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ID PMID Title PublicationDate abstract
22505697 Sex differences in pain scores and localization in inflammatory arthritis: a systematic re 2012 Jun OBJECTIVE: To systematically identify and examine reports of sex-stratified pain measurements in patients with inflammatory arthritis. METHODS: Data sources included PubMed (1950 to April 2010), Embase (1980 to April 2010), and manual searches of reference lists and conference abstracts. We included cohort studies and randomized trials comparing pain scores, treatment efficacy at reducing pain, or pain localization, between females and males with inflammatory arthritis [rheumatoid arthritis (RA), ankylosing spondylitis, psoriatic arthritis, and reactive arthritis]. RESULTS: Twenty-six cohorts and 1 randomized trial reported sex-stratified pain scores, and all but 1 cohort identified worse pain scores at enrollment in females. In a metaanalysis of mean visual analog scale (VAS) scores (0 to 10) in 16 RA cohort studies (reporting on 21,612 females and 6871 males), the standardized mean difference in VAS was 0.21 (95% CI 0.16, 0.26). Treatment with disease-modifying therapy results in improvement in mean scores for both sexes; however, female absolute scores remain higher. In 12 spondyloarthropathy cohorts reporting pain localization, females develop more peripheral arthritis during their disease course (68.9% vs 51.2%) but less inflammatory back pain (50.6% vs 66.4%). CONCLUSION: We identified important sex differences in pain scores in inflammatory arthritis, with higher pain levels in females. In spondyloarthritis, females develop more peripheral arthritis and have less frequent spinal involvement compared to males. These differences may affect a clinician's perception of disease severity and activity, and thus influence management decisions.
23163732 Orbital inflammatory disease: unusual presentation of enthesitis in an HLA-B27 spondyloart 2012 Dec BACKGROUND: Orbital inflammatory disease can complicate many systemic inflammatory disorders, including sarcoidosis, vasculitis, Crohn's disease, systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis and scleroderma, but has not been reported with spondyloarthropathies. OBSERVATIONS: The authors describe a 29-year-old woman who developed orbital myositis, in addition to anterior uveitis, sacroiliitis and peripheral arthritis, as a complication of an underlying HLA-B27 related spondyloarthropathy, which responded temporarily to corticosteroid therapy and more completely to adalimumab. CONCLUSIONS: The patient reported herein presents with orbital inflammation as an extra-articular manifestation of HLA-B27 associated undifferentiated spondyloarthropathy. We propose that enthesitis is the likely mechanism of orbital inflammation in this patient.
21513712 Toll-like receptors in rheumatic diseases: are we paying a high price for our defense agai 2011 Dec 1 In the last decade Toll-like receptor (TLR) research has led to new insights in the pathogenesis of many rheumatic diseases. In autoimmune diseases like systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis TLR signaling is likely to be involved in tolerance breakthrough and chronic inflammation via combined Fc gamma receptors and TLR recognition of immune complexes. Furthermore, inflammatory diseases like psoriatic arthritis and gout also show more and more evidence for TLR involvement. In this review we will discuss the involvement of TLR signaling in several rheumatic diseases and stress their similarities and differences based on recent findings.
