean value for all other samples (306 +/- 16, n = 217, p < 0.001). This corresponded with significantly lower EULAR pain and swelling scores, ESR and rheumatoid factor (RF) by latex fixation (p < 0.02 to 0.001) in the former, compared with the latter group. Furthermore, sHLA-DR was, respectively, 267 +/- 15 ng/ml (n = 182) in samples from patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs), and 358 +/- 31 (n = 72) without NSAIDs (p < 0.01). Lower sHLA-DR with NSAIDs contrasted with significantly higher scores for pain, swelling, CRP, and RF by latex fixation and by Waaler-Rose test (p < 0.05 to 0.001). Comparison of subgroups with or without the shared epitope of RA disease (Q)R/KRAA within the HLA-DR beta1-chain confirmed significantly higher parameters of disease activity and sHLA-DR in the presence of this disease associated epitope in our patients. Different mechanisms appear to be involved in sHLA-DR production or release, as their level correlates positively with disease activity under combined therapy with corticosteroids and methotrexate, but decreases with higher disease activity in patients treated with NSAIDs.
14734263 Pain-coping strategies in chronic pain patients: psychometric characteristics of the pain- 2003 This article presents a series of studies aimed at validating a comprehensive pain-coping inventory (PCI) that is applicable to various types of patients with chronic pain. Item and scale analyses were performed for patients with rheumatoid arthritis (RA), patients with chronic headache, and pain clinic outpatients. The following 6 scales were derived from a simultaneous component analysis: Pain Transformation, Distraction, Reducing Demands, Retreating, Worrying, and Resting, all of which were internally reliable. A higher order factor analysis grouped the PCI scales into active (transformation, distraction, reducing demands) and passive (retreating, worrying, resting) pain-coping dimensions. Differences in use of strategy found between RA patients and headache patients indicated that the PCI scales were sufficiently sensitive to measure differences between groups. Concurrent validity was assessed for patients with RA and patients with fibromyalgia and predictive validity was assessed for patients with recently diagnosed RA after 1 and 3 years. In both analyses the validity of the scales was supported, in particular the predictive validity of passive coping scales for future outcomes.
12856145 Intraspinal pannus formation at C6 in a patient with rheumatoid arthritis causing severe c 2003 Jul We report a rare case of cervical cord compression caused by intraspinal pannus formation at C6 in a patient with long-term rheumatoid arthritis. No atlantoaxial abnormalities were seen. The imaging findings are presented and the pathology discussed.
15642151 The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal 2005 Interleukin-17 (IL-17) is a T cell cytokine spontaneously produced by cultures of rheumatoid arthritis (RA) synovial membranes. High levels have been detected in the synovial fluid of patients with RA. The trigger for IL-17 is not fully identified; however, IL-23 promotes the production of IL-17 and a strong correlation between IL-15 and IL-17 levels in synovial fluid has been observed. IL-17 is a potent inducer of various cytokines such as tumor necrosis factor (TNF)-alpha, IL-1, and receptor activator of NF-kappaB ligand (RANKL). Additive or even synergistic effects with IL-1 and TNF-alpha in inducing cytokine expression and joint damage have been shown in vitro and in vivo. This review describes the role of IL-17 in the pathogenesis of destructive arthritis with a major focus on studies in vivo in arthritis models. From these studies in vivo it can be concluded that IL-17 becomes significant when T cells are a major element of the arthritis process. Moreover, IL-17 has the capacity to induce joint destruction in an IL-1-independent manner and can bypass TNF-dependent arthritis. Anti-IL-17 cytokine therapy is of interest as an additional new anti-rheumatic strategy for RA, in particular in situations in which elevated IL-17 might attenuate the response to anti-TNF/anti-IL-1 therapy.
