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ID PMID Title PublicationDate abstract
19150609 Involvement of sphingosine-1-phosphate and S1P1 in angiogenesis: analyses using a new S1P1 2009 Mar 15 Chemical lead 2 (CL2) is the first non-sphingosine-1-phosphate (Sph-1-P) analog type antagonist of endothelial differentiation gene-1 (Edg-1/S1P(1)), which is a member of the Sph-1-P receptor family. CL2 inhibits [(3)H]Sph-1-P/S1P(1) binding and shows concentration-dependent inhibition activity against both intracellular cAMP concentration decrease and cell invasion induced by the Sph-1-P/S1P(1) pathway. It also inhibits normal tube formation in an angiogenesis culture model, indicating that CL2 has anti-angiogenesis activity. This compound improved the disease conditions in two angiogenic models in vivo. It significantly inhibited angiogenesis induced by vascular endothelial growth factor in a rabbit cornea model as well as the swelling of mouse feet in an anti-type II collagen antibody-induced arthritis model. These results indicate that the Sph-1-P/S1P(1) pathway would have an important role in disease-related angiogenesis, especially in the processes of migration/invasion and tube formation. In addition, CL2 would be a powerful tool for the pharmacological study of the mechanisms of the Sph-1-P/S1P(1) pathway in rheumatoid arthritis, diabetes retinopathy, and solid tumor growth processes.
20173389 Type I interferon: a new player in TNF signaling. 2010 TNF and type I interferons (IFNs) are induced by microbial stimuli and mediate innate immune responses. They are also involved in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Activated macrophages are an important driving force of inflammatory reactions and one of the major producers of TNF in innate immunity and chronic inflammation. Despite the fact that cells at sites of damage are continuously exposed to both cytokines, little is known about mechanisms regulating TNF and type I IFN interactions during inflammation. In this review, we discuss the role of an IFN-beta-mediated autocrine loop in the regulation of gene expression program induced by TNF in myeloid cells.
20131230 Synovial fibroblasts self-direct multicellular lining architecture and synthetic function 2010 Mar OBJECTIVE: To define the intrinsic capacity of fibroblast-like synoviocytes (FLS) to establish a 3-dimensional (3-D) complex synovial lining architecture characterized by the multicellular organization of the compacted synovial lining and the elaboration of synovial fluid constituents. METHODS: FLS were cultured in spherical extracellular matrix (ECM) micromasses for 3 weeks. The FLS micromass architecture was assessed histologically and compared with that of dermal fibroblast controls. Lubricin synthesis was measured via immunodetection. Basement membrane matrix and reticular fiber stains were performed to examine ECM organization. Primary human and mouse monocytes were prepared and cocultured with FLS in micromass to investigate cocompaction in the lining architecture. Cytokine stimuli were applied to determine the capacity for inflammatory architecture rearrangement. RESULTS: FLS, but not dermal fibroblasts, spontaneously formed a compacted lining architecture over 3 weeks in the 3-D ECM micromass organ cultures. These lining cells produced lubricin. FLS rearranged their surrounding ECM into a complex architecture resembling the synovial lining and supported the survival and cocompaction of monocyte/macrophages in the neo-lining structure. Furthermore, when stimulated by cytokines, FLS lining structures displayed features of the hyperplastic rheumatoid arthritis synovial lining. CONCLUSION: This 3-D micromass organ culture method demonstrates that many of the phenotypic characteristics of the normal and the hyperplastic synovial lining in vivo are intrinsic functions of FLS. Moreover, FLS promote survival and cocompaction of primary monocytes in a manner remarkably similar to that of synovial lining macrophages. These findings provide new insight into inherent functions of the FLS lineage and establish a powerful in vitro method for further investigation of this lineage.
