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ID PMID Title PublicationDate abstract
11997108 Z39Ig is co-expressed with activated macrophage genes. 2002 Apr 12 Z39Ig is a recently-identified gene with immunoglobulin-like domains whose function is unknown. We examined expression of Z39Ig in 1432 human cDNA libraries, and found it primarily in synovium of patients with rheumatoid arthritis, in placenta, and in lung. We analyzed its co-expression pattern using the Guilt-by-Association (GBA) algorithm, and found that it is most similar in expression to early genes in the classical complement system (C1qA, C1qB, C1qC, C1r, and C1 inhibitor), MHC class II genes (HLA-DR alpha, HLA-DR beta 1, and HLA-DP alpha 1), Fc receptors (Fc gamma RIIa and Fc epsilon R1), lysosomal protein (LAPTm5), tissue transglutaminase, and macrophage receptors (MARCO and CD163/M130). The sequence and expression data suggest that Z39Ig is a cell surface receptor, expressed in activated macrophages, and linked with the classical complement system, most likely in phagocytosis preceding antigen presentation. Knowledge of this gene may contribute to better understanding of the role of complement and activated macrophages in rheumatoid arthritis and systemic lupus.
12209503 Efficacy of tacrolimus in rheumatoid arthritis patients who have been treated unsuccessful 2002 Aug OBJECTIVE: To assess the efficacy, safety, and optimal dose of tacrolimus monotherapy in patients with rheumatoid arthritis (RA). METHODS: This phase II, randomized, double-blind, placebo-controlled monotherapy study was set in 12 community sites and 9 university-based sites. Two hundred sixty-eight patients with RA who were resistant to or intolerant of methotrexate (mean dose 15.2 mg/week) and had active disease for at least 6 months (mean tender joint count 28.2, mean erythrocyte sedimentation rate 46.5 mm/hour) were randomized to receive treatment after discontinuation of methotrexate. Those who received at least 1 dose of tacrolimus were analyzed; 141 completed the study. Stable dosages of nonsteroidal antiinflammatory drugs and low-dose prednisone were allowed during treatment. All patients were given 1, 3, or 5 mg of tacrolimus or placebo once daily for 24 weeks. The American College of Rheumatology definition of 20% improvement (ACR20) and the tender and swollen joint counts at the end of treatment were the primary outcomes. RESULTS: ACR20 response rates demonstrated a clear dose response. The ACR20 response was observed in 15.5% of patients receiving placebo (95% confidence interval [95% CI] 7.1-23.9%), 29% of the 1 mg tacrolimus group (95% CI 18.3-39.7%) (P < 0.058); 34.4% of the 3 mg group (95% CI 22.7-46.0%) (P < 0.013), and 50% of the 5 mg group (95% CI 37.8-62.3%) (P < or = 0.001). The tender joint count improved statistically significantly in all tacrolimus groups. The swollen joint count, physical function, and patient-assessed pain improved statistically significantly in the 3 mg and 5 mg groups. The incidence of creatinine elevation > or =40% above baseline levels increased in a dose-dependent manner. Dropout rates were high (41-59%) and were more common for inefficacy in the placebo patients (71.4%), whereas they were more common for toxicity in the high-dose tacrolimus groups (31-33%). Discontinuation for creatinine elevation occurred in the 3 mg (3.1%) and 5 mg (10.9%) tacrolimus groups. CONCLUSION: Tacrolimus improved disease activity in methotrexate-resistant or -intolerant patients with RA. A dose response was observed when efficacy and toxicity were assessed at different doses. The optimal dose of tacrolimus appears to be >1 mg but < or=3 mg daily.
