Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
---|---|---|---|---|
22047640 | Initiation but no execution - modulation of peripheral blood lymphocyte apoptosis in rheum | 2011 Nov 3 | BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease, which causes synovial damage. Persistence of lymphocyte infiltrates in the rheumatoid synovium has been attributed to abnormal apoptosis. While not comprehensively investigated, perturbations in peripheral blood lymphocyte (PBL) apoptosis may also be involved in perpetuation of autoimmune processes in RA. METHODS: We investigated total, CD4+ and CD19+ PBL apoptosis in our study cohort by monitoring the translocation of phosphatidylserine using the Annexin-V assay. To examine the role of death receptor mediated apoptosis as well as activation-induced-cell-death (AICD), PBLs were labeled with CD95/Fas and CD69 markers and enumerated by flow cytometry. Proteolytic activity of initiator and executioner caspases was determined by luminometry. DNA fragmentation assays were used to examine whether apoptotic signals were transduced to the nucleus. Quantitative PCR arrays were used to investigate apoptotic pathways associated with RA-PBLs. Since heat-shock-protein-70 (HSP70) is an inducible protein which modulates apoptotic signals, we determined HSP70 levels by intra-cellular flow cytometry and western blots. RESULTS: The RA-PBLs showed signs of elevated apoptosis whilst in circulation. These include increases in the loss of plasma membrane asymmetry, indicated by increased externalization of phosphatidylserine (especially in B-lymphocytes). RA-PBLs showed a bias to CD95/Fas mediated apoptotic pathways, but low levels of the CD69 marker suggested that this was not associated with immune activation. Although downstream markers of apoptosis such as caspase-3/7 activity, were increased, no DNA fragmentation was observed in RA-PBLs. Interestingly, elevated levels of apoptosis did not correlate with absolute lymphocyte counts in RA patients. Levels of HSP70 were highly elevated in RA-PBLs compared to controls. CONCLUSION: The results suggest that while apoptosis may be initiated in RA-PBLs, they may lack commitment to fully executing the apoptotic program. This may be related to inhibition on apoptotic transduction by HSP70. This study provides evidence that abnormalities in RA-PBLs apoptosis may occur whilst still in circulation and may contribute to pathogenesis of the disease. | |
21383629 | Generic ABILHAND questionnaire can measure manual ability across a variety of motor impair | 2011 Jun | ABILHAND is, in its original version, a 46-item, 4-level questionnaire. It measures the difficulty perceived by patients with rheumatoid arthritis as they do various daily manual tasks. ABILHAND was originally built through Rasch analysis. In a later study, it was simplified to a generic 23-item, three-level questionnaire, showing both cross-cultural (Belgium vs. Italy) and cross-impairment (rheumatoid arthritis vs. stroke) validity. Later research returned to the development of impairment-specific versions, with modified item sets and levels. Each version has its own Rasch-derived item difficulty calibrations, which are required to extract the patient's measure from the individual string of responses, through computerized algorithms. All of these hamper the practical application of the scale in rehabilitation units, where patients with diverse conditions may share similar impairments and treatment approaches. In this study through Rasch analysis the 'generic' scale was applied to 126 chronic patients with different upper limb impairments, and to 24 healthy controls. It was supported that the generic questionnaire remains valid across a variety of motor impairments. To further facilitate clinical application, a normative cut-off (>79 of 100) is suggested. Rasch-based item calibrations are provided together with a software routine designed to calculate, on individual patients, linear 0-100 measures and error estimates from the raw scores. | |
22203849 | Resistance exercise reduces skeletal muscle cachexia and improves muscle function in rheum | 2011 | Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune, inflammatory disease associated with cachexia (reduced muscle and increased fat). Although strength-training exercise has been used in persons with RA, it is not clear if it is effective for reducing cachexia. A 46-year-old woman was studied to determine: (i) if resistance exercise could reverse cachexia by improving muscle mass, fiber cross-sectional area, and muscle function; and (2) if elevated apoptotic signaling was involved in cachexia with RA and could be reduced by resistance training. A needle biopsy was obtained from the vastus lateralis muscle of the RA subject before and after 16 weeks of resistance training. Knee extensor strength increased by 13.6% and fatigue decreased by 2.8% Muscle mass increased by 2.1%. Average muscle fiber cross-sectional area increased by 49.7%, and muscle nuclei increased slightly after strength training from 0.08 to 0.12 nuclei/μm(2). In addition, there was a slight decrease (1.6%) in the number of apoptotic muscle nuclei after resistance training. This case study suggests that resistance training may be a good tool for increasing the number of nuclei per fiber area, decreasing apoptotic nuclei, and inducing fiber hypertrophy in persons with RA, thereby slowing or reversing rheumatoid cachexia. | |
