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ID PMID Title PublicationDate abstract
17666449 Vitamin D intake and risks of systemic lupus erythematosus and rheumatoid arthritis in wom 2008 Apr OBJECTIVES: Vitamin D has immune-modulating effects and may protect against the development of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: We identified incident cases of SLE and RA among 186 389 women followed from 1980 to 2002 in the Nurses' Health Study and Nurses' Health Study II cohorts. We excluded subjects where SLE or RA was not confirmed by medical record review, and those who failed to return questionnaires. Semi-quantitative food frequency questionnaires assessed vitamin D intake from food and supplements. We used cumulative-updated total energy-adjusted dietary exposures for each 2-year cycle. Relationships between vitamin D intake and incident SLE and RA were examined in age-adjusted and Cox proportional hazards models, adjusted for confounders. Results were pooled using meta-analysis random effects models. RESULTS: We confirmed 190 incident cases of SLE and 722 of RA with dietary information. Increasing levels of vitamin D intake had no relationship to the relative risk of developing either SLE or RA. CONCLUSIONS: Vitamin D intake was not associated with risk of SLE or RA in these large prospective cohorts of women.
17765836 Hallux metatarsophalangeal arthroplasty in the rheumatoid forefoot. 2007 Sep Surgical options for treatment of the hallux valgus deformity in the rheumatoid forefoot are numerous, but long-term results of many of these procedures have been less than satisfactory. Controversy exists as to whether excision or fusion is preferred for the treatment of the hallux metatarsophalangeal (MTP) joint. The role of replacement arthroplasty needs to be evaluated. The available surgical options for treatment of the arthritic first MTP joint in rheumatoid arthritis include arthrodesis, excision of the metatarsal head with or without interposition of the soft tissues, excision of the proximal phalanx, and silicone hinge replacement. This article discusses the various types of arthroplasty of the first MTP joint and the reported outcomes in the rheumatoid forefoot.
17096696 A case report of leukocytapheresis for refractory leg ulcers complicated with rheumatoid a 2006 Oct Leukocytapheresis (LCAP) has recently been investigated for the treatment of drug-resistant rheumatoid arthritis (RA). In the present clinical study, we used LCAP in three patients with rheumatoid arthritis (RA), with drug-resistant leg ulcers. LCAP was carried out once a week for five weeks. Erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor titers and tender joint counts did not change when LCAP was used but the ulcers began to recede after the first treatment and, by the end of the fifth treatment, the ulcers had healed. The activated leukocytes that are the major part of the inflammation of skin ulcers are removed from the peripheral blood by LCAP. Thus, it is supposed that the activated leukocytes shift from the inflammatory skin ulcer to peripheral blood, causing the skin ulcer to recover. We hypothesize that LCAP is a useful treatment for refractory leg ulcers complicated with RA.
17325736 Reduced folate carrier-1 80G>A polymorphism affects methotrexate treatment outcome in rheu 2007 Dec The folate antagonist methotrexate (MTX) is a drug currently used in the treatment of rheumatoid arthritis (RA). MTX enters the cells through the reduced folate carrier (RFC-1) and is activated to polyglutamates. Previous studies have shown that RFC-1 expression may influence the efficacy of therapy with MTX. The studies suggest that G80A polymorphism in RFC-1 is associated with altered folate/antifolate levels and the subjects carrying homozygous mutant 80AA genotype tend to have higher plasma folate and MTX concentrations and higher erythrocyte polyglutamate levels compared with those with the wild type or heterozygous genotype. It is possible that this polymorphism might influence MTX treatment outcome in patients with RA. In the present study, we examined the association between RFC-1 G80A polymorphism and treatment outcome in patients with RA administered MTX. The study was carried out on 174 patients diagnosed with RA treated with MTX (7.5-15.0 mg weekly) plus low doses of methylprednisone. The RFC-1 80G>A polymorphism (resulting in a histidine-to-arginine substitution at codon 27 of RFC-1) was detected using a polymerase chain reaction-restriction fragment length polymorphism method. The probability of remission of RA symptoms was 3.32-fold higher in carriers of 80AA genotype as compared with patients with 80GG genotype (P=0.021, OR=3.32, 95% CI: 1.26-8.79). The frequency of A allele among MTX responders was 62.1, compared to 47.8% in a group of poor MTX responders (P=0.013, OR=1.78, 95% CI: 1.13-2.81). Moreover, the increase of aminotransferase activity was noted more frequently in carriers of 80AA genotype. The present data suggest that evaluation of RFC-1 gene 80G>A polymorphism may be a useful tool to optimize MTX therapy in patients with RA.
