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ID PMID Title PublicationDate abstract
15029266 [Multicenter study of radiosynoviorthesis. Clinical outcome in osteoarthritis and other di 2004 Mar AIM: Evaluation of the effectiveness of radiosynoviorthesis (RSO) in osteoarthritis and other disorders with concomitant synovitis versus rheumatoid arthritis by means of a standardized questionnaire. PATIENTS, METHODS: 803 RSO treatments were monitored in 691 patients by standardized questionnaires of 7 centers in 3 countries. Patients were assigned to 3 groups according to their age (20-40, 41-60, 61-80 years). Additionally, the data were analyzed separately for patients with rheumatoid arthritis (group A) and those with osteoarthritis, psoriasis arthritis, pigmental villonodular synovitis or persistent effusions after joint replacement (group B). RESULTS: Ameliorations of joint pain, swelling/effusion or flexibility were found in 80% of group A and 56% of group B (p >0.01). Quality of life improved in 78% of group A and 59% of group B (p >0.01). The response rate was similar for small- and large-sized joints in group A, but significantly higher for large-sized joints in group B (p >0.01). The positive effects on joint pain, swelling/effusion or flexibility lasted longer in group A (p >0.01). Repeated RSOs were as effective as initial ones. The clinical outcome was neither influenced by age, nor gender, nor transient immobilisation for 48 hours after RSO. CONCLUSION: Although slightly more efficient in rheumatoid arthritis, RSO represents an effective treatment option also in osteoarthritis and other disorders with concomitant synovitis.
12518417 [Seven cases of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) sy 2002 Nov Among the elderly patients with seronegative polyarthritis, McCarty et al. (1985) proposed a disease entity of "remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome", but only a few cases have been reported in Japan. Here we report 7 cases suspicious of RS3PE syndrome, 2 men and 5 women with an average age of 75.9 years, ranging from 67-82 years. Their common findings were (1) relatively acute onset, (2) polyarthritis, (3) pitting edema of the dorsum of both hands and both feet, and (4) negative rheumatoid factor and antinuclear antibody. McCarty et al. found that RS3 PE syndrome was more prevalent in men; however, in our experience, the opposite was observed. The clinical courses of all patients were good, and they were effectively treated either by small dosages of oral prednisolone, nonsteroidal antiinflammatory drugs, or Chinese herbal (Kampo) medicines. Since this syndrome might not be rare in Japan, it seems necessary to evaluate elderly patients with seronegative polyarthritis with pitting edema as RS3PE syndrome in their routine medical examinations.
12913922 Preferential induction of prodestructive matrix metalloproteinase-1 and proinflammatory in 2003 Aug OBJECTIVE: To assess expression and individual functional relevance of tumor necrosis factor receptor 55 (TNF-R55) and TNF-R75 in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial fibroblasts (SFB). METHODS: Seventh to 9th passage RA SFB and OA SFB were analyzed for TNF-R expression by FACS. The SFB were then stimulated with TNF-a (1-10 ng/ml) or agonistic anti-TNF-R55 (HTR-9) and anti-TNF-R75 (UTR-1) monoclonal antibodies (1-25 micro g/ml each). Matrix metalloproteinase-1 (MMP-1), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), interleukin 6 (IL-6), and prostaglandin E(2) (PGE(2)) in culture supernatants were quantified by ELISA, and DNA fragmentation by TUNEL assay. RESULTS: RA SFB variably expressed TNF-R55 (7.2 +/- 2.2% positive cells, mean +/- SEM) and TNF-R75 (0.6 +/- 0.3%), similarly to OA SFB (6.8 +/- 2.1% and 1.6 +/- 0.8%, respectively). RA SFB constitutively secreted large amounts of TIMP-1 (1700 ng/ml), but only small amounts of MMP-1 (23.7 ng/ml), IL-6 (4.4 ng/ml), and PGE(2) (0.34 ng/ml). OA SFB secreted comparable amounts of TIMP-1 (2470 ng/ml), MMP-1 (37 ng/ml), and IL-6 (5.0 ng/ml), but significantly higher amounts of PGE(2) (0.58 ng/ml; p RA) and by separate stimulation of both TNF receptors. TNF-a-induced PGE(2) release by RA SFB (92-fold) and OA SFB (56-fold) was mediated by both TNF receptors; however, predominantly by TNF-R55. DNA fragmentation was induced exclusively by high concentrations of anti-TNF-R55 Mab and only in RA SFB. CONCLUSION: These results indicate preferential induction of prodestructive and proinflammatory mediators in RA SFB by the TNF-R55, with potential implications for understanding the pathogenesis of RA and the development of more specific therapeutic strategies.
