Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 15509625 | Prevalence of Sjögren's syndrome in ambulatory patients according to the American-Europea | 2005 Feb | OBJECTIVE: To estimate the prevalence of Sjögren's syndrome (SS) in ambulatory patients attending a tertiary care centre, according to the American-European Consensus Group criteria, using a structured approach. METHODS: Three hundred patients from rheumatology and internal medicine clinics were randomly chosen. During the screening phase, a face-to-face interview, a screening questionnaire, a Schirmer-I test and a wafer test were carried out in all patients. During the second phase, patients with positive screening had confirmatory tests including fluorescein staining test, non-stimulated whole salivary flow and autoantibody testing. Confirmatory tests were also done in 13 patients with negative screening. In the last phase, lip biopsy was proposed to those patients who met pre-established criteria. RESULTS: Females constituted 79% of the study population. The mean age of the subjects was 42.8+/-15.7 yr. Two hundred and twenty patients (73%) had positive screening. Fifty-five (27%) out of 204 patients evaluated showed keratoconjunctivitis sicca and 28 (13%) out of 215 patients xerostomia. One hundred and sixty-eight patients met criteria for lip biopsy and it was performed in 80 subjects who accepted the procedure. Focal sialoadenitis was demonstrated in 39 patients (49%), but only 28 of them met criteria for SS. In total, 40 patients were classified as SS. The minimum prevalence of SS in the population studied was 13.3% (95% CI 9.5-17.1%). The structured approach used in this study allowed 24 (60%) undiagnosed cases of SS to be identified. CONCLUSION: SS is common among ambulatory patients attending a tertiary care centre and in most of them it is undiagnosed. | |
| 20476905 | Anakinra in the treatment of rheumatic disease. | 2006 May | Anakinra is a specific receptor antagonist of interleukin-1 that differs from naturally occurring interleukin-1 receptor antagonist by the presence of a methionine group. It is administered by daily subcutaneous injection. Anakinra improves the clinical signs and symptoms of rheumatoid arthritis, slows radiographic progression and improves patient physical function. The most common adverse event is an injection site reaction. Anakinra has been associated with an increased incidence of serious infections and has an increased standardized incidence ratio for lymphoma. It has not been found to be associated with the development of opportunistic infections, worsening of congestive heart failure or the development of demyelinating disease. It appears to be effective in treating adult Stills disease, systemic-onset juvenile idiopathic arthritis and chronic infantile neurological cutaneous and articular syndrome (also known as neonatal-onset multisystem inflammatory disease syndrome). | |
| 16273809 | DANBIO: a nationwide registry of biological therapies in Denmark. | 2005 Sep | Since the year 2000, Danish rheumatologists have been collecting data on a routine basis in the nationwide DANBIO registry, which includes all rheumatologic patients receiving biological drugs. Demographic data, markers of disease activity, current treatment, serious and non-serious adverse events and reasons for discontinuation are registered at each visit either on paper forms or on-line. By June 2005, approximately 3000 treatment courses (18,000 visits) were in the registry, corresponding to close to 90% of eligible patients. Rheumatoid arthritis was the most prevalent diagnosis (75%) followed by ankylosing spondylitis (11%) and psoriatic arthritis (7%). Infections occurred in 43% of the treatment series. | |
| 15851955 | [Optic neuritis associated with infliximab]. | 2005 Feb | Infliximab is a chimeric human-murine monoclonal antibody of the IgG1 type with a high affinity and specificity for tumor necrosis factor alpha (TNFalpha). Infliximab was used in Crohn disease, rheumatoid arthritis, spondyloarthropathy, juvenile idiopathic arthritis, Behcet's disease, Wegener's granulomatosis, HLA-B27-associated uveitis and chronic severe refractory uveitis. Reported adverse effects of this treatment were infections, development of antinuclear antibodies and anti double-stranded DNA, lymphomas, and exacerbation of demyelinating disease. We report a case of infliximab-associated optic neuritis with favorable outcome after systemic steroid treatment. | |