15039167 Rheumatoid arthritis of the hand and wrist: comparison of three imaging techniques. 2004 Apr OBJECTIVE: The purpose of this study was to compare the relative results from conventional high-field-strength 1.5-T MRI, 0.2-T low-field-strength dedicated extremity MRI, and radiography to detect and grade bone erosions, joint-space narrowing, and synovitis in the hands and wrists of patients with rheumatoid arthritis. SUBJECTS AND METHODS: Eighteen patients with rheumatoid arthritis underwent conventional high-field-strength MRI, low-field-strength dedicated extremity MRI, and conventional radiography of both hands and wrists. Two independent reviewers searched for the presence and extent of bone erosions, joint-space narrowing, and synovitis. Bone erosions (E scores) and joint-space narrowing (J scores) were evaluated at 14 and 13 sites, respectively, on conventional high-field-strength MRI, low-field-strength dedicated extremity MRI, and radiography, using the Sharp-Genant scoring system. Synovitis (S scores) were evaluated at 13 sites on conventional high-field-strength MRI and low-field-strength dedicated extremity MRI. RESULTS: For the detection of bone erosions, we found no significant difference (p = 0.71) between conventional high-field-strength MRI (mean +/- SD E score, 27.5 +/- 9.8) and low-field-strength dedicated extremity MRI (28.8 +/- 10.0), but a significant difference (p < 0.001) appeared between MRI and radiography (13.1 +/- 8.3). J scores derived from MRI (conventional high-field-strength MRI, 15.2 +/- 8.3; low-field-strength dedicated extremity MRI, 14.5 +/- 10.4) were higher than those derived from radiography (12.7 +/- 9.6), although the difference was not significant (p = 0.70). Conventional high-field-strength MRI (S score, 35.1 +/- 8.6) and low-field-strength dedicated extremity MRI (30.8 +/- 10.2) were equivalent (p = 0.14) for the evaluation of synovitis. The interobserver agreement for MRI scores was good to excellent (intraclass correlation coefficients, 0.83-0.94). CONCLUSION: Conventional high-field-strength MRI and low-field-strength dedicated extremity MRI showed similar results in terms of cross-sectional grading of bone erosions, joint-space narrowing, and synovitis in the hands and wrists of patients with rheumatoid arthritis.
12421111 Etanercept: an updated review of its use in rheumatoid arthritis, psoriatic arthritis and 2002 Etanercept is a subcutaneously administered biological response modifier that binds and inactivates tumour necrosis factor-alpha, a proinflammatory cytokine. In patients with early active rheumatoid arthritis, etanercept 25mg twice weekly was associated with a more rapid improvement in disease activity and a significantly greater cumulative response than methotrexate over 12 months of treatment in a randomised, double-blind trial. In addition, etanercept recipients showed a slower rate of radiographic progression and a more rapid improvement in quality of life than methotrexate recipients. The efficacy of etanercept was maintained at 3 years' follow-up. Etanercept was also significantly better than placebo at reducing disease activity in patients who had an inadequate response to previous treatment with disease-modifying antirheumatic drugs (DMARDs) in several well controlled trials. At study end (after 3 or 6 months' treatment), the percentage of patients achieving an American College of Rheumatology 20% (ACR20) response with etanercept (25mg or 16 mg/m(2) twice weekly) was 59 to 75% as monotherapy and 71% in combination with methotrexate; corresponding placebo response rates were 11 to 14% and 27%, respectively. Response has been maintained in patients who continued treatment for up to 5 years. In patients with psoriatic arthritis, etanercept 25mg twice weekly significantly reduced disease activity and improved skin lesions in two double-blind, placebo-controlled, 12- to 24-week trials. In the 24-week study, ACR20 response rates (50 vs 13%), psoriatic arthritis response rates (70 vs 23%) and the median improvement in skin lesions (33 vs 0%) were significantly greater in etanercept than in placebo recipients. In patients with polyarticular-course juvenile rheumatoid arthritis, etanercept resulted in improvements in all measures of disease activity and was significantly more effective than placebo at reducing disease flare. Eighty percent of patients receiving etanercept achieved a >or=30% reduction in disease activity over 7 months of treatment, and this was maintained for up to 2 years in a trial extension. Etanercept was generally well tolerated in children and adults in clinical trials; the most commonly occurring adverse effects included injection site reactions, infection, headache, rhinitis and dizziness. In conclusion, etanercept has emerged as an important new treatment option in inflammatory arthritis. Etanercept provides rapid and sustained improvements in disease activity in patients with early and DMARD-refractory rheumatoid arthritis and has been shown to inhibit radiographic progression in those with early disease. Well controlled studies have also demonstrated the efficacy of etanercept in patients with psoriatic arthritis or polyarticular-course juvenile rheumatoid arthritis.