22701193 | Stabilization of bilateral progressive rheumatoid corneal melt with infliximab. | 2012 | Purpose. To report the use of infliximab in the rapid stabilization of a case of progressive, bilateral rheumatoid peripheral ulcerative keratitis (PUK) that failed to respond to conventional immunosuppressive therapy. Methods. A single interventional case report. Results. A patient with rheumatoid arthritis presented with bilateral PUK following a 2-month history of ocular discomfort and redness. His systemic prednisolone (PDN) and methotrexate (MTX) were increased and, despite an initial favorable response, bilateral recurrent corneal perforations ensued. Both eyes underwent cyanoacrylate glue repair, amniotic membrane transplantation (AMT), and penetrating keratoplasty (PKP). Recurrence of the disease and bilateral perforations of the second PKP in both eyes prompted administration of intravenous infliximab immediately after the fourth PKP. The disease activity rapidly settled in both eyes, and at eighteen-month followup, after 12 infliximab infusions, the PUK remains quiescent with no further graft thinning or perforation. Conclusion. Infliximab can be used to arrest the progression of severe bilateral rheumatoid PUK in cases that are refractory to conventional treatment. | |
22611405 | Effects of xinfeng capsules on expression of platelet granule membrane protein 140 and pla | 2012 | Platelet GMP-140 and CD40L as specific markers of platelet activation play an important role in the morbidity and development of rheumatoid arthritis. The expression of GMP-140, CD40L increases in peripheral blood of AA rats. And they have correlation with voix pedis' swelling, AI. XFC could inhibit the inflammatory response through inhibiting platelet activation of AA rats, which means decreasing the expression of GMP-140, CD40L in peripheral blood. So, the voix pedis' swelling and AI were decreased as the result. | |
22174196 | Simultaneous juvenile idiopathic arthritis and diabetes mellitus type 1 -- a Finnish natio | 2012 Feb | OBJECTIVE: To describe the occurrence and main clinical and laboratory findings of patients having both juvenile idiopathic arthritis (JIA) and diabetes mellitus type 1 (DM-1) in a period of 30 years. METHODS: Eighty-two patients having simultaneous JIA and DM-1 were identified in the reimbursement registers of the Finnish National Institute of Insurance during the period 1976-2005. Data on their clinical histories were collected from patient files. RESULTS: Occurrence of simultaneous JIA and DM-1 increased 4.5-fold between the first (1976-85) and the last (1996-2005) decade. Prevalence of uveitis was 7%, of rheumatoid factor seropositivity 15%; 22% of patients had a third autoimmune disease [autoimmune disease (AID)], and 16% had serious psychiatric problems. CONCLUSION: The occurrence of patients with the 2 diseases, JIA and DM-1, increased over 3 decades. The prevalence of uveitis was low, the number of seropositive patients was high, and further cases of AID were frequent. Patients had multiple additional problems necessitating multiprofessional care. | |
23031278 | Association of circulating levels of MMP-8 with mortality from respiratory disease in pati | 2012 Oct 2 | INTRODUCTION: Matrix metalloproteinases (MMPs) are implicated in the destruction of the joint and have been shown to be strongly associated with inflammation in rheumatoid arthritis (RA). Circulating MMPs have also been associated with cardiovascular disease in the general population, and are predictive of cardiovascular mortality. The purpose of the present study was to determine whether circulating levels of MMPs are predictive of mortality in RA. METHODS: A multiplex suspension array system (Luminex®) was used to measure levels of MMPs (1, 2, 3, 8 and 9) in sera taken at recruitment of RA patients (n = 487) in a study of factors associated with mortality in RA. Patients were tracked on the National Health Service Central Register for notification of death, and the relationship between baseline MMP levels and mortality was analysed using Cox proportional hazards regression analysis. RESULTS: At the time of follow-up, 204/486 patients had died, of which 94 (46.1%) had died of circulatory diseases, 49 of malignancy (24.0%), and 42 (20.6%) of respiratory diseases. In a stepwise analysis which included all MMPs, only MMP-8 was