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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
18565266 Circulating survivin indicates severe course of juvenile idiopathic arthritis. 2008 Mar BACKGROUND: Survivin is an anti-apoptotic protein that has been recently suggested as a predictive marker of joint destruction in adult rheumatoid arthritis. We assessed the presence of extracellular survivin in patients with juvenile idiopathic arthritis (JIA). METHODS: Survivin levels were assessed in the circulation of 46 patients with JIA and in the age- and gender-matched controls (n=46) having no inflammatory disease, by ELISA. Survivin levels were analyzed with respect to the onset type and the activity of the joint disease. The intensity of inflammation and cartilage turnover was measured as levels of IL-6, serum amyloid A protein (SAA), and cartilage oligomeric matrix protein (COMP), respectively. RESULTS: The levels of extracellular survivin were significantly higher in JIA compared to the controls (p=0.0002). High levels of survivin (above mean + 2SD of the controls) were detected in 8/46 (17% JIA patients. High survivin expression was associated with polyarticular onset, active phase of arthritis. In contrast, survivin was neither related to the levels of IL-6, SAA, nor to COMP. CONCLUSION: Circulating survivin is expressed in a significant group of patients with JIA being associated to a severe course of the disease. It may be potentially used to select children with unfavorable prognosis of JIA who are in need of active pharmacologic treatment.
17763443 Targeting of Gr-1+,CCR2+ monocytes in collagen-induced arthritis. 2007 Sep OBJECTIVE: The chemokine receptor CCR2 is highly expressed on monocytes and considered a promising target for treatment of rheumatoid arthritis. However, blockade of CCR2 with a monoclonal antibody (mAb) during progression of collagen-induced arthritis results in a massive aggravation of the disease. In this study we investigated why CCR2 antibodies have proinflammatory effects, how these effects can be avoided, and whether CCR2+ monocytes are useful targets in the treatment of arthritis. METHODS: Arthritis was induced in DBA/1 mice by immunization with type II collagen. Mice were treated with mAb against CCR2 (MC-21), IgE, or isotype control antibodies at various time points. Activation of basophils and depletion of monocyte subsets were determined by fluorescence-activated cell sorter analysis and enzyme-linked immunosorbent assay. RESULTS: Crosslinkage of CCR2 activated basophils to release interleukin-6 (IL-6) and IL-4. In vivo, IL-6 release occurred only after exposure to high doses of MC-21, whereas application of low doses of the mAb circumvented the release of IL-6. Regardless of the dose level used, the antibody MC-21 efficiently depleted Gr-1+,CCR2+ monocytes from the synovial tissue, peripheral blood, and spleen of DBA/1 mice. Activation of basophils with high doses of MC-21 or with antibodies against IgE resulted in a marked aggravation of collagen-induced arthritis and an increased release of IL-6. In contrast, low-dose treatment with MC-21 in this therapeutic setting had no effect on IL-6 and led to marked improvement of arthritis. CONCLUSION: These results show that depletion of CCR2+ monocytes may prove to be a therapeutic option in inflammatory arthritis, as long as the dose-dependent proinflammatory effects of CCR2 mAb are taken into account.
16966512 Combined antiviral-immunosuppressive treatment in human T-lymphotrophic virus 1-Sjögren-a 2006 Sep BACKGROUND: In several studies, antiretroviral drugs (principally zidovudine) have been used with success in the treatment of myelopathy associated with human T-lymphotrophic virus 1 (HTLV-1) (tropical spastic paraparesis-HTLV-1-associated myelopathy). The retrovirus HTLV-1 has been implicated as a causative agent of Sjögren syndrome (SS) in clinical reports and murine experiments. Moreover, a recognized complication of primary SS is a myelopathy, which has been shown in case reports to respond to immunosuppressive treatment. OBJECTIVE: To describe a patient with a rapidly progressive, extensive myelopathy with evidence of HTLV-1 infection and SS (probably secondary to HTLV-1) in whom we achieved spectacular therapeutic success using combined immunosuppressive and antiviral therapy. DESIGN: Case report. SETTING: University hospital. Patient A young Haitian woman diagnosed with HTLV-1 and SS developed extensive myelopathy leading to severe disability. MAIN OUTCOME MEASURES: Clinical and radiological improvement. RESULTS: Spectacular radiological and clinical recovery as well as stabilization were achieved with combined antiviral and immunosuppressant treatment. Follow-up at 2 years showed no signs of relapse. CONCLUSIONS: Both tropical spastic paraparesis-HTLV-1-associated myelopathy and Sjögren myelopathy are potentially very disabling. Rapidly progressive myelopathy secondary to SS necessitates the introduction of immunosuppressant therapies. The presence of HTLV-1 may confer the necessity to add antiviral therapy.