21406498 GammadeltaT cells in juvenile idiopathic arthritis: higher percentages of synovial Vdelta1 2011 Jun OBJECTIVE: To analyze γδT cell subsets in peripheral blood (PB) and synovial fluid (SF) of patients with juvenile idiopathic arthritis (JIA), and to correlate γδT cell subsets with clinical characteristics. METHODS: γδT cell subsets as percentages of CD3+ T cells in samples of PB (n = 25) and SF (n = 93) were analyzed by flow cytometry in 93 JIA patients. The percentage of Vγ9+ γδT cells after 10 days of in vitro expansion with either interleukin 2 (IL-2) or isopentenyl pyrophosphate (IPP) plus IL-2 was determined. RESULTS: Both Vδ1+ and Vγ9+ γδT cell subsets were detected in SF of all patients, but only the percentage of Vδ1+ cells was higher in SF compared to PB (p < 0.01). The distribution of γδT cell subsets was similar in different JIA subgroups, whereas antinuclear antibody (ANA)-positive patients had a higher percentage of SF Vδ1+ T cells than ANA-negative patients (p < 0.01). The percentage of SF Vδ1+ T cells was inversely associated with age at onset, recurrence of synovitis, and erythrocyte sedimentation rate; and that of SF Vγ9+ T cells was inversely correlated with age at onset and was higher in patients who recovered from disease (n = 15). IPP-induced expansion of SF Vγ9+ T cells correlated with disease remission, whereas the expansion of SF Vγ9+ T cells in media with IL-2 alone was significantly greater in patients with uveitis. CONCLUSION: The percentage of Vδ1+ and Vγ9+ γδT cells among the SF T cells and their ability to respond to IPP or IL-2 correlated with specific outcomes of JIA, suggesting their role in the immunopathogenesis of this disease.
21689408 Combined treatment with dexamethasone and raloxifene totally abrogates osteoporosis and jo 2011 Jun 20 INTRODUCTION: Postmenopausal patients with rheumatoid arthritis (RA) are often treated with corticosteroids. Loss of estrogen, the inflammatory disease and exposure to corticosteroids all contribute to the development of osteoporosis. Therefore, our aim was to investigate if addition of the selective estrogen receptor modulator raloxifene, or estradiol, could prevent loss of bone mineral density in ovariectomized and dexamethasone treated mice with collagen-induced arthritis (CIA). METHODS: Female DBA/1-mice were ovariectomized or sham-operated, and CIA was induced. Treatment with dexamethasone (Dex) (125 μg/d), estradiol (E2) (1 μg/d) or raloxifene (Ral) (120 μg/day) alone, or the combination of Dex + E2 or Dex + Ral, was started after disease onset, and continued until termination of the experiments. Arthritic paws were collected for histology and one of the femoral bones was used for measurement of bone mineral density. RESULTS: Dex-treatment alone protected against arthritis and joint destruction, but had no effect on osteoporosis in CIA. However, additional treatment with either Ral or E2 resulted in completely preserved bone mineral density. CONCLUSIONS: Addition of raloxifene or estradiol to dexamethasone-treatment in experimental postmenopausal polyarthritis prevents generalized bone loss.
21624346 Keratan sulfate and related murine glycosylation can suppress murine cartilage damage in v 2011 Jun 17 Keratan sulfate (KS) proteoglycan side chains are abundant in the human cartilage matrix, but these chains have been said to be absent in murine skeletal tissues. We previously showed that KS suppresses cartilage damage and ameliorates inflammation in mice arthritis model. Because mice deficient of N-acetylglucosamine 6-O-sulfotransferase-1 (GlcNAc6ST-1) (KS biosynthesis enzyme) are now available, we decided to do further examinations. We examined, in culture, the difference between GlcNAc6ST-1(-/-) and wild-type (WT) mice for interleukin (IL)-1α-induced glycosaminoglycan (GAG) release from the articular cartilage. Arthritis was induced by intravenous administration of an anti-type II collagen antibody cocktail and subsequent intraperitoneal injection of lipopolysaccharide. We examined the differences in arthritis severities in the two genotypes. After intraperitoneal KS administration in phosphate-buffered saline (PBS) or PBS alone, we evaluated the potential of KS in ameliorating arthritis and protecting against cartilage damage in deficient mice. GAG release induced by IL-1α in the explants, and severity of arthritis were greater in GlcNAc6ST-1(-/-) mice than their WT littermates. Intraperitoneal KS administration effectively suppressed arthritis induction in GlcNAc6ST-1(-/-) mice. Thus, GlcNAc6ST-1(-/-) mice cartilage is more fragile than WT mice cartilage, and exogenous KS can suppress arthritis induction in GlcNAc6ST-1(-/-) mice. Vestigial KS chain or altered glycosylation in articular cartilage in GlcNAc6ST-1(-/-) mice may be protective against arthritis and associated cartilage damage as well as cartilage damage in culture. KS may offer therapeutic opportunities for chondroprotection and suppression of joint damage in inflammatory arthritis and may become a therapeutic agent for treating rheumatoid arthritis.
