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ID PMID Title PublicationDate abstract
17021714 Adenosine and cytokine levels following treatment of rheumatoid arthritis with dipyridamol 2006 Nov Adenosine can suppress the release of tumour necrosis factor-alpha (TNF-alpha) from activated monocytes and macrophages, and may contribute to the anti-inflammatory activities of methotrexate and sulphasalazine. Dipyridamole inhibits the cellular uptake and metabolism of adenosine and we have, therefore, examined the effects of dipyridamole in patients with rheumatoid arthritis in an attempt to alleviate their symptoms. Forty patients aged 18-75 years were randomised to receive dipyridamole 400 mg/day or placebo. Blood samples were taken at baseline and at monthly intervals for 6 months. Purines were determined by HPLC and cytokines by ELISA. After 3 months of treatment there were significant reductions in neopterin levels and in the modified Health Assessment Questionnaire score, but these were not maintained. Dipyridamole had no effect on disease severity or the levels of purine metabolites, interleukin-1beta (IL-1beta), IL-6, TNF-alpha, lipid peroxidation products, erythrocyte sedimentation rate or C-reactive protein. In conclusion, rheumatoid arthritis patients showed no clinical improvement following treatment with dipyridamole for 6 months.
16572444 High-resolution multipinhole single-photon-emission computed tomography in experimental an 2006 Apr OBJECTIVE: To image inflammatory arthritic lesions in experimental arthritis and in patients with arthritis, using a newly developed high-resolution multipinhole single-photon-emission computed tomography (MPH-SPECT) technique. METHODS: Six interleukin-1 receptor antagonist-deficient mice with arthritis of the front and back paws and 2 control BALB/c mice were imaged with MPH-SPECT and scored macroscopically for arthritis. SPECT imaging was performed with a conventional gamma camera upgraded with a pyramidal lead collimator affixed with MPH apertures. All images were reconstructed, and uptake in the paws was quantified in counts/weight and injected activity. To transfer the imaging technique to humans we examined the clinically dominant hand of 6 individuals (3 with established rheumatoid arthritis [RA], 1 with early RA, 1 with osteoarthritis, and 1 healthy control). RESULTS: MPH-SPECT images were high-resolution 3-dimensional tomographic images, which allowed exact localization and quantifiable observation of increased bone metabolism. MPH-SPECT counts of inflamed joints in mice correlated with macroscopic scoring and histologic joint analysis postmortem. In humans, MPH-SPECT images depicted a detailed visualization of tracer accumulation in bony structures of hand and finger joints, and were also capable of imaging increased bone metabolism that had appeared normal with other imaging modalities, e.g., magnetic resonance imaging. CONCLUSION: The MPH-SPECT technique represents a new diagnostic tool in the detection of bone pathology in small-animal arthritis research. Compared with macroscopic scoring, this new method provides a more objective and higher-precision quantifiable measurement of bone reaction, allowing visualization of inflammatory processes of the whole skeleton in vivo. These results suggest that MPH-SPECT may be useful as a diagnostic instrument for monitoring experimental arthritis, with further potential for use in human studies of RA.