significantly associated with all cause mortality (P = 0.0007, 0.6% hazard ratio increase per ng/ml). No association was found between MMP levels and mortality due to circulatory disease or malignancy. However MMP-8 levels were strongly associated with mortality due to respiratory disease (P < 0.0001, 1.3% hazard ratio increase per ng/ml). The association with respiratory disease related mortality remained highly significant in multivariate models which included smoking as well as markers of severity and disease activity such as rheumatoid factor, nodular disease, and C-reactive protein (CRP). CONCLUSIONS: The serum level of MMP-8 is a strong predictor of mortality in RA, especially that due to respiratory disease. This finding is consistent with increased activation of neutrophils in RA and identifies serum MMP-8 as a useful marker for increased risk of premature death. | |
21325061 | A mini-review: microRNA in arthritis. | 2011 May 1 | MicroRNA (miRNA) is a class of noncoding RNA that exhibits tissue- or developmental stage-specific expression patterns and negatively regulates gene expression. MiRNAs play an important role in human diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA). OA is characterized by the progressive destruction of articular cartilage, and several miRNAs exhibit altered expression, playing a role in regulating gene expression in OA pathogenesis, especially in catabolic factors such as matrix metalloproteinases (MMP) and aggrecanases. RA is an autoimmune disease that is characterized by irreversible joint destruction due to chronic synovial inflammation. MiRNAs play an important role in inflammatory response, synovial cell proliferation, and production of MMPs in RA synovial tissues. The expression level of several miRNAs in peripheral blood mononuclear cells correlates with RA disease activity. Recently, therapeutic trials aimed at targeting miRNA in vivo have been conducted. Targeting miRNA will enable a new advanced strategy toward arthritis treatment. | |
21489893 | Trans-pubic abdominal flap for reconstruction of the labia majora. | 2011 Nov | A flap is described for recreation of the labia majora. The flap was designed for a young woman who developed vulvar squamous cell carcinoma in-situ after immunosuppression for treatment of juvenile rheumatoid arthritis. The patient underwent removal of the labia majora, and was reconstructed with a bi-lobed abdominal flap tunneled through the mons pubis. The flap produced a normal genital contour and has functioned well to seven years follow-up. | |
22215120 | Anti-cyclic citrullinated peptide antibodies in scleroderma patients. | 2012 May | Anti-CCP (cyclic citrullinated peptide) is considered the most useful laboratory tool in the diagnosis of rheumatoid arthritis (RA). Some authors have also found this autoantibody in patients with scleroderma (SSc). The study aimed to investigate the prevalence of anti-CCP antibodies in SSc patients from Southern Brazil and their association with clinical and serological profile of the disease. We studied 76 patients with SSc and 100 healthy volunteers for presence of anti-CCP. SSc patients charts were reviewed for clinical and laboratory data. In the SSc group, the diffuse form was present in 20.5%; 62.8% had the limited form; 14.1% had overlap with systemic lupus or polymyositis and 2.5% had SSc sine scleroderma. Anti-CCP was found in nine of 78 (11.5%) SSc patients and in one of 100 healthy volunteers (p = 0.0054). No relationship was found with arthritis, skin Rodnan m score, esophageal dysmotility, myocarditis, pulmonary hypertension and lung fibrosis. Positive association was observed with arthralgias (p = 0.02). Also, no relationship was noted with the presence of anti-centromere antibodies, anti-Scl-70, anti-RNP or rheumatoid factor. Anti-CCP are more common in SSc patients than in controls. Arthralgias but not arthritis or rheumatoid factor are more frequent in anti-CCP positive patients. | |
21529300 | Emerging drugs to treat juvenile idiopathic arthritis. | 2011 Sep | INTRODUCTION: Juvenile idiopathic arthritis (JIA) differs markedly from adult rheumatoid arthritis (RA). It is not a single disease, but an exclusion diagnosis that gathers together all forms of arthritis that begin before the age of 16 years, persist for > 6 weeks and are of unknown origin. This heterogeneous group of disorders has been classified on clinical and laboratory features to try to identify homogeneous, mutually exclusives categories. While some of them appear to represent rather homogenous entities others still seem to include heterogeneous conditions. AREAS COVERED: The advent of new biological treatments has dramatically changed both the observed responses to treatment and the expectations of therapies. The implementation of an adequate legislation as well as the presence of international research networks of pediatric rheumatology have contributed to foster the conduct of controlled clinical trials and the development of validated outcome measures. EXPERT OPINION: Despite these progresses, there are still many problems to be solved to provide a better treatment for those patients who fail to adequately respond to current therapies. Some of the new drugs that are under investigation for RA could also be suitable in the future for improving the treatment of JIA. | |
