Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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12022351 | Oral and ocular manifestations in Sjögren's syndrome. | 2002 May | OBJECTIVE: Little is known about the relationship between lachrymal and salivary gland involvement in Sjögren's syndrome (SS). It is also of interest to know which eye test contributes most to the diagnosis of SS. We investigated the performance of different tear tests and how these tests relate to common serologic and salivary tests in SS. METHODS: In patients suspected of SS, the tear breakup time and the tear mucus score were evaluated in addition to the routine tests. Eighty consecutive patients were included, categorized into primary SS (pSS), secondary SS (sSS), and negative for SS. RESULTS: The tear breakup time and mucus score both performed insufficiently in diagnosing SS, in contrast to the Rose Bengal score. In pSS and sSS patients, a clear correlation was noted between tear and saliva quality and secretion rate, and between the Rose Bengal score and parotid sialography. Increased Rose Bengal scores also correlated significantly with hyperglobulinemia and presence of SSB antibodies in serum, with duration of subjective eye dryness, and with decreased tear gland function. CONCLUSION: The Rose Bengal score remains the eye test of choice having the highest specificity for SS. Hyperglobulinemia and especially positive SSB serology may warrant close monitoring of the eyes, since these serum findings appear to relate to the severity of ocular surface damage. Theoretically, a positive evaluation of either the ocular or oral component, in addition to positive serology or histopathology, could be sufficient to diagnose the syndrome for clinical purposes. | |
15552021 | [Rheumatologic manifestations of parvovirus B19 infection]. | 2004 Jul | Rheumatologic manifestations of parvovirus B19 infection is a recent individualization. They are rather frequent and varied and meet at the young adult's. Generally, it is responsible for acute, bilateral and symmetrical arthritis, usually involving distal joints and sometimes associated to signs caused by viral infections. Prolonged articular forms were discribed but are rare being able to sometimes feign a nocive rheumatoid arthritis because of their clinical aspect and of a seropositivity. Axial manifestations were also reported. The diagnosis of the recent infection by the parvovirus B19 can be confirmed by ELISA identification of specific IgM antibodies. The mechanism of the articular manifestations is still unknown and the link between parvovirus B19 and systemic vasculitis is questioned. | |
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. | |
15088297 | Polymorphisms of IL-1 beta gene in Japanese patients with Sjögren's syndrome and systemic | 2004 Apr | OBJECTIVE: Interleukin (IL)-1 beta is a proinflammatory cytokine involved in various immune responses. Five polymorphisms in the IL-1 beta gene have been described, and relationships between these polymorphisms and some autoimmune diseases have been reported. Evidence suggests that IL-1 beta may be involved in the destruction of salivary and lacrimal glands in Sjögren's syndrome (SS). We evaluated the significance of IL-1 beta gene polymorphisms in SS. METHODS: Blood samples were taken from 101 patients with SS, 103 patients with systemic lupus erythematosus (SLE, excluding those with secondary SS), and 106 healthy volunteers. Each polymorphism of the IL-1 beta gene was analyzed by polymerase chain reaction (PCR) amplification of the polymorphic site, followed by site-specific restriction digestion. Genotype frequencies of each polymorphism in SS patients were compared with those of the controls and SLE patients, and differences between primary and secondary SS patients were also compared. RESULTS: Genotypes CC, TT, and AA in positions -511, -31, and 3877, respectively, were significantly less frequent in SS patients than controls or patients with SLE. No significant differences were found in genotype frequencies of any of the polymorphisms between patients with primary SS and secondary SS. CONCLUSION: IL-1 beta gene polymorphisms may affect susceptibility to SS, but not SLE. | |