17852775 Increased platelet activation markers in rheumatoid arthritis: are they related with subcl 2008 Mar Atherosclerotic cardiovascular mortality is increased in rheumatoid arthritis (RA) patients. We evaluated the association of inflammatory response with platelet, endothelial, coagulation activation parameters; and subclinical atherosclerosis in RA patients. We included 27 RA patients (21 female; six male) and 19 healthy subjects (14 female; five male). Disease activity score (DAS28) in RA patients was calculated; and patients were divided into two groups as active and inactive. Flow cytometry was used to determine platelet CD62P expression, platelet microparticles (PMP), platelet-monocyte (PMC) and platelet-neutrophil complexes (PNC). Plasma E-selectin, thrombin-antithrombin (TAT) complex, and serum sCD40L levels were determined by ELISA. The intima-media thickness (IMT) of carotid arteries was determined by B-mode ultrasonography. In RA patients, platelet CD62P expression (p < 0.001), PMC (p = 0.037) and sCD40L (p < 0.001) levels were increased when compared to the control group. PNC (p = 0.07) and TAT levels (p = 0.1) were non-significantly higher, and PMP level (p = 0.075) was nonsignificantly lower in RA patients. Soluble E-selectin level was significantly higher in the active RA group than in the inactive RA group (p = 0.009). There was no correlation between carotid IMT and activity markers, the evaluated parameters (p > 0.05).The increase in markers of active platelets, CD62P and sCD40L, and PMC levels might be associated with the increased cardiovascular mortality in RA. Nevertheless, none of these parameters were associated with carotid IMT: this suggests that one cross-sectional value might not be a good marker for atherosclerosis
17307755 NKT cells: manipulable managers of joint inflammation. 2007 Apr The importance of T cell participation in the aetiology and pathogenesis of rheumatoid arthritis (RA) is now widely appreciated. The disease is mediated by activated pro-inflammatory, self-reactive T helper cells, instigating the chronic autoimmune response characteristic of rheumatoid inflammation. Natural killer T (NKT) cells are a distinctive population of T cells thought to protect self-tissues from damaging inflammatory immune responses, and are often recognized as a regulatory T cell subtype, regulating the magnitude or class of the immune response. Recently, a number of studies have provided insight concerning the role of NKT cells in different models of autoimmune joint inflammation, suggesting the involvement of this specialized T cell subset in controlling initiation and perpetuation of arthritic disease. The aim of this review is to provide rheumatologists with an introduction of the principal features of NKT cells, to give an overview of the data obtained in animal models of arthritis and to discuss the hypothesized mechanisms. Finally, we will speculate on future prospects with regard to NKT cell-targeted treatment of arthritic disease by use of glycolipids.
18668562 Synovial fluid is a site of citrullination of autoantigens in inflammatory arthritis. 2008 Aug OBJECTIVE: To examine synovial fluid as a site for generating citrullinated antigens, including the candidate autoantigen citrullinated alpha-enolase, in rheumatoid arthritis (RA). METHODS: Synovial fluid was obtained from 20 patients with RA, 20 patients with spondylarthritides (SpA), and 20 patients with osteoarthritis (OA). Samples were resolved using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by staining with Coomassie blue and immunoblotting for citrullinated proteins, alpha-enolase, and the deiminating enzymes peptidylarginine deiminase type 2 (PAD-2) and PAD-4. Proteins from an RA synovial fluid sample were separated by 2-dimensional electrophoresis, and each protein was identified by immunoblotting and mass spectrometry. Antibodies to citrullinated alpha-enolase peptide 1 (CEP-1) and cyclic citrullinated peptide 2 were measured by enzyme-linked immunosorbent assay. RESULTS: Citrullinated polypeptides were detected in the synovial fluid from patients with RA and patients with SpA, but not in OA samples. Alpha-enolase was detected in all of the samples, with mean levels of 6.4 ng/microl in RA samples, 4.3 ng/microl in SpA samples, and <0.9 ng/microl in OA samples. Two-dimensional electrophoresis provided evidence that the alpha-enolase was citrullinated in RA synovial fluid. The citrullinating enzyme PAD-4 was detected in samples from all 3 disease groups. PAD-2 was detected in 18 of the RA samples, in 16 of the SpA samples, and in none of the OA samples. Antibodies to CEP-1 were found in 12 of the RA samples (60%), in none of the SpA samples, and in 1 OA sample. CONCLUSION: These results highlight the importance of synovial fluid for the expression of citrullinated autoantigens in inflammatory arthritis. Whereas the expression of citrullinated proteins is a product of inflammation, the antibody response remains specific for RA.
17040963 Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: i 2007 May BACKGROUND: The cytokine B cell-activating factor of the TNF family (BAFF) is involved in the pathogenesis of autoimmune diseases. OBJECTIVE: To access changes in serum protein and mRNA levels of BAFF after rituximab treatment. METHODS: Serum and peripheral blood mononuclear cells (PBMCs) were isolated from five patients (two with lupus, two with Sjögren's syndrome, one with rheumatoid arthritis) before and 12 weeks (range 7-17) after a first course of rituximab infusion. Monocytes and B cells were selected from healthy controls and cocultured for 72 h. BAFF protein and mRNA levels were assessed by ELISA and real-time PCR, respectively. RESULTS: After rituximab treatment, median serum BAFF protein level and BAFF to actin mRNA ratio in PBMCs significantly increased. In monocytes cocultured with autologous B cells, BAFF protein level decreased, whereas the mRNA level was stable. In one closely monitored patient, the mRNA ratio of BAFF to actin in PBMCs increased later than the BAFF serum level. CONCLUSIONS: Two distinct mechanisms are probably involved in the increase in BAFF level after B cell depletion: (1) the decrease in its receptors leading to a release of BAFF; (2) a delayed regulation of BAFF mRNA transcription. This could favour the re-emergence of autoreactive B cells.
