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ID PMID Title PublicationDate abstract
15308517 Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arth 2004 Sep OBJECTIVES: To evaluate the diagnostic sensitivity of antibodies to cyclic citrullinated peptide (CCP) in recent onset rheumatoid arthritis (RA) at diagnosis and 3 years later, and to evaluate anti-CCP antibody as a predictor of the disease course during 3 years. METHODS: 242 patients with recent onset (< or =1 year) RA were followed up regularly during 3 years after inclusion in the Swedish multicentre study "TIRA" 1996-98. Anti-CCP antibodies were analysed by an enzyme immunoassay (EIA). Rheumatoid factors (RFs) were analysed by latex agglutination and two isotype-specific (IgM and IgA) EIAs. Disease activity was assessed by plasma CRP, ESR, 28 joint disease activity score, and the physician's global assessment of disease activity. Functional ability was evaluated by the Health Assessment Questionnaire. RESULTS: Overall, the diagnostic sensitivity of anti-CCP antibodies was 64% and the proportion of positive tests increased with the number of fulfilled classification criteria according to the American College of Rheumatology. The anti-CCP antibody results correlated with RF, but were better than RF as predictor of a more aggressive disease course. After 3 years 5/97 patients had changed anti-CCP status: 2 from negative to positive and 3 from positive to negative. The mean level of anti-CCP antibodies declined by 131 U/ml during the 3 year follow up (95% CI 34 to 228 U/ml). CONCLUSION: The anti-CCP antibody assay has a similar diagnostic sensitivity to that of RF in early RA, but is better as a predictor of the disease course over 3 years. Although the mean serum level declines, anti-CCP antibody positivity remains essentially unaltered 3 years after diagnosis and start of antirheumatic treatment.
12563369 [Anti-tissue transglutaminase antibodies in inflammatory and degenerative arthropathies]. 2002 Oct Recent studies identified tissue transglutaminase (tTG) as the antigen eliciting antiendomysial antibodies (EMA) in celiac disease (CD). Anti-tTG antibodies have therefore been proposed as a serological test for CD. Nevertheless, IgA anti-tTG but not EMA have also been found in inflammatory bowel disease patients, suggesting that these antibodies are linked to a tissue lesion rather than to an auto-immune component of CD. To confirm this hypothesis, we evaluated the presence of IgA anti-tTG in patients with inflammatory and degenerative diseases, in whom tissue lesions presented far away from the intestinal mucosa. The study was carried out on the serum and synovial fluid (SF) of 68 patients with rheumatoid arthritis (RA=33), psoriatic arthritis (PsA=26) and osteoarthritis (OA=9). In RA, PsA and OA sera, IgA anti-tTG were positive in 33%, 42% and 11% of patients, respectively. Serum anti-tTG levels were significantly higher in RA (p<0.0001), PsA (p<0.0001) and OA (p<0.02) with respect to healthy controls. SF anti-tTG levels were significantly higher in PsA (p<0.018) than in OA. A good correlation between serum and synovial fluid anti-tTG levels was found in all arthropathies This study suggests that tTG is not the only antigen of EMA and, furthermore, that IgA anti-tTG antibodies represent a general lesion-associated event. Moreover, the significant correlation between serum and synovial fluid anti-tTG levels allow us to hypothesise that these antibodies could be synthesized in the site of arthritic lesions.
12784896 Improved sleep may reduce arthritis pain. 2003 May Studies indicate that pain interferes with sleep and, in turn, sleep disturbances increase pain. Statistics show that up to 60% of those with arthritis experience pain during the night. But despite these findings, sleep is not generally addressed as a major treatment concern among this population. This article reviews the relationship between pain and sleep; sleep issues as they relate to 3 common types of arthritis--osteoarthritis, rheumatoid arthritis, and fibromyalgia; and holistic approaches that may be used by the patient in the self-management of pain and sleep.
