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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
16108239 Diagnostic tests for rheumatic disease: clinical utility revisited. 2005 Jul Establishing a diagnosis of systemic rheumatic disease requires an integration of a patient's symptoms, physical examination findings, and the results of diagnostic testing. There is often a temptation by clinicians to rely heavily on objective measures such as the presence or absence of an autoantibody. Medical textbooks and the medical literature may overestimate the diagnostic utility of many commonly ordered tests for rheumatic disease because the tests are usually analyzed among patients with established rheumatic disease rather than among patients with an uncertain cause of symptoms as is common in practice. Few diagnostic tests are highly sensitive, though the antinuclear antibody in systemic lupus erythematosus (SLE) and the erythrocyte sedimentation rate in temporal arteritis are notable exceptions. Conversely, few diagnostic tests are highly specific; anti-proteinase-3 and antimyeloperoxidase antibodies (types of antineutrophilic cytoplasmic antibodies) among patients with Wegener granulomatosis (and related vasculitides) and anti-double-stranded and anti-Smith antibodies among patients with SLE may be particularly helpful in the proper clinical settings due to their high specificity. Anticitrullinated cyclic protein (anti-CCP), a newly described autoantibody that may be highly specific for rheumatoid arthritis, requires additional study as its utility in clinical practice is uncertain.
15902525 Non-rheumatoid erosive arthritis associated with type I hereditary angioedema. 2005 Nov Hereditary angioedema (HAE) is an autosomal dominant disease that causes recurrent attacks of non-pitting edema of soft tissues, without pruritus. This disorder can also affect internal organs. The cause of HAE consists in quantitative or qualitative defective production of C1 inhibitor (C1-INH). Many autoimmune diseases such as systemic lupus erythematosus (SLE) (or SLE-like syndromes), Sjögren's syndrome, scleroderma, thyroiditis, glomerulonephritis, and inflammatory bowel disease have been described in patients suffering from HAE. A concomitance with pure arthritis was previously reported only in two adult patients. Here, we describe for the first time the association between HAE and a non-rheumatoid erosive oligoarthritis involving hips and wrists.
16213770 Chronic inflammatory joint disease revealing borderline leprosy. 2006 May Musculoskeletal symptoms are not infrequent in leprosy and, when inaugural, may be difficult to differentiate from other conditions, most notably rheumatoid arthritis. We report the case of a 24 year-old man with a 5 year history of intermittent inflammatory arthritis and fever. Physical findings and radiographs were normal initially. Several years later, he had severe wasting of the hand muscles, stocking-glove sensory loss, burn scars on the hands, and plantar ulcers. Electrophysiological test results indicated sensory-motor neuropathy with predominant demyelination. Laboratory tests showed inflammation without immunological abnormalities. A prominent endoneurial inflammatory infiltrate composed of mononuclear cells was seen on a nerve biopsy specimen, suggesting leprosy. A family study then revealed that the patient's aunt had been diagnosed with leprosy. Dapsone, clofazimine, and rifampin were given. The joint manifestations and laboratory tests for inflammation improved. However, no changes were noted in the neurological symptoms.
16095112 Adeno-associated virus vector-mediated anti-angiogenic gene therapy for collagen-induced a 2005 Jul OBJECTIVE: The goal of this study was to determine the utility of adeno-associated virus (AAV) vectors for anti-angiogenic gene therapy in a mouse model of collagen-induced arthritis (CIA). METHODS: CIA mice were generated by immunization with bovine type-II collagen and Freund's complete adjuvant. AAV vectors containing angiostatin and enhanced green fluorescent protein (eGFP) expression units (AAV-Ang/GFP) or the GFP and neomycin phosphotransferase (NeoR) expression units (AAV-GFP/NeoR) were injected into mouse knee joints before development of arthritis. The expression of transgenes was confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and immunostaining, and the incidence and severity of arthritis was determined histologically via assessment of synovial hyperplasia, cartilage erosion and bone erosion. Vascularity in the knee joint was evaluated by immunohistochemical staining with anti-von Willebrand factor antibody. RESULTS: AAV vectors were capable of efficient gene transfer into chondrocytes and synovial cells, and the extent of synovial hyperplasia and other parameters of arthritis were significantly reduced in the knee joints injected with AAV-Ang/GFP compared with the joints treated with either AAV-GFP/NeoR or phosphate-buffered solution (PBS). Reduction in the number of vessels was confirmed in AAV-Ang/GFP-treated joints. CONCLUSION: AAV-vector-mediated local expression of angiostatin efficiently inhibited the development of collagen-induced arthritis in the treated joint. Anti-angiogenic gene therapy using AAV vector may provide a new approach for the effective treatment of rheumatoid arthritis.
