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ID PMID Title PublicationDate abstract
17151710 Tumour necrosis factor inhibitors--what we need to know. 2006 Dec 1 Biologics have revolutionised the treatment of various autoimmune diseases. Earlier in 2006, New Zealand's Pharmaceutical Management Agency (PHARMAC) approved adalimumab (anti-tumour necrosis factor [TNF] agent) for treatment of severe, unresponsive rheumatoid arthritis in adult patients. Etanercept has been available for chronic juvenile arthritis in selected, younger patients in New Zealand. This review article describes some of the common adverse events related to anti-TNF inhibitors and the importance of establishing guidelines for surveillance in the New Zealand health system.
19002472 [Peripheral mechanisms of joint pain with special focus on the synovial fibroblast]. 2008 Dec Joint pain is one of the most common forms of pain and is experienced by almost a third of the population at some time. To date, it has not been possible to treat joint pain effectively and side effects of commonly prescribed drugs are often hazardous. Therefore, improvements in our understanding of causes and mechanisms associated with joint pain are required. Joints and their neighbouring structures are well endowed with nerve fibres which respond to mechanical stimuli. Following local inflammation, the activation threshold of these afferent nerve fibres is significantly decreased, such that even low level stimuli encode nociception.Currently, there is a lack about local mechanisms in synovial tissue. Various receptors, well known from the nervous system, are increasingly being detected in synovial fibroblasts. However, little is known about their function. Innovative new therapies are expected to emerge by targeting various receptors, e.g. the TRPV1- or the P(2)X(4) receptor system.
18508270 Characterising the clinical and biomechanical features of severely deformed feet in rheuma 2008 Nov PURPOSE: Foot deformity is a well-recognised impairment in patients with rheumatoid arthritis (RA) which results in functional disability. Deformity can occur at the rearfoot, midfoot, forefoot or in combination and the impact that site-specific foot deformities has on functional disability is largely unknown. The aim of this study was to describe the clinical and biomechanical characteristics of patients with severe rearfoot, forefoot or combined deformities and determine localised disease impact. METHODS: Twenty-eight RA patients with severe forefoot (FF group n=12), rearfoot (RF group n=10) or combined deformities (COMB group n=6) were recruited. Each patient underwent 3D gait analysis and plantar pressure measurements. Localised disease impact and foot-specific disease activity were determined using the Leeds Foot Impact Scale and clinical examination respectively. Comparison was made against a normative control group (n=53). RESULTS: Patients in the COMB group walked slowest and the double-support time was longer in the RF and COMB groups compared to those in the FF group. Patients in the RF and COMB group had higher levels of foot-related disability and demonstrated excessive rearfoot eversion and midfoot collapse compared to those in the FF group. Forefoot deformity was associated with reduced toe contact, high forefoot pressures and delayed heel lift. CONCLUSIONS: Abnormal gait patterns were identified and were distinguishable among those patients with predominantly forefoot, rearfoot or combined foot deformity.
16467182 The rheumatoid wrist. 2006 Feb Wrist involvement is common in patients with rheumatoid arthritis. Individual patient assessment is important in determining functional deficits and treatment goals. Patients with persistent disease despite aggressive medical management are candidates for surgery. Soft-tissue procedures offer good symptomatic relief and functional improvement in the short term. Extensor and flexor tendons may rupture because of synovial infiltration and bony irritation. When rupture occurs, direct repair usually is not possible. However, when joints that are motored by the ruptured tendon are still functional, tendon transfer or grafting may be considered. Because of the progressive nature of the disease, dislocation and end-stage arthritis often require stabilization with bony procedures. The distal radioulnar joint is usually affected first and is commonly treated with either the Darrach or the Sauvé-Kapandji procedure. Partial wrist fusion offers a compromise between achieving stability of the affected radiocarpal joint and maintaining motion at the midcarpal joint. For pancarpal arthritis, total wrist fusion offers reliable pain relief at the cost of motion. Total wrist arthroplasty is an alternative that preserves motion; however, the outcomes of total wrist replacement are still being evaluated.
