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ID PMID Title PublicationDate abstract
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.
16014552 Multiplexed immunoassay for detection of rheumatoid factors by FIDISTM technology. 2005 Jun Our objective was to (i) compare FIDIS Rheuma, a new multiplexed immunoassay designed for simultaneous detection of IgM class rheumatoid factors (RF) directed against Fc determinants of IgG from humans and animals, with agglutination and ELISA (conventional methods) and (ii) evaluate the clinical sensitivity and specificity of biological markers for rheumatoid arthritis (RA). To do this, FIDIS technology was employed using the Luminex system. It consists of distinct color-coded microsphere sets, a flow cytometer, and digital signal processing hardware and software. Agglutination and ELISA tests were performed with commercial kits. The study included 134 samples from RA patients and 105 from healthy blood donors. For human specificity, we compared FIDIS with latex agglutination and ELISA. Relative sensitivities were 98.9% and 88.5% and specificities were 90.2% and 94.6%, respectively. For animal specificity, we compared FIDIS with Waaler-Rose and ELISA. The results were 84.9% and 71.9% for the sensitivities and 97.5% and 98.4% for the specificities, respectively. Detection of IgG anti-CCP by ELISA and IgG antikeratin by immunofluorescence was also determined in order to compare their clinical sensitivity and specificity with IgM-RF, according to the method used. The results were: IgG anti-CCP 72.3%, 97.2%; IgG antikeratin 36.6%, 100%; latex agglutination 66.4%, 97.2%; Waaler-Rose 55.9%, 96.3%; FIDIS human 73.9%, 92.1%; FIDIS animal 49.2%, 97.2%; ELISA human 93.2%, 95.5%; and ELISA animal 74.6%, 91.3%. The results showed the efficiency of FIDIS with analytical performance equivalent to the conventional methods, but having the advantage of giving quantitative results (IU/mL).
15965689 Revision of the Sheehan total knee arthroplasty. 2005 Aug The use of the Sheehan knee prosthesis extended from 1971 to 2002. It incorporated a semi-constrained hinge with intra-medullary stems cemented into the femur and tibia. While some authors have reported excellent short-term results, others have reported revision rates of up to 31% at 5--10 years. The aim of this study was to review the senior author's experience in revising these arthroplasties. We review 54 Sheehan total knee replacements and discuss the difficulties encountered during first and subsequent revisions and the often-complex reconstruction techniques used to overcome these.
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.
16539817 Modification of neutrophil function by plasma of rheumatoid arthritis patients treated wit 2006 Jan OBJECTIVE: To examine whether the release of superoxide anions from neutrophils of healthy donors was affected when incubated with plasma from infliximab-treated rheumatoid arthritis (RA) patients. METHODS: Fifteen consecutive seropositive RA patients were treated with 3mg/kg infliximab on weeks 0, 2, 6, and 14. Disease activity was assessed by DAS28 score and by IL-6 level. Neutrophils from healthy donors were incubated with plasma drawn before each infliximab treatment. PMA-stimulated superoxide release was measured by the ferricytochrome C reduction method. RESULTS: 53% of the patients had a favorable clinical response. IL-6 levels showed a significant decline at week two, with a gradual increase thereafter. Treatment with infliximab did not change the superoxide production. However, when the group was divided retrospectively to responders (DeltaDAS28 > -1.2) and non-responders (DeltaDAS28 < -1.2), two different patterns were seen, although the pre-treatment levels were similar: Among the responders IL-6 remained low at its 2 weeks level till week 14, while in the non responders IL-6 increased 3 times (P < 0.03) from week 2 to 14. The responders showed mild, but continuous, reduction of superoxide release, while in the non-responders it increased significantly from week 2 on. CONCLUSION: The reduction in IL-6 in RA sera following anti-TNFalpha therapy has little influence on the capacity of these sera to stimulate healthy neutrophils to produce superoxide, suggesting the existence of non-TNFalpha non-IL-6 dependent neutrophil-stimulating mediators in RA sera. The increasing level of IL-6 among the non-responders after initial dramatic decline might represent an escape phenomenon, possibly caused by alternative mediator(s). Clinically, this IL-6 "escape" might be used as a tool for early identification of responders from non-responders.