22690385 | Biomarkers and prognostic stratification in psoriatic arthritis. | 2012 Jun 5 | In rheumatic diseases, biomarkers may serve as surrogate endpoints for diagnosis, prognosis, disease activity, therapeutic response and disease outcome. In recent years a great effort has been made to identify useful tools to establish early diagnosis, prognosis and therapeutic response especially in rheumatoid arthritis (RA). In psoriatic arthritis (PsA) serological biomarkers have been frequently borrowed from RA, but this approach have sometimes lead to inappropriate choices of biomarkers and incorrect conclusions. Furthermore, the heterogeneous spectrum of articular manifestation of PsA and the variable course of the disease can make diagnosis and prognosis difficult. Recently, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) identified two key areas for biomarkers development in psoriasis and PsA: the diagnosis of the articular disease in patients with psoriasis and the evaluation of joint damage in PsA. In this review we revised the currently available and the new potential markers for PsA, such as serum, genetic, cellular and histological biomarkers, clinical and imaging data, with particular attention on the prognostic aspect in order to identify progressive disease suitable for a more aggressive treatment. | |
20663815 | General characteristics of an early arthritis cohort in Argentina. | 2011 Jan | OBJECTIVE: The aim of the present study is to describe the general characteristics of a cohort of patients with early arthritis in Argentina. METHODS: CONAART (Consorcio Argentino de Artritis Temprana--Argentine Consortium for Early Arthritis) is an initiative of seven rheumatology centres across Argentina. Patients were included if they had at least one or more swollen joints and <2 years of disease duration. Social, demographic, familiar, hereditary, clinical and laboratory data were recollected. At first visit and every year, X-rays of hands and feet were performed and working characteristics and pharmaco-economic data were re-collected. RESULTS: A total of 413 patients were included. Of them, 327 (79.2%) were women with a median age of 49 years and a median disease duration of 6 months. Of the total, 183 (44.3%) had RA (ACR 1987) and 167 (40.4%) undifferentiated arthritis (UA). Other diagnoses included: 12 crystalics, 11 PsA, 6 uSpA, 6 other CTD, 1 AS and 27 other diagnosis. As 85% of our population had RA and UA, we only compared these two groups of patients. Patients with RA had significantly worse activity parameters of the disease (DAS of 28 joints), functional capacity (HAQ) and quality of life (Rheumatoid Arthritis Quality of Life) than patients with UA. The frequency of RF and anti-CCP, and symmetrical distribution were also significantly higher in patients with RA compared with UA patients. All patients with RA initiated early specific treatment, in a period no longer than 6 months from the beginning of the disease. CONCLUSION: Early arthritis clinics are a useful tool to identify and treat patients with different forms of joint involvement. | |
22089469 | The ClASsification for Psoriatic ARthritis (CASPAR) criteria--a retrospective feasibility, | 2012 Jan | OBJECTIVE: To evaluate the sensitivity, specificity, and feasibility of the ClASsification criteria for Psoriatic ARthritis (CASPAR) to retrospectively classify an existing research cohort. METHODS: In total, 480 patient records were reviewed from the Royal National Hospital for Rheumatic Diseases Psoriatic Arthritis (PsA) cohort and for 100 consecutive controls with inflammatory arthritis from a general rheumatology clinic. The CASPAR score was modified for retrospective use; both "inflammation" and "current psoriasis" were recorded as present if they had ever been confirmed in the rheumatology clinic. Sensitivity and specificity of the CASPAR criteria were compared with expert clinical diagnosis. RESULTS: A total of 480 database records were identified. Nine sets of records had been lost or destroyed. The diagnoses had changed in 15 cases, which were transferred to the control arm, leaving 456 patients with an expert diagnosis of PsA. Of 115 controls, 96 had rheumatoid arthritis, 5 osteoarthritis, 3 reactive arthritis, 3 seronegative arthritis, 3 undifferentiated arthralgia, 2 ankylosing spondylitis, 1 spondyloarthritis, and 2 systemic sclerosis. Sensitivity (99.7%) and specificity (99.1%) were both high and equivalent to previous reports. Sensitivity remained high even after inclusion of 7 PsA patients with insufficient data to complete the CASPAR assessment (sensitivity 98.2%, specificity 99.1%). The criteria were found to be easy and practical to apply to case records. CONCLUSION: Our study demonstrates that the feasibility, specificity, and sensitivity of the CASPAR are maintained when adapted for retrospective use to classify an established research cohort. | |
