Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
17785331 Antinucleosome antibodies and systemic lupus erythematosus. 2007 Aug The aim of this study is to investigate the prevalence of antinucleosome antibody in systemic lupus erythematosus (SLE) and their association with disease activity and renal involvement. The study included 131 patients with SLE, 74 rheumatoid arthritis, 26 systemic sclerosis, and 50 healthy individuals. Antinucleosome antibody and anti-dsDNA antibody were measured by an enzyme-linked immunosorbent assay (ELISA). Antinuclear antibody was tested by immunofluorescence using HEp-2 cells. Out of 131 SLE patients, 72 (54.9%) were seropositive for antinucleosome antibody, which was significantly higher than only 3 of 74 (4%) patients with rheumatoid arthritis (chi(2) = 52.82, P < 0.001); none of the patients with systemic sclerosis and 50 healthy individuals were seropositive. The sensitivity and specificity of antinucleosome antibodies in SLE were 83.6% and 70%, respectively. Fifty-one (38.9%) of SLE patients had renal involvement. Among these patients, the rate of antinucleosome positivity and anti-dsDNA were 74.5% and 78.4%, respectively. Antinucleosome antibodies were found to be 31.4% positive in SLE patients lacking anti-dsDNA antibody. Antinucleosome antibodies significantly correlated with disease activity (r = 0.428, P < 0.001) and anti-dsDNA (r = 0518, P < 0.001). The positivity of antinucleosome antibodies was significantly higher in patients with renal disease than the subjects without renal disease (chi(2) = 12.89, P < 0.001). The results of our study have revealed that in SLE patients, antinucleosome antibody could be a useful parameter for the assessment of disease activity or renal involvement.
16697661 Role of PTPN22 in type 1 diabetes and other autoimmune diseases. 2006 Aug We recently discovered that a single-nucleotide polymorphism (SNP) in the lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene on chromosome 1p13, correlates strongly with the incidence of type 1 diabetes (T1D) in two independent populations. This findings has now been verified by numerous studies and it has been expanded to rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, generalized vitiligo and other autoimmune disease. Here we review the genetics of the SNP and its association with autoimmunity, discuss the function of the phosphatase in signaling, the biochemistry of the disease-predisposing allele, and the possible mechanisms by which PTPN22 contributes to the development of human disease.
18557953 Targeting the chemotactic function of CD147 reduces collagen-induced arthritis. 2009 Jan CD147 is a type I transmembrane glycoprotein expressed on a wide variety of cell types, including all leucocytes. While CD147 is best known as a potent inducer of matrix metalloproteinases, it can also function as a regulator of leucocyte migration through its cell surface interaction with chemotactic extracellular cyclophilins. A potential role for CD147-cyclophilin interactions during inflammatory diseases, including rheumatoid arthritis (RA), is suggested from several studies. For example, CD147 expression is increased on reactive leucocytes in the synovial fluid and tissues of patients with arthritis. In addition, the synovial fluid of patients with RA contains high levels of extracellular cyclophilin A. In the current studies we investigated the contribution of the chemotactic function of CD147-cyclophilin interactions to joint inflammation using the mouse model of collagen-induced arthritis. Our data demonstrate that proinflammatory leucocytes, specifically neutrophils, monocytes and activated CD4(+) T cells, lose their ability to migrate in response to cyclophilin A in vitro when treated with anti-CD147 monoclonal antibody. Furthermore, in vivo treatment with anti-CD147 monoclonal antibody can reduce the development of collagen-induced arthritis in mice by >75%. Such findings suggest that CD147-cyclophilin interactions might contribute to the pathogenesis of RA by promoting the recruitment of leucocytes into joint tissues.