23037170 Anti-arthritic effect of eugenol on collagen-induced arthritis experimental model. 2012 This study was designed to test the efficacy of eugenol, a compound obtained from the essential oil of cloves (Syzygium aromaticum) in collagen-induced arthritis (CIA), a well characterized murine model of rheumatoid arthritis. Macroscopic clinical evidence of CIA manifests first as periarticular erythema and edema in the hind paws. Treatment with eugenol starting at the onset of arthritis (day 25) ameliorated these clinical signs of CIA. Furthermore, eugenol inhibited mononuclear cell infiltration into the knee joints of arthritic mice and also lowered the levels of cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ and tumor growth factor (TGF)-β) within the ankle joints. Eugenol treatment did not affect the in vitro cell viability as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Therefore, eugenol ameliorates experimental arthritis and could be useful as a beneficial supplement in treating human arthritis.
22949948 Minocycline-induced periarticular black bones in inflamed joints which underwent arthropla 2012 Sep BACKGROUND: Minocycline-induced pigmentation of bone (black bone) is well described in tooth-bearing intra-oral bone, but is less known in periarticular bone in patients who have undergone total joint arthroplasty. On a retrospective basis, we investigated the short-term clinico-radiological results of total joint arthroplasties in which the patient developed minocycline-induced periarticular black bone. METHODS: We found 5 cases (0.08%), in 4 patients, of periarticular bone pigmentation revealed during total joint arthroplasties (2 hips, 2 knees, and 1 ankle) in our series of total joint surgeries (6,548 cases) over a 10-year time period in our 3 institutes. Their mean age was 56 years at surgery. All patients had received long-term minocycline treatment. Mean dosage and duration of minocycline was 160 mg/day and 2.2 years, respectively. Minocycline had been prescribed for reactive arthritis (one), rheumatoid arthritis (two) and late infection after total joint arthroplasty (two patients). Mean follow-up period was 3.4 years after the surgeries. RESULTS: All cases had black or brown pigmentation in the periarticular bones during the surgery. There was no pigmentation in the cartilage or soft tissues of the joints. The mean Japanese Orthopaedic Association (JOA) score or Japanese Society for Surgery of the Foot (JSSF) scale for rheumatoid arthritis foot and ankle joints at latest follow-up (case 1, 66; case 2, 87; case 3, 77; case 4, 77; case 5, 80) improved compared to those of pre-surgery (case 1, 47; case 2, 45; case 3, 55; case 4, 34; case 5, 55). No implant loosening was noted on radiographic examination during the follow-up period. No abnormal bone formation, bone necrosis, hemosiderin deposition, malignancy or metallic debris was found on histological examination. CONCLUSIONS: No clinico-radiological symptoms of total joint arthroplasties showed in the patients with minocycline-induced periarticular black bone in the short-term. Systemic minocycline treatment has the potential to induce significant black pigmentation of many tissues. In particular, minocycline-induced pigmentation of periarticular bone may be accelerated by inflammation due to rheumatic or pyogenic arthritis. Surgeons should recognize the risk of bone pigmentation in inflamed joints due to the systemic treatment of minocycline and explore its influence on periarticular bone and total joint arthroplasty in the long-term.