17603432 Limited arthrodesis for wrist instability. 2006 Apr 28 The knowledge on limited (intercarpal, partial) wrist arthrodeses was summarized on the basis of the contemporary literature review. They are used to treat various conditions of painful wrist pathology such as limited intercarpal arthrosis, instability, scaphoid nonunion, Kienböck's disease and rheumatoid arthritis. The goal of the procedure was pain relieve and maintainance a functional range of motion. The indications, contraindications, limitations of range of motion, nonunion rates of the most frequently performed intercarpal arthrodeses: STT (scaphotrapeziotrapezoid), SC (scaphocapitate), SCL (scaphocapitatolunate), SL (scapholunate), LT (lunotriquetral), CLTH (capitolunotriquetrohamate or four-corner arthrodesis), RL (radiolunate), RSL (radioscapholunate) and RS (radioscaphoid) were presented.
16751702 [Mechanism of cartilage matrix remodeling by Wnt]. 2006 Jun Wnt proteins play central roles in a variety of developmental processes and regulate cell differentiation, cell fate and cell proliferation. It has been also demonstrated that Wnt proteins profoundly participate in cartilage development. Interestingly, activation of Wnt/beta-catenin signaling in chondrocytes induces a profile of matrix degradation enzymes quite similar to that of cartilage matrix degradation such as osteoarthritis and rheumatoid arthritis. In this review we discuss the involvement of Wnt/beta-catenin signaling in pathological cartilage matrix degradation.
17888176 IL-23 induces human osteoclastogenesis via IL-17 in vitro, and anti-IL-23 antibody attenua 2007 This study demonstrates that IL-23 stimulates the differentiation of human osteoclasts from peripheral blood mononuclear cells (PBMC). Furthermore, in vivo blockade of endogenous IL-23 activity by treatment with anti-IL-23 antibody attenuates collagen-induced arthritis in rats by preventing both inflammation and bone destruction. IL-23 induced human osteoclastogenesis in cultures of PBMC in the absence of osteoblasts or exogenous soluble-receptor activator of NF-kappaB ligand (RANKL). This IL-23-induced osteoclastogenesis was inhibited by osteoprotegerin, anti-IL-17 antibody, and etanercept, suggesting that RANKL, IL-17, and TNF-alpha are involved. In addition, we found the ratio of production levels of IL-17 to those of IFN-gamma from activated human T cells was elevated at 1 to 10 ng/ml IL-23. The inductive effect of IL-17 and the inhibitory effect of IFN-gamma on osteoclastogenesis indicate that the balance of these two cytokines is particularly important. We also demonstrated that IL-23 administered at a later stage significantly reduced paw volume in rats with collagen-induced arthritis, in a dose-dependent manner. Furthermore, anti-IL-23 antibody reduced synovial tissue inflammation and bone destruction in these rats. These findings suggest that IL-23 is important in human osteoclastogenesis and that neutralizing IL-23 after onset of collagen-induced arthritis has therapeutic potential. Thus, controlling IL-23 production and function could be a strategy for preventing inflammation and bone destruction in patients with rheumatoid arthritis.
20476924 Celecoxib and ankylosing spondylitis. 2008 May It is now over 100 years since the arrival of aspirin and, from the mid-20th Century onwards, we have seen numerous attempts at providing society with safer and more efficacious nonsteroidal drugs. Ironically, while aspirin went from strength to strength with an ever-increasing pharmaceutical profile, new nonsteroidal anti-inflammatory drugs arrived and disappeared with rapid succession. Finally, there appears to have been a breakthrough with the development of the coxibs but concern has recently developed because of potential toxic cardiovascular reactions. Although originally studied in rheumatoid arthritis and degenerative arthropathy, the coxibs have now been investigated in ankylosing spondylitis and efficacy appears to be favorable and, to date, there is little evidence of toxicity, although problems in the nonspondylarthropathic arena may spill over into the seronegative spondylarthritides.