14531959 | Recent advances in understanding molecular mechanisms in the pathogenesis and antibody pro | 2003 Aug | Sjögren's syndrome is a chronic autoimmune and rheumatic disorder of the mucous membranes caused by a lack of proper exocrine secretions, with prominent sicca complaints. The molecular mechanisms of the pathogenesis are virtually unknown, although progress has been made with regard to chemokines, B cell activating factor, and apoptosis. A large number of autoantibodies have been reported in Sjögren's syndrome, some of which relate to impairment of glandular function. Sjögren's syndrome is a female-dominant disease with a late age of onset; most patients contract the disease at the age of 40 to 50 years. Lately, attention has been drawn to the effects of adrenopause in Sjögren's syndrome and on dehydroepiandrosterone and its intracrine metabolism in target tissues. This can influence the maintenance and remodeling of exocrine glands and may explain, in part, another important disease symptom--fatigue. | |
12874643 | [Association between serum amyloid A (SAA) in salivary glands and high levels of circulati | 2003 | OBJECTIVES: The presence of secondary amyloidosis is a complication of different rheumatic diseases. We investigated the presence of Serum Amyloid A (SAA), marker of secondary amyloidosis, in salivary glands of patients (pts) with Sjögren Syndrome (SS) and correlated it to biohumoral parameters. MATERIALS AND METHODS: 141 pts with sicca syndrome who fulfilled 3 items of the European Criteria for SS by Vitali et al underwent biopsies of labial salivary glands, that were scored according to Chisholm and Mason index and evaluated for the presence of SAA. All pts were evaluated for ANA, ENA, rheumatoid factor, gamma-globulins, IgA, IgG, IgM, C3, C4, beta 2-microglobulin, erythrosedimentation rate, C reactive protein. RESULTS: Forty out of 141 pts, showed sialoadenitis (SL) with focus score 3-4 (definite SS), and 101 pts showed SL with focus score 1-2. Fourteen out of 101 pts (13.8%) with score 1-2 and 12/40 pts (30%) with definite SS were positive for SAA, respectively. SS pts were further divided in group A (positive for SAA) and group B (negative for SAA). These groups were compared to detect if differences could exist in biohumoral parameters: group A showed higher levels of biohumoral parameters than group B, but the difference was significant only for beta 2-microglobulin: 2653+610 ng/ml versus 1848+440 ng/ml; p< 0.025. CONCLUSION: Secondary amyloidosis is a complication of SS. In pts with SAA in salivary glands were detected high levels of beta 2-microglobulin, that could be considered a factor predicting the development of amyloidosis in SS. | |
12322807 | A primary Sjögren's syndrome patient with marked swelling of multiple exocrine glands and | 2002 Sep | A 55-year-old man suffered from nasal obstruction, swelling of the salivary glands, and diplopia caused by markedly enlarged lacrimal glands. The diagnosis of primary Sjögren's syndrome was made by a positive Schirmer's test and nasal mucosal biopsy with severe lymphocyte infiltration. He was also found to have swelling of the whole pancreas and increased wall thickness in the common bile duct and the gall bladder. His serum was positive for an anticarbonic anhydrase II antibody. Since carbonic anhydrase II is present in the ductal cells of various exocrine organs, this autoantibody is considered to be related to the pathogenesis of primary Sjögren's syndrome with a marked swelling of multiple exocrine organs. | |
12068153 | A case of calcium pyrophosphate dihydrate crystal deposition disease presenting as an acut | 2002 Jun | We report a case of calcium pyrophosphate dihydrate crystal deposition disease (CPDD) presenting as an acute polyarthritis. A 66-yr-old woman was admitted with a 5-day history of fever and multiple joint pain including wrists, elbows, shoulders, knees, and ankles developed 5 days before admission. Her plain radiographs of wrists, elbows, shoulders, knees, and ankles showed chondrocalcinosis. The pubic symphysis, lumbar intervertebral discs, and both hip joints, which were asymptomatic, also had calcium deposits. The compensated polarized microscopic examination of the joint fluid, aspirated from the right knee revealed intracellular and extracellular weakly positive birefringent crystals, confirming the CPDD. This case showed that CPDD may manifest as an acute polyarthritis mimicking acute onset rheumatoid arthritis. | |