15284119 Monocyte-like and mature macrophages produce CXCL13 (B cell-attracting chemokine 1) in inf 2004 Nov 15 The homeostatic chemokine CXCL13 (also called B cell-attracting chemokine 1 [BCA-1] or B-lymphocyte chemoattractant [BLC]) is constitutively expressed in secondary lymphoid tissue and initiates lymphoid neogenesis when expressed aberrantly in mice. CXCL13 has also been detected in chronic inflammation associated with human lymphoid neogenesis, suggesting a pathogenic role. Follicular dendritic cells (FDCs) are generally considered to be the major source of CXCL13 both in normal and aberrant lymphoid tissue. We show here, instead, that most CXCL13-expressing cells in rheumatoid arthritis and ulcerative colitis are of monocyte/macrophage lineage. They are located in irregular lymphoid aggregates within an FDC network, but also within and near smaller collections of B cells in diseased tissue where no FDCs are detected. Some of these CXCL13-expressing cells are CD14(+), suggesting derivation from recently extravasated monocytes. Interestingly, monocytes from healthy donors stimulated in vitro with lipopolysaccharide secrete CXCL13. This induced production is enhanced after in vitro maturation of the monocytes toward macrophages but markedly decreased after maturation toward dendritic cells. Together, our findings strongly suggest that newly recruited monocytes/macrophages play a role for lymphoid neogenesis in human inflammatory diseases. Circulating monocytes are therefore potential candidates for future targeted therapy of chronic inflammation.
12405459 Arthritis and use of dental services: a population based study. 2002 Sep BACKGROUND: Rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic systemic conditions that can have a profound effect on oral health as the result of physical disability, immunosuppressant and other medications and autoimmune disease. However, there is insufficient information available on the use of dental services by the people suffering from RA or OA. The purpose of this study was to investigate dental visits and factors associated with dental attendance in those with RA and OA in order to improve access to dental care in these groups. METHODS: The study used population based data from the 1995 National Health Survey (total n=53828). The main variables of interest were reported RA (n=1193) and OA (n=3091) and the main outcome variable was having visited a dental professional in the previous 12 months. Chi-square analysis was performed using SAS software. RESULTS: The proportion of people visiting a dental professional in previous 12 months was significantly less in both RA and OA respondents compared to non-arthritic respondents. Both males and females with RA and OA were found to be less likely to have visited a dental professional when compared to general population (p=0.001 in each case). Furthermore, the findings have revealed that RA and OA patients living in metropolitan centres were more likely to have a dental visit than those living in rural or remote areas (p=0.001 in each case). CONCLUSIONS: When compared to non-arthritic subjects, all patients with RA and OA were less likely to receive dental care, in particular preventive care. This is especially important in patients with Sjogren's Syndrome and those who are immunosuppressed.
15204089 Altered expression of the T cell receptor-CD3 complex in systemic lupus erythematosus. 2004 May SLE T cells may play a key role in autoantibody production in SLE B cells. In addition, accumulating evidence has shown that SLE T cells participate in the attack on target cells or tissues through the overproduction of pro-inflammatory cytokines or an increase in cell-to-cell adhesion. Thus, the functional abnormality of SLE T cells appears to be pivotal to an understanding of SLE pathogenesis. Accumulating evidence suggests that potential defects may reside in the proximal signal transduction around the TCR-CD3 complex. We have demonstrated that the expression of TCR zeta chain is significantly decreased in peripheral blood T cells from SLE patients. To explore the mechanism of defective expression of TCR zeta chain, we examined mRNA of TCR zeta, and found that two alternatively spliced variants such as exon 7 (-) and short 3'-UTR are detected in SLE. We review the possible role of the TCR zeta defects in autoimmunity and discuss how the splicing variants lead to downregulated protein expression of TCR zeta chain.