15982172 Navicular drop measurement in people with rheumatoid arthritis: interrater and intrarater 2005 Jul BACKGROUND AND PURPOSE: Navicular drop (ND) measurement may be a valuable examination technique for patients with rheumatoid arthritis (RA). However, no data exist on reliability for this technique in patients with RA. The purposes of this study were: (1) to determine interrater and intrarater reliability of ND measurements in people with RA, (2) to compare ND values of people with RA with published normative data, and (3) to investigate ND measurement error associated with the use of skin markings. SUBJECTS: Ten women (20 feet) with RA consented to participate. METHODS: Patients completed demographic and function questionnaires. Navicular height (NH) measurements were taken by 2 physical therapists and 1 physical therapist student, following four 1-hour training sessions, using standardized methods and a digital height gauge. Four different NH measurements were taken 3 times on each foot by each of the 3 examiners during a morning session and then repeated during an afternoon session on the same day. Navicular drop values were calculated, including ND1 (as reported in the literature), ND2 (compensating for skin error), and ND3 (single-limb stance). Intraclass correlation coefficients (ICCs) and standard errors of measurement (SEMs) were used to establish reliability. RESULTS: Means (+/-SD) for each ND measure for sessions 1 and 2, respectively, were as follows: ND1=8.36+/-5.29 mm and 8.29+/-5.24 mm, ND2=9.95+/-5.44 mm and 9.57+/-5.37 mm. The ICCs (2,1 and 2,k, respectively) for all interrater measurements ranged from .67 to .92 (SEM=2.0-3.3 mm) and from .85 to .97 (SEM=1.1-2.0 mm). The ICCs (2,1 and 2,k, respectively) for intrarater measurements ranged from .73 to .95 (SEM=1.3-2.8 mm) and from .90 to .98 (SEM=0.7-1.6 mm). Paired t tests showed the means of ND1 and ND2 for each examiner and for both sessions were significantly different. DISCUSSION AND CONCLUSION: The results suggest that ND measurements for people with RA can be taken reliably by clinicians with varied experience. The ND values for our subjects were slightly greater than reported normal values of 6 to 8 mm. Error associated with skin markings was statistically significant for all sessions and examiners.
17181916 Ultrasound imaging for the rheumatologist V. Ultrasonography of the ankle and foot. 2006 Sep Ultrasonography (US) is a useful tool for imaging, which can be used for the assessment of joints and periarticular structures in all rheumatological disorders. In patients with pain and/or swelling of the ankle and foot, US provides information about the presence of joint effusion, synovitis, tenosynovitis, tendinosis, and tendons tears, helping in the differential diagnosis between joint or tendon/enthesis involvement. Moreover, US allows clinicians to monitor and guide needle positioning to inject pharmaceutical substances more safely and effectively even in hard-to-reach sites. US represents an accurate, safe and low-cost technique that can be used for the examination of the ankle and foot in rheumatic disorders.
17153844 Cigarette smoking and autoimmune disease: what can we learn from epidemiology? 2006 Cigarette smoking has been causally linked to the development of multiple autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Graves' hyperthyroidism, and primary biliary cirrhosis, among others. We review the known biologic effects of cigarette smoke, in particular its actions on the immune system, and the epidemiologic evidence associating smoking with increased risk of each of these autoimmune diseases. Interactions between cigarette smoking and genetic and immunologic factors, such as the human leukocyte antigen (HLA)-shared epitope, rheumatoid factor, anti-cyclic citrullinated peptide antibodies, and anti-double stranded DNA antibodies, may point to mechanisms in disease pathogenesis.
16339293 Pharmacoeconomic study of patients with chronic inflammatory joint disease before and duri 2006 Jul OBJECTIVE: To evaluate medical and work disability costs for patients with chronic inflammatory joint disease during one year before and one year after institution of infliximab treatment in routine clinical practice. METHODS: Starting from 1999, clinical and laboratory variables for patients treated with biological agents for inflammatory rheumatic diseases were systematically recorded at Helsinki University Central Hospital. From this database clinical information was collected on 96 patients in whom infliximab was started during the period 1999 to 2001. Economic analyses were based on costs incurred because of outpatient and inpatient visits, orthopaedic operations, drugs used, and days on sickness or rehabilitation allowance. Medical and work disability costs were calculated separately for the one year period before (period I) and the one year period after institution of infliximab (period II). RESULTS: Of the study group of 96 patients (arthritis duration 16 years (range 3 to 43)), 74 completed one year of infliximab treatment. Their clinical and laboratory variables improved significantly. The mean increase in medical costs during period II was euro12 015 (95% confidence interval, 6496 to 18,076). A minimal decrease in work disability costs occurred-mean decrease euro130 (-1268 to 1072). CONCLUSIONS: One year treatment with infliximab in patients with longstanding aggressive arthritis showed a good clinical effect but raised medical costs significantly. Work disability costs failed to show a substantial decrease. Starting infliximab in the earlier stages of chronic arthritis could in the long term prevent work disability and thus decrease the total cost to society.