16760255 Lipids and inflammation: serial measurements of the lipid profile of blood donors who late 2007 Feb BACKGROUND: Rheumatoid arthritis is characterised by inflammation and an increased cardiovascular risk. It was recently shown that active early rheumatoid arthritis is associated with dyslipidaemia, which may partially explain the enhanced cardiovascular risk. However, it is unknown when this dyslipidaemia starts. OBJECTIVE: To investigate the progression of the lipid profile over time and the influence of inflammatory parameters on this lipid profile, in people who later developed rheumatoid arthritis. METHODS: Levels of total cholesterol, high-density lipoprotein cholesterol (HDLc), triglycerides, apolipoprotein AI (apo AI), apolipoprotein B (apo B) and lipoprotein(a) (Lp(a)) were determined in 1078 stored, deep-frozen, serial blood bank samples, collected between 1984 and 1999, of 79 blood donors who later developed rheumatoid arthritis. These samples were compared with 1071 control samples of unselected blood donors, matched for age, sex and storage time. RESULTS: Samples of patients who later developed rheumatoid arthritis showed, on average, 4% higher total cholesterol, 9% lower HDLc, 17% higher triglyceride and 6% higher apo B levels than matched controls (p< or =0.05). The magnitude of the differences in lipid levels between groups, explained by C reactive protein (CRP), was limited. For example, only 3.6% of the difference in HDLc levels between the groups was explained by the CRP concentrations. CONCLUSION: Patients who later develop rheumatoid arthritis have a considerably more atherogenic lipid profile than matched blood donors at least 10 years before onset of symptoms. As inflammation only marginally explains the differences between the two groups, a modulating effect of lipids on inflammatory processes is hypothesised.
16307908 T-cell receptor repertoire of circulating gamma delta T-cells in Takayasu's arteritis. 2006 Feb We studied T-cell receptor (TCR) repertoire of circulating gamma delta (gammadelta) T-cells in 20 patients with Takayasu's arteritis (TA), 20 healthy controls (HC), 7 follow up TA patients, and 10 patients with rheumatoid arthritis (RA) and 5 Wegener's granulomatosis (WG) patients as disease controls. Patients with TA (8.1 +/- 5.1%) compared to HC (3.7 +/- 2.1%, P = 0.014), RA (4.8 +/- 0.6%, P = 0.032), and WG (4.2 +/- 0.8%, P = 0.030) as well as active TA compared to inactive TA (13.9 +/- 4.1% vs. 4.9 +/- 1.5%; P < 0.001) had higher number of gammadelta T-cells. The numbers of Vdelta1+ cells were significantly higher in patients with TA (40.0 +/- 20.8%) than HC (13.1 +/- 8.0%; P = 0.001), RA (19.5 +/- 1.8%, P = 0.004), and WG (17.0 +/- 3.9%, P = 0.007). The numbers of gammadelta T-cells normalized in all the 7 patients after 180 days of follow up (13.9 +/- 4.1% vs. 6.9 +/- 2.5%; P = 0.001). We also observed higher number of activated and IFN-gamma producing gammadelta T-cells in active TA. Our data show that gammadelta T-cells particularly those bearing Vdelta1 TCR may have an important role in the immunopathogenesis of TA.
18206502 B cell-directed therapies for autoimmune disease and correlates of disease response and re 2008 Jan Recent advances have led to the development of mAbs that effectively deplete B cells in human beings and target pathways essential for B-cell development. B cell-directed therapies represent promising treatments for autoimmune disorders, although many questions remain about their optimal use in the clinic. Autoantibody depletion correlates with the clinical effectiveness of these drugs in some diseases but not all. This finding implies that self-reactive B cells are playing important pathogenic roles in autoimmune disorders beyond the production of autoantibodies. Clinical studies of B cell-directed therapies are beginning to illuminate the effects of B-cell modulation on immune function using a variety of mechanistic approaches, including delineation of B-cell subsets by flow cytometry, measurement of serum autoantibodies and cytokines, and tests of immunocompetence. Recent clinical studies have been performed in patients with rheumatoid arthritis and SLE suggesting the depletion of memory cells accounts at least in part for the clinical efficacy of rituximab therapy, but these findings, although provocative, require further investigation in larger cohorts. Memory B cells are not the only targets of depleting antibodies; therefore, other B-cell populations of therapeutic relevance may be modulated by these interventions. Moreover, pathologic B-cell responses may be favorably influenced by other targeted approaches such as those using anti-B-cell activating factor belonging to the TNF family (BAFF) or anti-CD22 antibodies.