14978666 The effect of tumor necrosis factor blockade on the response to pneumococcal vaccination i 2004 Feb OBJECTIVE: To assess the effect of anti-tumor necrosis factor (TNF) alpha therapies on the immunogenicity of pneumococcal vaccination in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: A group of 16 consecutive patients (11 with RA and 5 with AS) treated either with infliximab or etanercept, and a control group of 17 age-matched RA patients treated with disease-modifying medications other than anti-TNF-alpha, received intradeltoid injection with 0.5 mL of pneumococcal vaccine. Pneumococcal polysaccharide (PPS)-specific IgG to 7 vaccine PPS (representing high- and low-prevalence serotypes) was measured by enzyme-linked immunosorbent assay in sera obtained before and 1 month after pneumococcal immunization. RESULTS: One month after vaccination, both groups had significant increases in the geometric mean concentration of capsule PPS-specific antibody and in the mean fold increase in antibody levels to all 7 serotypes, compared with prevaccination levels. However, compared with the control group, the TNF-alpha blockade-treated patients tended to have lower antibody increases for all the serotypes tested except serotype 14. In addition, lower proportions of TNF-alpha blockade-treated patients responded to pneumococcal vaccination compared with patients on other therapies. Similarly, more TNF-alpha blockade-treated patients were poor responders compared with patients not on anti-TNF-alpha treatment. CONCLUSION: Treatment of groups of patients with etanercept or infliximab does not impair their mean antibody responses to pneumococcal vaccination. However, a larger proportion of RA patients may not respond adequately to pneumococcal vaccination once on TNF-alpha blockade therapies. Consequently, pneumococcal vaccination before starting TNF-alpha blockade therapy is recommended.
14677171 Variability of RANKL and osteoprotegerin staining in synovial tissue from patients with ac 2003 Nov OBJECTIVE: To assess the interpatient, interbiopsy, and intrabiopsy variability of receptor activator of nuclear factor kB ligand (RANKL) and osteoprotegerin (OPG) immunostaining within synovial tissue from rheumatoid knee joints with active synovitis, using digital image analysis. METHODS: Synovial biopsy specimens were obtained from patients with rheumatoid arthritis (RA) and active synovitis. Immunohistologic analysis was performed on frozen synovial tissue biopsy specimens from 6 patients using a monoclonal antibody (Mab) to detect RANKL (626) or OPG (805 or 8051). Patients with a minimum of 4 synovial biopsies were included in the study. Sections were evaluated by computer assisted image analysis to assess between-patient, between-biopsy, and intra-biopsy variability of OPG and RANKL protein expression. The study was designed to deliberately maximize the variability. RESULTS: Computerized image analysis of staining with Mab to RANKL and OPG revealed variance for each antibody across the 3 components of the total variability. CONCLUSION: Our study shows that variability in synovial immunostaining of RANKL and OPG protein is a significant and complex problem. We discuss methods to reduce this variability and suggest that the auspices of OMERACT may be employed to advance the study of synovium in collaborative international studies.
12378547 An approach to evidence-based therapeutic apheresis. 2002 This review is derived from a memorial lecture honoring Dr. Francis Morrison, a former President of the American Society For Apheresis (ASFA). The author had numerous professional contacts with Dr. Morrison through ASFA in the early 1990s, having served with him on the Board of Directors and followed him as President, and also came to know him well on a personal level. Professionally, Dr. Morrison stood out as a courtly gentleman with a marvelous baritone voice whose ability to facilitate organization contributed to a growing sense of dignity and purpose in the affairs of the society. On the personal side, however, there wasn't an ounce of pretension in him. He was accessible and down-to-earth; a genuine character with an active and appealing sense of humor. Not surprisingly, he seemed to have a wealth of insight and "common sense," and since the topic of this study is a kind of common sense approach to assessing the effectiveness of therapeutic apheresis, it seems a fitting way to honor his memory.
12847683 Role of Crk-associated substrate lymphocyte type in the pathophysiology of rheumatoid arth 2003 Jul OBJECTIVE: To investigate the role of Crk-associated substrate lymphocyte type (Cas-L), a downstream signaling molecule of beta1 integrins, in the pathophysiology of rheumatoid arthritis (RA). METHODS: We analyzed human T lymphotropic virus type I (HTLV-I) tax transgenic mice as well as samples from human RA patients. Splenocytes from tax transgenic mice were cultured on mouse endothelial cell-covered Transwell inserts, and cells migrating through the endothelial monolayer were counted. Biochemical studies were performed to analyze the protein expression and tyrosine phosphorylation of Cas-L. Immunohistochemical analysis was performed to detect Cas-L-positive cells that had infiltrated into the joints. RESULTS: Migratory activity of splenocytes from tax transgenic mice with arthritis (ATg) was much higher than that of tax transgenic mice without arthritis (NTg) and littermate control mice. The expression of Cas-L protein and its tyrosine phosphorylation were increased in ATg mice compared with NTg and control mice, and this was accompanied by enhanced autophosphorylation of Fyn and Lck. Immunohistochemical analysis demonstrated a large number of Cas-L-positive lymphocytes migrating into the affected joints. Furthermore, in human RA, Cas-L-positive lymphocytes were shown to infiltrate to the inflammatory lesions. CONCLUSION: These results strongly suggest that Cas-L plays an important role in the pathophysiology of RA.