18435803 Long-term anti-arthritic and anti-osteoporotic effects of raloxifene in established experi 2008 Jun Both oestrogen deficiency and the inflammatory disease contribute to the generalized bone loss seen in postmenopausal rheumatoid arthritis (RA). Oestradiol and the selective oestrogen receptor modulator raloxifene have been shown to ameliorate the disease in collagen-induced arthritis (CIA), a well-established animal model for human RA. The aim of this study was to investigate whether raloxifene-treatment would be beneficial in long-term treatment of established CIA, both regarding anti-arthritic and anti-osteoporotic properties. Female dilute brown agouti mice were ovariectomized and CIA was induced. Raloxifene or vehicle treatment was administered 5 days per week, and the clinical arthritis score was evaluated continuously. At termination, bone mineral density was analysed, paws were collected for histological examination and sera were analysed for markers of bone and cartilage turnover, as well as antibodies to type II collagen and levels of interleukin (IL)-6. Treatment with raloxifene is beneficial in long-term treatment of established CIA. It hampers the disease severity and frequency, protects the joints from destruction and protects against the development of osteoporosis. The proinflammatory cytokine IL-6 was down-regulated in raloxifene-treated mice compared with controls. The serum levels of antibodies to collagen were not affected by raloxifene-treatment. Long-term treatment with raloxifene has both anti-arthritic and anti-osteoporotic effects in established experimental postmenopausal polyarthritis.
16849504 MAPKAP kinase 2-deficient mice are resistant to collagen-induced arthritis. 2006 Aug 1 TNF-alpha is a pleiotropic cytokine considered a primary mediator of immune regulation and inflammatory response and has been shown to play a central role in rheumatoid arthritis (RA). MAPKAP kinase 2 (MK2) is a serine/threonine kinase that is regulated through direct phosphorylation by p38 MAPK, and has been shown to be an essential component in the inflammatory response that regulates the biosynthesis of TNF-alpha at a posttranscriptional level. The murine model of collagen-induced arthritis (CIA) is an established disease model to study pathogenic mechanisms relevant to RA. In this study, we report that deletion of the MK2 gene in DBA/1LacJ mice confers protection against CIA. Interestingly, the MK2 heterozygous mutants display an intermediate level of protection when compared with homozygous mutant and wild-type littermates. We show that MK2(-/-) and MK2(+/-) mice exhibit decreased disease incidence and severity in the CIA disease model and reduced TNF-alpha and IL-6 serum levels following LPS/d-Gal treatment compared with wild-type mice. Additionally, we show that levels of IL-6 mRNA in paws of mice with CIA correlate with the disease status. These findings suggest that an MK2 inhibitor could be of great therapeutic value to treat inflammatory diseases like RA.
17848187 Quantitative gait analysis as a method to assess mechanical hyperalgesia modulated by dise 2007 In the present study, azothioprine, chloroquine, D-penicillamine, methotrexate and sodium aurothiomalate (gold salt) were evaluated for possible disease-modifying effects in the adjuvant-induced arthritis model of human rheumatoid arthritis in rats. Gait analysis was used to examine the role of disease-modifying antirheumatic drugs in the development of pain. Body weights were also measured to monitor the progression of disease and the systemic antiarthritic effects of the test compounds used in this study, as well as their systemic toxicity. Our results showed that azothioprine (5 mg/kg/day), chloroquine (12.5 mg/kg/day), sodium aurothiomalate (2.5 mg/kg/day) and methotrexate (1 mg/kg/week) not only inhibited the macroscopic changes such as erythema and swelling of limbs, but also exhibited significant reversal of gait deficits seen in the untreated or saline-treated arthritic rats. No reduction in the body weights were observed in the arthritic rats treated with azothioprine, chloroquine, sodium aurothiomalate and methotrexate. D-Penicillamine (12.5 mg/kg/day), however, showed a significant reduction (P < 0.03) in the body weights of the arthritic rats over a period of 22 days; furthermore, it was unable to show any reduction in arthritic score (P < 0.1). In earlier experiments, chloroquine and methotrexate failed to suppress carageenan-induced edema, suggesting that the mode of antiarthritic action may be different from those of nonsteroidal anti-inflammatory agents. Since these disease-modifying antirheumatic drugs are reported to have an immunomodulatory role, especially the gold salt, which influences the monocyte-macrophage system, it is suggested that the observed antiarthritic effects of disease-modifying antirheumatic drugs may be partly attributed to their immunomodulatory activity.