17977211 Study of P53 in peripheral blood and synovial mononuclear cells of rheumatoid arthritis an 2005 Over expression of P53 has been described in many inflammatory conditions including rheumatoid arthritis (RA) and osteoarthritis (OA) as a protective mechanism to induce apoptosis of synovial cells. Lack of P53 function through mutation in human synoviocytes increases the development of normal synovial fibroblasts into transformed aggressive synovial fibroblasts. P53 levels were determined in supernatant of cultured mononuclear cells (MCs) isolated from peripheral blood (PBMCs) of patients with RA (n = 10) and OA (n = 10) as well as 10 normal healthy controls (C). P53 levels were also determined in supernatants of MCs isolated from synovial fluid (SFMCs) of RA and OA patients. Results of this work revealed that P53 level was significantly higher in PBMCs supernatant of RA group than those of both (C) and (OA) groups (P = 0.022). P53 level was non-significantly higher in SFMCs supernatant of RA than OA group. Significantly higher levels of P53 was detected in SFMCs culture supernatant than that of PBMCs within each RA (P = 0.003) and OA (P = 0.001) group. Results also showed a significantly positive correlation between P53 levels (in both PBMCs and SFMCs) and the disease activity score (DAS) in RA group (P = 0.01, P = 0.02 respectively) while insignificantly positive correlations between P53 level (in both PBMCs and SFMCs) and radiological grading of OA group were obtained. These results indicate that mutations and consequent dysfunction of P53 gene may result in chronic inflammation and hyperplasia in RA patients. In conclusion, gene therapy targeting P53-dependent pathway could be a promising therapy for RA and OA diseases.
16915399 Kinematic adaptation of locomotor pattern in rheumatoid arthritis patients with forefoot i 2007 Jan Rheumatoid arthritis (RA) is a leading cause of disability, which affects primarily the forefoot. Moreover, the forefoot is the final ground body interface for transmitting forces produced by the plantar flexors in order to move the body forward. Therefore, a dysfunction in patients with arthritis might induce important changes in gait, such as modifications in the coordination between legs to correct a reduced range of motion (ROM) and to produce smooth stride motions. First, we wanted to investigate the modifications of gait parameters in order to get a deeper understanding of the locomotor adaptation after a distal joint impairment. Second, we wanted to extract the mechanisms used to compensate for these impairments. In order to carry out this study, RA patients with forefoot impairment and healthy subjects were asked to walk along a straight line at two different velocities and were recorded by a motion analysis system. Patients were able to produce an efficient pattern despite a reduction of the ROM of the forefoot. At normal speed, the substantial modification of the locomotor pattern was linked to the adaptation of the lower-limb segment coordination and to the loss of ROM. Compensative mechanisms are the results of an efficient adaptation that offset the effect of the lesions. In contrast, at high speed, all of the kinematic modifications observed at natural speed vanished. It seems that pain and its associated sensory signals help to update the motor command and compel patients to adjust the descending command to the altered representation of distal mobility. Finally, the mechanical consequences of these changes are of particular interest since different levels of force exerted at the hip, knee and ankle might result in a supplementary structural alteration of these joints.
15781585 A role for fungal {beta}-glucans and their receptor Dectin-1 in the induction of autoimmun 2005 Mar 21 A combination of genetic and environmental factors can cause autoimmune disease in animals. SKG mice, which are genetically prone to develop autoimmune arthritis, fail to develop the disease under a microbially clean condition, despite active thymic production of arthritogenic autoimmune T cells and their persistence in the periphery. However, in the clean environment, a single intraperitoneal injection of zymosan, a crude fungal beta-glucan, or purified beta-glucans such as curdlan and laminarin can trigger severe chronic arthritis in SKG mice, but only transient arthritis in normal mice. Blockade of Dectin-1, a major beta-glucan receptor, can prevent SKG arthritis triggered by beta-glucans, which strongly activate dendritic cells in vitro in a Dectin-1-dependent but Toll-like receptor-independent manner. Furthermore, antibiotic treatment against fungi can prevent SKG arthritis in an arthritis-prone microbial environment. Multiple injections of polyinosinic-polycytidylic acid double-stranded RNA also elicit mild arthritis in SKG mice. Thus, specific microbes, including fungi and viruses, may evoke autoimmune arthritis such as rheumatoid arthritis by stimulating innate immunity in individuals who harbor potentially arthritogenic autoimmune T cells as a result of genetic anomalies or variations.