23024625 | Instability following total knee arthroplasty. | 2011 Oct | Background Knee prosthesis instability (KPI) is a frequent cause of failure of total knee arthroplasty. Moreover, the degree of constraint required to achieve immediate and long-term stability in total knee arthroplasty (TKA) is frequently debated. Questions This review aims to define the problem, analyze risk factors, and review strategies for prevention and treatment of KPI. Methods A PubMed (MEDLINE) search of the years 2000 to 2010 was performed using two key words: TKA and instability. One hundred and sixty-five initial articles were identified. The most important (17) articles as judged by the author were selected for this review. The main criteria for selection were that the articles addressed and provided solutions to the diagnosis and treatment of KPI. Results Patient-related risk factors predisposing to post-operative instability include deformity requiring a large surgical correction and aggressive ligament release, general or regional neuromuscular pathology, and hip or foot deformities. KPI can be prevented in most cases with appropriate selection of implants and good surgical technique. When ligament instability is anticipated post-operatively, the need for implants with a greater degree of constraint should be anticipated. In patients without significant varus or valgus malalignment and without significant flexion contracture, the posterior cruciate ligament (PCL) can be retained. However, the PCL should be sacrificed when deformity exists particularly in patients with rheumatoid arthritis, previous patellectomy, previous high tibial osteotomy or distal femoral osteotomy, and posttraumatic osteoarthritis with disruption of the PCL. In most cases, KPI requires revision surgery. Successful outcomes can only be obtained if the cause of KPI is identified and addressed. Conclusions Instability following TKA is a common cause of the need for revision. Typically, knees with deformity, rheumatoid arthritis, previous patellectomy or high tibial osteotomy, and posttraumatic arthritis carry higher risks of post-operative instability and are indications for more constrained TKA designs. Instability following TKA usually requires revision surgery which must address the cause of the instability for success. | |
22653707 | AA amyloidosis: basic knowledge, unmet needs and future treatments. | 2012 | Systemic AA amyloidosis is a long-term complication of several chronic inflammatory disorders, including rheumatoid arthritis, ankylosing spondylitis, autoinflammatory syndromes, Crohn's disease, malignancies and conditions predisposing to recurrent infections. Organ damage results from the extracellular deposition of proteolytic fragments of the acute-phase reactant serum amyloid A (SAA) as amyloid fibrils. A sustained high concentration of SAA is the prerequisite for developing AA amyloidosis. However, only a minority of patients with long-standing inflammation actually presents with this complication, pointing to the existence of disease-modifying factors, the best characterised of which being SAA1 genotype. The kidneys, liver and spleen are the main target organs of AA amyloid deposits. In more than 90% of patients proteinuria, nephrotic syndrome and/or renal dysfunction dominate the clinical picture at onset. If not effectively treated, this disease invariably leads to end stage kidney disease and renal replacement therapy, that are still associated with a poor outcome. Although the incidence of AA in rheumatoid arthritis and other chronic arthritides has continuously decreased over the past ten years, thanks to the increasing availability of more effective anti-inflammatory and immunosuppressive therapies, AA remains a life-threatening disease with several areas of uncertainty and unmet needs, deserving continuous efforts at prevention and effective treatment. The deeper understanding of the molecular mechanisms of amyloid formation and regression is now driving the development of novel treatments targeting different steps in the amyloidogenic cascade. These therapies will hopefully improve the quality of life and outcome of these patients in a near future. | |