22325471 CTLA4-FasL fusion product suppresses proliferation of fibroblast-like synoviocytes and pro 2012 Mar Fibroblast-like synoviocytes (FLSs) contribute significantly to the pathogenesis of Rheumatoid arthritis (RA). Through introducing apoptosis inducer FasL to suppress the proliferation of arthritic FLSs may provide an efficient approach for treatment of RA. CTLA4-FasL, a fusion product integrating two inhibitory elements of CTLA4 (which can induce T cell anergy through blocking costimulatory signal) and FasL (which may upregulate Fas-mediated apoptosis in inflammatory synoviocytes) into one molecule, might be a desirable engineered derivative of soluble FasL which exerts severe side effects and poor activities. In present study, we investigated the possible effect of CTLA4-FasL protein on suppressing the proliferation of inflammatory FLSs and inflammation in experimental model of RA. The purified CTLA4-FasL protein exerted a significant proliferation-inhibition activity to activated arthritic FLSs through both unbounded free and membrane-anchorage manners. CTLA4-FasL gene delivery by recombinant adeno-associated virus (rAAV) vector in joint, provided more powerfully preventive effects than mature FasL on rat adjuvant-induced arthritis (AIA) as reflected in clinical signs and typically histological characters. Treatment with rAAV.CTLA4-FasL also significantly decreased the levels of key proinflammatory cytokines in AIA joints. Our observations indicate that CTLA4-FasL protein represents a significantly suppressive effect on inflammatory FLSs' proliferation and CTLA4-FasL gene transfer profoundly suppresses AIA, implicating potential application for treatment of RA by local joint delivery of CTLA4-FasL.
22129323 Metastatic melanoma in a young woman treated with TNF-α inhibitor for psoriatic arthritis 2011 Sep 1 INTRODUCTION: The risk of cancer with the use of biologic agents in rheumatic diseases is still a matter of debate. Published data suggest that the extent of cancer risk might differ according to the type of cancer, and there is recent clinical evidence for a significant increased risk for skin cancer, including melanoma. In contrast with the extensive literature on cancer risk in rheumatoid arthritis, little has been reported on the development of malignancies in spondyloarthroparthies. CASE PRESENTATION: We report the case of an otherwise healthy 31-year-old Italian woman with psoriasic arthritis who developed a melanoma of left third toe with metastatic involvement of regional lymphnodes after a 3-year treatment with the TNF-alpha inhibitor adalimumab. CONCLUSION: This case illustrates the possibility of a causal relationship between TNF-alpha inhibitors and melanoma. We believe that vigilance should continue in patients treated with TNF-alpha blocking agents, until the question on the increased incidence of cancers, including skin cancers, associated with these drugs will be defined.
22782381 Chondroclasts are mature osteoclasts which are capable of cartilage matrix resorption. 2012 Aug Multinucleated cells termed chondroclasts have been observed on the deep surface of resorbed hyaline cartilage but the relationship of these cells to macrophages and osteoclasts and their role in rheumatoid arthritis (RA) and other arthritic conditions is uncertain. Multinucleated cells in RA and other arthritic conditions showing evidence of cartilage resorption were characterised immunohistochemically for expression of macrophage/osteoclast markers. Mature human osteoclasts formed from circulating monocytes and tissue macrophages were cultured for up to 4 days on slices of human cartilage and glycosaminoglycan (GAG) release was measured. Multinucleated cells resorbing unmineralised cartilage were seen in osteoarthritis, RA, septic arthritis, avascular necrosis and in four cases of giant cell tumour of bone that had extended through the subchondral bone plate. Chondroclasts expressed an osteoclast-like phenotype (TRAP+, cathepsin K+, MMP9+, CD14-, HLA-DR-, CD45+, CD51+ and CD68+). Both macrophages and osteoclasts cultured on cartilage released GAG. These findings indicate that chondroclasts have an osteoclast-like phenotype and that mature human osteoclasts are capable of cartilage matrix resorption. Resorption of unmineralised subchondral cartilage by chondroclasts and macrophages can be a feature of joint destruction in inflammatory and non-inflammatory arthropathies as well as inflammatory and neoplastic subchondral bone lesions.