17680722 Treatment with anti-gamma-glutamyl transpeptidase antibody attenuates osteolysis in collag 2007 Dec The effectiveness of a new antibody treatment on arthritis-associated osteolysis was studied by using CIA mice. GGT, a newly identified bone-resorbing factor, was upregulated in arthritic joints. We generated monoclonal antibodies against GGT and injected them into CIA mice. Mice treated with antibodies showed a reduction in osteoclast number and bone erosion. INTRODUCTION: Gamma-glutamyl transpeptidase (GGT) acts as a bone-resorbing factor that stimulates osteoclast formation. GGT expression has been detected in active lymphocytes that accumulate at inflammation sites, such as rheumatoid arthritis (RA). We hypothesize that GGT is an effective target for suppression of arthritis-related osteoclastogenesis and joint destruction. Here, we describe the therapeutic effect of neutralizing antibodies against GGT on joint destruction using a collagen-induced arthritis (CIA) mouse model. MATERIALS AND METHODS: GGT expression in the synovium of RA patients and CIA mice was determined by immunohistochemistry and RT-PCR. Monoclonal antibodies were generated against recombinant human GGT (GGT-mAbs) using BALB/c mice. Antibody treatment was performed by intraperitoneal injections of GGT-mAbs into CIA mice. Effects of antibody treatment on arthritis and bone erosion were evaluated by incidence score, arthritis score, and histopathological observations. The role of GGT in osteoclast development was examined by using the established osteoclastogenic culture system. RESULTS: GGT expression was significantly upregulated in inflamed synovium. Immunohistochemistry revealed that GGT was present in lymphocytes, plasma cells, and macrophages, as well as capillaries. Injection of GGT-mAbs significantly decreased the number of osteoclasts and attenuated the severity of joint destruction in CIA mice. In vitro examination showed that GGT enhanced RANKL-dependent osteoclast formation. GGT stimulated the expression of RANKL in osteoblasts and its receptor RANK in osteoclast precursors, respectively. CONCLUSIONS: This study indicates that inflamed synovial tissue-derived GGT acts as a risk factor for joint destruction and that the antibody-mediated inhibition of GGT significantly decreases osteoclast number and bone erosion in CIA mice. GGT antagonists might be novel therapeutic agents for attenuating joint destruction in RA patients.
17276893 Induction of immune tolerance by oral IVIG. 2007 Mar In the last years evidence has been provided for the importance of B cells in the pathogenesis of rheumatoid arthritis (RA). Several studies have supported the concept that humoral immunity, manifested by the production of autoantibodies, such as rheumatoid factors (RFs), plays a significant role in the course of the disease. Specific targeting of autoantibody-producing B cells, such as RF-producing B cells, should therefore be a promising new approach in the treatment of RA. We used a mouse model to induce human RF responses and asked the question whether oral treatment with the antigen (human IgG) recognized by RFs could induce immune tolerance to RF responses. Balb/c mice were orally treated with polyvalent human IgG before and after immunization with insoluble immune complexes (ICs) that triggered the induction of RFs. Serum titers of RFs were significantly reduced after both primary and booster immunization when human IgG was given as a single oral dose or continuously in drinking water. Continuous treatment with human IgG even prevented booster effects on RFs when treatment started after primary immunization. Treatment with IgG fragments provided evidence that the observed effect of human IgG was mediated by the Fc part and not the Fab part of IgG. Furthermore, transfer of spleen cells obtained from mice after oral treatment with human IgG suppressed RF responses in recipient mice. These data give promising indications that oral human IgG might represent an alternative approach for immunosuppressive B-cell targeted therapies in RA.
17907173 CXCR5- and CCR7-dependent lymphoid neogenesis in a murine model of chronic antigen-induced 2007 Oct OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with unknown etiology and only partially defined pathogenesis. The aim of this study was to establish a murine model of chronic arthritis in which the development of tertiary lymphoid tissue, a hallmark of human RA, is locally induced, and to characterize the roles of the homeostatic chemokine receptors CXCR5 and CCR7 in this process. METHODS: We developed a modified model of chronic antigen-induced arthritis (AIA) in mice with a strong bias toward inflammation. Disease pathology was assessed up to 9 months in wild-type, CXCR5-deficient, and CCR7-deficient mice by determination of knee joint swelling and cellular and humoral immune responses, as well as by histologic analysis of arthritic knee joints. RESULTS: In this novel model of AIA, mice developed organized ectopic lymphoid follicles with topologically segregated B cell and T cell areas, high endothelial venules, and germinal center formation within the chronically inflamed synovial tissue. Analysis of the initiation and progression of AIA in wild-type, CXCR5-/-, and CCR7-/- mice revealed a reduction of acute inflammatory parameters in both knockout strains as well as significantly reduced joint destruction in CXCR5-/- mice. Most importantly, the development and organization of tertiary lymphoid tissue were significantly impaired in CXCR5-deficient and CCR7-deficient mice. CONCLUSION: Our results suggest that an inflammatory microenvironment efficiently triggers lymphoid neogenesis in autoimmune diseases such as RA. Moreover, the generation of autoreactive tertiary lymphoid tissues, which is entirely dependent on homeostatic chemokines, may in turn maintain local aberrant chronic immune responses.