15899035 A web tool for finding gene candidates associated with experimentally induced arthritis in 2005 Rat models are frequently used for finding genes contributing to the arthritis phenotype. In most studies, however, limitations in the number of animals result in a low resolution. As a result, the linkage between the autoimmune experimental arthritis phenotype and the genomic region, that is, the quantitative trait locus, can cover several hundred genes. The purpose of this work was to facilitate the search for candidate genes in such regions by introducing a web tool called Candidate Gene Capture (CGC) that takes advantage of free text data on gene function. The CGC tool was developed by combining genomic regions in the rat, associated with the autoimmune experimental arthritis phenotype, with rat/human gene homology data, and with descriptions of phenotypic gene effects and selected keywords. Each keyword was assigned a value, which was used for ranking genes based on their description of phenotypic gene effects. The application was implemented as a web-based tool and made public at http://ratmap.org/cgc. The CGC application ranks gene candidates for 37 rat genomic regions associated with autoimmune experimental arthritis phenotypes. To evaluate the CGC tool, the gene ranking in four regions was compared with an independent manual evaluation. In these sample tests, there was a full agreement between the manual ranking and the CGC ranking for the four highest-ranked genes in each test, except for one single gene. This indicates that the CGC tool creates a ranking very similar to that made by human inspection. The exceptional gene, which was ranked as a gene candidate by the CGC tool but not in the manual evaluation, was found to be closely associated with rheumatoid arthritis in additional literature studies. Genes ranked by the CGC tools as less likely gene candidates, as well as genes ranked low, were generally rated in a similar manner to those done manually. Thus, to find genes contributing to experimentally induced arthritis, we consider the CGC application to be a helpful tool in facilitating the evaluation of large amounts of textual information.
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.
16237212 Layered peptide arrays: high-throughput antibody screening of clinical samples. 2005 Oct High-throughput methods to detect and quantify antibodies in sera and other patient specimens have use for many clinical and laboratory studies, including those associated with cancer detection, microbial exposures, and autoimmune diseases. We developed a new technique, termed layered peptide array (LPA), to serve as a screening tool to detect antibodies in a highly multiplexed format. We demonstrate here that a prototype LPA was capable of producing approximately 5000 measurements per experiment and appeared to be scalable to higher throughput levels. Sera and saliva from Sjögren's syndrome patients served as a test set to examine antibody titers in clinical samples. The LPA platform exhibited both a high sensitivity (100%) and high specificity (94%) for correctly identifying SSB antigen-positive samples. The multiplex capability of the platform was also confirmed when serum and saliva samples were analyzed for antibody reactivity to several peptides, including Sjögren's syndrome antigens A and B. The data indicate that LPA analysis will be a useful method for a number of screening applications.
15687979 [Recurrent facial palsy, primary Gougerot-Sjögren's syndrome and vitamin B12 deficiency]. 2005 Jan 29 INTRODUCTION: Differing cranial nerve involvement has been reported in the context of Gougerot-Sjögren's syndrome. Involvement of the V, III and VII nerves has been reported, the most characteristic being nerve V, notably its lower branch. Rare, well documented, cases of facial palsy have also been described. OBSERVATION: Recurrent facial palsy in a 40 year-old woman revealed a primary Sjögren's syndrome and vitamin B12 deficiency. DISCUSSION: The onset of facial palsy has been linked with Gougerot-Sjögren's syndrome. The contribution of vitamin B12 deficiency is discussed.
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.
15986351 Effective treatment of collagen-induced arthritis by adoptive transfer of CD25+ regulatory 2005 Jul OBJECTIVE: Regulatory T cells play an important role in the prevention of autoimmunity and have been shown to be effective in the treatment of experimental colitis, a T cell-mediated and organ-specific disease. We previously demonstrated that intrinsic CD25+ regulatory T cells modulate the severity of collagen-induced arthritis (CIA), which, in contrast to colitis, is a systemic antibody-mediated disease and an accepted model of rheumatoid arthritis. We undertook this study to determine whether regulatory T cells have the potential to be used therapeutically in arthritis. METHODS: We transferred CD4+,CD25+ T cells into mice exhibiting arthritis symptoms, both immunocompetent mice and mice subjected to lethal irradiation and rescued with syngeneic bone marrow transplantation. RESULTS: A single transfer of regulatory T cells markedly slowed disease progression, which could not be attributed to losses of systemic type II collagen-specific T and B cell responses, since these remained unchanged after adoptive transfer. However, regulatory T cells could be found in the inflamed synovium soon after transfer, indicating that regulation may occur locally in the joint. CONCLUSION: Our data indicate that CD25+ regulatory T cells can be used for the treatment of systemic, antibody-mediated autoimmune diseases, such as CIA.