17598336 Syndrome of remitting seronegative symmetrical synovitis with pitting oedema (RS3PE). 2007 Mar RS3PE syndrome, often mimicking rheumatoid arthritis (RA) or polymyalgia rheumatica (PMR), has puzzled the rheumatologists until late'80s. Though the nature of the disease still remains illusive, the outcome is excellent. This present study analyzes the clinical, radiological and immunogenetical characteristics of five patients diagnosed with RS3PE syndrome, with review of literature.
16546089 CTLA4Ig: bridging the basic immunology with clinical application. 2006 Mar After a very long and windy road, in December of 2005 the FDA approved CTLA4Ig for the treatment of rheumatoid arthritis. Orencia is the first-in-class antagonist of CD28 costimulation. In this perspective, we discuss the science that led to CTLA4Ig development and the clinical challenges in bringing the drug from the bench to the bedside.
17437664 Treatment of osteoarthritis with anakinra. 2007 Apr Osteoarthritis (OA) is the most common form of arthritis and one of the leading causes of disability worldwide. The incidence of OA increases with age, and as longevity increases, it will cause a significant socioeconomic burden. No disease-modifying therapy is available for OA. Recent research has highlighted the role of inflammation in the progression of OA. Interleukin-1 appears to have a significant role in disease progression. Since the interleukin-1 receptor antagonist (IL-1Ra) anakinra has been used successfully in the treatment of the inflammation and bone destruction of rheumatoid arthritis, some have suggested that it may be able to retard the disease progression of OA. This article reviews the data on the use of anakinra in OA treatment.
17228807 [Penicillamine-induced bronchiolitis obliterans diagnosed by transbronchial lung biopsy]. 2006 Feb A 57-year-old woman had been treated with penicillamine (200 mg/day) for degenerative arthritis initially misdiagnosed as rheumatoid arthritis since 2003. She presented with dyspnea and was admitted to our hospital in 2004. Pulmonary function tests revealed mixed pattern of dysfunction with severe airway obstruction. Chest computed tomography showed mosaic ground-glass opacities. Bronchoalveolar lavage fluid (BALF) demonstrated increase in total cells and lymphocytes. Since specimens of transbronchial lung biopsy (TBLB) showed lymphocytic infiltration in membranous bronchiole and occlusion of the membranous bronchiole lumen, bronchiolitis obliterans was diagnosed by TBLB. After penicillamine, which had been administered for 7 months, was stopped, she was successfully treated with steroid and macrolides.
17192581 Interleukin-6: a cytokine and/or a major modulator of the response to somatic stress. 2006 Nov The hypothalamic-pituitary-adrenal (HPA) axis and the proinflammatory cytokines (and interleukin-6 [IL-6] in particular) are enmeshed in the response to somatic stress, either in health or in acute or chronic disease. Usually IL-6 is elevated in states of septic (such as sepsis) or aseptic inflammation (such as rheumatoid arthritis). Exercise is a form of somatic stress. Local tissue IL-6 elevation is noted during shorter and less intense exercise, whereas brief peripheral IL-6 "bursts" are observed with longer and more intense exercise. Therapeutic interventions that target IL-6 or its soluble receptor are currently assessed, with an emphasis on autoimmune diseases and inflammatory conditions.
17021702 Imaging features of musculoskeletal involvement in systemic sclerosis. 2007 May This article describes the radiographic, sonographic and magnetic resonance (MR) features of musculoskeletal involvement in patients with systemic sclerosis (SSc). Conventional radiography is the traditional method of detecting digital calcifications, but ultrasonography (US) is also able to detect such calcifications before they appear on radiographs. MR imaging can be used to diagnose overlapping conditions (i.e., SSc and myositis or SSc and rheumatoid arthritis), and less frequently, to reveal neurologic complications of SSc. In patients with vascular ulcers, MR angiography is able to depict decreased flow within collateral digital arteries.