15001324 Therapeutic effect of the combination of etanercept and methotrexate compared with each tr 2004 Feb 28 BACKGROUND: Etanercept and methotrexate are effective in the treatment of rheumatoid arthritis but no data exist on concurrent initiation or use of the combination compared with either drug alone. We aimed to assess combination treatment with etanercept and methotrexate versus the monotherapies in patients with rheumatoid arthritis. METHODS: In a double-blind, randomised, clinical efficacy, safety, and radiographic study, 686 patients with active rheumatoid arthritis were randomly allocated to treatment with etanercept 25 mg (subcutaneously twice a week), oral methotrexate (up to 20 mg every week), or the combination. Clinical response was assessed by criteria of the American College of Rheumatology (ACR). The primary efficacy endpoint was the numeric index of the ACR response (ACR-N) area under the curve (AUC) over the first 24 weeks. The primary radiographic endpoint was change from baseline to week 52 in total joint damage and was assessed with the modified Sharp score. Analysis was by intention to treat. FINDINGS: Four patients did not receive any drug; thus 682 were studied. ACR-N AUC at 24 weeks was greater for the combination group compared with etanercept alone and methotrexate alone (18.3%-years [95% CI 17.1-19.6] vs 14.7%-years [13.5-16.0], p<0.0001, and 12.2%-years [11.0-13.4], p<0.0001; respectively). The mean difference in ACR-N AUC between combination and methotrexate alone was 6.1 (95% CI 4.5-7.8, p<0.0001) and between etanercept and methotrexate was 2.5 (0.8-4.2, p=0.0034). The combination was more efficacious than methotrexate or etanercept alone in retardation of joint damage (mean total Sharp score -0.54 [95% CI -1.00 to -0.07] vs 2.80 [1.08 to 4.51], p<0.0001, and 0.52 [-0.10 to 1.15], p=0.0006; respectively). The mean difference in total Sharp score between combination and methotrexate alone was -3.34 (95% CI -4.86 to -1.81, p<0.0001) and between etanercept and methotrexate was -27 (-3.81 to -0.74, p=0.0469). The number of patients reporting infections or adverse events was similar in all groups. INTERPRETATION: The combination of etanercept and methotrexate was significantly better in reduction of disease activity, improvement of functional disability, and retardation of radiographic progression compared with methotrexate or etanercept alone. These findings bring us closer to achievement of remission and repair of structural damage in rheumatoid arthritis.
12209506 Association between tumor necrosis factor receptor II and familial, but not sporadic, rheu 2002 Aug OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) binds the receptors TNFRI and TNFRII. Results of genome scans have suggested that TNFR2 is a candidate rheumatoid arthritis (RA) locus. A case-control study in a UK Caucasian population has shown an association between a TNFR2 genotype (196R/R in exon 6) and familial, but not sporadic, RA. The present study was undertaken to test this association in the French Caucasian population. METHODS: To test for an association in sporadic RA, 100 families were genotyped for the 196M/R polymorphism and analyzed using the transmission disequilibrium test and haplotype relative risk. To test for an association in familial RA, RA index cases from 100 affected sibpair (ASP) families were genotyped for 196M/R. Linkage analysis was performed with 3 TNFR2 microsatellite markers. RESULTS: The TNFR2 196R/R genotype was not associated with sporadic RA (odds ratio [OR] 0.59, P = 0.72), but was associated with familial RA (OR 4.0, P = 0.026). The association was most marked in the context of TNFR2 "twin-like" RA sibs (affected sibs sharing both TNFR2 haplotypes) (OR 9.2, P = 0.0017). Linkage analysis results were consistent with the association; most of the TNFR2 linkage evidence was found in the subgroup of families with 196R/R ASP index cases. CONCLUSION: This study is the first to replicate evidence of the involvement of TNFR2 in RA genetic heterogeneity. Our data refine the initial hypothesis, to suggest that a TNFR2 recessive factor, in linkage disequilibrium with the 196R allele, plays a major role in a subset of families with multiple cases of RA.