22855851 Total hip arthroplasty in the very young patient. 2012 Aug The surgical management of end-stage hip disease in patients aged <30 years remains a challenge. Hip-preserving surgical procedures in the setting of advanced disease often do not provide adequate pain relief, but the implications of joint arthroplasty surgery in the very young patient are a matter of concern. The outcome of total hip arthroplasty (THA) in these patients varies, largely because of the wide spectrum of diagnoses associated with hip disease in this group, the complexity of deformities requiring THA, and the need for prolonged durability. The greatest number of THAs in this population is performed for secondary osteoarthritis or osteonecrosis, whereas most reports in the orthopaedic literature have focused on the outcomes of cemented THA in patients with juvenile rheumatoid arthritis. Given the frequent complexity of THA in the very young patient, special attention should be given to preoperative planning, implant selection, and patient education as well as to joint-preservation techniques to facilitate future hip arthroplasty surgery.
22704838 Anti-Ro52 antibody testing influences the classification and clinical characterisation of 2012 Sep OBJECTIVES: To evaluate how determination of antibodies against the Ro52 antigen influences the classification and clinical characterisation of patients with suspected primary Sjögren's syndrome (SS). METHODS: The cohort study included 187 patients who fulfilled at least four of the six 1993 SS classification criteria, including positive autoantibodies (antinuclear antibodies [ANA], rheumatoid factor [RF], anti-Ro/SSA and/or anti-La/SS-B antibodies) as mandatory criterium. Anti-Ro/SSA antibodies were tested by qualitative ELISA using a commercial assay. Anti-Ro52 antibodies were detected by a semiquantitative ELISA. RESULTS: Anti-Ro52 antibodies were found in 70/187 (37%) patients. A significant percentage of patients with anti-Ro/SSA antibodies were negative for anti-Ro52 antibodies (22%), while 13 patients (12%) were negative for anti-Ro/SSA antibodies but positive for anti-Ro52 antibodies, meaning that they fulfilled the 2002 SS criteria while avoiding the need for a salivary biopsy. Higher mean titers of anti-Ro52 antibodies were associated with severe scintigraphic involvement, positive salivary gland biopsy, parotid enlargement, anaemia, leukopenia and RF. A statistical correlation was found between anti-Ro52 titers and age, gammaglobulin levels, RF titers and serum IgA and IgG. Patients with positive anti-Ro/SSA and anti-Ro52 antibodies had a higher frequency of positive salivary gland biopsy, parotid enlargement and positive RF, and higher levels of serum IgG and IgA levels in comparison with patients with positive anti-Ro/SSA but negative anti-Ro52 antibodies. CONCLUSIONS: Anti-Ro52 antibodies were closely associated with the main clinical, histopathological and immunological features of primary SS. Anti-Ro52 autoantibody testing may help to identify a specific subset of SS patients with more aggressive disease, in whom a closer follow-up and earlier, more robust therapeutic management may be necessary.
22215450 Temporal bone histopathology and immunoglobulin deposition in Sjogren's syndrome. 2012 Feb HYPOTHESIS: The histopathology of Sjogren's syndrome (SS) in the human inner ear correlates with mouse models of autoimmune inner ear disease. BACKGROUND: SS is an autoimmune disease in which 25% of patients have sensorineural hearing loss (SNHL). The inner ear histology in a SS mouse model has shown degeneration of the stria vascularis (SV) and immunoglobulin G deposition on the basement membrane of SV blood vessels. Correlation with human temporal bone histopathology has not been addressed. METHODS: The histopathology and immunohistochemistry of the inner ear in 4 patients with SS is described and compared with SS mouse models. RESULTS: The histopathology of the inner ear in 3 patients with SS and SNHL showed severe loss of the intermediate cells of the SV and immunoglobulin G deposition on the basement membrane of SV blood vessels. These results parallel those of known SS mouse models. Additionally, there was shrinkage of the spiral ganglia neurons in 2 patients, whereas vestibular ganglia neurons were preserved. The fourth patient with SS and normal hearing showed only mild SV atrophy. CONCLUSION: This is the first study describing the pathologic changes in the inner ear of 4 patients with SS. The 3 SS specimens with SNHL showed pathologic changes in the SV similar to the mouse model of autoimmune inner ear disease. Additionally, we propose that spiral ganglia neurons may be directly affected by SS pathology. These results highlight the importance of correlating the histopathology of human temporal bones with animal models to better understand inner ear disease in future research.