| 20477078 | New insights into eicosanoid biosynthetic pathways: implications for arthritis. | 2006 Mar | Eicosanoid is a collective term for the family of lipid mediators derived from arachidonic acid (AA) metabolism. This complex family of lipids is comprised of prostaglandins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and lipoxins (LXs). The most studied enzymatic pathway for AA metabolism proceeds via cyclooxygenase (COX). However, AA can also be metabolized by the lipoxygenases (LOXs) to LTs and HETEs, and recent studies have demonstrated a unique AA metabolic pathway mediated by both COX and LOX. Eicosanoids are also implicated as important mediators of several chronic inflammatory diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). Current therapies to treat RA and OA symptoms are directed toward the inhibition of enzymes and mediators generated within the eicosanoid pathway. This review will give insights into the current understanding of the eicosanoid biosynthetic pathway and its role in the RA and OA disease states. In addition, current therapies and future therapeutic targets within the eicosanoid pathway for the treatment of RA and OA will be discussed. | |
| 15880818 | Reversal of the immunosuppressive properties of mesenchymal stem cells by tumor necrosis f | 2005 May | OBJECTIVE: Adult mesenchymal stem cells (MSCs) represent promising tools for therapeutic applications such as tissue engineering and cellular therapy. Recent data suggest that, due to their immunosuppressive nature, MSCs may be of interest to enhance allogeneic hematopoietic engraftment and prevent graft-versus-host disease. Using a murine model of rheumatoid arthritis (RA), this study investigated whether the immunosuppressive properties of MSCs could be of therapeutic value to inhibit reactive T cells in autoimmune diseases such as RA. METHODS: In mice with collagen-induced arthritis (CIA), we injected various doses of C3 MSCs at the time of immunization or booster injection, and subsequently evaluated the clinical and immunologic parameters. The immunosuppressive properties of MSCs were determined in vitro in mixed lymphocyte reactions with or without the addition of tumor necrosis factor alpha (TNFalpha). RESULTS: In the CIA model of arthritis, MSCs did not confer any benefit. Both the clinical and the immunologic findings suggested that MSCs were associated with accentuation of the Th1 response. Using luciferase-expressing MSCs, we were unable to detect labeled cells in the articular environment of the knee, suggesting that worsening of the symptoms was unlikely due to the homing of MSCs in the joints. Experiments in vitro showed that the addition of TNFalpha was sufficient to reverse the immunosuppressive effect of MSCs on T cell proliferation, and this observation was associated with an increase in interleukin-6 secretion. CONCLUSION: Our data suggest that environmental parameters, in particular those related to inflammation, may influence the immunosuppressive properties of MSCs. | |
| 15917108 | Consequence or coincidence? The occurrence, pathogenesis and significance of autoimmune ma | 2005 Jun 10 | BACKGROUND: Viruses and virus-induced lymphokines may have an important role in the pathogenesis of autoimmunity (Schattner A. Clin Immunol Immunopathol; 1994). The occurrence and significance of autoimmune manifestations after the administration of viral vaccines remain controversial. METHODS: Medline search of all relevant publications from 1966 through June 2004 with special emphasis on search of each individual autoimmune manifestation and vaccination, as well as specifically searching each viral vaccine for all potential autoimmune syndromes reported. All relevant publications were retrieved and critically analyzed. RESULTS: The most frequently reported autoimmune manifestations for the various vaccinations, were: hepatitis A virus (HAV)--none; hepatitis B virus (HBV)--rheumatoid arthritis, reactive arthritis, vasculitis, encephalitis, neuropathy, thrombocytopenia; measles, mumps and rubella vaccine (MMR)--acute arthritis or arthralgia, chronic arthritis, thrombocytopenia; influenza--Guillain-Barre syndrome (GBS), vasculitis; polio--GBS; varicella--mainly neurological syndromes. Even these 'frequent' associations relate to a relatively small number of patients. Whenever controlled studies of autoimmunity following viral vaccines were undertaken, no evidence of an association was found. CONCLUSIONS: Very few patients may develop some autoimmune diseases following viral vaccination (in particular - arthropathy, vasculitis, neurological dysfunction and thrombocytopenia). For the overwhelming majority of people, vaccines are safe and no evidence linking viral vaccines with type 1 diabetes, multiple sclerosis (MS) or inflammatory bowel disease can be found. | |