17097389 Childhood acquired lipodystrophy: a retrospective study. 2006 Dec OBJECTIVE: We sought to describe the clinical characteristics and complications of children with acquired lipodystrophy (LD). METHODS: We conducted a retrospective chart review at a tertiary, academic children's hospital of children clinically given a diagnosis of acquired LD between January 1997 and December 2004. RESULTS: During the study period, 23 patients were identified. Their mean age at diagnosis was 9.74 +/- 3.98 years. Of patients, 61% were girls. The length of the follow-up was 4.8 +/- 3.5 years from the time of LD diagnosis. Of patients, 30% had evidence of localized disease (7 of 23), 26% (6 of 23) had localized partial disease, and 44% (10 of 23) had generalized LD. The most common underlying diagnosis was dermatomyositis (78%), alone or in association with other autoimmune diseases (juvenile rheumatoid arthritis 17%). Panniculitis with autoimmunity was noted in 17% of the patients. More than half of the patients had at least one complication attributable to LD such as acanthosis nigricans (22%), hyperpigmentation (22%), hepatomegaly (13%), hypertension (13%), protuberant abdomen (9%), and hyperlipidemia (4%). The only predictor for development of complications was the age of diagnosis of LD, with younger age being associated with increased risk (7 vs 12 years, P = .04). LIMITATIONS: Limitations were inherent to the retrospective design. CONCLUSIONS: Childhood acquired LD is seen more frequently in the context of autoimmunity. Affected children should be monitored for the development of complications, particularly if given a diagnosis of LD at a younger age.
17038468 Potential new targets in arthritis therapy: interleukin (IL)-17 and its relation to tumour 2006 Nov Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by chronic joint inflammation and destruction. Interleukin (IL)-17 is a T cell cytokine expressed in the synovium and synovial fluid of patients with RA. IL-17 is a potent inducer of various cytokines such as tumour necrosis factor (TNF) and IL-1. IL-17 has been shown to have additive or even synergistic effects with TNF and IL-1 during the induction of cytokine expression and joint damage in vitro and in vivo. TNFalpha and IL-1 are considered powerful targets in the treatment of RA because of their leading role in driving the enhanced production of cytokines, chemokines, and degradative enzymes. Besides anti-TNF and anti-IL-1 therapies, whose clinical efficacy is now established, new targets have been proposed for RA which is not responding to conventional treatments. This paper discusses the role of IL-17 in experimental arthritis and its interrelationship with TNF and IL-1, currently the most targeted cytokines in the treatment of RA. IL-17 is involved in both initiation and progression of murine experimental arthritis. Studies have shown that IL-17 not only synergises with TNF, but also enhances inflammation and destruction independent of IL-1 and TNF. On the basis of these studies, the authors propose IL-17 as an interesting additional target in the treatment of RA.