19271029 Glucosamine/chondroitin/primorine combination therapy for osteoarthritis. 2009 Jan Osteoarthritis (OA) is the most common arthritis affecting the aging population. This degenerative disease can cause significant pain and functional disability in affected individuals. Despite advances in the retardation of rheumatoid arthritis with disease-modifying agents, comparable oral agents have been relatively unavailable for OA. The mainstays of therapy continue to be acetaminophen and nonsteroidal antiinflammatory medications to manage symptoms. Unfortunately, these medications can precipitate severe adverse events in some patients or may be contraindicated, leaving few choices remaining to control pain and suffering. Glucosamine sulfate and chondroitin sulfate have been evaluated in many studies as agents to relieve pain, improve functional activity, and slow disease progression in OA especially of the hip and knee. Studies have reported conflicting results regarding improvement in the pain and disability associated with OA with the use of glucosamine and chondroitin as single agents; however, when improvement has been demonstrated, the formulation has primarily been glucosamine sulfate combined with chondroitin sulfate. Recently, as a result of information implicating the role of reactive oxygen species and oxidative cellular stress reactions on the onset of neurodegenerative and inflammatory disorders, it has been theorized that medications that could control or alter these reactions might improve or prevent the onset of these conditions. Primorine is a combination of products thought to alter these biochemical oxidative byproducts. Based on current evidence, the use of a combination product of glucosamine sulfate and chondroitin sulfate seems to have the greatest potential as a therapeutic intervention for patients at increased risk from the adverse events of accepted current oral therapies. The use of primorine and its combination of products as an intervention in OA has theoretical advantages but its benefits are unproven. A new product, relamine, is a combination of these three formulations. While no studies have evaluated glucosamine sulfate, chondroitin sulfate and primorine in a single product, it may be an option for those who wish to try an alternate therapy for OA, as there appears to be a low risk for serious adverse events.
19649332 Rilonacept in the treatment of chronic inflammatory disorders. 2009 Jun Rilonacept (IL-1 Trap/Arcalyst) is a long-acting interleukin-1 (IL-1) blocker developed by Regeneron Pharmaceuticals. Initially, Regeneron entered into a joint development effort with Novartis to develop rilonacept for the treatment of rheumatoid arthritis (RA) but this was discontinued following the review of phase II clinical data showing that IL-1 blockade appeared to have limited benefit in RA. In February 2008, Regeneron received Orphan Drug approval from the Food and Drug Administration for rilonacept in the treatment of two cryopyrin-associated periodic syndromes (CAPS) disorders, namely, familial cold-induced autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS), for children and adults 12 years and older. CAPS is a group of inherited inflammatory disorders consisting of FCAS, MWS, neonatal-onset multisystem inflammatory disease (NOMID), also known as chronic infantile neurologic, cutaneous and articular (CINCA) syndrome, all associated with heterozygous mutations in the NLRP3 (CIAS1) gene, which encodes the protein NLRP3 or cryopyrin. Prior to the discovery of the NLRP3 (CIAS1) mutations and the advent of IL-1-targeted therapy, treatment was aimed at suppressing inflammation but with limited success. The dramatic success of selective blockade of IL-1beta, initially with the IL-1 receptor antagonist (IL-1Ra; Kineret(R) or anakinra/ Amgen, Inc.), not only provided supportive evidence for the role of IL-1beta in CAPS but also demonstrated the efficacy of targeting IL-1beta for treatment of these conditions. A high-affinity protein called rilonacept has been produced by cytokine Trap technology and was developed by Regeneron. The desirable longer half-life of rilonacept offers potential alternatives to patients who do not tolerate daily injections very well or have difficulty with drug compliance. The initial evidence for the beneficial effects of rilonacept for MWS and FCAS suggests that it would also be a suitable treatment for CNICA/NOMID. It is yet to be determined whether rilonacept would be an effective treatment for other chronic inflammatory conditions such as gout, familial Mediterranean fever and systemic juvenile idiopathic arthritis.
19519926 Cartilage homeostasis in health and rheumatic diseases. 2009 As the cellular component of articular cartilage, chondrocytes are responsible for maintaining in a low-turnover state the unique composition and organization of the matrix that was determined during embryonic and postnatal development. In joint diseases, cartilage homeostasis is disrupted by mechanisms that are driven by combinations of biological mediators that vary according to the disease process, including contributions from other joint tissues. In osteoarthritis (OA), biomechanical stimuli predominate with up-regulation of both catabolic and anabolic cytokines and recapitulation of developmental phenotypes, whereas in rheumatoid arthritis (RA), inflammation and catabolism drive cartilage loss. In vitro studies in chondrocytes have elucidated signaling pathways and transcription factors that orchestrate specific functions that promote cartilage damage in both OA and RA. Thus, understanding how the adult articular chondrocyte functions within its unique environment will aid in the development of rational strategies to protect cartilage from damage resulting from joint disease. This review will cover current knowledge about the specific cellular and biochemical mechanisms that regulate cartilage homeostasis and pathology.