14652484 Intraspinal synovial cyst communicating with the C1-C2 facet joints and subarachnoid space 2003 Dec 1 STUDY DESIGN: The first case of intraspinal synovial cyst communicating with the C1-C2 facet joints and subarachnoid space associated with rheumatoid atlantoaxial instability is presented. OBJECTIVES: To describe the diagnosis and successful treatment of a synovial cyst of the C1-C2 junction in a patient with rheumatoid arthritis and atlantoaxial instability. SUMMARY OF BACKGROUND DATA: Intraspinal synovial cysts of the C1-C2 junction are extremely rare. Neither association with rheumatoid atlantoaxial instability nor communication with the C1-C2 facet joints and the subarachnoid space has been previously reported in a synovial cyst of the C1-C2 junction. MATERIALS AND METHODS: The clinical and radiologic features of a 71-year-old woman with a symptomatic synovial cyst of the C1-C2 junction with rheumatoid atlantoaxial instability are detailed. Posterior atlantoaxial fusion alone was performed. RESULTS: Preoperative magnetic resonance images demonstrated a large cystic mass around the dens, compressing the spinal cord. The mass was of low signal intensity on T1-weighted images, was of high signal intensity on T2-weighted images, and was enhanced marginally with gadolinium-DTPA on T1-weighted images. Computed tomograms performed after myelography disclosed the cyst around the dens communicating with the subarachnoid space and the C1-C2 facet joints. Spontaneous regression of the cyst was identified on the magnetic resonance images 3 months after surgery. One year after surgery, myelopathic symptoms were improved. CONCLUSION: An intraspinal cyst communicating with the C1-C2 facet joints and subarachnoid space associated with rheumatoid atlantoaxial instability was reported. Computed tomograms after myelography were useful in delineating the relationships among the synovial cyst, facet joints, and the subarachnoid space. Spontaneous regression of the cyst and clinical improvement were achieved by C1-C2 posterior fusion alone.
14640433 Peripheral keratitis following laser in situ keratomileusis. 2003 Nov PURPOSE: To report two different cases of sterile, peripheral keratitis following laser in situ keratomileusis (LASIK). METHODS: A report of two cases (two eyes of two patients). RESULTS: In two patients, peripheral infiltrates appeared 1 day after LASIK. One patient had a history of rheumatoid arthritis and both had peripheral corneal changes that may have represented prior inflammatory events. The presentations were quite different, with one occurring in association with an epithelial defect at the edge of the flap and the other occurring without an epithelial defect peripheral to the microkeratome cut. In the second case a similar infiltrate showed up in the unoperated fellow eye. Both patients were treated with aggressive antibiotic and corticosteroid therapy. Both patients recovered well with no loss of best spectacle-corrected visual acuity. CONCLUSION: Peripheral keratitis can occur in patients following LASIK; preoperative evidence of previous inflammation may be a marker for patients at higher risk. Rheumatoid arthritis patients may be at increased risk for this complication. With careful and aggressive management excellent visual outcomes are still possible.
15500899 Self-management interventions for chronic illness. 2004 Oct 23 An increasing number of interventions have been developed for patients to better manage their chronic illnesses. They are characterised by substantial responsibility taken by patients, and are commonly referred to as self-management interventions. We examine the background, content, and efficacy of such interventions for type 2 diabetes, arthritis, and asthma. Although the content and intensity of the programmes were affected by the objectives of management of the illness, the interventions differed substantially even within the three illnesses. When comparing across conditions, it is important to recognise the different objectives of the interventions and the complexity of the issues that they are attempting to tackle. For both diabetes and asthma, the objectives are concerned with the underlying control of the condition with clear strategies to achieve the desired outcome. By contrast, strategies to deal with symptoms of pain and the consequences of disability in arthritis can be more complex. The interventions that were efficacious provide some guidance as to the components needed in future programmes to achieve the best results. But to ensure that these results endure over time remains an important issue for self-management interventions.