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.
24223017 Traumatic intratendinous flexor digitorum profundus rupture: A case report. 2005 Fall Intratendinous ruptures of a flexor digitorum profundus tendon are rare in patients who do not have rheumatoid arthritis. A case of a patient with no history of autoimmune disease who suffered a traumatic rupture of the flexor digitorum profundus tendon to the ring finger in the mid-palm is reported.
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.
16491834 A case of polychondritis in a patient with Behçet's disease. 2005 Dec Polychondritis is an inflammatory disorder that affects various catilagenous structures, and the clinical features include auricular, nasal and respiratory tract chondritis. It also involves the eyes, audiovestibular apparatus, joints and vascular structures. Polychondritis can be associated with several rheumatologic diseases such as systemic lupus erythematosus, rheumatoid arthritis and systemic vasculitis. However, polychondritis is a rare complication of Behçet's disease (BD) and only ten cases with combined BD and polychondritis have been reported on around the world. In this report, we describe a 40-year-old Korean man with BD who suffered from polychondritis that manifested as bilateral auricular chondritis, conjunctivitis and arthritis.
15971421 Lack of association between TNF-308 polymorphism and the clinical and immunological charac 2005 May OBJECTIVE: To investigate the previously reported association of tumor necrosis factor alpha (TNF) -308 single nucleotide polymorphism (SNP) with the clinical course and immunological features in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). METHODS: The studied group consisted of 113 consecutive SLE and 65 pSS patients. TNF -308 SNP was determined by the polymerase chain reaction-restriction fragment length polymorphism technique. Clinical and immunological characteristics were assessed according to a standard protocol that included disease activity (SLEDAI) and damage (SLICC Damage Index). Serum TNFalpha levels were measured in samples collected from 32 patients with SLE and 16 with pSS by enzyme-linked immunosorbent assay. RESULTS: The TNF2 allele (A) was observed in 46% and 54% of SLE and pSS patients, respectively. We failed to find any significant association between the -308 SNP and disease manifestations, the presence of autoantibodies or cytokine levels in either group. CONCLUSION: TNF -308 SNP (TNF2) does not exhibit a significant influence on the disease course or immunological response in SLE and pSS. Other genetic and/or environmental factors seem to be required and to be more important than TNF2 allele for the progression of these diseases.
15850591 Reversible cortical lesions in primary Sjögren's syndrome presenting with meningoencephal 2005 May 15 We report a 50-year-old woman with primary Sjögren's syndrome (SjS) who initially showed forgetfulness, and later developed disturbance of consciousness. In addition to aseptic meningoencephalitis revealed by cerebrospinal fluid examination and magnetic resonance imaging (MRI), the presence of serum anti-SS-A and anti-SS-B antibodies and inflammatory findings in lip biopsy indicated primary SjS. Fluid attenuated inversion recovery (FLAIR) of MRI revealed well defined small, high signal intensity areas in the cortex involving the subcortical white matter. Corticosteroid therapy resulted in rapid and nearly complete resolution of the cortical lesions with marked improvement of the clinical manifestations. Memory disturbance is a rare initial manifestation in meningoencephalitis associated with SjS. Our patient with SjS showed inflammatory cortical lesions on MRI, which were reversed by corticosteroid therapy.
17205841 Oral and dental aspects of Sjögren's syndrome. 2006 Winter Sjögren's syndrome is a common condition which can result in significant physical and emotional debility. Dentists can play a pivotal role in the prompt diagnosis, investigation and management of patients with Sjögren's syndrome. A sound understanding of the pathogenesis, presentation and current management of Sjögren's syndrome, will enable the general dental practitioner to make a significant contribution to the oral health and general well-being of those affected by the disease. This article aims to provide the general dental practitioner with a comprehensive and practical guide to current developments and best practise in the care of these individuals.