22208657 Primary Sjögren's syndrome and the type I interferon system. 2012 Aug Patients with primary Sjögren's syndrome (pSS) have an activated type I interferon (IFN) system that contribute to the etiopathogenesis and clinical manifestations of the disease. The type I IFN system consists of the stimuli for type I IFN production, the receptors, cells and transcription factors involved in the synthesis of type I IFNs, the type I IFN-receptor and the effects on target cells. Increased type I IFN activity has been demonstrated in sera from patients with pSS and IFN-α, the main type I IFN, has been detected in the minor salivary glands. Gene expression profiling of peripheral blood mononuclear cells (PBMCs) and minor salivary glands from pSS patients display an up-regulation of type I IFN-induced genes, an "IFN signature". The professional IFN-α producing plasmacytoid dendritic cell (pDC) shows a reduced frequency in the peripheral blood, but has been detected in the salivary glands, possibly due to tissue recruitment. Polymorphisms in the interferon regulatory factor 5 (IRF5) and signal transducer and activator of transcription 4 (STAT4) genes in the type I IFN system, are associated with increased risk for pSS. A postulated disease model is that an initial viral infection induces type I IFN production in the salivary glands with subsequent activation of the adaptive immune system resulting in the production of autoantibodies against the RNA-binding proteins SSA/SSB/RNP. Interferogenic immune complexes are formed, which trigger the pDCs to an ongoing type I IFN production, which sustain the disease process. Potential therapeutic targets can be identified within the type I IFN system.
22426566 MRI assessment of bone marrow in children with juvenile idiopathic arthritis: intra- and i 2012 Jun BACKGROUND: Bone marrow oedema (BMO) is included in MRI-based scoring systems of disease activity in adults with rheumatoid arthritis. Similar systems in juvenile idiopathic arthritis (JIA) are lacking. OBJECTIVE: To assess the reproducibility in a multi-centre setting of an MRI BMO scoring system in children with JIA. MATERIALS AND METHODS: Seventy-six wrist MRIs were read twice, independently, by two experienced paediatric radiologists. BMO was defined as ill-defined lesions within the trabecular bone, returning high and low signal on T2- and T1-weighted images respectively, with or without contrast enhancement. BMO extension was scored for each of 14 bones at the wrist from 0 (none) to 3 (extensive). RESULTS: The intra-observer agreement was moderate to excellent, with weighted kappa ranging from 0.85 to 1.0 and 0.49 to 1.0 (readers 1 and 2 respectively), while the inter-observer agreement ranged from 0.41 to 0.79. The intra- and inter-observer intraclass correlation coefficients were excellent and satisfactory, respectively. CONCLUSION: The scoring system was reliable and may be used for grading bone marrow abnormality in JIA. The relatively large variability in aggregate scores, particularly between readers, underscores the need for thorough standardisation.
22389056 Anti-inflammatory effect of piperine in adjuvant-induced arthritic rats--a biochemical app 2012 Aug The present study was undertaken to investigate the anti-inflammatory effect of piperine against adjuvant-induced arthritis in rats, an experimental model for rheumatoid arthritis and compared it with that of the non-steroidal anti-inflammatory drug indomethacin. Administration of heat-killed Mycobacterium tuberculosis (0. 1 ml) intradermally into the right hind paw of rats resulted in increased paw volume, lysosomal enzymes, glycoproteins and tissue marker enzymes and decreased body weight. However, these changes were reverted to near normal levels upon piperine (30 mg/kg body weight, i.p.) treatment. Histopathological analysis of joints also revealed that synovial hyperplasia and mononuclear infiltration observed in arthritic rats were alleviated by piperine. Thus, the present study clearly indicated that piperine possesses promising anti-inflammatory effect against adjuvant-induced arthritis by suppressing inflammation and cartilage destruction.