14634081 Aberrant extracellular and dendritic cell (DC) surface expression of heat shock protein (h 2003 Dec 1 We describe, in rheumatoid arthritis (RA), abnormalities in the expression and distribution of heat shock protein (hsp) and dendritic cells (DCs) that are conducive to cross-priming and DC cross-talk. As detected by ELISA, inducible (i)hsp70 was dramatically increased in RA synovial fluid (RASF) vs normal human and RA sera and osteoarthritis and gout synovial fluid. Immunoblot analysis of fresh RASF cells revealed marked increases in ihsp70 and activation of its transcription factor heat shock factor-1, compared with fresh normal peripheral blood cells. Flow cytometry and microscopy demonstrated high levels of ihsp70 on the surface of RASF myeloid DCs (but not normal myeloid DCs) that occurred concurrently with hspRs (CD91/CD14). ihsp70 present in RASF exhibited chaperoning potential, as indicated by the capture of ihsp70 present in RASF on the surface of normal DCs. Binding was partially competitively inhibited by excess alpha(2)-macroglobulin, indicating that hspRs in addition to CD91 participate in the capture process. These data indicate that ihsp70 may chaperone autologous Ags into immature RASF DCs via hspRs, and that cross-talk between DCs coexpressing hsp/hspRs reflects a disease process in RA. The induction of surface ihsp70 on normal cells after sublethal heat stress and the release of ihsp70 from normal DCs after inflammatory stress also suggest that the pattern of ihsp70 expression in RASF occurs in response to sustained stress.
12084005 TNF inhibition as therapy for rheumatoid arthritis. 2002 Jul The introduction of TNF- alpha -inhibiting biologicals has been a major therapeutic breakthrough in rheumatoid arthritis therapy. Against a background of conventional disease-modifying antirheumatic drug experience, this review focuses on present experiences and possible future developments. TNF inhibition results in profound improvement in the majority of rheumatoid arthritis patients, but non-response and adverse effects need attention. Adalimumab is being filed for approval. Other monoclonal antibodies or receptor constructs are in late development. Small molecule inhibitors of TNF production or signalling are a hot topic. One emerging target is nuclear factor kappa B and selective inhibition has proved effective in animal models of arthritis. Synovial proliferation in rheumatoid arthritis is characterised by diminished apoptosis of fibroblasts, whereas bone marrow precursor cells undergo accelerated apoptosis in active rheumatoid arthritis. Both abnormalities are seemingly ameliorated by TNF inhibition. Anti-apoptotic strategies will soon go into development for control of unresponsive rheumatoid arthritis.
12017856 [High resolution ultrasound diagnosis of the annular tendon system of the hand]. 2002 Mar High-resolution ultrasonography has gained wide acceptance in the evaluation of tendons and tendon sheaths of the finger flexors. The annular pulleys are depicted as a hypoechoic band surrounding the flexor tendons. In patients with trigger finger or polyarthritis, the tendons as well as the pulleys are of interest to the investigator. Ultrasonography allows direct or indirect diagnosis of partial and total disruptions of the pulleys. Loss of (parts of) the pulleys can be seen as a direct sign and bowstringing of the tendons during forced flexion as an indirect sign. We provide a review of the literature regarding this topic and present our experiences with better visualization employing the latest ultrasonographic equipment (such as Sono-CT).