16924694 Diagnostic utility of anti-cyclic citrullinated peptide antibodies for very early rheumato 2006 Dec OBJECTIVE: To compare the diagnostic utility of anti-cyclic citrullinated peptide (anti-CCP) antibodies with other serological markers including rheumatoid factor (RF), anti-agalactosyl immunoglobulin G (IgG) antibody, and matrix metalloproteinase (MMP)-3 in very early rheumatoid arthritis (RA). METHODS: Serum concentrations of anti-CCP antibodies, RF, anti-agalactosyl IgG antibody, and MMP-3 were measured in 262 patients with RA ("total RA") including 55 patients with disease duration of less than 6 months who had not been treated before entry ("very early RA") and 116 patients with rheumatic diseases other than RA. RESULTS: The diagnostic sensitivity of anti-CCP antibodies was 82.4% in total RA and 67.3% in very early RA and was lower than that of RF (84.0% total RA, 83.6% very early RA) and anti-agalactosyl IgG antibody (90.5%, 90.9%), whereas specificity, positive predictive value, and diagnostic accuracy were the best among markers tested both in total RA and in very early RA. The presence of either anti-CCP antibodies or RF increased the sensitivity, but any combination of serological markers was not significantly better in diagnostic accuracy than anti-CCP antibodies alone. The rates of RF-positive subjects in anti-CCP antibody-negative patients both in total RA (43.5%) and in very early RA (61.1%) were higher than those of anti-CCP antibody-positive subjects in RF-negative patients (38.1% and 22.2%, for total RA and early RA, respectively). CONCLUSION: Measurement of anti-CCP antibodies, by itself, is useful for the diagnosis of RA; however, combined use of anti-CCP antibodies with RF may be more useful than either method alone for the diagnosis of very early RA.
17934103 Could toll-like receptors provide a missing link in chronic inflammation in rheumatoid art 2007 Nov In the last decade the development of a number of biological therapies has revolutionised the treatment of rheumatic diseases. The first and most widely used of these approaches, tumour necrosis factor (TNF) blockade (infliximab, entanercept, adalimumab), has now been administered to over a million patients. However, the success of these biological therapies has also highlighted their limitations. None of these treatments has shown a 100% patient response; normally responses are in the 50-70% range. As proteins, these drugs cannot be given orally and they are expensive to produce, a cost ultimately borne by the patient/health provider that can seriously limit the availability of these drugs. Lastly, these treatments, whether involving the systemic neutralisation of a cytokine (eg, TNF or IL6 receptor blockade (tocilizumab)), the ablation of a B cell population (anti-CD20, rituximab), or the potential disruption of important cellular interactions as with CTLA4-Ig (abatacept), can cause major perturbations of the immune system, the long-term effects of which are still unclear. At present, treatments such as TNF blockade can result in an increased infectious risk and the reactivation of tuberculosis can be a major issue in certain populations. As with all therapies, there is an increasing large refractory population over time. Therefore, despite the undoubted success of these therapies, there is room for improvement. Although it might be too much to expect any new treatment to affect a "cure" (all the current biological therapies require repeated administrations), there are definite gains to be made in terms of cost, oral bioavailability and a more selective interference with the immune-inflammatory response.