19228655 Use of the T-SPOT.TB assay to detect latent tuberculosis infection among rheumatic disease 2009 Mar OBJECTIVE: We evaluated the T-SPOT.TB assay to identify latent tuberculosis infection (LTBI) in patients with rheumatic disease receiving immunosuppressive medication including tumor necrosis factor (TNF) antagonists. METHODS: A total of 200 patients seen in the Arthritis Center at Brigham and Women's Hospital were enrolled for study. Most patients were US-born women with rheumatoid arthritis. A medical history was obtained using a questionnaire, whole blood was drawn for the T-SPOT.TB assay, and tuberculin skin testing (TST) was performed. RESULTS: Both tests were performed on 179 subjects, who had no history of a positive TST. All subjects had a strong response to the T-SPOT.TB test positive control, and there were no indeterminate results. Among these 179 subjects, 2 had a positive TST and 10 had a positive T-SPOT.TB test. No subject was positive for both tests. Patients with a positive T-SPOT.TB test did not have typical risk factors for LTBI based on clinical evaluation. CONCLUSION: The lack of concordance between the TST and the T-SPOT.TB assay may indicate that the immunoassay is more sensitive, particularly in a patient population taking immunosuppressive medications. It is equally likely that the low prevalence of LTBI in this low-risk population led to an increase in the false-positive rate despite the high sensitivity and specificity of the T-SPOT.TB assay. In the context of our patient population, the T-SPOT.TB assay is likely to be most useful in evaluation of patients with a positive TST, since these patients have a higher pretest probability of having LTBI.
20889599 Increased fracture risk in patients with rheumatic disorders and other inflammatory diseas 2010 Nov OBJECTIVE: To identify the risk of hip and vertebral fractures in patients with rheumatic disorders (RD) and inflammatory bowel diseases (IBD). METHODS: This population-based case-control study assessed the fracture risk of patients with rheumatoid arthritis, juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), systemic lupus erythematosus, polymyositis/dermatomyositis (PM/DM), systemic sclerosis (SSc), Crohn's disease, and ulcerative colitis (UC). The study cohort comprised 53,108 patients with fracture (66% women) and 370,602 age-matched and sex-matched controls. Conditional logistic regression analysis was performed and results were expressed as OR with corresponding 95% CI. RESULTS: There was a statistically significant increased fracture risk for all RD and for IBD compared with controls. The magnitude of fracture risk was higher for patients with RD (OR 3, 95% CI 2.9-3.2) than for those with IBD (OR 1.6, 1.4-1.8). The OR in RD ranged from 2.6 (1.3-4.9) for SSc to 4 (3.4-4.6) for AS. The largest increased fracture risk for vertebral fractures was seen in AS (OR 7.1, 6-8.4) and for hip fractures in JIA (OR 4.1, 2.4-6.9). CONCLUSION: Our results highlight the existence of an increased fracture risk from a variety of underlying causes in patients with RD and IBD. In many inflammatory diseases, implementation of fracture prevention strategies may be beneficial.
27022516 STIFF ELBOW TREATMENT BY INTERPOSING ARTHROPLASTY ASSOCIATED TO HINGED EXTERNAL FIXATOR. 2009 Jan OBJECTIVE: Assess the results of the elbow/fascia lata interposing arthroplasty technique associated to the use of a hinged external fixator in the treatment of stiff elbow. METHODS: Between 2001 and 2006, five cases of stiff elbow were operated and followed up by the Shoulder and Elbow Group of the Santa Casa Misericórdia de São Paulo Medical Sciences School, establishing the following as inclusion criteria: patients with below-functional elbow range of motion associated to degeneration on that joint, for whom total prosthesis had not been indicated. Patients' ages ranged from 21 to 55 years (mean: 38). Male gender was prevalent (four cases), and, in all cases, the dominant side was operated. Concerning etiology, two cases of infectious arthritis sequels, one post-trauma sequel, and two rheumatoid arthritis were found. Preoperative range of motion ranged from 20° to 30° of flexion-extension; in two cases, fixed contracture existed in flexion at 30° and 65°. The patients were assessed according to Bruce-modified AMA criteria. RESULTS: The mean follow up time was 54 months. All patients showed improvement of the Bruce index, which, preoperatively, was 43.5, increasing to 88.2 postoperatively. We found two excellent cases, one good, one fair, and one poor. CONCLUSION: Fascia lata interposing arthroplasty associated to the use of a dynamic external fixator on stiff elbows is a feasible alternative for patients not indicated to total elbow arthroplasty.