12048292 Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis. 2002 Jun OBJECTIVE: To study (i) the influence of methotrexate (MTX) therapy on homocysteine and folate metabolism in patients with rheumatoid arthritis (RA), (ii) the influence of the C677T mutation in the methylenetetrahydrofolate reductase gene (MTHFR) on the change in plasma homocysteine levels during MTX treatment, and (iii) the interference of folate and homocysteine metabolism with the efficacy and toxicity of treatment with MTX. METHODS: The 113 patients enrolled in this study were participating in a 48-week, multicentre, double-blind, placebo-controlled study comparing the efficacy and toxicity of MTX treatment with and without folic or folinic acid supplementation. The MTX dose was 7.5 mg/week initially and increased to a maximum of 25 mg/week if necessary. Concentrations of total folate, 5-methyl tetrahydrofolate (in serum and in erythrocytes) and of homocysteine, cysteine and cysteine-glycine and the MTHFR genotype were determined before the start of the study, after 6 weeks, and after 48 weeks or on withdrawal from the study. Blood was drawn from fasting patients at a standardized time in the morning, 16 h after intake of MTX. The laboratory results were related to parameters of efficacy and toxicity of MTX treatment. RESULTS: Baseline values were distributed equally in the three treatment groups. The mean plasma homocysteine level (normal range 6-15 micromol/l) before the start of MTX was relatively high in all groups: 15.4 micromol/l [95% confidence interval (CI) 13.5 to 17.2] in the MTX plus placebo group (n=39), 14.3 micromol/l (95% CI 12.2 to 16.4) in the MTX plus folic acid group (n=35) and 15.9 micromol/l (95% CI 13.7 to 18.1) in the MTX plus folinic acid group (n=39). After 48 weeks of MTX therapy, the mean homocysteine level showed an increase in the placebo group (+3.6 micromol/l, 95% CI 1.7 to 5.6). In contrast, a decrease was observed in the groups supplemented with folic or folinic acid (folic acid, -2.7 micromol/l, 95% CI -1.4 to -4.0; folinic acid, -1.6 micromol/l, 95% CI -0.1 to -3.0). The differences in the change in plasma homocysteine level between the placebo group and each of the two folate-supplemented groups were statistically significant (P<0.0001), contrary to the difference between the folic and folinic acid groups (P=0.26). Linear regression analysis showed that the change in plasma homocysteine level was statistically significantly associated with folic or folinic acid supplementation (P=0.0001) but not with the presence or absence of the C677T mutation in the MTHFR gene. Homozygous mutants had a higher plasma homocysteine concentration at baseline. No relationship was found between the change in disease activity and the change in homocysteine concentration or the mean homocysteine concentration after 48 weeks of MTX therapy. Toxicity-related discontinuation of MTX treatment was not associated with the change in homocysteine concentration. CONCLUSIONS: Low-dose MTX treatment in RA patients leads to an increased plasma homocysteine level. Concomitant folate supplementation with either folic or folinic acid decreases the plasma homocysteine level and consequently protects against potential cardiovascular risks. No relationship was found between the change in homocysteine concentration and the presence or absence of the C677T mutation in the MTHFR gene. Homocysteine metabolism was not associated with efficacy or toxicity of MTX treatment.
14716651 Posterior cruciate ligament-substituting total knee arthroplasty in young rheumatoid patie 2004 Jan The integrity and strength of the posterior cruciate ligament (PCL) in the rheumatoid knee are known to be suboptimal. However, the results of PCL-substituting total knee arthroplasty in rheumatoid patients are not well documented. We reviewed 86 PCL-substituting total knee arthroplasties in 52 rheumatoid patients with grade IV or V radiographic disease. The mean age at surgery was 41.9 years. All patients underwent follow-up evaluation for an average of 7.8 years. Revision was performed for 1 knee because of aseptic loosening of the tibial component, and for 3 knees because of deep infection. An isolated insert exchange was performed on one knee. Using revision of any component for aseptic loosening or radiographic loosening as the end point, the mean 10-year survival rate was 94.0%.
12102278 Weekly dose of leflunomide for the treatment of refractory rheumatoid arthritis: an open p 2002 May AIMS: To assess the therapeutic effect of leflunomide in weekly dose of 100 mg in patients with refractory rheumatoid arthritis. MATERIAL AND METHODS: Sixteen patients were included (18-72 years, disease duration 2-32 years). Eight patients received a weekly dose of 100 mg of leflunomide and 8 the conventional dose. Current treatment was not modified. All patients underwent a monthly evaluation for one year, applying the 1995 ACR preliminary definition of improvement in rheumatoid arthritis. RESULTS: After 2 months, the group treated with the conventional leflunomide dose evidenced a remarkable improvement (7/8 patients achieving ACR 20), while the group receiving the weekly dose, the improvement was not as clearly evident (3/8 patients achieving ACR 20). By the fourth to sixth month, the response was comparable on both groups (6/6 and 6/8 patients achieving ACR 50 in the daily and weekly dose, respectively) and prevailed through the end of the study. There were no statistical differences between groups at any evaluation. Side effects made itself clear in 6 patients in the daily leflunomide group, and 2 patients withdrawn leflunomide because severe gastrointestinal symptoms and hepatotoxicity, respectively. In the group of weekly leflunomide 2 patients presented side effects which disappeared spontaneously. CONCLUSION: The use of leflunomide in a weekly dose of 100 mg proved to have similar therapeutic benefit as that of the conventional scheme and might represent a new option for the treatment of refractory rheumatoid arthritis patients.