18500457 Etanercept as a rescue agent in patient with adult onset Still's disease complicated with 2008 Nov Adult onset Still's disease (AOSD) is an uncommon disorder of unknown cause. The clinical symptoms of AOSD are a spiking fever, a typical rash, arthralgia or arthritis, sore throat, lymphadenopathy, and splenomegaly. Pleuropulmonary and cardiac involvement are rare. We report a patient with a two-year history of AOSD with myocarditis refractory to cyclosporine and glucocorticoid. Significant congestive heart failure due to left ventricle dysfunction and hyperferritinemia developed during the hospital course. After therapy with etanercept, the patient's clinical manifestations recovered and she regained normal left ventricular systolic function.
18481155 Dramatic regression of mesenteric abnormalities demonstrated on angiography following pred 2008 A 63-year-old woman, who had been followed for Sjögren's syndrome, was admitted due to cryoglobulinemia, leukocytoclastic vasculitis, and mononeuritis multiplexa. In spite of the administration of 60 mg prednisolone, fecal occult blood was strongly positive. The colonoscopy showed multiple colonic ulcers, and a diagnosis of polyarteritis nodosa (PAN) was made because abdominal angiography revealed markedly serpentine and narrowed superior and inferior mesenteric arteries. After steroid pulse therapy and daily oral administration of cyclophosphamide were initiated, her symptoms improved and abdominal angiographic findings were finally normalized. Although there are only three case reports on improvements in abdominal angiographic findings of PAN in the literature, our case and previously reported cases suggest that improvements in angiographic findings may reflect a good prognosis of PAN.
18296721 Is Inhibitor of differentiation 3 involved in human primary Sjögren's syndrome? 2008 Apr OBJECTIVES: Inhibitor of differentiation 3 (Id3)-deficient mice show sicca symptoms, lymphocyte infiltration of exocrine glands and positive anti-Ro/SSA and anti-La/SSB antibodies, all hallmarks of primary Sjögren's syndrome (pSS). The impairment of Id3 in T cells and, possibly, in salivary glandular epithelial cells (SGECs) seems to be involved. This animal model prompted us to investigate the role of Id3 in human pSS. METHODS: Quantitative Id3 expression in peripheral T cells, cultured SGECs and in total minor salivary glands was assessed by RT-PCR in pSS patients and controls. After Id3 sequencing, we investigated two single nucleotide polymorphisms (SNPs) (c.313G>A and g.-156A>G) in a case-control study of 212 Caucasian pSS patients and 168 controls. RESULTS: Quantitative Id3 expression was not decreased in pSS patients nor in SGECs, in T cells or in minor salivary glands. As well, patients and controls did not differ in allele and genotype frequencies of Id3 SNPs (P = 0.67 and P = 0.71 for the c.313G>A and the g.-156A>G, respectively). Neither SNP was associated with a pattern of autoantibody secretion. CONCLUSION: Although the Id3-deficient mouse model represents an attractive model for human pSS, Id3 expression is not impaired in SGECs, peripheral T cells and in labial salivary glands in pSS patients and Id3-relevant SNPs do not give evidence of genetic predisposition in Caucasian pSS patients.
18276741 Reduction of fatigue in Sjögren syndrome with rituximab: results of a randomised, double- 2008 Nov OBJECTIVE: Primary Sjögren syndrome (pSS) causes significant systemic symptoms including fatigue as well as glandular dysfunction. There are currently no effective systemic therapies; however, open label series have suggested that rituximab may be beneficial for systemic and glandular manifestations. Therefore, we performed a double blind, placebo-controlled, randomised pilot study of the efficacy of rituximab in reducing fatigue in pSS. METHODS: A total of 17 patients with pSS and a score on fatigue visual analogue scale (VAS) >50 were randomised to receive either 2 infusions of rituximab 1 g or placebo; patients also received oral and intravenous steroids. Outcome measures included: the proportion of patients with >20% reduction in fatigue VAS, changes in pSS related symptoms, health related quality of life and immunological parameters of pSS. These were measured 6 months after therapy. RESULTS: There was significant improvement from baseline in fatigue VAS in the rituximab group (p<0.001) in contrast to the placebo group (p = 0.147). There was a significant difference between the groups at 6 months in the social functioning score of SF-36 (p = 0.01) and a trend to significant difference in the mental health domain score of SF-36 (p = 0.06). There was one episode of serum sickness in the rituximab treated group. CONCLUSIONS: This is the first double blind study of rituximab in pSS to show benefit; further studies are justified.