18504279 Interaction between rheumatoid arthritis and pregnancy: correlation of molecular data with 2008 Jun OBJECTIVE: The factors that induce remission of RA during pregnancy and the relapse occurring after delivery remain an enigma. In a previous study, we investigated gene-expression profiles of peripheral blood mononuclear cells (PBMC) in patients with RA and healthy women in late pregnancy and postpartum. Profiles of samples from both groups were similar in late pregnancy with elevated monocyte and decreased lymphocyte signatures. Postpartum, in RA PBMC the high level of monocyte transcripts persisted. Further increase was observed in adhesion, migration and signalling processes related to monocytes but also in lymphocytes despite similar clinical activity due to intensified drug treatment. This prompted us to investigate correlations between clinical parameters of disease activity and gene profiles. METHODS: Transcriptome data were correlated with RADAI, CRP, monocyte and lymphocyte counts. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations, monocytes and lymphocytes signatures were used as reference information. RESULTS: Comparative analysis of PBMC expression profiles from RA patients during and after pregnancy with RADAI and CRP revealed a correlation of these disease activity parameters predominantly with monocyte transcripts. Genes related to cellular programs of adhesion, migration and response to infections were upregulated. Comparing clinically active and not-active RA patients postpartum revealed a cluster of 19 genes that could also identify active disease during pregnancy. CONCLUSION: The data suggest that an increase of the RADAI and an elevation of CRP is a consequence of molecular activation of monocytes. Furthermore, they indicate that molecular activation of T lymphocytes may remain clinically unrecognized postpartum. It is conceivable that a set of 19 genes may qualify as molecular disease activity marker.
16573350 Abatacept. 2006 Abatacept (Orencia) is the first in a new class of biologics known as selective costimulation modulators. It inhibits full activation of T cells and interacts with other cell types to affect additional mediators of the inflammatory cascade. The clinical efficacy of abatacept in patients with active rheumatoid arthritis, despite prior treatment with methotrexate or anti-tumor necrosis factor-alpha (anti-TNFalpha) therapies, has been investigated in two randomized, double-blind, placebo-controlled, multicenter, phase III trials of 6 or 12 months' duration. In these trials, patients received intravenous abatacept (fixed-dose regimen based on bodyweight) or placebo in addition to background disease-modifying anti-rheumatic drugs (DMARDs) other than anti-TNFalpha therapies. Relative to placebo, abatacept significantly improved signs and symptoms of disease assessed using American College of Rheumatology (ACR) 20, 50, and 70 criteria and specific improvement in physical function as measured by the Health Assessment Questionnaire Disability Index at 6 months and significantly slowed structural damage progression in joints at 12 months. Improvements in ACR 20, 50, and 70 response rates were maintained at the final assessment in the 12-month trial. Abatacept infusions were generally well tolerated. Acute infusion-related reactions occurred in 9% of abatacept and 6% of placebo recipients in phase III trials. Integrated safety data from five clinical trials showed that serious adverse events were reported in 13.6% of abatacept and 12.3% of placebo recipients and the incidence of serious infections was 3.0% and 1.9%. Abatacept administered with background biologic DMARDs appears to be less well tolerated than abatacept plus background nonbiologic DMARDs.