11817586 A fibronectin fragment induces type II collagen degradation by collagenase through an inte 2002 Jan OBJECTIVE: To examine the effects of a fibronectin (FN) fragment containing the COOH-terminal heparin-binding domain (HBFN-f) on chondrocyte-mediated type II collagen (CII) cleavage by collagenase and proteoglycan (PG) degradation in articular cartilage in explant culture. METHODS: Intact FN or HBFN-f was added to explant cultures of mature bovine articular cartilage. We investigated collagenase-mediated cleavage of CII caused by HBFN-f in explant cultures using a new immunoassay for detection and measurement of the primary collagenase cleavage site of CII. CII denaturation in cartilage was also measured using a specific enzyme-linked immunosorbent assay. Degradation of PG (principally aggrecan) was analyzed by a dye-binding assay. APMA and/or a matrix metalloproteinase 13 (MMP-13) preferential inhibitor or interleukin-1 receptor antagonist (IL-1Ra) were added to some cultures to examine the presence of latent procollagenase or the involvement of MMP-13 or IL-1, respectively, in cartilage breakdown induced by HBFN-f. Secretion of MMP-3 and MMP-13 into media was detected by immunoblotting. RESULTS: In contrast to intact FN, HBFN-f was shown to stimulate CII cleavage by collagenase in a dose-dependent manner following PG degradation, similar to cartilage breakdown induced by IL-1. Treatment with HBFN-f also resulted in elevated denaturation of CII. Immunoblotting demonstrated that HBFN-f enhanced pro-matrix metalloproteinase 13 (proMMP-13) production as well as that of proMMP-3. APMA, which activates latent proMMPs, enhanced the HBFN-f-mediated cleavage of CII by collagenase. An MMP-13 preferential inhibitor or IL-1Ra suppressed HBFN-f-induced collagen cleavage to control levels. CONCLUSION: Our data demonstrate that HBFN-f can induce early PG degradation and subsequent CII cleavage. The latter is probably mediated by early proMMP-13 induction involving an IL-1-dependent pathway. Activation of latent collagenase is delayed. This new information, together with existing data on other FN fragments, reveals that increased levels of these fragments, found in diseased joints such as in osteoarthritis and rheumatoid arthritis, may stimulate cartilage breakdown by mechanisms of the kind demonstrated in the present study.
12110140 Studies of T-cell activation in chronic inflammation. 2002 The strong association between specific alleles encoded within the MHC class II region and the development of rheumatoid arthritis (RA) has provided the best evidence to date that CD4+ T cells play a role in the pathogenesis of this chronic inflammatory disease. However, the unusual phenotype of synovial T cells, including their profound proliferative hyporesponsiveness to TCR ligation, has challenged the notion that T-cell effector responses are driven by cognate cartilage antigens in inflamed synovial joints. The hierarchy of T-cell dysfunction from peripheral blood to inflamed joint suggests that these defects are acquired through prolonged exposure to proinflammatory cytokines such as tumour necrosis factor (TNF)-alpha. Indeed, there are now compelling data to suggest that chronic cytokine activation may contribute substantially to the phenotype and effector function of synovial T cells. Studies reveal that chronic exposure of T cells to TNF uncouples TCR signal transduction pathways by impairing the assembly and stability of the TCR/CD3 complex at the cell surface. Despite this membrane-proximal effect, TNF selectively uncouples downstream signalling pathways, as is shown by the dramatic suppression of calcium signalling responses, while Ras/ERK activation is spared. On the basis of these data, it is proposed that T-cell survival and effector responses are driven by antigen-independent, cytokine-dependent mechanisms, and that therapeutic strategies that seek to restore T-cell homeostasis rather than further depress T-cell function should be explored in the future.