12653852 Elevated angiogenin levels in synovial fluid from patients with inflammatory arthritis and 2003 Apr Angiogenesis is a key process in the pathogenesis of inflammatory arthritis. Angiogenin is one of the most potent inducers of neovascularization in experimental models in vivo. To look for evidence that angiogenin is involved in inflammatory joint disease, we examined plasma and synovial fluid (SF) samples from rheumatology patients and synovial fibroblast cell culture supernatants. Angiogenin levels were determined by radioimmunoassay and ELISA. Plasma angiogenin concentrations ranged from 96 to 478 ng/ml, with no significant difference between patients and normal controls. In SF, angiogenin concentrations were significantly higher in patients with acute or chronic synovitis (rheumatoid arthritis (RA): median, 104 ng/ml; range 13-748, n = 14; crystal-induced arthritis (CIA): median, 149 ng/ml; range, 37-616, n = 14, and other chronic inflammatory arthritis: median, 42 ng/ml; range, 15-205; n = 9) than in the 18 patients with osteoarthritis (OA) (median, 20 ng/ml; range 8-116) (P < 0.0001, anova). Angiogenin levels in SF from RA patients in remission with secondary OA were similar to those achieved in primary OA, and decreased in parallel with the resolution of acute gout. Angiogenin protein was released by cultured synovial fibroblasts from OA and RA patients, and reached 1.18 ng/106 cells/day. These data suggest that angiogenin may mediate local inflammation in arthritis via effects on angiogenesis and leucocyte regulation.
14567872 Consultation computer use to improve management of chronic disease in general practice: a 2003 BACKGROUND: Computers have become widespread in primary care but their potential to improve clinical effectiveness has not been completely fulfilled. One explanation for this is the difficulty in evaluating their impact on the process of care. AIM: To determine the effects of computers in consulting rooms on the management of chronic disease. METHODS: Before and after study with concurrent control group, matching six practices moving from paper-based recording to a consultation-based computer environment, with six practices using paper-based systems. Data were collected retrospectively via case note review for the year preceding the arrival of the computers and for the subsequent year. All patients with diagnosed diabetes mellitus (n = 1070) or rheumatoid disease (n = 202) were included. The main outcome measure was recording of disease management items. RESULTS: The computer group improved recording for seven of the eight diabetic and four of the seven rheumatoid items studied. Increases were significant for height (5% increase; 95% confidence interval (CI): 1.2% to 8.8%), weight (6.6%; 95% CI: 2.2% to 11.0%), foot pulses (8.7%; 95% CI: 4.1% to 13.4%), foot sensation (8.6%; 95% CI: 5.2% to 11.9%), blood pressure (12.6%; 95% CI: 2.0% to 23.2%) and urinalysis (20.2%; 95% CI: 11.0% to 29.4%). The control group improved for two diabetic and five rheumatoid items, the only significant increase being for urinalysis (1.1%; 95% CI: 0.2% to 22.0%). Computer use was associated with increased recording of each diabetes item except fundoscopy, and with increased blood pressure recording for rheumatoid disease. The larger the practice, the larger the effects observed. CONCLUSIONS: Use of computers can improve management of chronic disease in primary care. Impact is most clearly seen in those items easily recorded on computer during consultations. Effects are most evident in practices with larger patient numbers.
15077296 Augmented production of chemokines by the interaction of type II collagen-reactive T cells 2004 Apr OBJECTIVE: To determine the impact of type II collagen (CII)-reactive T cells on the production of chemokines in the joints of patients with rheumatoid arthritis (RA). METHODS: T cell proliferative responses to bovine CII were assayed in synovial fluid (SF) mononuclear cells and peripheral blood mononuclear cells. CII-stimulated T cells were cocultured with fibroblast-like synoviocytes (FLS). The expression of interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1 alpha (MIP-1 alpha) in the sera, SF, and supernatant of the CII-stimulated T cells and FLS coculture was measured by enzyme-linked immunosorbent assays. RESULTS: The levels of IL-8, MCP-1, and MIP-1 alpha in SF were significantly higher than those in paired sera of RA patients. IL-8, MCP-1, and MIP-1 alpha levels in SF were strongly correlated with T cell responses to CII. When FLS were cocultured with CII-stimulated T cells, the production of IL-8, MCP-1, and MIP-1 alpha was significantly increased. This increase correlated well with the T cell proliferative response to CII. Chemokine production by coculture of CII-stimulated T cells and FLS was mediated mainly by direct cell-cell contact through CD40 ligand-CD40 engagement. CONCLUSION: Our data indicate that the presence of CII-reactive T cells in RA joints can increase the production of chemokines such as IL-8, MCP-1, and MIP-1 alpha through interaction with FLS. This chemokine production is mediated by cell-cell contact, including CD40 ligand-CD40 engagement. These results suggest that CII-reactive T cells play a crucial role in the amplification and perpetuation of the inflammatory process in the rheumatoid synovium.