21046803 [Efficacy of ceramic on ceramic hip prosthesis in young patients undergoing total hip arth 2010 Oct OBJECTIVE: To investigate the methodology and efficacy evaluation of ceramic on ceramic hip prosthesis in total hip arthroplasty for young patients. METHODS: The clinical data from 65 patients (75 hips) who received ceramic on ceramic hip prosthesis for total hip arthroplasty between February 2004 and September 2006, including unilateral replacement in 55 cases and bilateral replacement in 10 cases. Of 65 patients, there were 41 males and 24 females with an average age of 43.2 years (range, 18-56 years), including 6 cases of femoral head comminuted fractures, 44 cases of aseptic necrosis femoral head, 7 cases of developmental dysplasia of hip with osteoarthritis, 3 cases of congenital dislocation of hip, 2 cases of traumatic arthritis secondary to postoperative acetabulum fracture, 1 case of rheumatoid arthritis, and 2 cases of ankylosing spondylitis. The Harris score was 54.3 +/- 6.7. The disease duration was 1 year and 4 months to 10 years and 7 months with an average of 3 years and 2 months. RESULTS: Healing of incision by first intention was achieved in all patients; no dislocation, infection, and deep venous thrombosis of lower limbs occurred. All patients were followed up 3 years and 2 months to 5 years and 7 months with an average of 4 years and 9 months. The Harris score was significantly improved to 89.0 +/- 9.4 at last follow-up, showing significant difference when compared with preoperative one (P < 0.01). The mean eversion angle and anteversion angle of the acetabular component were (43.6 +/- 8.4) degrees and (21.5 +/- 3.5) degrees, respectively. In follow-up period, no prosthetic loosening, subsidence, dislocation, and ceramic component fracture occurred. Osteolysis was not found in all the cases. CONCLUSION: Ceramic on ceramic hip prosthesis in total hip arthroplasty for young patients can effectively decrease the complications of prosthetic loosening and subsidence caused by wearing of joint interface; the surgical skill is important in decreasing dislocation and fraction of ceramic on ceramic hip prosthesis.
20697481 Primary cemented total hip arthroplasty: 10 years follow-up. 2010 Jul BACKGROUND: Primary cemented total hip arthroplasty is a procedure for non-traumatic and traumatic affections of the hip. Long term follow-up is required to assess the longevity of the implant and establish the procedure. Indo-Asian literature on long term result of total hip arthroplasty is sparse. We present a 10-year follow-up of our patients of primary cemented total hip arthroplasty. MATERIALS AND METHODS: We operated 31 hips in 30 patients with primary cemented total hip arthroplasty. We followed the cases for a minimum period of 10 years with a mean follow-up period of 12.7 years. The mean age of the patients was 60.7 years (range 37-82 yrs) male to female ratio was 2:1. The clinical diagnoses included - avascular necrosis of femoral head (n=15), sero positive rheumatoid arthritis (n=5), seronegative spondylo-arthropathy (n=4), neglected femoral neck fractures (n=3), healed tubercular arthritis (n=2) and post traumatic osteoarthritis of hip (n=2). The prostheses used were cemented Charnley's total hip (n=12) and cemented modular prosthesis (n=19). The results were assessed according to Harris hip score and radiographs taken at yearly intervals. RESULTS: The mean follow-up is 12.7 yrs (range 11-16 yrs) Results in all operated patients showed marked improvement in Harris hip score from preoperative mean 29.2 to 79.9 at 10 years or more followup. However, the non-inflammatory group showed more sustained long term improvement as compared to the inflammatory group, as revealed by the Harris hip score. Mean blood loss was 450ml (+/-3.7 ml), mean transfusion rate was 1.2 units (+/-.3). The complications were hypotension (n=7), shortening >1.5 cm (n=9), superficial infection (n=2) and malposition of prosthesis (n=1). CONCLUSION: The needs of Indian Asian patients, vary from what is discussed in literature. The pain tolerance is greater than western population and financial constraints are high. Thus revision surgery among Indian-Asian patients is less compared to western yard sticks.