18822171 Decreased levels of the gelsolin plasma isoform in patients with rheumatoid arthritis. 2008 INTRODUCTION: Gelsolin is an intracellular actin-binding protein involved in cell shape changes, cell motility, and apoptosis. An extracellular gelsolin isoform, plasma gelsolin circulates in the blood of healthy individuals at a concentration of 200 +/- 50 mg/L and has been suggested to be a key component of an extracellular actin-scavenging system during tissue damage. Levels of plasma gelsolin decrease during acute injury and inflammation, and administration of recombinant plasma gelsolin to animals improves outcomes following sepsis or burn injuries. In the present study, we investigated plasma gelsolin in patients with rheumatoid arthritis. METHODS: Circulating and intra-articular levels of plasma gelsolin were measured in 78 patients with rheumatoid arthritis using a functional (pyrene-actin nucleation) assay and compared with 62 age- and gender-matched healthy controls. RESULTS: Circulating plasma gelsolin levels were significantly lower in patients with rheumatoid arthritis compared with healthy controls (141 +/- 32 versus 196 +/- 40 mg/L, P = 0.0002). The patients' intra-articular plasma gelsolin levels were significantly lower than in the paired plasma samples (94 +/- 24 versus 141 +/- 32 mg/L, P = 0.0001). Actin was detected in the synovial fluids of all but four of the patients, and immunoprecipitation experiments identified gelsolin-actin complexes. CONCLUSIONS: The plasma isoform of gelsolin is decreased in the plasma of patients with rheumatoid arthritis compared with healthy controls. The reduced plasma concentrations in combination with the presence of actin and gelsolin-actin complexes in synovial fluids suggest a local consumption of this potentially anti-inflammatory protein in the inflamed joint.
16473729 Reliability and validity of a self-report of hand function in persons with rheumatoid arth 2006 Jan The purpose of this study was to examine the test-retest reliability and the concurrent validity of the Duruöz Hand Index (DHI) in persons with rheumatoid arthritis (RA). Forty participants with RA and no other major medical problems completed the DHI, a self-report of hand function, at two points in time to assess test-retest reliability. To determine concurrent validity, participants were also administered three performance-based tests, the Arthritis Hand Function Test (AHFT), the Hand Mobility in Scleroderma Test (HAMIS), and the Keitel Functional Test (KFT), and two self-report questionnaires of functional ability, the Health Assessment Questionnaire (HAQ) and the Scleroderma Functional Assessment Questionnaire (SFAQ). Test-retest reliability intraclass correlation coefficients for the DHI ranged from 0.83 to 0.90. Scores on the DHI were significantly correlated with scores on the AHFT (r(s)=0.36-0.54), the HAMIS (r(s)=0.39), the HAQ (r(s)=0.78), the HAMIS (r(s)=0.39), and the SFAQ (r(s)=0.85). Scores on the DHI did not correlate with KFT scores. The results from this study show the DHI to be a reliable and valid test for hand function in persons with RA.