16339574 Aberrant expression of the autoantigen heterogeneous nuclear ribonucleoprotein-A2 (RA33) a 2005 Dec 15 Human TNF-alpha transgenic (hTNFtg) mice develop erosive arthritis closely resembling rheumatoid arthritis (RA). To investigate mechanisms leading to pathological autoimmune reactions in RA, we examined hTNFtg animals for the presence of RA-associated autoantibodies including Abs to citrullinated epitopes (anti-cyclic citrullinated peptide), heterogeneous nuclear ribonucleoprotein (hnRNP)-A2 (anti-RA33), and heat shock proteins (hsp) (anti-hsp). Although IgM anti-hsp Abs were detected in 40% of hTNFtg and control mice, IgG anti-hsp Abs were rarely seen, and anti-cyclic citrullinated peptide Abs were not seen at all. In contrast, >50% of hTNFtg mice showed IgG anti-RA33 autoantibodies, which became detectable shortly after the onset of arthritis. These Abs were predominantly directed to a short epitope, which was identical with an epitope previously described in MRL/lpr mice. Incidence of anti-RA33 was significantly decreased in mice treated with the osteoclast inhibitor osteoprotegerin and also in c-fos-deficient mice lacking osteoclasts. Pronounced expression of hnRNP-A2 and a smaller splice variant was seen in joints of hTNFtg mice, whereas expression was low in control animals. Although the closely related hnRNP-A1 was also overexpressed, autoantibodies to this protein were infrequently detected. Because expression of hnRNP-A2 in thymus, spleen, brain, and lung was similar in hTNFtg and control mice, aberrant expression appeared to be restricted to the inflamed joint. Finally, immunization of hTNFtg mice with recombinant hnRNP-A2 or a peptide harboring the major B cell epitope aggravated arthritis. These findings suggest that overproduction of TNF-alpha leads to aberrant expression of hnRNP-A2 in the rheumatoid joint and subsequently to autoimmune reactions, which may enhance the inflammatory and destructive process.
16265690 Skin cancer, rheumatoid arthritis, and tumor necrosis factor inhibitors. 2005 Nov OBJECTIVE: To determine the rates of reported non-melanoma skin cancer (NMSC) in a large cohort of patients with rheumatoid arthritis (RA) in comparison to patients with osteoarthritis (OA) and to determine risk factors for the development of NMSC in patients with RA. METHODS: Self-reported information from 15,789 patients with RA and 3,639 patients with OA were collected through semi-annual questionnaires since 1999. Survival analyses were used to determine incidence rates for NMSC among patients with RA and OA. Multivariate Cox proportional hazard models were used to estimate hazard ratios (HR) for the development of NMSC. Separate analyses were performed for patients with RA to explore associations between use of immunosuppressive medication and development of NMSC. RESULTS: The crude (unadjusted) incidence rate for reported NMSC among patients with RA and OA were 18.1 and 20.4 per 1000 patient years, respectively. OA patients were older, more likely to be Caucasian, and had higher past incidence of NMSC. Age, male sex, Caucasian race, and history of NMSC prior to entry into the database were associated with an increased risk of NMSC in multivariate Cox proportional hazard models. After adjustment for covariates, RA was associated with an increased risk of NMSC (HR 1.19, p = 0.042). Among RA patients, the development of NMSC was associated with use of prednisone (HR 1.28, p = 0.014) and tumor necrosis factor (TNF) inhibitors alone or with concomitant methotrexate (HR 1.24, p = 0.89 and HR 1.97, p = 0.001, respectively) in addition to established risk factors including fair skin, age, male sex, and previous history of NMSC. No association was found between use of methotrexate or leflunomide and development of NMSC (HR 1.12, p = 0.471, HR 0.83, p = 0.173, respectively). CONCLUSION: In this large, national cohort, RA was associated with an increased risk for development of NMSC. Among patients with RA, use of TNF inhibitors and prednisone were associated with an increased risk of NMSC.