17893998 Accelerated atherosclerosis in rheumatoid arthritis. 2007 Jun Cardiovascular disease is a leading cause of mortality in rheumatoid arthritis (RA). Endothelial dysfunction often precedes manifest atherosclerosis. Both traditional, Framingham risk factors and inflammation-associated factors are involved in RA-associated atherosclerosis. Among imaging techniques, the early determination of common carotid intima-media thickness (ccIMT), flow-mediated vasodilation (FMD), and nitroglycerine-mediated vasodilation (NMD) may be useful to determine atherosclerosis and endothelial dysfunction. We and others found increased ccIMT and impaired FMD in RA patients. Among immunological and metabolic laboratory markers, anticyclic citrullinated peptide (anti-CCP) antibodies, IgM rheumatoid factor, circulating immune complexes, pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), Th0/Th1 T cells, homocysteine, dyslipidemia, decreased folate and vitamin B12 production, and impaired paraoxonase activity may all be involved in the development of vascular disease in RA. The early diagnosis of endothelial dysfunction and atherosclerosis, active immunosuppressive treatment, the use of drugs that control atherosclerosis, changes in sedentary lifestyle, and the close follow-up of RA patients may help to minimize cardiovascular risk in these individuals.
16924455 [A postoperative infectious complication in a patient with rheumatoid arthritis treated wi 2006 Dec Tumor necrosis factor (TNF) blocking agents, such as adalimumab, are well tolerated and provide improvement in the symptoms and signs of rheumatoid arthritis (RA). Due to its immunosuppressive effect, an increased risk of infection has been suggested, but so far no differences between adalimumab and placebo groups have been found in pivotal trials. Patients with RA succumb to postoperative complications because they have a systemic disease and use medication with immunosuppressive effects. We report on a patient with longstanding, active RA who had received adalimumab 40 mg every other week with prolonged infection, wound dehiscence and pseudoarthrosis following reconstructive forefoot surgery due to deformities secondary to RA. The postoperative infection occurred although adalimumab therapy had been stopped 8 days before surgery. The half-life of adalimumab is 10.0-13.6 days following a single intravenous dose. Whether patients under therapy with adalimumab are at an increased risk of developing postoperative complications is unclear, a retrospective analysis of the pivotal studies would be helpful in estimating the risk of perioperative (wound) infections in patients receiving anti-TNF. Moreover, it is not clear when therapy should be stopped prior to surgical intervention. Obviously prospective clinical trials would be more convincing.
17826752 Comparison of second- and third-generation anti-cyclic citrullinated peptide antibodies as 2007 Nov BACKGROUND: The aims of the present study were to compare the diagnostic and clinical value of seven commercially available assays for second-generation anti-cyclic citrullinated peptide (CCP2) antibodies, anti-keratin antibodies (AKA) and rheumatoid factor (RF) determination in patients with rheumatoid arthritis (RA), and to check the potential advantages of a third-generation anti-CCP (CCP3) antibodies assay. METHODS: Serum samples from 120 RA patients and from 170 controls were used to determine the sensitivity, the specificity, the positive (PPV) and negative predictive values (NPV) of CCP2 and CCP3 antibodies, AKA and RF assays. The respective performances of these tests were compared using a receiver-operating characteristics (ROC) curves methodology. RESULTS: We found no significant differences in sensitivity and specificity between the tested anti-CCP assays. The CCP3 antibodies assay we evaluated was not significantly more sensitive than those of the second generation. Compared with RF technique, all anti-CCP assays showed better specificity, but lower sensitivity. In contrast, while of equivalent specificity, they proved to be more sensitive than AKA in the discrimination of RA from other rheumatic diseases. CONCLUSIONS: Anti-CCP antibodies determination proved to be a powerful diagnostic tool, especially in RA patients with negative AKA or RF. The investigated CCP3 antibodies assay had no better diagnostic performances than the second-generation assays.