22325451 Heme oxygenase-1 end-products carbon monoxide and biliverdin ameliorate murine collagen in 2012 Jan OBJECTIVES: Heme oxygenase-1 (HO-1) which degrades Heme to free iron, biliverdin and carbon monoxide (CO) plays an important role in inflammation. There are, however, conflicting data concerning the role of HO-1 in rheumatoid arthritis (RA) and the therapeutic potential of individual heme degradation products remains to be determined. We therefore investigated the effect of CO and biliverdin upon therapeutic administration in the murine collagen induced arthritis (CIA) model of RA. METHODS: CIA was induced in DBA/1 mice. Anti-CII antibody levels were determined by ELISA. Mice were scored for paw swelling and grip strength. After the first clinical signs of arthritis one group of animals was treated with biliverdin, the second group was treated with CO. After 60 days all animals were sacrificed and analysed for histomorphological signs of arthritis. RESULTS: All animals immunised with CII developed serum anti-CII antibodies. Antibody levels were decreased in the CO-treated group. Both, Biliverdin and the CO-treated animals, showed an improvement in clinical disease activity. Histological analysis revealed significantly less inflammation, erosion and reduced numbers of osteoclasts in CO-treated animals only, whereas cartilage degradation was prevented in both biliverdin and CO-treated animals. CONCLUSIONS: Our data demonstrate a beneficial effect of CO, in particular, and biliverdin, on inflammation and bone destruction in the CIA mouse model.
21530496 Inhibition of TNF-α-mediated inflammatory responses by a benzodioxolylacetylamino-linked 2011 May 20 The pathologic processes of rheumatoid arthritis are mediated by a number of cytokines, chemokines, and matrix metalloproteinases, the expressions of which are controlled by NF-κB. This study was performed to explore the effects of a benzothiazole analog, SPA0537, on the control of the NF-κB activation pathway. We also investigated whether SPA0537 had any anti-inflammatory effects in human rheumatoid fibroblast-like synoviocytes (FLS). SPA0537 inhibited the nuclear translocation and the DNA binding of NF-κB subunits, which correlated with the inhibitory effects on IKK phosphorylation and IκBα degradation in TNF-α-stimulated rheumatoid FLS. These events further suppressed chemokine production, matrix metalloproteinase secretion, and TNF-α-induced cell proliferation. In addition, SPA0537 inhibited the osteoclast differentiation induced by macrophage colony-stimulating factor (MCSF) and receptor activator of the NF-κB ligand (RANKL) in bone marrow macrophages. These findings suggest that SPA0537 exerts anti-inflammatory effects in rheumatoid FLS through the inhibition of the NF-κB pathway. Therefore, it may have therapeutic value for the treatment of rheumatoid arthritis.
21658295 Recent advances in the immunogenetics of idiopathic inflammatory myopathy. 2011 May 26 This review summarizes the previous and current literature on the immunogenetics of idiopathic inflammatory myopathy (IIM) and updates the research progress that has been made over the past decade. A substantial part of the genetic risk for developing adult- and juvenile-onset IIM lies within the major histocompatibility complex (MHC), and a tight relationship exists between individual human leukocyte antigen alleles and specific serological subtypes, which in turn dictate clinical disease phenotypes. Multiple genetic regions outside of the MHC are increasingly being identified in conferring IIM disease susceptibility. We are still challenged with the task of studying a serologically and clinically heterogeneous disorder that is rarer by orders of magnitude than the likes of rheumatoid arthritis. An ongoing and internationally coordinated IIM genome-wide association study may provide further insights into IIM immunogenetics.