17032248 Anti-TNF effects on destructive fibroblasts depend on mechanical stress. 2006 Nov Joint destruction in rheumatoid arthritis (RA) starts typically at sites of mechanically stressed inserts of the synovial membrane near the cartilage/bone border. In the therapy of RA, tumour necrosis factor (TNF) antagonists have rapidly emerged as a valuable class of anti-rheumatic agents that reduce joint destruction. The aim of this study was to investigate and profile genes involved in the interaction between articular movement and anti-TNF therapy in an in vitro model. Murine LS48 cells, an established substitute for invasive RA synovial fibroblasts, were cultured, stretched and/or treated with anti-TNF-alpha antibody for 24 h. RNA was isolated and gene transcript levels were determined using U74Av2 Affymetrix GeneChips to identify transcriptional events. Positive findings were verified by polymerase chain reaction (PCR). We identified 170 differentially regulated genes, including 44 of particular interest. Gene expression fell into different functional groups that can be explained by RA pathogenesis and experimental conditions. For 21 genes of the 44 of particular interest, regulation could be confirmed by real-time PCR. Remarkably, we found structural as well as functional genes differently regulated between stretched cells, anti-TNF-treated cells, and stretched cells treated with anti-TNF antibody. Additionally, we also found a large number of genes that are apparently not related to the experimental conditions. Mechanical exertion modulates gene expression and subsequently cellular response to anti-TNF therapy. Results in exerted cells correspond to current knowledge regarding RA pathogenesis and underline the relevance of our experimental approach. Finally, the central function of the interleukin-18 system in joint destruction could be confirmed by our findings.
16927760 [Ophthalmological involvement in rheumatic disease]. 2006 PURPOSE: The main objective of this study was to identify the prevalence of ocular manifestations in rheumatic patients admitted in a specialized clinic. METHODS: Information regarding rheumatic and ocular diseases was extracted from medical records system available in "Dr. I. Cantacuzino" Clinical Hospital from Bucharest. The prevalence of ocular involvement reported passively by rheumatologists (retrospective descriptive study of 375 different cases of rheumatic patients) was compared with the literature data. RESULTS: There were 45 cases of ocular manifestations. Keratoconjunctivitis sicca was noted in 16 patients with rheumatoid arthritis, two patients with systemic lupus erythematosus and one patient with scleroderma. Anterior uveitis was found in seven patients with ankylosing spondylitis, one patient with reactive arthritis, two patients with psoriatic arthritis and one patient with LES. Conjunctivitis was present in two patients with reactive arthritis. In LES ocular involvement also included four cases of retinal vasculitis. Complications clearly related to steroid therapy were nine cases of cataracts. One case with typical "bull's eye" maculopathy due to Hydroxychloroquine treatment was detected. CONCLUSIONS: The main conclusion of our study is that the rheumatic patients need to be referred to an ophthalmologist for the diagnosis and the optimal treatment of ocular involvement.
18684326 Increased susceptibility to collagen-induced arthritis in female mice carrying congenic Ci 2008 INTRODUCTION: Collagen-induced arthritis (CIA) in mice is a commonly used experimental model for rheumatoid arthritis (RA). We have previously identified a significant quantitative trait locus denoted Cia40 on chromosome 11 that affects CIA in older female mice. This locus colocalizes with another locus, denoted Pregq2, known to affect reproductive success. The present study was performed to evaluate the role of the Cia40 locus in congenic B10.Q mice and to identify possible polymorphic candidate genes, which may also be relevant in the context of RA. METHODS: Congenic B10.Q mice carrying an NFR/N fragment surrounding the Cia40/Pregq2 loci were created by 10 generations of backcrossing (N10). The congenic mice were investigated in the CIA model, and the incidence and severity of arthritis as well as the serum levels of anti-collagen II (CII) antibodies were recorded. RESULTS: Significant effects on onset, incidence, severity, and anti-CII antibody titers were observed in female mice carrying a heterozygous congenic Cia40/Pregq2 fragment of NFR/N origin, containing one or more polymorphic genes. Congenic male mice did not show increased incidence of CIA, but males carrying a heterozygous fragment showed a significant increase in severity in comparison with wildtype B10.Q males (littermates). CONCLUSION: The Cia40/Pregq2 locus at chromosome 11 contains one or more polymorphic genes of NFR/N origin that significantly influence both incidence and severity of CIA in heterozygous congenic mice of the B10.Q strain. The major polymorphic candidate genes for the effects on CIA are Cd79b, Abca8a, and Map2k6. The congenic fragment also contains polymorphic genes that affect reproductive behavior and reproductive success. The Sox9 gene, known to influence sex reversal, is a candidate gene for the reproductive phenotype.