18575276 BiP, an anti-inflammatory ER protein, is a potential new therapy for the treatment of rheu 2008 The endoplasmic reticulum chaperone and stress protein BiP has hitherto been considered as having only crucial intracellular cell protective functions. However, we have shown that BiP can be present in the extracellular environment and that it binds to a putative but as yet uncloned cell surface receptor. It will stimulate human monocytes via this receptor to express a gene profile that is anti-inflammatory. It will generate T cells with a regulatory function from human peripheral blood most likely by altering dendritic cell development. Intravenous BiP will both prevent and treat ongoing collagen induced arthritis in the DBA/1 mouse. Part of the suppression of arthritis is linked to interleukin (IL)4 as BiP-specific lymph node and spleen cells from these mice secrete IL4, and BiP has no suppressive effect on collagen induced arthritis in IL4 knockout mice. Lymph node and spleen cells isolated from mice administered intravenous BiP will suppress arthritis when transferred intravenously into recipient arthritic mice without any further BiP having to be given. Thus, both in vitro work with human peripheral blood mononuclear cells and in vivo work in the collagen arthritis model lead to the conclusion that BiP induces regulatory cells. Finally, intravenous BiP will ablate the inflammatory cell infiltrate and inflammatory cytokine expression in rheumatoid synovial membrane tissue transplanted subcutaneously into SCID mice. The conclusion from all this experimental work is that BiP may be a novel therapy for the treatment of patients with rheumatoid arthritis.
19635418 Long-term follow-up on 33 TPR ankle joint replacements in 26 patients with rheumatoid arth 2009 BACKGROUND: There exist very few long-term follow-up studies, on total ankle replacement (TAR). In the present study a cohort of rheumatoid arthritic (RA) were followed for up to 23 years. METHODS: Thirty-three TAR were performed in 26 RA patients from 1980 to 1993. Removal of the prostheses and radiolucency was considered endpoints. All patients were followed to prosthesis failure or until death of the patients or until January 2008. RESULTS: Two patients with 3 prostheses were still alive with their prosthesis in place. Eighteen patients with 23 prostheses had died with their prosthesis in place. Two patients had their ipsilateral leg amputated 12 and 14 years after operation of unrelated causes. Five prostheses in 4 patients had been removed. The 10 years prosthesis survival was 85%, when removal is the endpoint. CONCLUSIONS: The long-term survival of this first generation type of TAR adds some optimism to the development of TAR.
18383391 Defective proliferative capacity and accelerated telomeric loss of hematopoietic progenito 2008 Apr OBJECTIVE: In rheumatoid arthritis (RA), telomeres of lymphoid and myeloid cells are age-inappropriately shortened, suggesting excessive turnover of hematopoietic precursor cells (HPCs). The purpose of this study was to examine the functional competence (proliferative capacity, maintenance of telomeric reserve) of CD34+ HPCs in RA. METHODS: Frequencies of peripheral blood CD34+,CD45+ HPCs from 63 rheumatoid factor-positive RA patients and 48 controls matched for age, sex, and ethnicity were measured by flow cytometry. Proliferative burst, cell cycle dynamics, and induction of lineage-restricted receptors were tested in purified CD34+ HPCs after stimulation with early hematopoietins. Telomere sequences were quantified by real-time polymerase chain reaction. HPC functions were correlated with the duration, activity, and severity of RA as well as its treatment. RESULTS: In healthy donors, CD34+ HPCs accounted for 0.05% of nucleated cells; their numbers were strictly age dependent and declined at a rate of 1.3% per year. In RA patients, CD34+ HPC frequencies were age-independently reduced to 0.03%. Upon growth factor stimulation, control HPCs passed through 5 replication cycles over 4 days. In contrast, RA-derived HPCs completed only 3 generations. Telomeres of RA CD34+ HPCs were age-inappropriately shortened by 1,600 bp. All HPC defects were independent of disease duration, disease activity, and smoking status, and were present to the same degree in untreated patients. CONCLUSION: In RA, circulating bone marrow-derived progenitor cells were diminished, and concentrations stagnated at levels typical of those in old control subjects. HPCs from RA patients displayed growth factor nonresponsiveness and sluggish cell cycle progression; marked telomere shortening indicated proliferative stress-induced senescence. Defective HPC function independent of disease activity markers suggests bone marrow failure as a potential pathogenic factor in RA.