| 21289933 | Influence of tumor necrosis factor α in rheumatoid arthritis. | 2005 Dec 21 | OBJECTIVE: Rheumatoid arthritis (RA) is the most prevalent inflammatory rheumatic disorder. It is a chronic and incurable disease that leads to painful inflammation, often irreversible joint damage, and eventually to functional loss. Conventional treatment is based on unspecific immunosuppressive agents, e.g. Methotrexate, Azathioprin or Gold. However, the longterm outcomes of these approaches have been poor with frequently ongoing inflammatory disease activity, functional decline, and temporary or permanent work disability. More recently, antagonists of the human cytokine Tumor Necrosis Factor α (TNF-α) have been introduced that are potent suppressors of inflammatory processes. Infliximab is a chimeric antibody against TNF-α. Etanercept is a soluble human TNF-α receptor. The report assesses the efficacy of TNF-α-antagonists to down-regulate inflammation, improve functional status and prevent joint damage in RA with particular regard to the following indications: Treatment of severe, refractory and ongoing disease activity despite adequate use of conventional antirheumatic agents; and treatment of early RA before conventional treatment failure has been demonstrated. METHODS: A systematic review of the literature is been performed using established electronic databases. The literature search is supplemented by a hand search of journals and publications relevant to RA, reviews of websites of national and international rheumatologic expert societies, as well as contacts to manufacturers. A priori defined inclusion and exclusion criteria are used for literature selection. Analysis and evaluation of included publications are based on standardised criteria sets and checklists of the German Scientific Working Group for Technology Assessment in Health Care. RESULTS: Health Technology Assessment reports and metaanalyses cannot be identified. A total of 12 clinical trials are analysed, as well as national and international expert recommendations and practice guidelines. Numerous non-systematic reviews are found and analysed for additional sources of information that is not identified through the systematic search. Case reports and safety assessements are considered as well. A total of 137 publications is included. The primary outcome measures in clinical trials are suppression of inflammatory disease activity and slowing of structural joint damage. Clinical response is usually measured by standardised response criteria that allow a semi-quantitative classification of improvement from baseline by 20%, 50%, or 70%. In patients with RA refractory to conventional treatment, TNF-α-antagonists are unequivocally superior to Methotrexate with regard to disease activity, functional status and prevention of structural damage. In patients with early RA, TNF-α-antagonists show a more rapid onset of anti-inflammatory effects than Methotrexate. However, differences in clinical response rates and radiologic progression disappear after a few months of treatment and are no longer statistically significant. Serious adverse events are rare in clinical trials and do not occur significantly more often than in the control groups. However, case reports and surveillance registries show an increased risk for serious infectious complications, particularly tuberculosis. Expert panels recommend the use of TNF-α-antagonists in patients with active refractory RA after failure of conventional treatment. Studies that compare Infliximab and Etanercept are lacking. There are no pharmacoeconomic studies although decision analytic models of TNF-α-antagonists for the treatment of RA exist. Based on the results of the models, a combination therapy with Hydroxychloroquin (HCQ), Sulfaslazin (SASP) and Methotrexate as well as Etanercept/Methotrexate can be considered a cost-effective treatment for Methotrexate-resistant RA. CONCLUSIONS: TNF-α-antagonists are clearly effective in RA patients with no or incomplete response to Methotrexate and superior to continuous use of Methotrexate. It refers to both, reduction of inflammatory disease activity including pain relief and improved functional status, and prevention of structural joint damage. Therefore, TNF-α-antagonism is an important new approach in the treatment of RA. There is still insufficient evidence that early use of TNF-α-antagonists in RA prior to standard agents is beneficial and further studies have to be awaited. An analytic model suggests that TNF-α-antagonists are, due to their clinical effectiveness in patients with no or incomplete response to Methotrexate, a cost-effective alternative to common therapies chosen in the subpopulations of patients. Nevertheless, it has to be borne in mind that the acquisition costs of TNF-α-antagonists lead to high incremental costs and C/E ratios, which exceed the common frame of assessing the cost-effectiveness of medical methods and technologies. Hence, society's willingness-to-pay is the critical determinant in the question whether TNF-α-antagonists shall be reimbursed or not, or to define criteria for reimbursement. Changes in the quality of life attributable to the use of TNF-α-antagonists in RA have not yet been assessed which might assist the decision making. With respect of the questions mentioned above and the potential financial effect of a systematic use of TNF-α-antagonists in the treatment of RA, we come to the conclusion that TNF-α-antagonists should not introduced as a standard benefit reimbursed by the statutory health insurers in Germany. | |