15245537 Rheumatoid papules treated with dapsone. 2004 Jul A patient with a long history of seropositive rheumatoid arthritis presented with a progressive papular eruption on the trunk. A skin biopsy showed a neutrophilic and palisaded granulomatous dermatitis compatible with rheumatoid papules. The eruption failed to respond to topical and systemic corticosteroids and the patient was treated with dapsone with complete resolution of the rash. Rheumatoid papules are a rare disorder seen in a variety of collagen vascular diseases. The literature concerning the treatment of rheumatoid papules is scanty. In this patient, dapsone was an effective treatment.
15221280 Trisomy 7 in synovial fluid cells of patients with rheumatoid arthritis. 2005 Oct OBJECTIVE: Recent studies revealed trisomy 7 as a chromosomal abnormality in non-neoplastic disorders such as rheumatoid arthritis (RA). In the present study, we investigated the presence of trisomy 7 in the synovial fluid cells of patients with RA using fluorescence in situ hybridisation (FISH) analysis. METHODS: Synovial fluid from 15 patients with RA was collected from knee joints. The control group consisted of seven patients with traumatic synovial effusion in their knee joints. The arthrocenteses were performed under aseptic conditions. Dual-colour FISH analysis was performed using chromosome-7-specific LSI D7S522 (7q31) and chromosome-5-specific LSI EGR1 (5q31)/D5S721 (5p15.2) probes on the slides prepared from synovial fluid of RA patients and controls. RESULTS: The slides of our cases were analysed using two different DNA probes. When the slides hybridised with chromosome-5-specific probes were analysed, no trisomic or monosomic cells were revealed in both patients and controls. However, in eight of 15 patients, trisomy 7 occurred in variable percentages of cells (23% to 48%) of synovial fluid. No monosomic 7 cells were detected in these specimens. All control cases were disomic for chromosome 7. CONCLUSION: The results of the present investigation suggest that trisomy 7 may play a role in the pathogenesis of synovial hyperproliferation in RA.
15295001 Ex vivo homeostatic proliferation of CD4+ T cells in rheumatoid arthritis is dysregulated 2004 Aug 15 The systemic CD4(+) T cell compartment in patients with rheumatoid arthritis (RA) is characterized by TCR repertoire contraction, shortened telomere lengths, and decreased numbers of recent thymic emigrants, suggesting a disturbed CD4(+) T cell homeostasis. In mice, homeostatic proliferation of peripheral CD4(+) T cells is regulated by TCR interaction with self peptide-MHC complexes (pMHC) and can be reproduced in vitro. We have established an ex vivo model of homeostatic proliferation, in which self-replication of human CD4(+) T cells is induced by cell-cell contact with autologous monocytes. In healthy individuals, blockade of TCR-pMHC class II contact resulted in decreased CD4(+) T cell division. In contrast, homeostatic proliferation in RA patients was not inhibited by pMHC blockade, but increased during the initial culture period. The anti-TNF-alpha Ab cA2 inhibited homeostasis-driven ex vivo proliferation in healthy controls and in RA patients. In addition, treatment of RA patients with infliximab decreased the ex vivo rate of homeostatic proliferation of CD4(+) T cells. Our results suggest a disturbed regulation of CD4(+) T cell homeostasis leading to the repertoire aberrations reported in RA. Membrane-anchored TNF-alpha appears to be a cell-cell contact-dependent stimulus of homeostatic proliferation of CD4(+) T cells, possibly favoring self-replication of autoreactive CD4(+) T cells in patients with RA.