20074280 Blocking interleukin-1 in rheumatic diseases. 2009 Dec The role of the potent proinflammatory cytokine IL-1 in disease could clinically be investigated with the development of the IL-1 blocking agent anakinra (Kineret), a recombinant IL-1 receptor antagonist. It was first tested in patients with sepsis without much benefit but was later FDA approved for the treatment of patients with rheumatoid arthritis. More recently IL-1 blocking therapies are used successfully to treat a new group of immune-mediated inflammatory conditions, autoinflammatory diseases. These conditions include rare hereditary fever syndromes and pediatric and adult conditions of Still's disease. Recently the FDA approved two additional longer acting IL-1 blocking agents, for the treatment of cryopyrin-associated periodic syndromes (CAPS), an IL-1 dependent autoinflammatory syndrome. The study of autoinflammatory diseases revealed mechanisms of IL-1 mediated organ damage and provided concepts to a better understanding of the pathogenesis of more common diseases such as gout and Type 2 diabetes which show initial promising results with IL-1 blocking therapy.
19999620 [Arthroplasty of both hips and knees]. 2009 Jul INTRODUCTION: The total joint replacement of the four great human articulations concerns patients with extreme functional impairment of the locomotor system (musculoskeletal system). Most frequently this regards patients with rheumatoid arthritis (RA) or the ones treated operatively in childhood for DDH (Developmental Dysplasia/Dislocation of the Hip) or patients with idiopathic arthritis of the hip and knee. MATERIALS AND METHODS: Eight patients underwent total join replacement of both hips and both knees (four-joint arthroplasty) between 1986 and 2006. For six patients the cause of treatment was RA, for one patient it was an implication of DDH and for the last one it was an implication of idiopathic osteoarthritis of hips and knees. The operative treatment was a multistage process (during one operation only one joint was replaced). The mean age of the patient at the time of the last procedure was 51 years (range 36 to 70 years). The mean follow-up, of four-joint replacement, was 6 years). The mean follow-up of four-joint replacement, was 6 years. We based our outcome evaluation on clinical (HHS, KSS, WOMAC) and radiological examination. RESULTS: The average preoperative Harris score for the group of patients was 35.3, WOMAC score--79.5, and Knee Society Score--38.1. After an average of 6 years follow-up all hips and knees were considered excellent, with average Harris score of 99.4, WOMAC Score of 4.5 and Knee Society Score of 98.3. All patients had increased function and decreased pain. The radiograms of all patients revealed that the acetabular and femoral components and the femoral and tibial ones were correctly positioned with no radiographic evidence of loosening in the last examination. CONCLUSION: Clinical and radiological evaluation of our material showed that total replacement of both hips and knees allows regaining good lower limb function, which helps the patients staying less dependant on the surrounding environment.
19950261 Progressive multifocal leukoencephalopathy: a national estimate of frequency in systemic l 2009 Dec OBJECTIVE: Progressive multifocal leukoencephalopathy (PML) is a rare, typically fatal, central nervous system demyelinating disease that results from reactivation of the JC virus, which generally occurs in immunosuppressed hosts. The aim of this study was to generate a national estimate of the frequency of PML among patients with rheumatic diseases. METHODS: Data were obtained from the Nationwide Inpatient Sample database. This is a 20% sample of all hospital discharges, weighted to represent the entire US inpatient population. Data were analyzed for the years 1998-2005 inclusive, representing 297,797,180 hospital discharges. Cases of PML, systemic lupus erythematosus (SLE), and other rheumatic diseases were identified by diagnostic codes from the International Classification of Diseases, Ninth Revision, Clinical Modification. RESULTS: A total of 9,675 cases of PML were identified. The majority were associated with human immunodeficiency virus (HIV; 7,934 patients [82.00%]), hematologic cancers (813 patients [8.40%]), and solid cancers (274 patients [2.83%]). Among the rheumatic diseases, 43 cases of PML (0.44%) were associated with SLE, 24 (0.25%) with rheumatoid arthritis (RA), and 25 (0.26%) with other connective tissue diseases (CTDs). When patients with other potential risk factors for PML (HIV, malignancy, bone marrow or other organ transplantation) were excluded, the rates of PML per 100,000 discharges coded for SLE, RA, and other CTDs were 4, 0.4 and 2, respectively, compared with a rate of PML in the background population of 0.2/100,000 discharges. CONCLUSION: This study was confined to hospitalized patients with rheumatic diseases, and it was also limited by the lack of information regarding immunosuppressive therapy. Nevertheless, the findings suggest that, although rare overall, PML occurs more commonly in SLE than in other rheumatic diseases.