12846056 Biological relevance of the polymorphism in the CCR5 gene in refractory and non-refractory 2003 May OBJECTIVE: The aim of this study was to analyze the frequencies of the CCR5 delta 32 deletion and HLA class II alleles in Mexican Amerindian populations and its relevance in the development and severity of RA. METHODS: We studied 212 Mexican Mestizo subjects (40 patients with refractory RA, 102 patients with non-refractory RA and 70 healthy individuals). At the same time, to evaluate the ethnicity of the CCR5 delta 32 deletion we also studied 192 individuals from three Mexican Amerindian populations (70 Mayo (Capomo) individuals, 61 Teenek individuals, and 61 Mazatecan Indians). The delta 32 deletion in the CCR5 structural gene and HLA-DRB1 were determined by a PCR-SSP and a PCR-SSO procedure, respectively. RESULTS: In the non-refractory RA group the CCR5 delta 32 gene frequency was 0.019 and the following genotype frequencies were observed: CCR5/CCR5 = 98.0%, CCR5/CCR5 delta 32 = 1.9% and CCR5 delta 32/CCR5 delta = 1.0%. In the refractory RA group the CCR5 delta 32 gene frequency was 0.025 and the genotype distribution was similar to that in the non-refractory RA group. The deletion was not detected in the Mexican Mestizo healthy group, or among the Teenek and Mayo Amerindians, all being individuals homozygous for the wild type allele. In the Mazatecan group the deletion frequency was 1.6% (g.f. = 0.016). We observed a significant increase in the frequency of the DRB1*07 allele in severe RA patients in relation to the non-severe RA group (p = 0.02, OR = 5.65, 95% CI = 0.95-43.05). CONCLUSION: Our results suggest that the CCR5 delta 32 deletion is not common in Mexican Amerindian populations and this study does not support an important role of CCR5 delta 32 in the pathogenesis of RA or a severe form of the disease in Mexicans.
14675085 Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathw 2003 Dec BACKGROUND: Activation of coagulation and fibrinolysis play a role in the pathophysiology of experimental arthritis. OBJECTIVE: To determine the extent of activation of the coagulation and fibrinolytic pathways in different joint diseases in humans and to ascertain the factors that may influence fibrin deposition within the joint. METHODS: Plasma from normal subjects (controls, n= 21) and plasma and synovial fluid samples from patients with rheumatoid arthritis (RA; n = 64), osteoarthritis (OA; n = 29), spondyloarthropathy (SpA; n = 22) and crystal arthritis (CA; n = 25) were analyzed for the levels of TF (tissue factor) and tissue factor pathway inhibitor (TFPI) activities, thrombin-antithrombin III (TAT) complexes, and F1 + 2 (thrombin fragment), fibrin d-dimer and thrombin-activated fibrinolysis inhibitor (TAFI) antigenic levels. The measurements were analyzed by pairwise correlation with each other as well as with standard parameters of inflammation [C-reactive protein (CRP), joint leukocyte count]. Inter-group comparisons were performed to look for disease-specific differences. RESULTS: Compared with healthy controls, patients with joint diseases had higher levels of TAT, F1 + 2 and d-dimers in their plasma. In the synovial fluid, TF activity, TAT, d-dimers, and TAFI were significantly higher in inflammatory arthritides than in OA. The levels were highest in RA patients. In the plasma, TF activity was correlated with TAT and d-dimer levels with CRP, TFPI, and TAT. In the synovial fluid, TF activity correlated with plasma CRP levels, synovial fluid leukocyte count, and synovial TAT and TAFI levels. In addition, synovial d-dimers correlated with CRP, and synovial TAFI levels were correlated with synovial F1 + 2 and TAT. CONCLUSIONS: Activation of the coagulation and fibrinolytic cascades in the joint and in the circulation is evident in both inflammatory and degenerative joint diseases. Within the joint, inflammatory mechanisms leading to TF-mediated activation of the coagulation pathway and subsequent fibrin deposition is the most likely explanation for the observed findings. In the plasma, the link between inflammation (CRP increase) and TF activation is weak, and a non-TF-mediated mechanism of coagulation activation could explain these findings. RA is characterized by significantly higher levels of TAT in the synovial fluid and plasma than other arthritides. Although fibrinolytic activity is linked to inflammation, the increased amounts of TAFI in the joint, particularly in RA, may explain why fibrin formation is so prominent in this condition compared with other joint diseases.