11977385 [Functional and molecular aspects of anti-inflammatory effects of low-dose radiotherapy]. 2002 Jan PURPOSE: Low-dose radiotherapy (LD-RT) with single fractions between 0.1 and 1.0 Gy is known to exert an antiinflammatory effect. Although different mechanisms for the clinical efficiency were proposed, only few experimental data are still available. This paper focuses on functional and molecular aspects of LD-RT. METHODS AND RESULTS: The antiinflammatory efficiency of LD-RT in clinical studies could be confirmed in experimental models of osteoarthritis and rheumatoid arthritis. In a model of adjuvants arthritis, 5 x 1.0 Gy as well as 5 x 0.5 Gy, given at the maximum of the acute inflammation, could prevent clinically and histologically progression of the disease without affecting existing signs of inflammation. The effect of LD-RT on the adhesion of peripheral blood mononuclear cells (PBMC) and endothelial cells (EC) was analyzed in in-vitro assays. In the dose range between 0.3 and 0.7 Gy almost 4 hours after irradiation adherent cells reached a relative minimum of adhesion compared to unirradiated controls. In PBMC an discontinuous increase of apoptosis with a maximum between 0.3 and 0.5 Gy, the proteolytic shedding of L-selectin and an increased expression of the antiinflammatory cytokine interleukin 10 as well as downregulation of TNF alpha could be identified as potential mechanisms for the observed reduced adhesion. Conversely, reduced expression of E-selectin and an increased induction of transforming growth factor beta (TGF beta 1) with a maximum at 0.5 Gy could be observed in endothelial cells. Macrophages immigrating the site of inflammation are known to express inducible nitrix-oxide synthase (iNOS), which in turn mediates cytotoxic and immunmodulatory effects by producing nitric oxide (NO). LD-RT of stimulated macrophages within the dose range between 0.6 and 1.25 Gy reduced NO production and iNOS-protein expression without affecting iNOS-mRNA expression. CONCLUSION: Our experimental data have confirmed the antiinflammatory efficiency of LD-RT in vitro and in vivo, indicating effects on different cellular components and mechanisms of inflammation. The regulation of the adhesion between PBMC and endothelial cells and the effects on activated macrophages may mediate the antiinflammatory properties of LD-RT. Ongoing experiments will help to clarify the molecular mechanism.
12610484 Stress shielding and bone resorption in shoulder arthroplasty. 2003 Jan The radiographs of 64 patients with 70 humeral head replacements were reviewed for signs of stress shielding. Of these, 49 were implanted for rheumatoid arthritis and 21 for osteoarthritis. The radiographic follow-up averaged 5.3 years. Measurements of cortex thickness were performed in 4 regions along the stem of the implant, and the differences between the postoperative radiograph and the radiograph at follow-up were calculated. The size of the stem in relation to the diameter of the humerus was calculated with the use of validated measures, resulting in the relative stem size. In 6 patients (9%) a significant reduction in cortical thickness was observed in the proximal-lateral region of the humeral stem, 5 in rheumatoid patients and 1 in an osteoarthritic patient. In the stress shielding group, the relative stem size was found to be significantly higher than that in the non-stress shielding group (0.58 vs 0.48). Osteoporosis, especially present in rheumatoid arthritis, could well be a risk factor. It was concluded that stress shielding is a long-term complication of shoulder arthroplasty and that the relative stem size is an important factor in its genesis.
11921607 [Aspects of colchicine therapy. 2. Additional classical indications and new therapeutic as 2002 Feb The complex actions of colchicine, which are attributable to its stabilising action on the cytoskeleton and cell membranes and its special pattern of distribution, form the basis of the results presented here; results that relating to the prophylactic and/or therapeutic actions of colchicine in a whole range of other diseases.