18535115 Improvements in clinical response between 12 and 24 weeks in patients with rheumatoid arth 2008 Oct BACKGROUND: Whereas many patients respond quickly to treatment with tumour necrosis factor (TNF) inhibitors, some patients may experience significant but delayed responses. OBJECTIVE: To evaluate the clinical response between 12 and 24 weeks in subjects with rheumatoid arthritis from the Trial of Etanercept and Methotrexate with Radiographic Patient Outcomes. METHODS: Clinical response was assessed at 24 weeks in 12-week non-responders, according to American College of Rheumatology (ACR) response criteria. The proportion of subjects who successfully maintained response to 52 weeks was analysed, as were radiographic outcomes. RESULTS: Data from 682 subjects were included in the analysis. Non and partial responders in all three groups (etanercept, methotrexate and etanercept plus methotrexate) at week 12 showed an improvement in responses at week 24. Over 80% of the week 24 ACR20/50/70 responders in the etanercept plus methotrexate arm sustained their response to 52 weeks. In the etanercept arms, a delayed clinical response was not associated with increased radiographic progression at week 52. CONCLUSION: A significant proportion of non and partial responders to etanercept with or without methotrexate therapy at week 12 achieved a good clinical response or improved their overall clinical response at week 24. Discontinuing TNF inhibitor therapy at 12 weeks may be premature in some rheumatoid arthritis patients.
18647852 Residual inflammation after rituximab treatment is associated with sustained synovial plas 2009 Jun OBJECTIVE: To investigate the clinical effects of rituximab treatment in relation to immunological effects of rituximab on tissue-derived B lineage cells and repopulation of circulating B cells. METHODS: A total of 24 patients with rheumatoid arthritis (RA) were treated with 2x1000 mg rituximab and assessed clinically at 4, 12, 18 and 24 weeks using a 44-joint Disease Activity Score (DAS(44)). Synovial biopsies were analysed with immunohistochemistry at baseline and 12 weeks after treatment. Peripheral blood mononuclear cells were analysed by high sensitivity flow cytometry at all timepoints. RESULTS: In this study, a cohort of patients was dichotomised according to those who achieved a low disease activity score (DAS(44)<2.4: LoA group) and those with persistent disease activity (DAS(44)>2.4: HiA group) at any time after rituximab treatment. At baseline, the low activity (LoA) group had significantly lower DAS(44) scores (median 3.33, range 2.84 to 4.23) than the high activity (HiA) group (median 3.73, range 3.03 to 5.23; p = 0.022) and significantly less histological inflammation in synovium (median 6.7, range 1 to 15 vs 16.6, range 4 to 22; p = 0.036). DAS(44) scores before and after rituximab treatment were associated with synovial infiltration of CD79a+ CD20- B cells, morphologically resembling plasma cells. Following treatment with rituximab, the LoA group had significantly reduced repopulation of circulating pre-switched IgD+ B cells (median 0.044%, range 0.002 to 0.66 vs 0.45%, range 0.07 to 9.47; p = 0.006) and post-switched CD27+ B cells (median 0.17%, range 0.04 to 0.39 vs 0.67, range 0.08 to 2.05; p = 0.005) compared to the HiA group. CONCLUSION: The present study demonstrated that a low disease activity state following rituximab was associated with reduced infiltration of CD79a+ CD20- plasma cells in synovium and reduced B cell repopulation.
16651616 Cadherin-11 induces rheumatoid arthritis fibroblast-like synoviocytes to form lining layer 2006 May The synovial lining of diarthrodial joints is composed of a condensed network of synoviocytes that form an intact layer via cell-to-cell contacts with significant intercellular matrix spaces. However, the molecular basis for synovial lining formation and its structural integrity has not been previously defined. In this study, using a three-dimensional fibroblast-like synoviocyte in vitro organ culture system, we provide evidence that cadherin-11 expressed in fibroblast-like synoviocytes plays a determining role in establishing the synovial lining layer. Fibroblast-like synoviocytes that were grown in three-dimensional matrices demonstrated formation of a lining structure at the interface between the matrix and the fluid phase. Treatment of fibroblast-like synoviocyte organ cultures with a cadherin-11-Fc fusion protein efficiently abrogated lining layer organization. Moreover, because E-cadherin-expressing fibroblasts failed to organize a lining layer structure at the tissue boundary, this effect appears to be a distinct characteristic of fibroblasts expressing cadherin-11. We found that cadherin-11 mediated fibroblast-like synoviocyte cell-to-cell adhesion via formation of adherens junctions that were linked to and remodeled the actin cytoskeleton. Together, these studies implicate cadherin-11 in synovial tissue and lining layer formation and provide an in vitro system to model fibroblast-like synoviocyte behavior and function in organizing the synovial tissue.