22308189 | Potential roles of microsomal prostaglandin E synthase-1 in rheumatoid arthritis. | 2011 Mar | Rheumatoid arthritis (RA) is a chronic autoimmune disease which primarily affects the synovial joints leading to inflammation, pain and joint deformities. Nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, both of which inhibit cyclooxygenase (COX), have been extensively used for treating RA patients. Prostaglandin E synthase (PGES) is a specific biosynthetic enzyme that acts downstream of COX and converts prostaglandin (PG) H(2) to PGE(2). Among PGES isozymes, microsomal PGES-1 (mPGES-1) has been shown to be induced in a variety of cells and tissues under inflammatory conditions. The induction of mPGES-1 in the synovial tissue of RA patients is closely associated with the activation of the tissue by proinflammatory cytokines. Although selective mPGES-1 inhibitors have not yet been widely available, mice lacking mPGES-1 (mPGES-1(-/-) mice) have been generated to evaluate the physiological and pathological roles of mPGES-1 in vivo. Recent studies utilizing mPGES-1(-/-) mice have demonstrated the significance of mPGES-1 in the process of chronic inflammation and evocation of humoral immune response in autoimmune arthritis models. These recent findings highlight mPGES-1 as a novel therapeutic target for the treatment of autoimmune inflammatory diseases, including RA. Currently, both natural and synthetic chemicals are being tested for inhibition of mPGES-1 activity to produce PGE(2). The present review focuses on the recent advances in understanding the role of mPGES-1 in the pathophysiology of RA. | |
22144754 | Hydroxyapatite crystal deposition causing rapidly destructive arthropathy of the hip joint | 2011 Nov | Destructive arthropathy of the hip joint can be attributed to various etiologies like rheumatoid arthritis, aseptic necrosis of the femur head, Charcot's joint, subacute septic arthritis, and tubercular arthritis. A disease that results in much rapid destruction of the hip joint and is not associated with clinical syndrome of above mentioned disease has been reported way back in 1970. However, no evidence-based study has been published to support hydroxyapatite (HA) crystals as a probable cause of rapidly destructive arthropathy of the hip joint. We report a case with microscopic and biochemical confirmation of HA crystal deposition causing destructive arthropathy of the hip joint. | |
21723947 | The road forward: the scientific basis for tetracycline treatment of arthritic disorders. | 2011 Dec | The potential role of a collagenase inhibitor for treatment of arthritis was recognized almost immediately after the discovery of vertebrate collagenase. Yet despite vast efforts from the pharmaceutical industry, no such drug has been approved for such use by a regulatory agency. Although two semisynthetic antimicrobial tetracyclines, viz. minocycline and doxycycline, have been shown to have modest clinical benefits in over a dozen trials in rheumatoid arthritis, neither drug is in widespread use. The almost universal use of methotrexate and the rapid development of potent biologic agents have eclipsed the potential usage of TETs for RA. Ironically, it is in osteoarthritis, where there has only been one clinical trial which essentially failed, that the best potential exists for use of an MMP-inhibiting TET. | |
23029038 | An inflammation loop orchestrated by S100A9 and calprotectin is critical for development o | 2012 | OBJECTIVE: The S100A9 and S100A8 proteins are highly expressed by neutrophils and monocytes and are part of a group of damage-associated molecular pattern molecules that trigger inflammatory responses. Sera and synovial fluids of patients with rheumatoid arthritis (RA) contain high concentrations of S100A8/A9 that correlate with disease activity. METHODS: In this study, we investigated the importance of S100A9 in RA by using neutralizing antibodies in a murine lipopolysaccharide-synchronized collagen-induced arthritis model. We also used an in vitro model of stimulation of human immune cells to decipher the role played by S100A9 in leukocyte migration and pro-inflammatory cytokine secretion. RESULTS: Treatment with anti-S100A9 antibodies improved the clinical score by 50%, diminished immune cell infiltration, reduced inflammatory cytokines, both in serum and in the joints, and preserved bone/collagen integrity. Stimulation of neutrophils with S100A9 protein led to the enhancement of neutrophil transendothelial migration. S100A9 protein also induced the secretion by monocytes of proinflammatory cytokines like TNFα, IL-1β and IL-6, and of chemokines like MIP-1α and MCP-1. CONCLUSION: The effects of anti-S100A9 treatment are likely direct consequences of inhibiting the S100A9-mediated promotion of neutrophil transmigration and secretion of pro-inflammatory cytokines from monocytes. Collectively, our results show that treatment with anti-S100A9 may inhibit amplification of the immune response and help preserve tissue integrity. Therefore, S100A9 is a promising potential therapeutic target for inflammatory diseases like rheumatoid arthritis for which alternative therapeutic strategies are needed. |