12810425 Analysis of the cell infiltrate and expression of proinflammatory cytokines and matrix met 2003 Jul BACKGROUND: Synovial tissue (ST) from end stage destructive rheumatoid arthritis (RA) and arthroscopic biopsies obtained during active inflammation might exhibit different characteristics. OBJECTIVE: To define the cell infiltrate and the expression of proinflammatory cytokines, angiogenic factors, and matrix metalloproteinases (MMPs) in ST selected at arthroscopy compared with that from end stage RA. METHODS: Synovial biopsy specimens were obtained from the actively inflamed knee joints of 13 patients with chronic RA by arthroscopy and compared with ST from 10 patients with end stage, destructive RA. Immunohistological analysis was performed to detect T cells, plasma cells, macrophages, fibroblast-like synoviocytes (FLS), and the expression of interleukin (IL)1beta, IL6, tumour necrosis factor alpha (TNFalpha), MMP-1, MMP-3, MMP-13, TIMP-1, and VEGF. RESULTS: The expression of CD68+ macrophages was significantly higher in ST selected at arthroscopy than in samples obtained at surgery, both in the intimal lining layer and in the synovial sublining. The expression of CD3+ T cells also tended to be higher in arthroscopic samples. The expression of TNFalpha, IL6, MMP-1, MMP-3, MMP-13, TIMP-1, and VEGF was on average higher in ST obtained at arthroscopy. In contrast, the expression of IL1beta was on average higher in surgical samples. CONCLUSION: Active arthritis activity is associated with increased cell infiltration, expression of proinflammatory cytokines, MMPs, and angiogenic growth factors in synovial biopsy samples selected at arthroscopy. Increased expression of IL1beta in the synovium of patients with destructive RA requiring joint replacement may well reflect the important role of IL1beta in cartilage and bone destruction.
12934220 Bone morphology in relation to the migration of porous-coated anatomic knee arthroplasties 2003 Aug The quality of the subchondral bone in total knee arthroplasty (TKA) may be important for the outcome. We correlated a histomorphologic analysis of the prosthetic bone bed to micromotion as analyzed by roentgen stereophotogrammetric analysis (RSA). Twenty-three knees, both osteo- and rheumatoid arthritic were studied. The mean migration after 1 year was 1 mm (0.21-2.68), with no correlation to the bone variables or diagnosis. One patient underwent revision after 3 years because of pain. One patient underwent revision after 15 years because of aseptic loosening. This patient appeared stable according to changes in maximum total point motion (MTPM), but the prosthesis migrated continuously according to segment motion. Prosthetic migration increased after 10 years, zones started to evolve, and the patient became symptomatic after 13 years. A biopsy of the bone bed was taken in all patients. A larger percentage of trabecular bone and a larger relative area of unmineralized osteoid surface were found in patients with rheumatoid arthritis compared with those with osteoarthritis. The latter finding is probably a result of increased bone turnover. In conclusion, no support currently exists for the idea that preoperative bone quality, evaluated as bone histomorphometry, has any impact on prosthetic micromotion in knee prostheses.
12094150 The assessment of quality of life as a measure of gold salts treatment efficacy in rheumat 2002 Jun BACKGROUND: In the evaluation of functional status of patients with rheumatoid arthritis (RA) the health related quality of life is currently considered important because of its approach to various components of life, such as social, psychological, and physical aspects. We used the Stanford Health Assessment Questionnaire (HAQ) to assess the improvement of functional status in patients with RA treated with gold salts. METHODS: In a prospective investigation 91 patients with RA in anatomical stage I, II, or III, 66 females and 25 males, with a mean age of 53.17 years, were evaluated during medical treatment in a 1-year follow-up. The treatment consisted in sodium aureothiosulphate, plus corticosteroids and NSAID. The assessments were done during ambulatory visits, at baseline and after 6 and 12 months of treatment, by HAQ as well as by other parameters such as Ritchie Index, visual analog scale (VAS), and morning stiffness. A group of 19 RA patients included by the same criteria and treated only by corticosteroids and NSAID was used as control for the first 6 months of the study. RESULTS: HAQ scores and other parameters were significantly lower (p=0.0001) at the 6th and 12th month measurements when compared with baseline. In the control group only a significant difference in the VAS score was detected. CONCLUSIONS: All the parameters measured in our study were useful in detecting clinical improvement in RA patients treated with sodium aureothiosulphate plus corticosteroids and NSAIDs, but the HAQ provides a more global assessment of the patient's status.