| 16457341 | [A case of sarcoidosis manifesting as acute febrile polyarthritis following bronchoalveola | 2005 Dec | A 32-year-old man was incidentally found to have abnormal shadows on a chest X-ray film and was admitted on May 2004. His chest images showed mediastinal and bilateral hilar lymphadenopathy. The serum level of angiotensin-converting enzyme was elevated. We also found non-caseating epithelioid cell granulomas in transbronchial lung biopsy specimens, and confirmed the diagnosis of sarcoidosis. We carried out bronchoalveolar lavage (BAL) for evaluation of disease activity of sarcoidosis. After BAL, he suffered high fever and polyarthralgia. Both ankles were extremely inflamed. We suspected infectious arthropathy caused by atypical pathogens and thus administered antibiotics, but they had no effect at all. Also, no findings suggesting collagen-vascular disorders, including rheumatoid arthritis, were detected. His symptoms improved after three-weeks of treatment with non-steroidal anti-inflammatory drugs. Thus, this case was diagnosed as having acute sarcoid polyarthritis. BAL may have influenced the onset of febrile arthritis in this patient This case indicates that sarcoidosis should be considered as a possible cause of acute febrile polyarthritis. | |
| 15683449 | Genetic segregation of spontaneous erosive arthritis and generalized autoimmune disease in | 2005 Feb | The BXD2 strain of mice is one of approximately 80 BXD recombinant inbred (RI) mouse strains derived from an intercross between C57BL/6J (B6) and DBA/2J (D2) strains. We have discovered that adult BXD2 mice spontaneously develop generalized autoimmune disease, including glomerulonephritis (GN), increased serum titres of rheumatoid factor (RF) and anti-DNA antibody, and a spontaneous erosive arthritis characterized by mononuclear cell infiltration, synovial hyperplasia, and bone and cartilage erosion. The features of lupus and arthritis developed by the BXD2 mice segregate in F2 mice generated by crossing BXD2 mice with the parental B6 and D2 strains. Genetic linkage analysis of the serum levels of anti-DNA and RF by using the BXD RI strains shows that the serum titers of anti-DNA and RF were influenced by a genetic locus on mouse chromosome (Chr) 2 near the marker D2Mit412 (78 cm, 163 Mb) and on Chr 4 near D4Mit146 (53.6 cm, 109 Mb), respectively. Both loci are close to the B-cell hyperactivity, lupus or GN susceptibility loci that have been identified previously. The results of our study suggest that the BXD2 strain of mice is a novel model for complex autoimmune disease that will be useful in identifying the mechanisms critical for the immunopathogenesis and genetic segregation of lupus and erosive arthritis. | |
| 17083618 | Strain differences and the role for HSP47 and HSP70 in adjuvant arthritis in rats. | 2006 Dec | Because of high sequence homology between microbial and endogenous heat shock proteins (HSP), immunological cross-reactivity to microbial HSP has been suggested as a possible cause of the development of autoimmune diseases, such as rheumatoid arthritis. The present study aimed to determine a potential role of HSP47, a molecular chaperone involved in the synthesis and assembly of collagen molecules, and microbial HSP71 (mHSP71) in adjuvant arthritis (AA) in two rat strains: Dark Agouti (DA), susceptible to AA induction and Albino Oxford (AO), which is resistant to AA induction. Immunization with complete Freund's adjuvant (CFA) induced an increased expression of HSP47 in joints of DA rats, which exhibited severe clinical signs of AA at the time of disease peak, while this protein was not detectable in joints of AO rats. In contrast, no strain differences in HSP72 (rat analogue of mHSP71) expressions in joints were observed. The increased levels of anti-HSP47 antibodies were detected in sera of DA rats during the AA peak, while the immunization with CFA increased levels of anti-mHSP71 antibodies in sera of AO rats. HSP47 and mHSP71 reduced proliferation of draining inguinal lymph node cells (LNC) in resistant AO rat strain, leading to a hypothesis that both HSP participated in AA control. Finally, mHSP71 potentiated the apoptotic response of LNC in susceptible DA rat strain. In conclusion, our findings indicate involvement of HSP47 in the development of AA in the rat, and point out to the regulatory role for both HSP47 and mHSP71. | |