18078619 Comparison of anti-agalactosyl IgG antibodies, rheumatoid factors, and anti-cyclic citrull 2007 Sep OBJECTIVE: Anti-agalactosyl IgG antibodies [anti-Gal(0) IgG] have been regarded as a useful serological marker for rheumatoid arthritis (RA). Our aim was to evaluate the clinical usefulness of anti-Gal(0) IgG in the differential diagnosis of rheumatic disorders that mimic RA compared to rheumatoid factors (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP). METHODS: Sera were collected from 39 patients with RA, 49 patients with primary Sjögren's syndrome (pSjS), 47 patients with systemic lupus erythematosus (SLE), 65 patients with chronic hepatitis B viral infection (HBV), 68 patients with chronic hepatitis C viral infection (HCV) and 19 normal individuals. RF-IgM was measured by the nephelometeric method, and RF-IgA, anti-Gal(0) IgG and anti-CCP were measured by the respective ELISA assays. RESULTS: Anti-Gal(0) IgG titers were remarkably elevated in patients with RA (191.0 +/- 250.8 AU/ml) compared to pSjS (37.9 +/- 42.6 AU/ml), SLE (10.3 +/- 13.6 AU/ml), chronic HBV with (36.1 +/- 38.4 AU/ml) or without rheumatic symptoms (9.6 +/- 19.4 AU/ml), RF(+) chronic HCV without rheumatic symptoms (19.0 +/- 14.8 AU/ml), chronic HCV with rheumatic symptoms (15.2 +/- 17.4 AU/ml) and healthy individuals (2.6 +/- 0.7 AU/ml). The specificity of anti-Gal(0) IgG could be greatly enhanced by elevating the cut-off value from 12 AU/ml to 40 AU/ml (68.6% vs. 85.6%, p < 0.001) without significantly compromising its sensitivity (76.9% vs. 61.5%, p > 0.05). CONCLUSION: The serum titer of anti-Gal(0) IgG is much higher in rheumatoid arthritis than in mimicking diseases. The specificity of anti-Gal(0) IgG is enhanced when the cut-off value is raised. However, anti-CCP remains the most specific biomarker for RA.
17768022 Value of contrast-enhanced ultrasound in rheumatoid arthritis. 2007 Nov The purpose of this review is to describe the spectrum of sonographic findings in rheumatic diseases with respect to the diagnostic potential using US contrast media which prove activity or inactivity in synovial tissue where new treatment regimes target. Synovial activity can be found in non-erosive and erosive forms of primary and secondary osteoarthritis, and in inflammatory forms of joint diseases like rheumatoid arthritis and peripheral manifestations of spondyloarthritis including, ankylosing spondylitis, Reiter's syndrome, psoriatic arthritis and enteropathic arthritis. It can also be present in metabolic and endocrine forms of arthritis, in connective tissue arthropathies like systemic lupus erythematosus or scleroderma and in infectious arthritis. Ultrasound should be used as first-line imaging modality in suspected early cases of RA and other forms of arthritis, whereas contrast-enhanced ultrasound (CEUS) can further enable for sensitive assessment of vascularity which correlates with disease activity.
17942788 Development of a high-throughput screening assay based on the 3-dimensional pannus model f 2007 Oct The 3-dimensional (3-D) pannus model for rheumatoid arthritis (RA) is based on the interactive co-culture of cartilage and synovial fibroblasts (SFs). Besides the investigation of the pathogenesis of RA, it can be used to analyze the active profiles of antirheumatic pharmaceuticals and other bioactive substances under in vitro conditions. For a potential application in the industrial drug-screening process as a transitional step between 2-dimensional (2-D) cell-based assays and in vivo animal studies, the pannus model was developed into an in vitro high-throughput screening (HTS) assay. Using the CyBitrade mark-Disk workstation for parallel liquid handling, the main cell culture steps of cell seeding and cultivation were automated. Chondrocytes were isolated from articular cartilage and seeded directly into 96-well microplates in high-density pellets to ensure formation of cartilage-specific extracellular matrix (ECM). Cell seeding was performed automatically and manually to compare both processes regarding accuracy, reproducibility, consistency, and handling time. For automated cultivation of the chondrocyte pellet cultures, a sequential program was developed using the CyBio Control software to minimize shear forces and handling time. After 14 days of cultivation, the pannus model was completed by coating the cartilage pellets with a layer of human SFs. The effects due to automation in comparison to manual handling were analyzed by optical analysis of the pellets, histological and immunohistochemical staining, and real-time PCR. Automation of this in vitro model was successfully achieved and resulted in an improved quality of the generated pannus cultures by enhancing the formation of cartilage-specific ECM. In addition, automated cell seeding and media exchange increased the efficiency due to a reduction of labor intensity and handling time.