12079908 Decreased flares of rheumatoid arthritis during the first year of etanercept treatment: fu 2002 Jul OBJECTIVE: To determine the incidence of disease flare during the first year of etanercept treatment for 88 patients with rheumatoid arthritis (RA) and compare it with the incidence of flare in those same patients in the year before etanercept use. METHODS: The outpatient clinic charts of all patients with RA who were prescribed etanercept in or before September 1999, who also had at least one year's follow up in the same outpatient clinic, were surveyed. The primary outcome measure was the number of disease flares in one year before and after etanercept use. The secondary outcome measures included the number of patients who did and did not flare, how flares were treated, and the drug alterations that were necessary during the same two time intervals. RESULTS: The total number of flares for all patients in the year before etanercept treatment was 214 (mean (SD) 2.43 (1.75)). The number of flares in the first year of etanercept treatment decreased to 83 (mean 0.94 (1.07)) (p<0.0001). The total number of patients who had at least one flare in the year before etanercept use was 80; eight had no flares. In their first year of etanercept treatment, 50 patients had at least one flare; 38 had no flares (p<0.0001). Twenty one patients (24%) stopped using etanercept before completing one year's treatment. CONCLUSION: This study of patients with RA in the "real world" shows that etanercept is effective in reducing the number of RA flares.
14568965 Blockade of vascular endothelial growth factor receptor I (VEGF-RI), but not VEGF-RII, sup 2003 Nov 1 It was recently shown that vascular endothelial growth factor (VEGF), a growth factor for endothelial cells, plays a pivotal role in rheumatoid arthritis. VEGF binds to specific receptors, known as VEGF-RI and VEGF-RII. We assessed the physical and histological effects of selective blockade of VEGF and its receptors in transgenic K/BxN mice, a model of rheumatoid arthritis very close to the human disease. Mice were treated with anti-mouse VEGF Ab, anti-mouse VEGF-RI and -RII Abs, and an inhibitor of VEGF-RI tyrosine kinase. Disease activity was monitored using clinical indexes and by histological examination. We found that synovial cells from arthritic joints express VEGF, VEGF-RI, and VEGF-RII. Treatment with anti-VEGF-RI strongly attenuated the disease throughout the study period, while anti-VEGF only transiently delayed disease onset. Treatment with anti-VEGF-RII had no effect. Anti-VEGF-RI reduced the intensity of clinical manifestations and, based on qualitative and semiquantitative histological analyses, prevented joint damage. Treatment with a VEGF-RI tyrosine kinase inhibitor almost abolished the disease. These results show that VEGF is a key factor in pannus development, acting through the VEGF-RI pathway. The observation that in vivo administration of specific inhibitors targeting the VEGF-RI pathway suppressed arthritis and prevented bone destruction opens up new possibilities for the treatment of rheumatoid arthritis.
12729054 Evaluation of clinical and laboratory features of antiphospholipid syndrome: a retrospecti 2003 We retrospectively analysed the data of 1519 antiphospholipid antibody (APLA) positive patients between 1986 and 1999. Among them 637 were considered to have antiphospholipid syndrome (APS) based on the 1999 preliminary classification criteria, while 704 patients had no clinical signs of the syndrome. Our aim was to compare the autoantibody profile and clinical characteristics of primary and secondary APS, moreover to evaluate the associations between different APLA and specific symptoms attributable to APS. In our results, the APLA profiles for primary and SLE-associated secondary APS were similar. Among the evaluated clinical symptoms, cerebrovascular thrombosis was found to be more frequent in the SLE-associated, than in the primary APS group (P = 0.04). We identified important differences in the clinical profile of patient populations with various types of APLA. Venous thrombosis occurred more frequently in subjects withlupus anticoagulant (LA), than in those with IgG or IgM type ACLA (P < 0.0001), while coronary, carotid and peripheral artery thrombosis occurred more often in subjects with IgG or IgM ACLA (P < 0.0001). These findings may support the role of antibodies to cardiolipin or its cofactor, beta2glycoprotein I (beta2-GPI) in the initiation and progression of atherosclerosis. Cerebrovascular thrombosis was detected in larger proportion of LA or IgG ACLA-positive patients compared with to IgM ACLA-positive subjects, while the occurrence of foetal loss was similar in all three groups.