16513103 Prevalence of anti-3-nitrotyrosine antibodies in the joint synovial fluid of patients with 2006 Aug BACKGROUND: Increased reactive nitrogen species (RNS) production has been suggested in the pathogenesis of rheumatoid arthritis (RA), osteoarthritis (OA) as well as in systemic lupus erythematosus (SLE). They are known to have direct toxicity to cells. High concentrations of serum nitrite/nitrate and elevated urinary nitrate:creatine ratio has been found in patients with RA, OA and SLE. Reactive nitrogen species play a role in the chronicity of inflammatory reaction such as cartilage and bone destruction seen in patients with RA and OA. Arthritis is also associated with increased intra-articular formation of 3-nitrotyrosine (3-NT), which may contribute to joint damage. There is growing evidence that nitrative injury plays an important role in oxidative stress in the etiology and pathogenesis of SLE. 3-nitrotyrosine is thought to be a relatively specific marker of nitrosative damage mediated by nitric oxide (NO) and its by-products. METHODS: Commercially available poly l-tyrosine was exposed to nitrating species resulting in the formation of 3-nitrotyrosine. Antibodies present in synovial fluid and sera of 30 patients with rheumatoid arthritis, 15 patients with osteoarthritis and 15 patients with SLE were studied for their recognition of 3-NT by direct binding ELISA. RESULTS: IgG from the synovial fluid (SF) of RA and OA patients, purified on protein A-Sepharose matrix, exhibited increased recognition of 3-NT, than the IgG isolated from the sera of RA and OA patients in competitive ELISA, whereas IgG isolated from the sera of SLE patients exhibited increased recognition of 3-NT, than the IgG isolated from the synovial fluid. There was a higher prevalence of antibodies against 3-NT in the synovial fluid than in the sera of patients with RA and OA. Higher level of anti-3-NT antibodies were found in the synovial fluid in the later stages of SLE when compared to the early stages but was not more than that found in the sera. CONCLUSION: The RNS may be produced within the inflamed joints of RA and OA patients but not in SLE patients. The 3-NT levels also correlated directly with disease activity.
18952480 Intra-articular botulinum toxin A as an adjunctive therapy for refractory joint pain in pa 2009 Mar We report the use of intra-articular Botulinum toxin A in two RA patients with persistently painful monoarthritis in ankle/feet joints. Both patients had monarticular pain despite a good response of all other joints to a combination therapy that included anti-tumor necrosis factor therapy. Both patients had failed intra-articular corticosteroid injections and declined surgical options. After a single, "off-label", intra-articular injection of Botulinum toxin A into the right ankle (100 unit) and left first metatarsophalangeal joint (25 unit), respectively, pain and function improved significantly (> or =40%) in both patients. Durable response with improvement of pain and function lasting 15-18 months was noted (follow-up continuing). Ankle joint swelling resolved by 15 months and MTP joint swelling by one month. Intra-articular BoNT/A may be an additional therapeutic option in RA patients with persistent monoarthritis. A randomized study is underway to confirm these findings.
16646989 Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid ar 2006 We investigated lipid profiles and lipoprotein modification after immuno-intervention in patients with early rheumatoid arthritis (ERA). Fifty-eight patients with ERA who met the American College of Rheumatology (ACR) criteria were included in the study. These patients had disease durations of less than one year and had not had prior treatment for it. Smokers or patients suffering from diabetes mellitus, hypothyroidism, liver or kidney disease, Cushing's syndrome, obesity, familiar dyslipidemia and those receiving medications affecting lipid metabolism were excluded from the study. Sixty-three healthy volunteers (controls) were also included. Patients were treated with methotrexate and prednisone. Lipid profiles, disease activity for the 28 joint indices score (DAS-28) as well as ACR 50% response criteria were determined for all patients. The mean DAS-28 at disease onset was 5.8 +/- 0.9. After a year of therapy, 53 (91.3%) patients achieved the ACR 20% response criteria, while 45 (77.6%) attained the ACR 50% criteria. In addition, a significant decrease in the DAS-28, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were observed. ERA patients exhibited higher serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides, whereas their serum high-density lipoprotein cholesterol (HDL-C) levels were significantly lower compared to controls. As a consequence, the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was significantly higher in ERA patients compared to controls. After treatment, a significant reduction of the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was observed, a phenomenon primarily due to the increase of serum HDL-C levels. These changes were inversely correlated with laboratory changes, especially CRP and ESR. In conclusion, ERA patients are characterized by an atherogenic lipid profile, which improves after therapy. Thus, early immuno-intervention to control disease activity may reduce the risk of the atherosclerotic process and cardiovascular events in ERA patients.