19050049 Pendrin is a novel autoantigen recognized by patients with autoimmune thyroid diseases. 2009 Feb CONTEXT: Pendrin is an apical protein of thyroid follicular cells, responsible for the efflux of iodide into the follicular lumen via an iodide-chloride transport mechanism. It is unknown whether pendrin is recognized by autoantibodies. OBJECTIVE: Our objective was to examine the prevalence of pendrin antibodies in autoimmune thyroid diseases and compare with that of thyroglobulin, thyroperoxidase, TSH receptor, and sodium iodide symporter antibodies. DESIGN: In a prevalent case-control study, we analyzed the sera of 140 autoimmune thyroid disease cases (100 with Graves' disease and 40 with Hashimoto's thyroiditis) and 80 controls (50 healthy subjects, 10 patients with papillary thyroid cancer, 10 with systemic lupus erythematosus, and 10 with rheumatoid arthritis). Pendrin antibodies were measured by immunoblotting using extract of COS-7 cells transfected with pendrin and a rabbit polyclonal pendrin antibody. RESULTS: Pendrin antibodies were found in 81% of the cases and 9% of controls (odds ratio = 44; P < 0.0001). Among cases, pendrin antibodies were more frequent and of higher titers in Hashimoto's thyroiditis than in Graves' disease. Pendrin antibodies correlated significantly with thyroglobulin, thyroperoxidase, and sodium iodide symporter antibodies but not with TSH receptor antibodies. Pendrin antibodies were equally effective as thyroglobulin and thyroperoxidase antibodies in diagnosis of autoimmune thyroid diseases, especially Hashimoto's thyroiditis. CONCLUSIONS: The study identifies pendrin as a novel autoantigen recognized by patients with autoimmune thyroid diseases and proposes the use of pendrin antibodies as an accurate diagnostic tool.
19188093 Comparisons of affinities, avidities, and complement activation of adalimumab, infliximab, 2009 May The TNF antagonists adalimumab, infliximab, and etanercept are effective treatments for rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis, but only adalimumab and infliximab have been found to be efficacious in Crohn's disease. The present studies evaluated the TNF-binding and complement-activating properties of adalimumab, infliximab, and etanercept to determine whether these properties may explain differences in their clinical efficacy profiles. Association and dissociation rates of binding to soluble TNF were measured by surface plasmon resonance, and were found to be similar for adalimumab, infliximab, and etanercept, as were their calculated binding affinities. Avidity of binding to soluble TNF, measured by KinExA technology, was 10- to 20-fold greater for soluble etanercept (K(D)=0.4 picomolars [pM]) than for soluble adalimumab or infliximab (K(D)=8.6 and 4.2 pM, respectively). (125)I-adalimumab, -infliximab, and -etanercept bound to membrane TNF (mTNF) on mTNF-transfected cells with similar affinities (K(D)=483, 468, and 445 pM, respectively) that were each lower than for soluble TNF. Complement-dependent cytotoxicity (CDC) was induced in mTNF-transfected cells by adalimumab and infliximab, but was not induced in activated normal human PBMC by any of the 3 agents. In conclusion, the binding properties of adalimumab, infliximab, and etanercept were similar for soluble TNF, and very similar for mTNF, yet none of the 3 was able to induce CDC in activated PBMC. These results suggest that the different clinical efficacy profiles of these agents are not explained by differences in either TNF-intrinsic binding properties or complement lysis.