| 17048275 | Vaccination against IL-17 suppresses autoimmune arthritis and encephalomyelitis. | 2006 Nov | Interleukin 17 is a T cell-derived cytokine that induces the release of pro-inflammatory mediators in a wide range of cell types. Recently, a subset of IL-17-producing T helper cells (Th17) distinct from Th1 and Th2 cells has been described, which constitutes a new T cell polarization state. Aberrant Th17 responses and overexpression of IL-17 have been implicated in a number of autoimmune disorders including rheumatoid arthritis and multiple sclerosis. Molecules blocking IL-17 such as IL-17-specific monoclonal antibodies have proved to be effective in ameliorating disease in animal models. Hitherto, active immunization targeting IL-17 is an untried approach. Herein we explore the potential of neutralizing IL-17 by active immunization using virus-like particles conjugated with recombinant IL-17 (IL-17-VLP). Immunization with IL-17-VLP induced high levels of anti-IL-17 antibodies thereby overcoming natural tolerance, even in the absence of added adjuvant. Mice immunized with IL-17-VLP had lower incidence of disease, slower progression to disease and reduced scores of disease severity in both collagen-induced arthritis and experimental autoimmune encephalomyelitis. Active immunization against IL-17 therefore represents a novel therapeutic approach for the treatment of chronic inflammatory diseases. | |
| 16971957 | A distinct inflammatory gene expression profile in patients with psoriatic arthritis. | 2006 Oct | Psoriatic arthritis (PsA) is a systemic inflammatory condition featuring polyarthritis associated with psoriasis. Apart from clinical indicators, few biomarkers exist to aid in the diagnosis and management of PsA. We hypothesized that whole blood gene expression profiling would provide new diagnostic markers and/or insights into pathogenesis of the disease. We compared whole blood gene expression profiles in PsA patients and in age-matched controls. We identified 310 differentially expressed genes, the majority of which are upregulated in PsA patients. The PsA expression profile does not significantly overlap with profiles derived from patients with rheumatoid arthritis or systemic lupus erythematosus. Logistic regression identified two lymphocyte-specific genes (zinc-finger protein 395 and phosphoinositide-3-kinase 2B) that discriminate PsA patients from normal controls. In addition, a highly coregulated cluster of overexpressed genes implicated in protein kinase A regulation strongly correlates with erythrocyte sedimentation rate. Other clusters of coregulated, yet suppressed genes in PsA patient blood include molecules involved in T-cell signaling. Finally, differentially expressed genes in PsA fall into diverse functional categories, but many downregulated genes belong to a CD40 signaling pathway. Together, the data suggest that gene expression profiles of PsA patient blood contain candidate novel disease markers and clues to pathogenesis. | |
| 17185416 | Ethanol prevents development of destructive arthritis. | 2007 Jan 2 | Environmental factors are thought to play a major role in the development of rheumatoid arthritis. Because the use of ethanol is widespread, we assessed the role of ethanol intake on the propensity to develop chronic arthritis. Collagen type II-immunized mice were given water or water containing 10% (vol/vol) ethanol or its metabolite acetaldehyde. Their development of arthritis was assessed, as well as the impact of ethanol on leukocyte migration and activation of intracellular transcription factors. Mice exposed daily to this dose of ethanol did not display any liver toxicity, and the development of erosive arthritis was almost totally abrogated. In contrast, the antibody-mediated effector phase of collagen-induced arthritis was not influenced by ethanol exposure. Also, the major ethanol metabolite, acetaldehyde, prevented the development of arthritis. This antiinflammatory and antidestructive property of ethanol was mediated by (i) down-regulation of leukocyte migration and (ii) up-regulation of testosterone secretion, with the latter leading to decreased NF-kappaB activation. We conclude that low but persistent ethanol consumption delays the onset and halts the progression of collagen-induced arthritis by interaction with innate immune responsiveness. | |