15355745 Targeting cytokines beyond tumor necrosis factor-alpha and interleukin-1 in rheumatoid art 2004 Oct Targeting tumor necrosis factor-a has proven of considerable value in treatment for rheumatoid arthritis, with substantial benefits achieved in a proportion of treated patients. However, a significant number of patients do not achieve sufficient improvement and as a result there remains considerable unmet clinical need. A number of cytokines have recently been described with proinflammatory activity in rheumatoid arthritis synovitis, including interleukin (IL) -6, IL-12, IL-15, and IL-18. We review recent data that support the notion that some or all of these moieties offer therapeutic potential. The possibility that some may be useful in partial responders to tumor necrosis factor blocking agents or in synergy with the latter is discussed.
15049939 Clustering of autoimmune disease in parents of siblings from the Type 1 diabetes Warren re 2004 Apr AIMS: Autoimmune disorders co-exist in the same individuals and in families, implying a shared aetiology. The aim of this study was to compare the prevalence of the common autoimmune diseases in the parents of siblings from the Type 1 diabetes Warren repository with the general population. METHODS: Between 1989 and 1996, 505 British families with at least two siblings affected by Type 1 diabetes were recruited. Clinical information was collected regarding the presence of autoimmune disease in the parents and the prevalence of disease in the parents was compared with that expected in the general population. RESULTS: The prevalence of autoimmune disease in the parents was significantly higher in the repository compared with that expected in the general population [P-value = 1.98 x 10(-5) (female), P-value = 1.1 x 10(-8) (male)]. Type 1 diabetes was recorded in 63/1010 (6.2%) parents with a marked paternal preponderance (9.5 vs. 3%P = 0.002). Other autoimmune diseases affected 27% of parents with diabetes and 13.2% of parents without diabetes (P < 0.01). CONCLUSION: These data confirm the importance of family history as a significant risk factor for the development of Type 1 diabetes and support the hypothesis that the common autoimmune diseases share at least some aetiological mechanisms.
12115173 Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radio 2002 Jun OBJECTIVE: To compare the clinical and radiographic outcomes in patients with rheumatoid arthritis (RA) who received monotherapy with either etanercept or methotrexate (MTX) for 2 years and to assess the safety of this therapy. METHODS: In the Enbrel ERA (early rheumatoid arthritis) trial, 632 patients with early, active RA were randomized to receive either twice-weekly subcutaneous etanercept (10 mg or 25 mg) or weekly oral MTX (mean dosage 19 mg per week) for at least 1 year in a double-blind manner. Following the blinded phase of the trial, 512 patients continued to receive the therapy to which they had been randomized for up to 1 additional year, in an open-label manner. Radiograph readers remained blinded to treatment group assignment and the chronologic order of images. RESULTS: At 24 months, more 25-mg etanercept patients than MTX patients met American College of Rheumatology 20% improvement criteria (72% and 59%, respectively; P = 0.005), and more had no increase in total score and erosion scores on the Sharp scale (P = 0.017 and P = 0.012, respectively). The mean changes in total Sharp score and erosion score in the 25-mg etanercept group (1.3 and 0.66 units, respectively) were significantly lower than those in the MTX group (3.2 and 1.86 units, respectively; P = 0.001). Significantly more patients in the 25-mg etanercept group (55%) than in the MTX group (37%) had at least 0.5 units of improvement in the Health Assessment Questionnaire disability index (P < 0.001). Fewer patients in the etanercept group than in the MTX group experienced adverse events or discontinued treatment because of adverse events. CONCLUSION: Etanercept as monotherapy was safe and was superior to MTX in reducing disease activity, arresting structural damage, and decreasing disability over 2 years in patients with early, aggressive RA.