15249323 Renal clearance and daily excretion of cortisol and adrenal androgens in patients with rhe 2004 Aug BACKGROUND: In rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), patients demonstrate low levels of adrenal hormones. OBJECTIVE: To investigate whether increased renal clearance and daily excretion contribute to this phenomenon. METHODS: Thirty patients with RA, 32 with SLE, and 54 healthy subjects (HS) participated. Serum and urinary levels of cortisol, cortisone, 17-hydroxyprogesterone (17OHP), androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulphate (DHEAS) were measured. RESULTS: Clearance of DHEAS and DHEA was lower in patients than in HS, and clearance of androstenedione was somewhat higher in patients than in HS, but daily excretion of this latter hormone was low. Clearance of cortisol, cortisone, and 17OHP was similar between the groups. The total molar amount per hour of excreted DHEA, DHEAS, and androstenedione was lower in patients than HS (but similar for cortisol). Serum DHEAS levels correlated with urinary DHEAS levels in HS and patients, whereby HS excreted 5-10 times more of this hormone than excreted by patients. Low serum levels of adrenal androgens and cortisol in patients as compared with HS were confirmed, and proteinuria was not associated with changes of measured renal parameters. CONCLUSIONS: This study in patients with RA and SLE demonstrates that low serum levels of adrenal androgens and cortisol are not due to increased renal clearance and daily loss of these hormones. Decreased adrenal production or increased conversion or conjugation to downstream hormones are the most likely causes of inadequately low serum levels of adrenal hormones in RA and SLE.
11930657 Interleukin-1 gene polymorphism disease activity and bone mineral metabolism in rheumatoid 2002 Jan OBJECTIVE: To determine whether interleukin-1 alpha and 1 beta gene polymorphism is associated with rheumatoid arthritis disease activity and bone mineral metabolism, and whether there is any relationship between IL-1 beta and rheumatoid arthritis (RA) motif gene. METHODS: IL-1 gene polymorphisms were analyzed in 65 RA patients who met American College of Radiology (ACR) criteria and 60 controls. From genomic DNA, 2 polymorphisms in each gene for IL1 alpha-889 and IL-1 beta + 3953 were typed by PCR-RFLP and HLA-DRB1 allele typing was also undertaken by PCR-SSOP. Some clinical and laboratory parameters were collected. The allelic frequencies and carriage rates were compared between RA patients and controls and between patients with active and quiescent disease. Comparison was also made between IL-1 polymorphism and parameters of bone mineral metabolism and between patients with the HLA-DRB1 RA motif plus IL-1 beta 2 and patients without the two alleles. Fisher test and the analysis of variance was used to analyze the data. RESULTS: There was no significant difference in the frequency and carriage rate of IL-1 alpha polymorphisms between RA patients and the controls. The beta 2/2 genotype of IL-1 beta was more common in female RA patients compared with controls (P = 0.001). A lower carriage rate of IL-1 beta 2 occurred in male RA patients (P = 0.001). A higher carriage rate of IL-1 alpha 2 is associated with a higher ESR (P = 0.008), HAQ score (P = 0.03), and vit-D3 (P < 0.001), but conversely a lower SJC (p = 0.002), a lower RF (P = 0.002) and a lower BMD at the lumbar spine (P = 0.001). A higher frequency of IL-1 alpha 1 is associated with a lower CRP value (P = 0.009). An increased IL-1 beta 2 carriage is associated with active rheumatoid disease as indicated by a higher CRP (P < 0.001), ESR (P < 0.001) and pain score (P = 0.001) and a higher BMD at the lumbar spine (P = 0.007), lower vit-D3 and. Udpd/Crea level The presence of the HLA DRB1 RA motif and IL-1 beta allele 2 at same time did not contribute to disease activity. CONCLUSION: Polymorphisms of the IL-beta gene may affect the RA occurrence. Carriage of IL-1 beta 2 polymorphisms is associated with more active disease in RA and the presence of both the IL-1 alpha 2 and the IL-1 beta 1 allele in RA influences bone resorption.