15562139 Use of macrolides and tetracyclines for chronic inflammatory diseases. 2005 Jan OBJECTIVE: To review the efficacy of macrolides and tetracyclines in several chronic inflammatory conditions. DATA SOURCES: Searches of MEDLINE (1966-March 2004) and an extensive bibliography search were undertaken. Key terms included acne, blepharitis, cardiovascular disease, cystic fibrosis, periodontitis, rosacea, and rheumatoid arthritis. STUDY SELECTION AND DATA EXTRACTION: Data were obtained primarily from randomized placebo-controlled trials upon which key recommendations are based. DATA SYNTHESIS: Antibiotics are often prescribed for months or even years for treatment of chronic inflammatory conditions such as acne, blepharitis, cardiovascular disease, cystic fibrosis, periodontitis, rosacea, and rheumatoid arthritis. Randomized controlled trials have shown that azithromycin is useful in the management of cystic fibrosis and the tetracyclines are beneficial in the management of rheumatoid arthritis, acne, blepharitis, and periodontitis. Several large, randomized controlled trials have failed to show any benefit of macrolides in the secondary prevention of cardiovascular disease. No randomized placebo-controlled clinical trials have been performed to assess the efficacy of macrolides or tetracyclines in patients with rosacea. CONCLUSIONS: The use of tetracyclines and macrolides for rosacea is based primarily on anecdotal reports or open-label trials. Limited clinical trials support the use of tetracyclines or macrolides in acne, blepharitis, periodontitis, rheumatoid arthritis, and cystic fibrosis. Trials to date do not support the use of antibiotics for secondary prevention of cardiovascular disease.
17062647 Rheumatoid synovial endothelial cells produce macrophage colony-stimulating factor leading 2007 Apr OBJECTIVES: Periarticular osteoporosis and joint destruction are major complications in rheumatoid arthritis (RA), caused by osteoclast-mediated bone resorption. However, the mechanisms of monocyte/osteoclast maturation and role of RA endothelial cells (RAECs) in the control of osteoclastogenesis remain unclear. The present study was designed to determine the most important factors that influence monocyte accumulation and osteoclast formation among the many factors produced by RAEC. METHODS: We analysed the expression profiles of various genes in human endothelial cells from various organs (RA synovium, umbilical vein, skin, liver sinusoid, renal glomerulus and brain) using oligonucleotide microarrays. Specifically, up-regulated gene in RAECs was assessed by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and immunostaining of RA synovia. Migration of monocytes was assessed by the chemotactic chamber EZ-TAXIScan. Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell (MNC) formation was observed by microscopy. RESULTS: Among many epithelial-expressed factors, macrophage colony-stimulating factor (M-CSF) gene was abundantly expressed specifically in RAECs. Genes of fibroblast growth factor-2, interleukin-6 and osteoprotegerin were also overexpressed in RAECs. Migration of monocytes and osteoclast formation in co-cultures promoted by culture supernatants of RAECs were inhibited by M-CSF neutralizing antibody. CONCLUSIONS: M-CSF produced by RAECs is involved in osteoclastogenesis from monocytes, migration and TRAP-positive MNC formation.
15805202 Long-term results of the modified Hoffman procedure in the rheumatoid forefoot. 2005 Apr BACKGROUND: Rheumatoid arthritis commonly affects the forefoot, causing metatarsalgia, hallux valgus, and deformities of the lesser toes. Various types of surgical correction have been described, including resection of the lesser-toe metatarsal heads coupled with arthrodesis of the great toe, resection arthroplasty of the proximal phalanx or metatarsal head, and metatarsal osteotomy. We report the results at an average of five and a half years following thirty-seven consecutive forefoot arthroplasties performed in twenty patients by one surgeon using a technique involving resection of all five metatarsal heads. METHODS: All patients were treated with the same technique of resection of all five metatarsal heads through three dorsal incisions. All surviving patients were asked to return for follow-up, which included subjective assessment (with use of visual analogue pain scores, AOFAS [American Orthopaedic Foot and Ankle Society] foot scores, and SF-12 [Short Form-12] mental and physical disability scores), physical examination, and radiographic evaluation. RESULTS: All results were satisfactory to excellent in the short term (six weeks postoperatively), and no patient sought additional surgical treatment for the feet. A superficial infection subsequently developed in two feet, and two feet had delayed wound-healing. At an average of 64.9 months postoperatively, the average AOFAS forefoot score was 64.5 points and the average hallux valgus angle was 22.3 degrees . There were no reoperations. CONCLUSIONS: Resection of all five metatarsal heads in patients with metatarsalgia and hallux valgus associated with rheumatoid arthritis can be a safe procedure that provides reasonable, if rarely complete, relief of symptoms.