15248214 Amplification of the synovial inflammatory response through activation of mitogen-activate 2004 Jul OBJECTIVE: To determine the signal transduction pathways in CD14+ synovial cells from patients with rheumatoid arthritis (RA) after CD40 ligation, and to examine their role in amplifying synovial inflammation in affected joints. METHODS: Expression of messenger RNA was analyzed using quantitative reverse transcription-polymerase chain reaction. Cytokines and chemokines were measured using enzyme-linked immunosorbent assay. Activation of kinases was detected using Western blotting. Nuclear translocation of NF-kappaB was examined using immunohistochemistry. CD14+ synovial cells were enriched using magnetic cell sorting. Fibroblast-like synoviocytes (FLS) were obtained by passaging primary synovial cell culture. RESULTS: Stimulation of CD14+ synovial cells from RA patients by recombinant soluble CD154 (rsCD154) significantly induced expression of tumor necrosis factor alpha (TNFalpha), interleukin-1alpha (IL-1alpha), and IL-1beta. CD14+ RA synovial cells stimulated with rsCD154 plus interferon-gamma (IFNgamma) induced significantly higher production of IL-6, IL-8, and monocyte chemoattractant protein 1 by FLS compared with unstimulated CD14+ synovial cells, through TNFalpha-, IL-1alpha-, and IL-1beta-mediated pathways. Stimulation with rsCD154 plus IFNgamma induced the activation of ERK-1/2, p38 MAPK, and NF-kappaB. Specific inhibitors of MAPK/ERK-1/2 kinases and p38 MAPK significantly reduced the production of TNFalpha and IL-1beta by rsCD154 plus IFNgamma-stimulated CD14+ synovial cells, and also inhibited production of these cytokines by freshly isolated synovial cells from RA patients. CONCLUSION: These data indicate that the CD40-CD154 interaction activates the ERK, p38, and NF-kappaB pathways in CD14+ synovial cells from RA patients to produce TNFalpha, IL-1alpha, and IL-1beta, which in turn amplifies inflammatory responses by stimulating FLS. Inhibition of the CD40-CD154 interaction or its signal transduction pathways would be a strong and efficient strategy for the management of synovial inflammation in RA.
11995248 [The effect of low dose methotrexate treatment on bone mineral density in patients with rh 2002 Feb To evaluate the bone mineral density (BMD) in patients with rheumatoid arthritis (RA) treated with MTX or SF. The study consisted of 56 premenopausal women diagnosed with rheumatoid arthritis (RA). Bone mineral density (BMD) of the lower lumbar spine was assessed before starting treatment, and again after 12 months of treatment. DEXA scanning was used to evaluate BMD. Corticosteroids or other substances known to affect bone metabolism were not administered. 45 women completed the study, of whom 23 were treated using SF and 22 MTX. The average dosage of MTX used was calculated to be 590 mg. A significant difference in the BMD of SF and MTX patients was not observed in the pretreatment phase, nor after 12 months of treatment. However, in all patients a significant reduction of BMD was observed, irrelevant of the choice of drug. The average loss of bone mass was 1.7% and 1.4% in the MTX and SF groups, respectively. MTX therapy administered in low doses as assessed after 12 months did not cause a rapid decrease of bone density in patients with RA.
14611106 Use of human chondrocyte cell cultures to identify and characterize reactive antibodies in 2003 Sep OBJECTIVE: To study the reactivity of rheumatoid arthritis (RA) sera with human chondrocyte populations isolated from normal cartilage and expanded in vitro. METHODS: Human articular chondrocytes were cultured as adherent (non-differentiated) cells on plastic dishes or in suspension (differentiated) on dishes previously coated with a thin layer of 1% agarose. Sera from 28 RA patients and 5 paired synovial fluids were tested on lysates from chondrocytes and fibroblasts as control by immunoblot. Antigen expression on the cell membrane was evaluated by flow cytometry in a few sera. RESULTS: In 9/28 RA sera IgG antibodies specific for chondrocyte antigens (97 kDa, 74 kDa, 67 kDa, 60 kDa, 54 kDa, 48 kDa and 37 kDa) were detected. Twelve sera reacted with proteins expressed both on chondrocytes and fibroblasts and 7 with fibroblasts only; two sera had no reactivity. When lysates from adherent or suspension chondrocytes were compared, RA sera reacted with higher intensity and detected more antigens on chondrocytes cultured in suspension. Flow cytometry assay demonstrated that RA sera are able to recognize antigens expressed on the cell membrane of the human chondrocytes. CONCLUSION: Our data indicate that: a) 32% of the RA sera contain antibodies reactive with antigens expressed exclusively by chondrocytes, but this value rises to 75% if antigens expressed both by chondrocytes and fibroblasts are considered; b) the reactivity of fully differentiated chondrocytes in suspension culture is higher than the reactivity of chondrocytes cultured in monolayer; and c) some of the chondrocyte-specific antigens identified are associated with the chondrocyte membrane. Thus, in vitro cultured chondrocytes may be used to study both the specificity and the biological activity of autoantibodies in RA.