| 15902618 | [Asymptomatic myocarditis after infection of the upper respiratory tract]. | 2005 May 27 | HISTORY AND CLINICAL FINDINGS: A 20-year-old patient was hospitalized with persistent high fever after tonsillitis and swelling of the talocalcanean joint. INVESTIGATIONS: The ECG showed a partial right bundle branch block pattern and pathological T inversions on the left precordial leads. Cardiac Troponin I levels were slightly elevated and echocardiography revealed a dyscinetic area at the right ventricular apex. The anti-streptolysin titer was elevated. DIAGNOSIS: Post-streptococcal rheumatic myocarditis. THERAPY AND FOLLOW-UP: Antibiotic therapy for 2 weeks. The patient showed subjective full recovery after 6 weeks. The anti-streptolysin titer further increases. Nuclear spin tomography of the heart reveal postinflammatory alterations at the apex of the right ventricle. CONCLUSION: Rheumatoid fever is a rare diagnosis in developed countries. This case, however, illustrates that the true prevalence of rheumatoid carditis might be underestimated in the presence of only minimal heart-and joint-specific symptoms. | |
| 16670827 | Use of antibodies recognizing cyclic citrullinated peptide in the differential diagnosis o | 2007 Apr | OBJECTIVE: To determine the prevalence of anti-cyclic citrullinated peptide (CCP) antibodies in systemic sclerosis (SSc) and to assess any association between the presence of anti-CCP, radiographic features, and clinical manifestations. MATERIALS AND METHODS: Anti-CCP antibodies and rheumatoid factor (RF) were tested in serum samples from 75 patients with SSc (64 women and 11 men), with a mean age of 59.4 years (range 24-85) with either diffuse (dcSSc) and limited (lcSSc) cutaneous involvement. As a control group, 22 age- and sex-matched healthy controls (HCs) were examined. Standard radiographs of the hands and wrists were examined in each patient. RESULTS: The presence of anti-CCP was found in sera of 10.6% (8/75) patients with SSc (lcSSc 3 of 44, 6.8%; dcSSc 5 of 31, 16.1%). None of the HCs was positive for anti-CCP. The positivity of RF was observed in 19 of 75 (25.3%) SSc patients (lcSSc 10 of 44, 22.7%; dcSSc 9 of 31, 29%). Statistically significant association was found between anti-CCP positivity and the presence of arthritis (p<0.0001) and marginal erosions (p=0.001). CONCLUSION: Our data show that joint involvement is a common presenting feature of SSc. In this report, we show that anti-CCP antibodies can be detected also in patients with SSc, but they are generally less commonly present than in adults with rheumatoid arthritis (RA). Thus, the finding of high titers of anti-CCP antibodies may help to define the diagnosis of overlap syndrome SSc/RA and facilitate diagnosis and appropriate treatment. | |
| 16242302 | Effect of Candida albicans cell wall glucan as adjuvant for induction of autoimmune arthri | 2005 Sep | Collagen-induced arthritis (CIA) is an experimental model of rheumatoid arthritis (RA) and has aided research into the pathogenesis of inflammatory joint disease. Typically, Type II collagen (CII) emulsified with Freund's complete adjuvant (FCA) is injected into DBA/1 mice. After a booster injection, the mice develop inflammation of the paws. But the fact that the immunization of CII alone does not induce arthritis suggests that activation of the immune system by an adjuvant is necessary for induction of the arthritis. In the present study, we investigated the ability of beta-glucans derived from Candida albicans to act as an adjuvant to induce autoimmune arthritis. DBA/1 mice were injected with CII emulsified with FCA or particulate beta-glucan, OX-CA, on day 0 and given a booster at day 21. Mice immunized with CII plus OX-CA developed arthritis at around 7-10 days after the booster injection. Similarly, mice administered CII emulsified with FCA developed arthritis with the same time course. The mice immunized with CII and OX-CA had a more severe arthritis than those immunized with CII and FCA. Histological changes and production of anti-CII antibody were observed regardless of the type of injection. In addition, components of C. albicans were also tested for their ability to induce arthritis as an adjuvant. The results showed that CSBG, which is a soluble beta-glucan, acted as an adjuvant for CIA but CAWS, which is a mannoprotein-beta-glucan complex, did not. In conclusion, beta-glucan derived from C. albicans acted as an adjuvant and the injection with CII resulted in arthritis with the production of anti-CII autoantibody. The results strongly suggested that fungal metabolites such as beta-glucans have the capacity to induce and exacerbate autoimmune diseases such as RA. | |