16575870 Peripheral blood T lymphocytes from patients with early rheumatoid arthritis express RANKL 2006 Apr OBJECTIVE: To investigate the osteoclastogenic potential of T cells from the peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) on autologous monocytes, and to study the cytokines implicated in this process. METHODS: T cells and monocytes were isolated from the PB of 20 healthy subjects and 20 patients with early RA, and from the SF of 20 patients with established RA. Autologous T cell/monocyte cocultures were established in the absence of exogenous cytokines or growth factors in order to examine spontaneous ex vivo osteoclast differentiation by tartrate-resistant acid phosphatase staining and calcified matrix resorption activity. RESULTS: Surface RANKL was expressed on freshly isolated T cells from the PB of patients with early RA and the SF of patients with established RA. In addition, surface interleukin-15 (IL-15) was detected on freshly isolated T cells and monocytes from the PB of patients with early RA and the SF of patients with established RA. Autologous T cell/monocyte cocultures derived from the SF of patients with established RA and from the PB of patients with early RA, but not from the PB of healthy controls, resulted in osteoclast differentiation that was significantly inhibited by osteoprotegerin (OPG) and by neutralizing monoclonal antibodies to IL-15, IL-17, tumor necrosis factor alpha (TNFalpha), and IL-1beta. OPG, anti-TNFalpha, and anti-IL-1beta demonstrated a cooperative inhibitory effect. At 1-year followup, surface RANKL and IL-15 and ex vivo osteoclastogenesis were no longer observed on PB T cells or monocytes from patients with early RA in whom clinical remission had been achieved with treatment. CONCLUSION: T cells are important contributors to the pathogenesis of bone erosions in RA through interaction with osteoclast precursors of the monocyte/macrophage lineage.
17471309 Recruitment of CD16+ monocytes into synovial tissues is mediated by fractalkine and CX3CR1 2007 Apr CD16+ monocytes, identified as a minor population of monocytes in human peripheral blood, have been implicated in several inflammatory diseases, including rheumatoid arthritis (RA). Fractalkine (FKN, CX3CL1), a member of the CX3 C subfamily, is induced by pro-inflammatory cytokines, while a receptor for FKN, CX3CR1, is capable of mediating both leukocyte migration and firm adhesion. Here, we investigated the role of FKN and CX3CR1 in activation of CD16+ monocytes and their recruitment into synovial tissues in RA patients. High levels of soluble FKN were detected in the synovial fluid and sera of RA patients. Circulating CD16+ monocytes showed a higher level of CX3CR1 expression than CD16- monocytes in both RA patients and healthy subjects. High level expression of CX3CR1 was also seen in CD16+ monocytes localized to the lining layer in RA synovial tissue. In the in vitro culture experiments, IL-10 induced CX3CR1 expression on the surface of monocytes, and TNFalpha induced membrane-bound FKN as well as soluble FKN expression in synovial fibroblasts. Moreover, soluble FKN was capable of inducing IL-1beta and IL-6 by activated monocytes. These results suggest that FKN might preferentially mediate migration and recruitment of CD16+ monocytes, and might contribute to synovial tissue inflammation.
18063670 Th1 but not Th17 cells predominate in the joints of patients with rheumatoid arthritis. 2008 Sep OBJECTIVES: Recent animal studies have revealed critical roles of interleukin (IL)17, which is produced by a newly identified subset of helper T cells, Th17 cells, in the development of autoimmune diseases including arthritis. However, in human rheumatoid arthritis (RA), detailed characteristics and the prevalence of Th17 cells are unclear. METHODS: Peripheral blood mononuclear cells (PBMC) were obtained from 123 patients with RA and 28 healthy controls. Mononuclear cells were also prepared from synovial membrane or synovial fluid of 12 patients with RA. IL17 (IL17A) positive T cells were identified by a flow cytometer after ex vivo stimulation with phorbol myristate acetate and ionomycin. Disease activity was assessed with the 28-joint Disease Activity Score (DAS28). RESULTS: IL17 positive cells were detected in CD45RO+ CD4 T cells. Most IL17 positive T cells produced neither interferon (IFN)gamma nor IL4, but tumour necrosis factor (TNF)alpha similar to murine Th17 cells. The frequency of Th17 cells was neither increased in RA nor correlated with DAS28. Unexpectedly, the frequency of Th17 cells was significantly decreased in the joints compared with PBMC of the same patients with RA, whereas Th1 cells were more abundant in the joints than in PBMC. CONCLUSIONS: We could not obtain evidence that positively supports predominance of Th17 cells in RA. Further careful investigation is necessary before clinical application of IL17-targeting therapy.