17058361 Intra ocular pressure in chronic users of oral glucocorticoids for rheumatoid arthritis. 2006 Apr OBJECTIVE: To evaluate intra ocular pressure (IOP) among rheumatoid arthritis (RA) patients who are chronic oral glucocorticoid users in low to moderate doses. MATERIAL AND METHODS: We have studied 125 subjects: 72 glucocorticoid users and 53 controls. The glucocorticoid users were RA patients treated with 5 to 40 mg/day of prednisone or equivalent. Controls were patients with osteoarthritis or with soft tissue rheumatic syndromes who had never used glucocorticoid orally or locally. The IOP was measured three times with Perkins tonometer in both eyes and the mean value was compared between groups. For statistical analysis we used the mean value between the IOP of both eyes. RESULTS: Among RA glucocorticoid users the mean dose was 9.7 mg of prednisone daily during a mean period of 71.1 months. The IOP of glucocorticoid users was 5.8% higher than controls. This difference did not reach statistical significance. The rise in IOP was not affected by the duration of glucocorticoid treatment or by the dose. No RA patient using oral glucocorticoids was found to have abnormal IOP in this study. CONCLUSIONS: Low dose glucocorticoids causes a small (5.8%), non significant increase in intraocular pressure.
17543144 Is Taurolidine a candidate for treatment of rheumatoid arthritis? 2007 Mar OBJECTIVE: To study the therapeutic potential of taurolidine (TRD), a derivative of taurine with known anti-inflammatory and anti-proliferative properties, in various experimental models of synovitis. METHODS: In vitro: fibroblast-like synoviocytes (RA FLS) isolated from the synovial tissue of patients with rheumatoid arthritis (RA) were cultured in the presence of either TRD or polyvinylpyrrolidine (PVP), the pharmaceutical stabilizer of TRD, which was used as a control. Proliferation of RA FLS and cytokine (IL-6 and IL-8) release were measured. In vivo: (A). The effect of systemic TRD treatment on the development of collagen-induced arthritis (CIA) in female DBA1/J mice was investigated. Mice were treated either with intraperitoneal injections of 1 ml of 2% Taurolin Boehringer Ingelheim (TRD +PVP) or with PVP as placebo. The incidence of arthritis, myeloperoxidase (MPO) activity in periarticular tissue, as well as serum concentration of IgG specific to collagen II (IgG alphaCII) were determined. (B). The effect of intra-articular TRD treatment was studied in rabbits with antigen-induced monoarthritis (AIA). After the induction of AIA of right knees rabbits were treated either with intra-articular injections of 0.5 ml of 2% Taurolin or 0.5ml PVP ( placebo). The animals were examined for clinical signs of arthritis and diameter of joints was measured. After termination of the experiment, the arthritic knees were examined and histopathology of the joints was assessed. In addition, serum amyloid A (SAA) concentration was measured. RESULTS: n vitro: TRD exerted cytotoxic effect on RA FLS when applied at concentrations >100 microM. TRD at non-cytotoxic concentrations, inhibited PDGF-triggered RA FLS proliferation, reduced IL-1beta - stimulated production of IL-6 and slightly decreased intracellular content of IL-8. In vivo: (A). Intraperitoneal treatment with Taurolin significantly reduced the incidence (30%) of CIA when compared to the control mice (79%). However, Taurolin failed to control the development of CIA in mice with high serum level of IgG alphaCII (>1000 U).(B). Intra-articular application of 2% Taurolin resulted in amelioration of AIA in all treated rabbits (reduced diameter of arthritic joints and smaller rise of SAA level as compared to the control animals). Histopathologic evaluation revealed pannus formation in both groups and extensive necrotic lesions of synovial tissue treated with TRD, suggesting synoviorthesis-like effect. CONCLUSION: Results from AIA and from in vitro RA FLS studies suggest that intra-articular administration of TRD could be used as a "pharmacological scalpel" to remove the inflamed synovium. Our data confirmed anti-inflammatory and anti-proliferative properties of TRD in all experimental models encouraging further studies which should evaluate its therapeutic potential in RA.