18512715 Prevalence and associations of hallux valgus in a primary care population. 2008 Jun 15 OBJECTIVE: To determine the population prevalence and examine factors associated with hallux valgus in a primary care population. METHODS: A questionnaire was mailed to all adults age >30 years registered with 2 general practices. Validated instruments assessed self-reported hallux valgus, nodal osteoarthritis, and knee pain. The questionnaire also asked about big toe pain, joint replacement, and history of osteoarthritis and rheumatoid arthritis. Hallux valgus prevalence was calculated and standardized by the source population in terms of age, sex, knee pain, osteoarthritis, and rheumatoid arthritis. A nested case-control study was undertaken and age-sex adjusted odds ratios (ORs) were calculated between hallux valgus and age, sex, body mass index, nodal osteoarthritis, knee pain, big toe pain, joint replacement, self-reported osteoarthritis, and self-reported rheumatoid arthritis, using a binary logistic regression model. RESULTS: A total of 13,684 questionnaires were mailed and 4,249 (32%) responses were received. The standardized prevalence of hallux valgus was 28.4%. Hallux valgus was associated with age (adjusted OR 1.61 per decade; 95% confidence interval [95% CI] 1.52-1.69), female sex (adjusted OR 2.64; 95% CI 2.26-3.08), nodal osteoarthritis (adjusted OR 1.66; 95% CI 1.26-2.17), knee pain (adjusted OR 1.96; 95% CI 1.65-2.32), big toe pain (adjusted OR 3.28; 95% CI 2.48-4.33), self-reported osteoarthritis (adjusted OR 1.41; 95% CI 1.15-1.72), and self-reported rheumatoid arthritis (adjusted OR 2.04; 95% CI 1.43-2.91). CONCLUSION: Hallux valgus is prevalent in the community and is associated with age, female sex, and components of generalized osteoarthritis such as nodal osteoarthritis, knee pain, big toe pain, and self-reported osteoarthritis.
16728269 HLA and RA revisited: citrullinated food for the SE hypothesis, the DR6 effect, and NIMA. 2006 Jun An obvious way to unravel the apparently complex association between human leukocyte antigen (HLA) and rheumatoid arthritis (RA) is to reduce the heterogeneity of this multifactorial disease. Recently we have discovered that shared epitope (SE)-positive HLA-DRB1 alleles are exclusively associated with a subgroup of RA patients that test positive for auto-antibodies against cyclic citrullinated peptides. Further studies suggested that SE-positive alleles are classical immune response genes for the development of these antibodies. On the basis of these and other data we formulated a two-hit model for the pathogenesis of RA which incorporates a novel "citrullinated" SE hypothesis. About 5 years ago Zanelli et al. reported that HLA-DR6 (*1301 and *1302) and some other DR alleles that share the DERAA-sequence on amino acids 70-74 of their third hypervariable region are associated with protection from (severe) RA. Recently we corroborated these data in a large prospective cohort study and demonstrated that protection was observed both in the presence and in the absence of a SE susceptibility allele on the other haplotype. Finally we review the state of the art of the association of noninherited maternal HLA antigens with both susceptibility to and protection from RA.
17557889 Vitamin D and autoimmunity: new aetiological and therapeutic considerations. 2007 Sep Vitamin D is frequently prescribed by rheumatologists to prevent and treat osteoporosis. Several observations have shown that vitamin D inhibits proinflammatory processes by suppressing the enhanced activity of immune cells that take part in the autoimmune reaction. Moreover, recent evidence strongly suggests that vitamin D supplementation may be therapeutically beneficial, particularly for Th1-mediated autoimmune disorders. Some reports imply that vitamin D may even be preventive in certain disorders such as multiple sclerosis and diabetes type 1. It seems that vitamin D has crossed the boundaries of calcium metabolism and has become a significant factor in a number of physiological functions, specifically as a biological inhibitor of inflammatory hyperactivity.