19386818 Anti-cyclic citrullinated peptide and anti-keratin antibodies in patients with idiopathic 2009 Jun OBJECTIVE: To investigate the prevalence of anti-cyclic citrullinated peptide (anti-CCP) and anti-keratin antibodies (AKAs) in a cohort of patients with idiopathic inflammatory myopathy. METHODS: In a cross-sectional study, we determined the presence of anti-CCP and AKAs by ELISA and IIF, respectively, in a cohort of 90 consecutive patients with idiopathic inflammatory myopathy. Associations between anti-CCP and clinical manifestations or other autoantibodies were determined with the chi-square and Mann-Whitney U-tests. Radiographs of hands were retrospectively evaluated. Serum autoantibody profile was determined in all patients. RESULTS: Twelve patients were positive to anti-CCP (13.3%); in eight cases values were moderate-high. AKAs were not detected in any patient. Comparison between patients positive and negative to anti-CCP did not show clinical or biological differences. Arthritis joint erosions or positive status to anti-synthetase antibodies were not more frequent in patients with anti-CCP antibodies. Prevalence of RF was the only variable significantly associated with the presence of these antibodies (P = 0.043). CONCLUSIONS: High titres of anti-CCP can occasionally be found in patients with inflammatory myopathy. Therefore, a possible diagnosis of RA should be considered with caution in these patients.
21199457 Exacerbation of adult-onset Still's disease, possibly related to elevation of serum tumor 2010 Oct Adult-onset Still's disease (AOSD) is a systemic inflammatory disease of unknown etiology. A 44-year-old male patient presented with AOSD complicated by macrophage activation syndrome after etanercept therapy. His serum tumor necrosis factor-α (TNF-α) level was increased dramatically after etanercept therapy. The clinical course of this case suggests that the increased TNF-α level by etanercept administration might cause macrophage activation syndrome in this case.
20399690 Expression of Toll-like receptors 7, 8, and 9 in primary Sjögren's syndrome. 2010 Jun OBJECTIVE: The objective of this study was to investigate the level of Toll-like receptors (TLRs) 7, 8, and 9 in peripheral mononuclear blood cells (PMBCs) from patients with primary Sjögren's syndrome (pSS) and whether TLR7 and 9 exist in the parotid glands of pSS patients. METHODS: TLR7, 8, and 9 mRNA levels in PMBC from 37 pSS patients and 24 controls were determined using real-time polymerase chain reaction. TLR7- and TLR9-positive cells in parotid glands from 20 pSS patients and 10 controls were observed using immunofluorescence and immunohistochemistry, respectively. Statistical analysis was performed by Student t test. RESULTS: TLR7 and TLR9 mRNA levels were 2.17- and 2.33-fold higher in pSS patients than control subjects, respectively (P < .05), whereas TLR8 levels were not. TLR7- and TLR9-positive cells of the pSS group were localized in the epithelial islands, lymphocytes, and ductal epithelial cells of the parotid glands and were more abundant than the TLR7- and TLR9-positive cells that were only localized to the ductal epithelial cells of parotid glands (P < .05). CONCLUSION: TLR7 and TLR9 mRNA levels are up-regulated in the PMBC of pSS patients, and TLR7- and TLR9-positive cells exist in the epithelial islands, lymphocytes, and ductal epithelial cells of the parotid glands of individuals affected by pSS, but are limited to the ductal epithelial cells of controls.
19671451 B cell-targeted therapies in Sjögren's syndrome. 2010 Feb Sjögren's syndrome (SS) or autoimmune epithelitis is characterized by focal lymphocytic infiltrates surrounding the tubular epithelium of exocrine glands and by overactivity of the B-cell population. Although T cells were long considered the main effectors in SS, recent findings indicating a key role for B cells have prompted studies of treatments designed to deplete the B-cell population. Among molecules that can be targeted to achieve B-cell depletion, CD20 and CD22 are surface antigens expressed specifically by B lymphocytes; and the cytokine B-cell-activating factor belonging to the TNF family (BAFF) is a TNF receptor ligand involved in B-cell differentiation, survival, and activation. The aim of this review is to discuss the clinical outcomes of SS patients treated with B-cell depletion.