| 16086083 | Distribution of Epstein-Barr virus in systemic rheumatic disease (rheumatoid arthritis, sy | 2005 Jul | Among systemic rheumatic diseases (SRDs), lymphadenopathy is frequently found in patients with rheumatoid arthritis (RA) and systemic lupus erythematous (SLE). Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs) may occur in patients following methotrexate therapy for RA and dermatomyositis (DM). However, little is known about the distribution of EBV in reactive LPDs in patients with SRDs who had no history of methotrexate therapy. We analyzed 49 such patients (SLE=25, RA=23, DM=1) for the presence and distribution of EBV+ cells using Epstein-Barr virus (EBV)-encoded small RNA (EBER) specific in situ hybridization. A positive signal for EBERs was identified in 9 (SLE=5, RA=4) (18%) of 49 cases, and 3 main distribution patterns of EBER+cells could be delineated: pattern A, more than 500 EBER-positive cells were located in the germinal centers as well as interfollicular area (SLE=2); pattern B, EBER + cells were located in a few germinal centers (RA=2); and pattern C, up to 100 EBER+ cells were located in the interfollicular area (SLE=3, RA=2). Recent EBV infection may be a cause of lymph node lesion in only 2 cases of patients with pattern A. However, the pathognomonic significance of pattern B and pattern C EBER + cell distribution patterns still remains unclear. Our study indicates that the underlying immune deficits of patients with SRDs may also play an important role in the development of EBV-associated LPDs in SRDs, as previously suggested by several authors. | |
| 17117102 | Prominent premalar and cheek swelling: a sign of thyroid-associated orbitopathy. | 2006 Nov | PURPOSE: To describe prominent premalar and cheek swelling as a previously undescribed clinical feature of thyroid-associated orbitopathy (TAO). DESIGN: Retrospective interventional case series. METHODS: A retrospective case review of patients with prominent premalar and/or cheek swelling and TAO was undertaken. All patients who presented from March 2002 to February 2005 with complaints of premalar and/or cheek swelling in TAO were analyzed. RESULTS: Six female patients between the ages of 28 and 66 years (average, 44.2 years) who had complaints of prominent premalar and/or cheek swelling and TAO were included in the study, among 326 new patients with TAO (incidence: 1.84%). Five of the 6 patients had Graves hyperthyroidism. One initially had Hashimoto thyroiditis, which converted to Graves hyperthyroidism. In all cases, TAO preceded the thyroid disease or developed simultaneously (average time from TAO to thyroid disease was 3.0 months). No patient had received corticosteroids before premalar and/or cheek swelling. The premalar and/or cheek swelling was bilateral in all cases, but 2 of 6 were asymmetric. No diurnal fluctuation or tenderness in premalar and/or cheek swelling was noted. All improved incompletely over several months. Brow, eyelid swelling, and orbital-fat hypertrophy on radiologic examination was coincidentally noted in 5 of 6 cases. Pretibial myxedema was noted in one case. One case was associated with another autoimmune disease (rheumatoid arthritis). CONCLUSIONS: Prominent premalar and cheek swelling should be considered among the clinical features of TAO. The true incidence will become apparent as we question and examine patients more carefully regarding this entity and as we review premorbid photographs. | |
| 16393762 | Localization of human glucocorticoid receptor in rheumatoid synovial tissue of the knee jo | 2005 Nov | OBJECTIVE: This study was conducted to investigate the localization of human glucocorticoid receptors (GCRs) in the knee synovium of patients with rheumatoid arthritis (RA) and to evaluate the correlation between GCR expression and the clinical profiles. METHODS: Twenty synovial specimens from RA knees, six from knees with osteoarthritis (OA), and five from knees with traumatic arthritis (TA) were obtained at surgery. The GCRs were stained immunohistochemically. The immunopositive cells were counted at random in the lining (synoviocytes) and sublining layers (fibroblastic and lymphoid cells). The relationship between the GCR-expressing cells and clinical profiles was analysed statistically. RESULTS: GCRs were expressed in the nuclei of synoviocytes and the fibroblastic and lymphoid cells in the sublining layer. The GCR-positivity rate of synoviocytes was 67.1+/-18.4% in RA, 58.7+/-13.5% in OA, and 49.4+/-19.7% in TA, differences between the three groups being statistically insignificant. There was a significant difference in the GCR-positivity rate of sublining fibroblastic cells (p = 0.029), but not synoviocytes or sublining lymphoid cells, from RA patients treated with and without prednisolone, while there was no correlation between the rate for synoviocytes and that for sublining fibroblastic cells from RA patients treated with prednisolone. CONCLUSIONS: GCRs are localized not only on inflammatory lymphoid cells but also on synoviocytes, suggesting that glucocorticoids could act directly on these cells. Furthermore, the rate of GCR expression on synoviocytes and sublining lymphoid cells is less suppressed with low-dose prednisolone, regardless of the duration of treatment. |