17407222 Macrophage migration inhibitory factor upregulates angiogenic factors and correlates with 2007 May OBJECTIVE: To investigate the relationship between macrophage migration inhibitory factor (MIF) levels and clinical measures in rheumatoid arthritis (RA), and the potential for regulation of angiogenesis in RA. METHODS: Serum and synovial fluid (SF) levels of MIF and vascular endothelial growth factor (VEGF) in patients with RA were determined by sandwich ELISA, and the relationships among MIF, VEGF, and RA clinical measures were analyzed. RA synovial fibroblasts were cultured with recombinant human MIF (rhMIF) and the production of VEGF and interleukin 8 (IL-8) were measured in the conditioned media. The angiogenic effect of MIF was examined using established measures of angiogenesis in vitro. RESULTS: Erythrocyte sedimentation rate, C-reactive protein, and the daily dosage of oral prednisolone were correlated with SF levels of MIF. The SF levels of MIF were found to be higher in patients with bony erosion than in those without (69.2 +/- 11.4 ng/ml vs 44.0 +/- 6.2 ng/ml; p = 0.045). MIF levels had good correlation with VEGF levels (r = 0.52, p < 0.001 in sera, and r = 0.6, p < 0.001 in SF). Production of the angiogenic factors VEGF and IL-8 was enhanced in cultured RA synovial fibroblasts stimulated by rhMIF. Endothelial tube formation was augmented when the endothelial cells were cultured with the conditioned media from rhMIF-pretreated SF mononuclear cells, and this phenomenon was reversed by anti-VEGF antibody. CONCLUSION: SF MIF may reflect the clinical activity in patients with RA, and rhMIF induces the angiogenic factors in RA synovial fibroblasts. These results suggest that MIF may be an important cytokine in the perpetuation of the angiogenic and inflammatory processes in patients with RA.
19017998 Infiltrated neutrophils acquire novel chemokine receptor expression and chemokine responsi 2008 Dec 1 Various inflammatory diseases are characterized by tissue infiltration of neutrophils. Chemokines recruit and activate leukocytes, but neutrophils are traditionally known to be restricted in their chemokine receptor (CR) expression repertoire. Neutrophils undergo phenotypic and functional changes under inflammatory conditions, but the mechanisms regulating CR expression of infiltrated neutrophils at sites of chronic inflammation are poorly defined. Here we show that infiltrated neutrophils from patients with chronic inflammatory lung diseases and rheumatoid arthritis highly express CR on their surface that are absent or only marginally expressed on circulating neutrophils, i.e., CCR1, CCR2, CCR3, CCR5, CXCR3, and CXCR4, as measured by flow cytometry, immunohistochemistry, and confocal microscopy. The induction of CR surface expression on infiltrated neutrophils was functionally relevant, because receptor activation by chemokine ligands ex vivo modulated neutrophil effector functions such as respiratory burst activity and bacterial killing. In vitro studies with isolated neutrophils demonstrated that the surface expression of CR was differentially induced in a cytokine-mediated, protein synthesis-dependent manner (CCR1, CCR3), through Toll-like (CXCR3) or NOD2 (CCR5) receptor engagement, through neutrophil apoptosis (CCR5, CXCR4), and/or via mobilization of intracellular CD63(+) granules (CXCR3). CR activation on infiltrated neutrophils may represent a key mechanism by which the local inflammatory microenvironment fine-tunes neutrophil effector functions in situ. Since the up-regulation of CR was exclusively found on infiltrated neutrophils at inflammatory sites in situ, the targeting of these G protein-coupled receptors may have the potential to site-specifically target neutrophilic inflammation.