12231210 The effect of sulfasalazine on rheumatoid arthritic synovial tissue chemokine production. 2002 Oct Rheumatoid arthritis (RA) is an aggressive inflammatory disease in which chemokines are thought to recruit leukocytes and induce angiogenesis. The aim of this study was to investigate the effects of sulfasalazine (SASP) and its metabolites, sulfapyridine (SP), and 5-aminosalicylic acid (5ASA) on chemokine production by RA synovial tissue explants and interleukin (IL)-1beta-stimulated RA synovial tissue fibroblasts using enzyme-linked immunosorbent assays and flow cytometry. Synovial tissue explants from RA patients secreted a decreased amount of the chemokines IL-8 and growth-related gene product alpha (GROalpha) when treated with SASP over a broad range of concentrations based on the typical clinical dosage of 2 g/day. SP had a significant effect in that it decreased RA synovial tissue explant secretion of IL-8 (22%), GROalpha (55%), and monocyte chemotactic protein-1 (MCP-1) (42%) (P < 0.05). 5ASA had no effect on RA synovial tissue explant production of IL-8 and MCP-1, while increasing GROalpha production. In IL-1beta-stimulated RA synovial tissue fibroblasts, SASP significantly increased chemokine secretion, while SP significantly decreased IL-8 (24%) and GROalpha (21%) secretion (P < 0.05). Flow cytometry showed that the number of IL-8 expressing RA synovial tissue fibroblasts did not significantly change following SP treatment. These data suggest that SASP may function to reduce inflammation in RA through the effects of its metabolite SP to reduce the secretion of the inflammatory chemokines IL-8, GROalpha, and MCP-1.
12873794 Effect of calcitonin gene-related peptide, neuropeptide Y, substance P, and vasoactive int 2003 Aug 15 In the present study, we have investigated the in vitro effect of calcitonin-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP) and vasoactive intestinal peptide (VIP) at concentrations of 10(-8), 10(-9) and 10(-10) M on the production of different proinflammatory cytokines or chemokines such as IL-1beta, IL-6 and TNFalpha by peripheral whole blood cells from patients with rheumatoid arthritis, as well as from osteoarthritis patients studied as a control group without immunoinflammatory background. We have found that CGRP, NPY, SP and VIP stimulated significantly the production of those cytokines and chemokines in rheumatoid arthritis patients. In general, the stimulation was higher at the 10(-9) M concentration, with SP and VIP, and in rheumatoid arthritis patients compared to osteoarthritis ones. Neuropeptides did not significantly modify the LPS-induced cytokine production by whole blood cells. The results indicate that physiological concentrations of the neuropeptides studied can modulate the inflammatory and immunological response, stimulating significantly the production of inflammatory cytokines by human whole blood cells in rheumatoid arthritis patients, as well as, in a minor way, in osteoarthritis patients.
12076385 Short-term low-dose corticosteroids vs placebo and nonsteroidal antiinflammatory drugs in 2002 BACKGROUND: The effectiveness of low dose corticosteroids, equivalent to 15 mg prednisolone daily or less, in patients with rheumatoid arthritis has been questioned. We therefore performed a systematic review of trials which compared corticosteroids with placebo or non-steroidal, anti-inflammatory drugs. OBJECTIVES: To determine whether short-term (i.e. as recorded within the first month of therapy), oral low-dose corticosteroids (corresponding to a maximum of 15 mg prednisolone daily) is superior to placebo and non steroidal, antiinflammatory drugs in patients with rheumatoid arthritis. SEARCH STRATEGY: Medline Silverplatter, The Cochrane Controlled Trials Register, reference lists and a personal archive. Date of last search Nov 2001. SELECTION CRITERIA: This review is an update to a previous review which was peer-review and published in the Cochrane