12207202 [Long term study on the efficacy and safety of lornoxicam in rheumatoid arthritis]. 2002 Aug BACKGROUND: To assess the long term safety and therapeutic action of lornoxicam, a new non steroidal anti-inflammatory agent, in rheumatoid arthritis. METHODS: Open trial was carried out on different dosage schedules of lornoxicam (4 or 8 mg bid and 4mg tid) administered for six to twelve months. Patients of both sexes were enrolled, with classical or definite rheumatoid arthritis according to the A.R.A. criteria. RESULTS: Thirty-four patients (28 F, 6 M) were admitted, mean age (+/- SD) 53.9+/-14.2 years, mean duration of illness 9.2+/-10.7 years. Lornoxicam 8-16 mg/day showed good safety and therapeutic activity in long term treatment. Clinical improvement was limited, but progression of the disease was controlled. No adverse events were complained. CONCLUSIONS: Lornoxicam presented a worth-while therapeutic action and a good tolerability in rheumatoid arthritis long term treatment.
12932282 Aging, autoimmunity and arthritis: T-cell senescence and contraction of T-cell repertoire 2003 Rheumatoid arthritis (RA), like many other autoimmune syndromes, is a disease of adults, with the highest incidence rates reported in the elderly. The immune system undergoes profound changes with advancing age that are beginning to be understood and that need to be incorporated into the pathogenetic models of RA. The age-related decline in thymic function causes extensive remodeling of the T-cell system. Age-dependent changes in T-cell homeostasis are accelerated in patients with RA. The repertoire of naive and memory T cells is less diverse, possibly as a result of thymic insufficiency, and it is biased towards autoreactive cells. Presenescent T cells emerge that are resistant to apoptosis and that often expand to large clonal populations. These cells are under the regulatory control of nonconventional costimulatory molecules, display potent effector functions, and appear to be critical in the synovial and extra-articular manifestations of RA.
11792883 Helicobacter pylori infection in rheumatoid arthritis: effect of drugs on prevalence and c 2002 Jan OBJECTIVE: The aim of this study was to investigate the impact of Helicobacter pylori infection on clinical features in patients with rheumatoid arthritis (RA) under medication with non-steroidal anti-inflammatory drugs. METHODS: One hundred and eighty-four patients with RA were tested for the presence of H. pylori infection. Clinical features and gastroduodenal lesions were compared between H. pylori-positive and -negative patients. RESULTS: One hundred and thirteen patients were positive and 71 patients were negative for H. pylori. The age, severity of RA, prevalence of gastrointestinal symptoms and gastroduodenal lesions and the class of gastroprotective drugs were not different between the two groups. Reflux oesophagitis was less frequent and sulphasalazine was less frequently administered in the H. pylori-positive group. CONCLUSIONS: The severity of RA, prevalence of gastroduodenal lesions other than reflux oesophagitis and the application of gastroprotective drugs do not seem to depend upon H. pylori infection in RA patients. Sulphasalazine may be protective against H. pylori infection.
12574387 Synoviocyte-derived CXCL12 is displayed on endothelium and induces angiogenesis in rheumat 2003 Feb 15 CXCL12 (stromal cell-derived factor-1) is a potent CXC chemokine that is constitutively expressed by stromal resident cells. Although it is considered a homeostatic rather than an inflammatory chemokine, CXCL12 has been immunodetected in different inflammatory diseases, but also in normal tissues, ant its potential functions and regulation in inflammation are not well known. In this study, we examined the cellular sources of CXCL12 gene expression and the mechanism and effects of its interactions with endothelial cells in rheumatoid arthritis synovium. We show that CXCL12 mRNA was not overexpressed nor induced in cultured rheumatoid synoviocytes, but it specifically accumulated in the rheumatoid hyperplastic lining layer and endothelium. CXCL12 gene expression was restricted to fibroblast-like synoviocytes, whereas endothelial cells did not express CXCL12 mRNA, but displayed the protein on heparitinase-sensitive factors. CXCL12 colocalized with the angiogenesis marker alpha(v)beta(3) integrin in rheumatoid endothelium and induced angiogenesis in s.c. Matrigel plugs in mice. The angiogenic activity of rheumatoid synovial fluid in vivo was abrogated by specific immunodepletion of CXCL12. Our results indicate that synoviocyte-derived CXCL12 accumulates and it is immobilized on heparan sulfate molecules of endothelial cells, where it can promote angiogenesis and inflammatory cell infiltration, supporting a multifaceted function for this chemokine in the pathogenesis of rheumatoid arthritis.