17301515 Membraneous glomerulonephritis and non-Hodgkin's lymphoma in a patient with primary Sjögr 2007 The most common renal manifestation of Sjögren's syndrome is tubulointerstitial nephritis, and glomerular disease is rare (3). A 62-year-old woman with primary Sjögren's syndrome developed nephrotic syndrome. Kidney biopsy was consistent with membraneous glomerulonephritis. Steroid pulse therapy was not effective. Three months later she was diagnosed with non-Hodgkin's lymphoma of the tongue, and she was given CHOP therapy and radiation. Both the lymphoma and membraneous glomerulonephritis were resolved.
18931819 Estrogen and testosterone attenuate extracellular matrix loss in collagen-induced arthriti 2008 Nov Rheumatoid arthritis (RA) is a sexually dimorphic, autoimmune inflammatory disorder affecting the joints. Joint disability in RA results primarily from loss of matrix components (collagen and glycosoaminoglycan) in the cartilage and synovium. This study was carried out to understand the effect of physiological levels of testosterone, estrogen, and progesterone on oxidative stress-induced changes in matrix composition in rat synovium in arthritis. Arthritis induction in castrated and ovariectomized rats resulted in enhanced oxidative stress and this was assessed by lipid peroxidation levels and depletion of antioxidants. This, in turn, led to significantly (p < 0.01) increased levels of TNF-alpha and matrix metalloproteinase-2 (MMP-2), subsequently resulting in loss of collagen, elastin, and glycosoaminoglycan (GAG) and disorganization of reticulin as evidenced by biochemical quantitation and also by staining for collagen, reticulin, and elastin. Treatment with physiological doses of dihydrotestosterone (25 mg topically) and estrogen (5 microg/0.1 ml subcutaneously) restored the antioxidant levels significantly (p < 0.05) and reduced the levels of TNF-alpha and MMP-2, with estrogen exhibiting a higher potency. This, in turn, attenuated the damage to reticulin organization as well as the loss of collagen and GAG in the articular tissues. However, elastin loss could not be attenuated by either treatment. Progesterone (2 mg/0.1 ml subcutaneously) was not shown to have any significance in disease modification, and on the contrary, it inhibited the protective effects of estrogen. However, progesterone contributed to increased collagen levels in the tissues.
17614971 Amelioration of lacrimal gland inflammation by oral administration of K-13182 in Sjögren' 2007 Sep Regulation of the adhesion of mononuclear cells to endothelial cells is considered to be a critical step for the treatment of inflammatory diseases, including autoimmune diseases. K-13182 was identified as a novel inhibitor for these adhesions. K-13182 inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1, CD106) on human umbilical vein endothelial cells (HUVECs) and on mouse vascular endothelial cell line (MAECs) induced by tumour necrosis factor (TNF)-alpha. K-13182 also inhibited the adhesion of mononuclear cells to these HUVECs and MAECs, indicating that K-13182 suppressed these adhesions mediated by cellular adhesion molecules including VCAM-1. To evaluate the therapeutic effect in autoimmune disease model mice, K-13182 was orally administered to non-obese diabetic (NOD) mice as Sjögren's syndrome (SS) model mice. Severe destructive inflammatory lesions were observed in the lacrimal glands of vehicle-treated control mice; however, 8-week administration of K-13182 inhibited the mononuclear cell infiltration into the inflammatory lesions of the lacrimal glands. In K-13182-treated mice, the decrease in tear secretion was also prevented compared to the control mice. In addition, the apoptosis and the expression of FasL (CD178), perforin, and granzyme A was suppressed in the lacrimal glands of K-13182-treated mice. Therefore, K-13182 demonstrated the possibility of therapeutic efficacy for the inflammatory region of autoimmune disease model mice. These data reveal that VCAM-1 is a promising target molecule for the treatment of autoimmune diseases as a therapeutic strategy and that K-13182 has the potential as a new anti-inflammatory drug for SS.