Library. All randomised studies comparing an oral corticosteroid (not exceeding an equivalent of 15 mg prednisolone daily) with placebo or a non steroidal, antiinflammatory drug were eligible if they reported clinical outcomes within one month after start of therapy. DATA COLLECTION AND ANALYSIS: Decisions on which trials to include were made independently by two observers based on the methods sections of the trials only. Standardised effect measures were used for the statistical analyses; the random effects model was used if P<0.10 for the test of heterogeneity. MAIN RESULTS: Ten studies, involving 320 patients, were included in the meta-analysis. Prednisolone had a marked effect over placebo on joint tenderness (standardised effect size 1.31, 95% confidence interval 0.78 to 1.83), pain (standardised effect size 1.75, 0.87 to 2.64) and grip strength (standardised effect size 0.41, 0.13 to 0.69). Measured in the original units, the differences were 12 tender joints (6 to 18) and 22 mm Hg (5 to 40) for grip strength. Prednisolone also had a greater effect than non steroidal, antiinflammatory drugs on joint tenderness (standardised effect size 0.63, 0.11 to 1.16) and pain (standardised effect size 1.25, 0.26 to 2.24), whereas the difference in grip strength was not significant (standardised effect size 0.31, -0.02 to 0.64). Measured in the original units, the differences were 9 tender joints (5 to 12) and 12 mm Hg (-6 to 31). The risk of adverse effects, also during moderate- and long-term use, seemed acceptable. REVIEWER'S CONCLUSIONS: Prednisolone in low doses (not exceeding 15 mg daily) may be used intermittently in patients with rheumatoid arthritis, particularly if the disease cannot be controlled by other means. Since prednisolone is highly effective, short-term placebo controlled trials studying the clinical effect of low-dose prednisolone or other oral corticosteroids are no longer necessary.
12799384 Molecular heterogeneity of the SHAP-hyaluronan complex. Isolation and characterization of 2003 Aug 29 We previously found that a covalent complex of SHAPs (serum-derived hyaluronan-associated proteins), the heavy chains of inter-alpha-trypsin inhibitor family molecules, with hyaluronan (HA) is accumulated in synovial fluid of patients with rheumatoid arthritis, and the complex is circulated in patient plasma at high concentrations. How the SHAP-HA complex participates in this disease is unknown. To address this question, it is essential to clarify the structural features of this macromolecule. The SHAP-HA complex purified from synovial fluid of the patients by three sequential CsCl isopycnic centrifugations was heterogeneous in density, and the fractions with different densities had distinct SHAP-to-HA ratios. Agarose gel electrophoresis and column chromatography revealed that there was no apparent difference in the size distribution of HA to which SHAPs were bound between the fractions with different densities. The SHAP-HA complex in the higher density fraction had fewer SHAP molecules per HA chain. Therefore, the difference between the fractions with different densities was due to a heterogeneous population of the SHAP-HA complex, namely the different number of SHAP molecules bound to an HA chain. Based on the SHAP and HA contents of the purified preparations, we estimated that an HA chain with a molecular weight of 2 x 106 has as many as five covalently bound SHAPs, which could give a proteinaceous multivalency to HA. Furthermore, we also found that the SHAP-HA complex tends to form aggregates, judging from the migration and elution profiles in agarose gel electrophoresis and gel filtration, respectively. The multivalent feature of the SHAP-HA complex was also confirmed by the negative staining electron micrographic images of the purified fractions. Taken together, those structural characteristics may underlie the aggregate-forming and extracellular matrix-stabilizing ability of the SHAP-HA complex.