16835876 Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat model 2006 Oct Many studies have been carried out in recent years on the pharmacological effects of nigella sativa seeds that have uncovered their antiinflammatory and immunological effects. The objective of this study was to explore the antiinflammatory effects of thymoquinone on arthritis in rat models. Rats with arthritis induced by Freund's incomplete adjuvant were assigned into five groups: group 1: controls 0.9% NaCl (n = 7); group 2: 2.5 mg/kg thymoquinone (n = 7); group 3: 5 mg/kg thymoquinone (n = 7); group 4: Bacilli Chalmette Guerin (BCG) 6 x 10(5) CFU (n = 7); group 5: methotrexate 0.3 mg/kg (n = 7). Signs of inflammation on the claw and radiological signs were searched for and TNF-alpha and IL-1beta were measured. The results of control and other groups were compared. As a result, thymoquinone, confirmed clinically and radiologically, suppressed adjuvant-induced arthritis in rats.
16734620 Hydroxychloroquine potentiates Fas-mediated apoptosis of rheumatoid synoviocytes. 2006 Jun Inadequate apoptosis may contribute to the synovial hyperplasia associated with rheumatoid arthritis (RA). The Fas-associated death domain protein (FADD)-like interleukin (IL)-1beta-converting enzyme (FLICE)-inhibitory protein (FLIP), which is an apoptotic inhibitor, has been implicated in the resistance to Fas-mediated apoptosis of synoviocytes. This study investigated whether hydroxychloroquine (HCQ), an anti-rheumatic drug, induces the apoptosis of rheumatoid synoviocytes, and modulates the expression of FLIP. Fibroblast-like synoviocytes (FLS) were prepared from the synovial tissues of RA patients, and were cultured with various concentrations of HCQ in the presence or absence of the IgM anti-Fas monoclonal antibodies (mAb) (CH11). Treatment with HCQ, ranging from 1 to 100 microM, induced the apoptosis of FLS in a dose- and time-dependent manner. The increase in synoviocytes apoptosis by HCQ was associated with caspase-3 activation. A combined treatment of HCQ and anti-Fas mAb increased FLS apoptosis and caspase-3 activity synergistically, compared with either anti-Fas mAb or HCQ alone. The Fas expression level in the FLS was not increased by the HCQ treatment, while the FLIP mRNA and protein levels were decreased rapidly by the HCQ treatment. Moreover, time kinetics analysis revealed that the decreased expression of FLIP by HCQ preceded the apoptotic event that was triggered by HCQ plus anti-Fas mAb. Taken together, HCQ increases the apoptosis of rheumatoid synoviocytes by activating caspase-3, and also sensitizes rheumatoid synoviocytes to Fas-mediated apoptosis. Our data suggest that HCQ may exert its anti-rheumatic effect in rheumatoid joints through these mechanisms.
16829303 Human Fc receptors: critical targets in the treatment of autoimmune diseases and transplan 2006 Jul The receptors for the Fc region of immunoglobulins (FcR) are members of the immunoglobulin superfamily. They are expressed on various hematopoietic cells and constitute a link between humoral and cell-mediated immunity. The activation and downmodulation of immune responses are controlled by signals from activating and inhibitory FcR, expressed on the surface of immune cells. The signaling regions, defined as immunoreceptor-tyrosine-based activation motif and immunoreceptor-tyrosine-based inhibitory motif, are contained within the cytoplasmic domain of FcR or of the adaptor proteins associated with FcR. Activating and inhibitory FcR are usually coexpressed on the surface of the same cell and coengaged by the same ligand, functioning in concert to keep a balanced immune response. Impairment of the functional balance between activating and inhibitory FcR leads either to hyperactivity to foreign and self antigens or to unresponsiveness as seen in many autoimmune diseases and infections. Pathologic conditions in which immunoglobulin-FcR interactions play a major role, as well as the outcome of treatment with intravenous immunoglobulin and monoclonal antibodies, may be influenced by targeting FcR.