17564780 Clinical and radiological results of non-cement impaction bone-graft method of total hip a 2007 We performed total hip arthroplasty using the non-cement impaction auto-bone-grafting method with the resected femoral head for acetabular protrusion that is not combined with the destruction of acetabular rim or dysplasia of the hip joint. Ten patients (eight women and two men) with rheumatoid arthritis who showed acetabular protrusion underwent total hip arthroplasty using this method. All patients were able to walk with full weight within 5 days after surgery. The short-term results of our cases were very good. The postoperative periods of the radiographic-bone incorporation of the grafting bone were 2 months after surgery in four joints, 3 months after surgery in four joints, and 4 months after surgery in three joints. There were no cases that showed any migration or radiolucency around the acetabular component at the time of follow-up. Our operative technique is simple and easy, and it is a useful method for the treatment of protrusion in patients with rheumatoid arthritis.
17570008 A comparison of the frequency of antibodies to cyclic citrullinated peptides using a third 2008 Jan The objective was to investigate the frequency of anti-cyclic citrullinated peptides (CCP) antibodies in systemic sclerosis (SSc) and primary biliary cirrhosis (PBC), utilizing a new "third generation" anti-CCP ELISA (anti-CCP3) kit and a conventional anti-CCP2 assay. Patients with PBC, SSc, RA, and normal controls were included in the study. Serum samples were screened for autoantibodies by indirect immunofluorescence (IIF), antibodies to CCP by a second- and third-generation ELISA, antibodies to "scleroderma" antigens (CENP B, Scl-70, PM/Scl and fibrillarin-Scl-34) by a line immunoassay (LIA), and IgM RF by ELISA. The frequency of anti-CCP2 antibodies in SSc and PBC samples was 14.8% (11/74) and 6.2% (5/80), respectively, and the frequency of anti-CCP3 antibodies in SSc was 13.5% (10/74) and in PBC was 3.7% (3/80). By comparison, in the RA group the frequency of anti-CCP3 and anti-CCP2 antibodies was 79.1% (38/48) and 77% (37/48), respectively. Anti-CCP3 ELISA had a sensitivity, specificity, and positive and negative likelihood ratios (LR) of 79% (95% confidence interval [CI] = 64-89%), 93% (95% CI = 88-96%), 11.8 (95% CI = 6.8-20.3), and 0.22 (95% CI = 0.12-0.38), respectively. By comparison, the anti-CCP2 assay had a sensitivity, specificity, and positive and negative LRs of 77% (95% CI = 62-87), 90% (95% CI = 85-94), 8.3 (95% CI = 5.2-13.2), and 0.25 (95% CI = 0.15-0.42), respectively. In patients with SSc, there was an association of anti-CCP2 antibodies with the presence of arthritis, but there was no association of anti-CCP2 or anti-CCP3 with anti-CENP B, anti-Scl 70, or RF. This study confirmed the high specificity and sensitivity of both anti-CCP assays for the diagnosis of RA. The presence of anti-CCP antibodies in SSc was only correlated with the presence of arthritis.
19017992 Inhibitors of TLR8 reduce TNF production from human rheumatoid synovial membrane cultures. 2008 Dec 1 The advent of anti-TNF biologicals has been a seminal advance in the treatment of rheumatoid arthritis (RA) and has confirmed the important role of TNF in disease pathogenesis. However, it is unknown what sustains the chronic production of TNF. In this study, we have investigated the anti-inflammatory properties of mianserin, a serotonin receptor antagonist. We discovered mianserin was able to inhibit the endosomal TLRs 3, 7, 8, and 9 in primary human cells and inhibited the spontaneous release of TNF and IL-6 from RA synovial membrane cultures. This suggested a role for these TLRs in production of TNF and IL-6 from RA which was supported by data from chloroquine, an inhibitor of endosomal acidification (a prerequisite for TLRs 3, 7, 8, and 9 activation) which also inhibited production of these cytokines from RA synovial cultures. Only stimulation of TLR 3 or 8 induced TNF from these cultures, indicating that TLR7 and TLR9 were of less consequence in this model. The key observation that indicated the importance of TLR8 was the inhibition of spontaneous TNF production by imiquimod, which we discovered to be an inhibitor of TLR8. Together, these data suggest that TLR8 may play a role in driving TNF production in RA. Because this receptor can be inhibited by small m.w. molecules, it may prove to be an important therapeutic target.