16882787 Smoking rates and the state of smoking interventions for children and adolescents with chr 2006 Aug Engaging in smoking is particularly risky for children and adolescents with chronic illness whose health status is already compromised because of disease- and treatment-related complications. Yet, some of these youngsters smoke at rates at least comparable to those of their healthy peers. To date, few randomized smoking-prevention and cessation trials have been conducted in children with chronic medical problems. In this review we report on the smoking rates among youngsters with chronic illness, identify specific disease- and treatment-related complications that can be exacerbated by smoking, examine risk factors associated with tobacco use among medically compromised youngsters, and review smoking interventions that have been conducted to date with pediatric populations in the health care setting. The following chronic illnesses are included in this review: asthma, cystic fibrosis, cancer, sickle cell disease, juvenile-onset diabetes, and juvenile rheumatoid arthritis. Objectives for a tobacco-control agenda and recommendations for future tobacco studies in chronically ill pediatric populations are provided. Finally, tobacco counseling strategies are suggested for clinicians who treat these youngsters in their practices.
17266088 Economic impact of juvenile idiopathic arthritis. 2007 Feb 15 OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a potentially devastating chronic pediatric disease. Although high costs have been well described in adult arthritis, little is known about the economic impact of JIA. Our objective was to describe direct medical costs for children with JIA compared with controls. METHODS: Consecutive clinic attendees (n = 155) with JIA were enrolled from 2 tertiary referral pediatric centers. Outpatient clinic controls without JIA (n = 181) were recruited at the respective centers. Data on direct medical costs were obtained at 3-month intervals. Average annualized direct medical costs were calculated, expressed in 2005 Canadian dollars. RESULTS: The total difference in annualized average direct medical costs for children with JIA versus controls was $1,686 (95% confidence interval $875, $2,500). JIA subjects had substantially higher costs concerning medication use, visits to specialists and allied health care professionals, and diagnostic tests. Multiple linear regression models for the JIA sample revealed that higher active joint count was independently associated with greater total direct medical costs. Also, JIA type was a predictor of greater direct costs, with higher costs for patients with polyarthritis (rheumatoid factor positive or negative) or systemic JIA. CONCLUSION: The economic impact of JIA is substantial, and higher active joint count is independently associated with greater costs. This may be of particular significance given the emergence of new, costly medications for use in JIA. Insights into the relationship between disease activity and cost in JIA should assist policy makers regarding resource allocation in the setting of competing demands. Ultimately, decisions regarding access to therapies should be considered in terms of overall cost-benefit ratios.
16431337 NFAT transcription factors--new players in the pathogenesis of inflammatory arthropathies? 2006 Feb Inflammatory arthropathies are characterized by major changes in gene expression, which-ultimately-result from differential activities of intracellular signaling pathways and their associated inducible transcription factors. The nuclear factor of activated T cells' (NFAT) family of transcription factors plays diverse roles in a variety of processes in the immune system and other tissues. Preliminary evidence has recently emerged implicating NFAT family members directly in the pathogenesis of inflammatory arthropathies. Specific anti-NFAT drug therapy may add to the pharmacologic armamentarium against rheumatoid arthritis, other inflammatory arthropathies, and related autoimmune disorders.
18936235 Blockade of tumor necrosis factor in collagen-induced arthritis reveals a novel immunoregu 2008 Oct 27 IL-17 is implicated in the pathogenesis of rheumatoid arthritis (RA) and has previously been shown to be induced by tumor necrosis factor (TNF) in vitro. The aim of this study was to assess the impact of TNF inhibition on IL-17 production in collagen-induced arthritis, a model of RA. TNF blockade using TNFR-Fc fusion protein or anti-TNF monoclonal antibody reduced arthritis severity but, unexpectedly, expanded populations of Th1 and Th17 cells, which were shown by adoptive transfer to be pathogenic. Th1 and Th17 cell populations were also expanded in collagen-immunized TNFR p55(-/-) but not p75(-/-) mice. The expression of IL-12/IL-23 p40 was up-regulated in lymph nodes (LN) from p55(-/-) mice, and the expansion of Th1/Th17 cells was abrogated by blockade of p40. Treatment of macrophages with rTNF also inhibited p40 production in vitro. These findings indicate that at least one of the ways in which TNF regulates Th1/Th17 responses in arthritis is by down-regulating the expression of p40. Finally, although TNF blockade increased numbers of Th1 and Th17 cells in LN, it inhibited their accumulation in the joint, thereby providing an explanation for the paradox that anti-TNF therapy ameliorates arthritis despite increasing numbers of pathogenic T cells.