16926186 Comparison of Disease Activity Score (DAS)28- erythrocyte sedimentation rate and DAS28- C- 2007 Mar OBJECTIVE: To estimate the disease activity score (DAS)28-C-reactive protein (CRP) threshold values that correspond to DAS28-erythrocyte sedimentation rate (ESR) values for remission, low disease activity and high disease activity in patients with rheumatoid arthritis. METHODS: DAS28 data were analysed using a large observational study (Institute of Rheumatology Rheumatoid Arthritis) database of 6729 patients with rheumatoid arthritis. Firstly, the relationship between the DAS28-ESR and the DAS28-CRP values was analysed. Secondly, the best DAS28-CRP trade-off values for each threshold were calculated using receiver operating characteristic (ROC) curves. RESULTS: The correlation coefficient of ESR versus CRP was 0.686, whereas that of DAS28-ESR versus DAS28-CRP was 0.946, showing the strong linear relationship between DAS28-ESR and DAS28-CRP values. DAS28-CRP threshold values corresponding to remission, low disease activity and high disease activity were 2.3, 2.7 and 4.1, respectively. The sensitivity and specificity from the ROC curves were gradually reduced as DAS28 values became lower. CONCLUSIONS: This study showed that DAS28-CRP and DAS28-ESR were well correlated, but the threshold values should be reconsidered. As the results were derived from only Japanese patients, it is essential to compare DAS28-CRP threshold values in people of other ethnic groups.
18468489 Molecular mechanisms of inflammatory bone damage: emerging targets for therapy. 2008 Jun Chronic inflammatory bone diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis and periodontal disease, demonstrate the major impact of chronic inflammation on both bone metabolism and bone architecture. During the past decade, scientists have gained increasing insight into the link between inflammation and bone. As a result of new discoveries about the molecular mechanisms of inflammatory bone loss, several molecules have been identified that are attractive and novel targets for the treatment of inflammatory bone loss. These novel therapeutic approaches include anti-tumor necrosis factor (TNF)-alpha blocking agents, neutralizing antibodies against certain pro-inflammatory cytokines, such as interleukin (IL)-6 and IL-17, and a set of other promising targets that still require extensive research, such as the Wnt signaling network.
17133544 Characteristics of diffuse large B cell lymphomas in rheumatoid arthritis. 2006 Dec OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, with a correlation between RA disease severity and lymphoma risk, most pronounced for diffuse large B cell lymphomas (DLBCLs), which also constitute the majority of RA-associated lymphomas. DLBCLs can be further subdivided into germinal center (GC)-like and non-GC-like subtypes, with different cellular origins and prognoses. This study was undertaken to investigate whether RA displays a specific association with any of the DLBCL subtypes. METHODS: We identified 139 patients with DLBCLs within a population-based case-control study of 378 RA patients with lymphoma. The DLBCLs were examined for CD10, Bcl-6, and interferon regulatory factor 4 expression patterns, subclassified into GC and non-GC subtypes, and then correlated with clinical parameters. RESULTS: We found a statistically significant predominance of the non-GC subtype (97 patients; 70% of all DLBCLs). These patients more often had an advanced stage of lymphoma at diagnosis and had a worse 5-year overall survival rate (16% versus 33%) compared with patients with the GC subtype. There was a strong association with RA disease activity in both subtypes, with >70% of the GC and non-GC cases occurring in RA patients with the highest overall disease activity scores. CONCLUSION: These findings suggest that severe RA is particularly associated with the non-GC subtype of DLBCL, and indicate a critical role of activated peripheral B cells as the cells of origin in these lymphomas.