15293087 Contrast-enhanced power Doppler sonography of knee synovitis in rheumatoid arthritis: asse 2004 Aug The aim of this study was to evaluate the ability of power Doppler sonography (PDS) with ultrasound contrast agent to assess the synovial perfusion changes induced by intra-articular steroid injection therapy in the knee joints of patients with rheumatoid arthritis (RA). Eighteen RA patients (16 women, 2 men) with a history and signs of active knee synovitis were studied. Tenderness was evaluated using Thompson's modified index of synovitis activity. All patients underwent joint aspiration followed by intra-articular injection of 40 mg of triamcinolone hexacetonide. Gray-scale ultrasonography and PDS with an intravenous ultrasound contrast agent (Levovist) examinations were carried out before and 3 weeks after the intra-articular steroid injection. The calculation of the time--intensity curves provided a quantitative estimation of the synovial perfusion. The median values of the index of synovitis activity decreased significantly from 7.0 (95% confidence interval (CI) 6.0-8.0) to 3.0 (95% CI 2.0-4.0) ( p<0.01) 3 weeks after the intra-articular steroid injection. All patients showed a reduction of PDS signal after intra-articular steroid therapy and the baseline and follow up median values of the area underlying time-intensity curves were 7.48 (95% CI 5.79-8.73) and 2.45 (95% CI 1.92-3.61), respectively. The comparison between baseline and follow-up median values of the area under the curves showed a statistically significant reduction of PDS findings ( p<0.01). At follow-up examinations the changes in the index score of the synovitis activity were significantly correlated to the changes in the values of the area underlying time-intensity curves ( r=0.785; p<0.01). A significant correlation was also observed between baseline values of the area underlying time-intensity curves and C-reactive protein (CRP) ( r=0.548; p=0.023). In conclusion, PDS with an intravenous ultrasound contrast agent has been shown to be able to detect changes in synovial perfusion after intra-articular steroid injection and may be an additional useful method in the evaluation of synovial inflammation and in the assessment of the therapeutic response.
12209508 Detection of antibodies to deiminated recombinant rat filaggrin by enzyme-linked immunosor 2002 Aug OBJECTIVE: To assay antifilaggrin autoantibodies, we developed an enzyme-linked immunosorbent assay (ELISA) using a "citrullinated" recombinant rat filaggrin. Our objectives were to assess its value for diagnosing rheumatoid arthritis (RA) and to compare the results with those obtained using 4 other reference methods for detection of antifilaggrin autoantibodies, including the commercially available ELISA that uses a modified "citrullinated" synthetic peptide derived from the sequence of human filaggrin (CCP-ELISA). METHODS: We analyzed 711 sera from patients with well-characterized rheumatic diseases, including 240 patients with RA. Antifilaggrin autoantibodies were detected by an ELISA using a recombinant rat filaggrin deiminated in vitro as immunosorbent (ArFA-ELISA). The results considered were the differences between the optical densities obtained on deiminated and nondeiminated proteins. Antibodies to rat esophagus epithelium were detected by indirect immunofluorescence, while antibodies to human filaggrin were detected by immunoblotting and by a recently described ELISA using a deiminated recombinant human filaggrin. Finally, CCP-ELISA was performed according to the manufacturer's recommendations. RESULTS: At the titer thresholds allowing diagnostic specificities of 0.95, 0.985, and 0.99 to be reached, the diagnostic sensitivities of the ArFA-ELISA were 0.76, 0.67, and 0.65, respectively. At these 3 thresholds, the sensitivities were significantly higher than those of the 4 other tests. Despite incomplete overlapping of the 5 tests, the high diagnostic performance of the ArFA-ELISA allows us to propose this test to replace all the other methods for antifilaggrin autoantibody detection. CONCLUSION: ArFA-ELISA appears to be the most efficient test among those available for the detection of antifilaggrin autoantibodies, in terms of diagnostic accuracy for RA. Its diagnostic performance in early RA and its prognostic value are currently under evaluation.