18387513 Modulation of adjuvant arthritis in the rat by 2-methoxyestradiol: an effect independent o 2008 May Angiogenesis is a prominent feature in rheumatoid arthritis. 2-methoxyestradiol (2ME2) inhibits endothelial cell proliferation, and angiogenesis in vivo. We evaluated the effect of 2ME2 in rats with adjuvant arthritis (AA), an autoimmune T-cell-dependent polyarticular arthritis induced by immunization with Mycobacterium organisms. Rats were immunized with Mycobacterium butyricum and arthritis was assessed clinically, by radiolabeled blood neutrophil (PMNL) migration to joints and by histology. Treatment with 2ME2 (30 mg/kg/d or 100 mg/kg/d) from day 6 post-immunization inhibited arthritis severity on day 14 (vehicle clinical score=11.2; 2ME2 groups=7-8, p<0.05). When treatment was delayed until signs of clinical arthritis on day 10 post-immunization, 2ME2 treatment still inhibited arthritis severity. PMNL migration to the joints was significantly inhibited (by 35-40%; p<0.01) by early 2ME2 treatment (day 6-14). Treatment with 2ME2 inhibited PMNL migration to dermal inflammation induced by TNF-alpha but not by LPS or C5a. Joint histology revealed decrease in leukocyte infiltration and especially in cartilage damage. However, synovial vascularity was not affected by 2ME2 treatment. The marked splenomegaly, splenitis and lymphoid hyperplasia associated with AA were prevented by 2ME2 therapy. Furthermore, the ex vivo proliferative response to mycobacterial antigen (PPD) of lymphocytes from 2ME2-treated rats with AA was markedly diminished, although response to mitogens was unaffected. Thus 2ME2 has anti-arthritic properties with a disease-modifying action, separate from its anti-angiogenic properties. The selective inhibition of TNF-alpha-induced leukocyte recruitment, lymphoid hyperplasia and attenuated recall response to antigen suggests both immunomodulatory and anti-inflammatory actions of 2ME2.
18688674 Reactive and undifferentiated arthritis in North Africa: use of PCR for detection of Chlam 2009 Jan Little is known about the possible role of Chlamydia in patients with reactive or unclassified arthritis in North Africa. This study used polymerase chain reaction (PCR) to survey this population. In addition, we compared the results in three different laboratories for PCR analyses for Chlamydia trachomatis (Ct) in synovial fluid (SF) and tissue (ST) from these North African patients with reactive arthritis (ReA), undifferentiated arthritis (UA), and in rheumatoid arthritis (RA) and osteoarthritis (OA). Eight ReA (six posturethritic, two postenteritic), 23 UA, 13 OA, and 12 RA patients were studied in Algeria, Morocco, and Tunisia. Serum, SF, and ST were obtained from each patient. Ct-PCR was performed in the three different laboratories and compared to Ct-serology [microimmunofluorescence (MIF) and anti-hsp60 enzyme-linked immunosorbent assay (ELISA)] performed in one laboratory. The rate of Ct-PCR positivity in SF/ST was low: none out of the eight ReA and three out of 23 UA patients. In the controls, Ct DNA was detected in two OA SF and in one RA SF. There was no concordance for Ct-PCR positivity between the three laboratories. MIF suggested previous Ct infection (IgG-positive) in two out of five posturethritic ReA, none out of one postenteritic ReA, one out of 17 UA, and nine out of 21 RA/OA patients tested. No MIF-positive patient was PCR-positive from SF or ST. However, anti-hsp60 IgG was detected in all four out of four patients positive by PCR and in 11 out of 44 PCR-negative patients (p = 0.002). In this multinational comparative study, the rate of Ct-PCR-positive synovial specimens in North African ReA/UA patients was low. Concordance among the three PCR testing laboratories was poor indicating the need for test standardization. All Ct-PCR-positive patients were found positive by anti-hsp60 IgG serology.