19223981 Proinflammatory role of vascular endothelial growth factor in the pathogenesis of rheumato 2008 Recent experimental and clinical studies have placed new emphasis on the role of angiogenesis in chronic inflammatory disease. Vascular endothelial growth factor (VEGF) and its receptors are the best characterized system in the regulation of rheumatoid arthritis (RA) by angiogenesis. Furthermore, in addition to its angiogenic role, VEGF can act as a direct proinflammatory mediator during the pathogenesis of RA, and protect rheumatoid synoviocytes from apoptosis, which contributes to synovial hyperplasia. Therefore, the developments of synovial inflammation, hyperplasia, and angiogenesis in the joints of RA patients seem to be regulated by a common cue, namely, VEGF. Agents that target VEGF, such as anti-VEGF antibody and aptamer, have yielded promising clinical data in patients with cancer or macular degeneration, and in RA patients, pharmacologic modulations targeting VEGF or its receptor may offer new therapeutic approaches. In this review, the authors integrate current knowledge of VEGF signaling and information on VEGF antagonists gleaned experimentally and place emphasis on the use of synthetic anti-VEGF hexapeptide to prevent VEGF interacting with its receptor.
17178564 Tolerizing DNA vaccines for autoimmune arthritis. 2006 Dec Current therapies for rheumatoid arthritis (RA) and other autoimmune diseases non-specifically suppress immune function, and there is great need for fundamental approaches such as antigen-specific tolerizing therapy. In this paper we describe development of antigen-specific tolerizing DNA vaccines to treat collagen-induced arthritis (CIA) in mice, and use of protein microarrays to monitor response to therapy and to identify potential additional autoimmune targets for next generation vaccines. We demonstrate that tolerizing DNA vaccines encoding type II collagen (CII) reduced the incidence and severity of CIA. Atorvastatin, a statin drug found to reduce the severity of autoimmunity, potentiated the effect of DNA vaccines encoding CII. Analysis of cytokines produced by collagen-reactive T cells derived from mice receiving tolerizing DNA encoding CII, as compared to control vaccines, revealed reduced production of the pro-inflammatory cytokines IFN-gamma and TNF-alpha. Arthritis microarray analysis demonstrated reduced spreading of autoantibody responses in mice treated with DNA encoding CII. The development of tolerizing DNA vaccines, and the use of antibody profiling to guide design of and to monitor therapeutic responses to such vaccines, represents a promising approach for the treatment of RA and other autoimmune diseases.
16341699 Psychological distress and personality traits in early rheumatoid arthritis: A preliminary 2006 Jul OBJECTIVES: To investigate psychiatric manifestations, personality traits, and ego mechanisms of defense involved in early rheumatoid arthritis (RA). METHODS: Twenty-two unselected early RA outpatients with disease duration less than 1 year participated in the study. The majority of participants were females (72.7%), married (81.8%), aged 51.0+/-14.6 years. Thirty-four subjects matched for age, sex and educational level served as "healthy" controls. General Heath Questionnaire, Symptom Distress Checklist, Defense Style Questionnaire and Hostility and Direction of Hostility Questionnaire were used; disease activity was estimated by disease activity for 28-joint indices score. RESULTS: Seven patients (31.8%) presented psychological distress scores indicative of possible psychiatric caseness, expressing obsessive-compulsive symptoms and depression, as compared to six (17.6%) of controls. Social dysfunction distress and somatization were prominent psychiatric manifestations in early RA group. Early RA patients tend to adopt a less adaptive defense style than controls. Although disease activity was not correlated to psychological distress, a significant association between disease activity and patients' defensive style was observed: as the disease is exacerbated, there was a shift from "non-adaptive" to "immature image distorting or borderline" defense style, suggesting a rather fragile underlying personality structure. CONCLUSION: Psychological distress is a relatively common experience in early RA. Social dysfunction, along with the less adaptive defense style, which under the stress of the disease exacerbation turns to "borderline", underlines the importance of a careful assessment and consultation in early RA patients in order to face the distress shortly after diagnosis and highlights potential risk factors for future adaptation to exacerbations of the disease.