15541045 Differential adherence of osteoarthritis and rheumatoid arthritis synovial fibroblasts to 2004 Nov In osteoarthritis (OA), cartilage and bone fragments have been described within the synovial tissue which are surrounded by synovial cells (i.e. detritus synovitis). These cells appear to attach actively to the cartilage and bone fragments. In rheumatoid arthritis (RA), on the other hand, synovial fibroblasts (SF) have also been shown to be localized at sites of invasion into cartilage and bone and to degrade extracellular matrix (ECM) by secreting proteolytic enzymes. One prerequisite for exerting their aggressive properties is the attachment to cartilage and bone ECM. This attachment appears to be mediated by the expression of different adhesion molecules for which corresponding binding sites on ECM components are known. As it has not been addressed to which ECM proteins SF adhere and with which affinity this process takes place, we investigated the adherence of SF from patients with OA and RA to different cartilage and bone matrix proteins. Synovial tissue samples were obtained during synovectomy or arthroplastic surgery and used for isolating and culturing SF. Synovial cells attaching to cartilage/bone fragments were characterized using immunohistochemistry. The adherence of SF to ECM proteins was examined using an adhesion assay with the following proteins coated on 96-well plates: aggrecan (AGG), bone sialoprotein (BSP), cartilage oligomeric matrix protein (COMP), collagen type I, II and VI, proline arginine-rich, end leucine-rich repeat protein (PRELP), osteopontin (OPN) and recombinant chondroadherin (CHAD). Bovine serum albumin was used as negative control. In addition, adhering fibroblasts were photographed using a phase-contrast microscope. As compared with RA-SF, significantly higher numbers of OA-SF adhering to collagen type II, OPN and CHAD could be detected (P < 0.05). In contrast, RA-SF showed increased attachment to collagen type II, OPN and BSP. Adhesion to AGG, COMP and PRELP appeared not to be significantly increased and differed widely among the SF samples, and, apart from one exception (BSP), OA-SF adhered in higher numbers to the matrix proteins than did RA-SF. Using immunohistochemistry, synovial cells attached to cartilage/bone fragments could be shown to predominantly express CD68 (>/=50%). The CD68-negative population was of the fibroblast phenotype (AS02 positive). The study demonstrates that the binding pattern of OA-SF and RA-SF to ECM proteins differs considerably and therefore provides novel insights into the difficult pathophysiology of OA and RA. In general, it appeared that SF adhere primarily to ECM proteins that contain known binding sites for adhesion molecules (e.g. integrins: collagen/integrin alpha(2)beta(1)) and that higher numbers of OA-SF adhered to the cartilage and bone matrix proteins than did RA-SF.
14667206 Aplastic anemia following administration of a tumor necrosis factor-alpha inhibitor. 2003 Nov Upregulation of tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of several inflammatory conditions, including rheumatoid arthritis. Therapeutic agents such as antibodies or soluble TNF-alpha receptor analogs, which block TNF-alpha activity are a recent addition to the therapeutic armamentarium for the conditions. We describe a patient who developed aplastic anemia complicated by sepsis after receiving etanercept, a TNF-alpha receptor analog, for the treatment of rheumatoid arthritis. Pancytopenia resolved within 3 wk of discontinuing etanercept. To our knowledge, this is the first report of aplastic anemia associated with TNF-alpha blockade.
12741727 Involvement of natural killer T cells in C57BL/6 mouse model of collagen-induced arthritis 2003 Mar A subset of murine T lymphocytes sharing receptor structures with natural killer cells, named natural killer T cells, has characteristics distinct from conventional T cells and natural killer cells. The DBA/1 strain commonly used for collagen-induced arthritis induction does not express the natural killer 1.1 molecule, a marker for defining murine natural killer T cells. Therefore, collagen-induced arthritis was induced in the C57BL/6 strain carrying natural killer 1.1 marker and the role of natural killer T cells was examined in this model. The collagen-induced arthritis was induced successfully in the C57/BL6 strain with near 70% incidence. Lower percentages of natural killer T cells in lymphoid organs including spleen and lymph node and higher percentages of natural killer T cells in synovium were found in mice with severe inflamed joints as compared with those with mild inflamed joints. The results suggested an infiltration of natural killer 1.1+ CD3+ natural killer T cells into inflamed synovium in the model of collagen-induced arthritis. Although the preliminary results of natural killer 1.1 monoclonal antibody depletion experiments failed to alleviate the gravity of arthritis, such a C57BL/6 mouse model of collagen-induced arthritis may provide a tool in the study of therapeutic manipulation of natural killerT cells in human autoimmune diseases such as rheumatoid arthritis.
15600041 [Polymyalgia rheumatica (arteritica)]. 2004 Nov 11 Polymyalgia rheumatica occurs mainly in patients older than 60 years of age. Differential diagnostically, the condition can be identified on the basis of a number of laboratory parameters (ESR, CRP, CK, autoantibodies) and, if the findings are not unequivocal, the additional use of electromyography and muscle biopsy. Some 40-50% of the patients have concomitant giant cell arteritis. Treatment of polymyalgia rheumatica is glucocorticoids are applied, usually for a period of at least one year. The initial and the tapered dose is dependent on whether an associated arteritis is present.