16917962 Parvovirus B19 and immune disorders. 2007 Nov Parvovirus B19 (PVB19) is the causative agent of erythema infectiosum and sometimes the infection is correlated with severe haematological complications, or in pregnancy to fetalis hydrops. Moreover some authors suggest an infection involvement in some autoimmune diseases. To this purpose we evaluated seroprevalence for PVB19 in following the autoimmune or dysreactive pathologies: systemic lupus erythematosus (SLE), cryoglobulinemia, idiopathic systemic--ANCA associated vasculitis, rheumatoid arthritis (RA). In the case of LES, 31/42 patients were positive for PVB19 versus 21/42 of blood donors, as controls subjects (73.8% vs. 50%; significant difference for p < 0.05), moreover a significant difference for p < 0.001 was detected comparing mean titre values of IgGs against PVB19 of two groups (UI 1.94 +/- 0.90 vs. 1.24 +/- 0.80). In contrast no significant differences were found in the case of percent seropositivity of cryoglobulinemic subjects (37/57 = 64.9%, the majority of whom were HCV+) in comparison with the control group (50%). However mean units index (UI) was 1.63 +/- 0.81; p = 0.019 versus the control group. Similar result, with regard to the percentage of seropositivity, was found for vasculitis (9/17 = 52.9%). The data reported here can confirm a possible correlation between PVB19 prior infection and LES and also suggest possible implications in the case of cryoglobulinemia. In fact, most of our patients were affected by a nephropathic or systemic form of HCV+ cryoglobulinemia and the presence of other infective cofactors could be suggestive in the evolution of this clinical situation.
17103175 Gliostatin/thymidine phosphorylase-regulated vascular endothelial growth-factor production 2007 Apr Gliostatin/thymidine phosphorylase (GLS/TP) is known to have angiogenic and arthritogenic activities. The purpose of this study was to elucidate whether GLS/TP is involved in the regulation of the angiogenic cytokine vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLSs) from patients with RA were cultured and stimulated with recombinant human GLS (rHuGLS) and interleukin (IL)-1beta. Immunohistochemistry showed that GLS/TP and VEGF were detectable in the synovial lining cells. In cultured FLSs, both VEGF mRNA and protein levels were markedly increased by rHuIL-1beta treatment. rHuGLS increased VEGF mRNA expression in a dose-dependent manner. We detected high concentrations of VEGF165 protein in culture supernatants from FLSs treated with rHuGLS (300 ng/ml), which were comparable to GLS levels found in synovial fluid of RA patients. These findings indicate that GLS/TP and VEGF have synergistic effects on angiogenesis in rheumatoid synovitis, and that GLS/TP has a role in regulating VEGF.
18281367 The relation between composite ultrasound measures and the DAS28 score, its components and 2008 Apr OBJECTIVES: Ultrasound (US) provides measurements of synovial morphology and vascularity. However, on an individual joint basis in RA, US measures do not relate well to clinical signs. This study investigates the relationship between composite US measures and the 28-joint disease activity score (DAS28), its components and acute phase markers in adult RA. METHODS: RA synovial disease activity was recorded in 50 patients by: (i) the DAS28 score; (ii) ESR and CRP; and (iii) US using Grey scale (GS) and power Doppler (PD) measures of PIP and MCP joints to derive composite US scores based on abnormal counts and severity. A total of 25 control subjects were studied to define normal US appearances. The relation between each measure of synovial disease was determined by Spearman correlation analysis. RESULTS: There was a significant relation between the DAS28 and the GS joint count (GSJC, Spearman's r = 0.4; P = 0.004) and severity score (GSJS, r = 0.34; P = 0.016) and the PD joint count (PDJC, r = 0.32; P = 0.028). There was a significant relation between the ESR and PDJC (r = 0.37; P = 0.007) and PD joint severity score (PDJS, r = 0.38; P = 0.006) and between the CRP and PDJS (r = 0.29; P = 0.04). The remaining components of the DAS28 related poorly to all US measures, except the tender joint count, which related significantly to the GS but not the PD measures. CONCLUSIONS: Composite US markers of synovial disease relate significantly to the DAS28 score and ESR/CRP in adult RA, but not as well with individual clinical joint counts and the patient's global assessment.