12555177 Cementless acetabular replacement in patients with rheumatoid arthritis: a 6- to 14-year p 2003 Jan Sixty-three consecutive patients who had 82 Harris-Galante porous acetabular cups (HGP1) (Zimmer Inc, Warsaw, IN) implanted for the treatment of rheumatoid arthritis were prospectively assessed since 1986. At last examination, 12 patients (16 hips) had died, and 1 patient (1 hip) was lost to follow-up. A total of 65 hips in 50 patients were available for the latest review. The follow-up period was 6.8 years to 14 years (mean, 9.1 years). There had been 6 revisions: 1 for deep infection and 5 for polyethylene cup wear. Survivorship analysis for all failures estimated that 75% of hips would still be revision-free after 4558 days (12.5 years). Polyethylene wear has been identified in a further 7 cases at last examination. The average linear cup wear per year was 0.05 mm(range, 0.00-0.66 mm). There were no cases of acetabular loosening or acetabular migration. These results demonstrate the excellent durability of fixation of the HGP1 cups in patients with rheumatoid arthritis. However, a 32-mm head should probably not be used with this cup given the high associated incidence of polyethylene wear.
12966590 Increase of soluble FcgRIIIa derived from natural killer cells and macrophages in plasma f 2003 Sep OBJECTIVE: FcgRIII (CD16), one of the low affinity IgG Fc receptors, is found in 2 alternative forms, a transmembrane FcgRIIIa expressed on natural killer (NK) cells and macrophages, and a glycosylphosphatidylinositol-linked FcgRIIIb present on neutrophils. Both FcgRIII are released from the cell surface by proteolytic cleavage and these soluble forms (sFcgRIII) are present in plasma. Since NK cells and macrophages will be activated locally, leading to shedding of FcgRIIIa and its subsequent release into blood, we investigated whether sFcgRIIIa plasma concentrations would be a good marker for disease activity in patients with rheumatoid arthritis (RA). METHODS: We measured sFcgRIIIa with an immuno-PCR in plasma of NA(1+,2-) phenotyped donors. In this assay, we used CD16 GRM1, which recognizes NA2-FcgRIIIb and FcgRIIIa. We also analyzed precipitated sFcgRIIIa derived from plasma with immunoblotting with CD16 CLB-LM6.30. RESULTS: The concentration of sFcgRIIIa in patients with RA was about 3 times higher than in healthy controls. In controls, the sFcgRIIIa levels in plasma correlated with the number of NK cells in peripheral blood. In RA patients, sFcgRIIIa levels were increased directly proportionally to the concentrations of IgG, IgA, or IgM and to erythrocyte sedimentation rate or Lansbury Index. The electrophoretic mobility of plasma sFcgRIIIa corresponded with sFcgRIIIa derived from NK cells and/or macrophages. In general, plasma sFcgRIIIa originated from both cell types; however, the ratio of sFcgRIIIaNK to sFcgRIIIaMf varied in the RA patients. CONCLUSION: Increased sFcgRIIIa levels in RA patients were found to be caused by NK cell and/or macrophage activation. Plasma sFcgRIIIa levels may serve as a marker for disease activity in RA.
12672224 Economic evaluation of programs or interventions in the management of rheumatoid arthritis 2003 Apr Improvement in the quality of economic evaluation could be documented as a consequence of international and national standardization efforts. One such effort is the recommendation that all economic evaluations in a given field produce findings in a standard format using a reference case. A reference case-based economic evaluation would adhere to specific settings with regard to outcomes, comparators, modeling techniques, and use of costs to facilitate comparisons among economic evaluations performed with the same objective. In the past, the Outcome Measures in Rheumatology Clinical Trials (OMERACT) consensus conference has successfully developed widely used, consensus-based outcome criteria for clinical improvement in rheumatoid arthritis (RA). Present efforts are being directed at the development of recommendations for the type and format of a reference case economic evaluation for newly developed disease modifying antirheumatic drugs (DMARD). This document discusses 13 important elements that experts considered to be relevant for the development of a reference case recommendation for economic evaluations in RA. We provide the rationale for each element and discuss how each element has been addressed in published economic evaluations of DMARD.