15331395 Evidence for negative association of the chemokine receptor CCR5 d32 polymorphism with rhe 2005 Mar BACKGROUND: Ligands of chemokine receptor CCR5, including MIP-1 alpha, MIP-1 beta, and RANTES, have been implicated in rheumatoid arthritis. OBJECTIVE: To test whether CCR5 d32 polymorphism has a negative association with rheumatoid arthritis in a New Zealand cohort. METHODS: 516 white patients with rheumatoid arthritis and 985 healthy controls were investigated by PCR amplification of the region flanking the known CCR5 d32 deletion, and the frequencies of CCR5 d32 compared. An early rheumatoid arthritis (ERA) cohort of 92 patients was followed prospectively for two years; disease severity and outcome were correlated with CCR5 d32 status. RESULTS: 12 control subjects (1.2%) were homozygous for d32; no d32 homozygous rheumatoid patients were detected (p = 0.012); 56 patients (10.9%) were heterozygous for the d32 polymorphism (d32/wt), compared with 169 controls (17.2%) (p = 0.0011). The CCR5 d32 allele frequency was lower in the rheumatoid patients than in the controls (frequencies of 0.054 and 0.098, respectively; p = 3.7 x 10(-5)). The frequency of CCR5 d32 did not differ significantly according to disease severity or outcome in the prospective ERA cohort, nor with HLA-DRB1 status. CONCLUSIONS: This study provides further evidence for a protective effect of the CCR5 d32 variant on rheumatoid arthritis, consistent with a role for CCR5 and its ligands in disease pathogenesis.
12189720 Gene therapy strategies to prevent autoimmune disorders. 2002 Sep Autoimmunity accounts for a significant percentage of human disease and remains a challenging syndrome to treat. While systemic immunosuppression can be beneficial, the associated toxicity of the pharmacologic agents necessitates an antigen-specific approach to silence, eradicate or prevent the genesis of autoreactive immune cells. Gene therapy offers the possibility of providing precise antigen-targeted therapies, thereby sparing the patient the significant toxicity associated with lifelong commitment to chemical immunosuppressives. Gene-based therapies could include, but are not limited to the manipulation of immune networks of tolerance by antigen presenting cell engineering, pro-inflammatory cytokine blockade using soluble antagonists expressed from viral vectors as well as modulation of immune regulatory networks. The potential utility of gene therapy strategies promoting tolerance in two model autoimmune disorders, type I diabetes mellitus and rheumatoid arthritis are discussed in this review.
12788007 Five year results of selective patellar resurfacing in cruciate sparing total knee replace 2003 Jun We performed a prospective study on 129 knees with a selective approach to patellar resurfacing. One hundred and five knees were followed up at an average of 57 months. Of these, 48 knees met the eligibility criteria, thus leaving 57 knees with unresurfaced patellas. Mean follow up was 57 months. Parameters studied included HSS scores, pain, function, range of motion and patellofemoral symptoms including the ability to rise from a chair and to negotiate stairs. Approximately 90% good to excellent results were observed in both groups. The incidence of anterior knee pain and patellofemoral related problems was lower than the average reported in literature. None of the knees was revised for patellofemoral problems. Our findings suggest that the results of patellofemoral resurfacing with modern TKR designs are dependent on a careful patient selection and meticulous surgical technique. With a selective approach to resurfacing, one can achieve a high percentage of good results in both groups. Post-operative anterior knee pain is probably not related to the fact as to whether the patella is resurfaced or not.