24728116 | [Not Available]. | 2002 Sep | Ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are common inflammatory rheumatic diseases who belong to the spectrum of the spondyloarthritides (SpA). The therapeutic options for these conditions have been rather limited in the past decades. Standard treatment consists of drug therapy with nonsteroidal anti-inflammatory agents (NSAIDs), intraarticular steroids and physiotherapy. The peripheral symptoms of SpA respond partly to treament with disease modifying anti-rheumatic drugs (DMARDs). Several findings of the last years have indicated that TNFα plays a role in the pathogenesis of the SpA. Treatment with TNFα antagonists (monoclonal antibodies and receptor fusion proteins directed against TNFα) have been successfully used in patients with rheumatoid arthritis (RA), a pathogenetically distinct form of chronic joint inflammation. After stimulating pilot studies there is now increasing evidence from randomized controlled trials that these antagonists are very efficacious in the treatment of SpA, especially of AS and PsA, for both, axial and peripheral symptoms of disease. This therapy seems to be even more effective in SpA than in RA being comparable to the efficacy of corticosteroid therapy for polymyalgia rheumatica. There is international consensus that the availabilitiy of TNFα antagonists is a major breakthrough in the therapy of rheumatic diseases. | |
14577724 | Distal interphalangeal joint arthrodesis: treatment with Herbert screw. | 2003 Fall | From 1996 to 2000, 20 patients with a mean age of 53 underwent 20 arthrodeses with Herbert screws. There were 16 (80%) distal interphalangeal joint (DIP) and 4 (20%) thumb interphalangeal (IP) joint arthrodeses. Average follow-up was 25 months (range, 6-39 months). The diagnoses included rheumatoid arthritis in 10 patients, degenerative arthritis in 4, and post-traumatic arthritis in 6. Arthrodesis relieved pain and restored stability in all patients. Solid osseous union occurred in 19 patients (95%). The average interval to fusion was 8 weeks for DIP and 12 weeks for IP joint arthrodesis. Solid osseous union occurred in 19 patients (95%). The average interval to fusion was 8 weeks for distal interphalangeal joint arthrodesis and 12 weeks for interphalangeal joint of the thumb. There were three complications: one delayed union, one nonunion because of a short screw, and one dorsal skin necrosis with amputation. It was shown that distal interphalangeal joint arthrodesis with a Herbert screw is a technique with several advantages: good clinical results, high rates of fusion, early mobilization, and the screw does not need to be removed after the fusion heals. Potential complications may be avoided by using the Herbert mini-screw. | |
12539154 | Efficacy of interleukin-10 gene electrotransfer into skeletal muscle in mice with collagen | 2003 Feb | BACKGROUND: Gene therapy is very promising in the treatment of rheumatoid arthritis (RA). Electrotransfer is a recent method reported to enhance in vivo intramuscular DNA transfection. Interleukin-10 (IL-10) has antiinflammatory effects in RA and in collagen-induced arthritis (CIA), a murine model of RA. In order to improve our strategy of gene therapy, we used electrotransfer to enhance penetration into skeletal muscle with CIA of plasmids encoding IL-10. METHODS: CIA was induced in DBA/1 mice by immunization with bovine type II collagen. Injection into the tibial cranial muscle of low-dose (200 ng) pCOR plasmid encoding murine IL-10 (pCOR-CMV-mIL-10) was immediately followed by application of square-wave electric pulses (8 pulses of 200V/cm, 20 ms duration at 2 Hz). Control groups received empty plasmid or saline before electrotransfer. RESULTS: When electrotransfer was performed twice on days 10 and 25 postimmunization, CIA was significantly delayed (P < 0.05) and attenuated (P < 0.001) in groups treated by electrotransfer or pCOR-CMV-mIL-10 plasmid vs. control groups. When electrotransfer of pCOR-CMV-mIL-10 plasmid was performed on days 25 and 40 postimmunization, at disease onset, the clinical severity of CIA was reduced (P < 0.05). All groups which had been electrotransferred early or late by pCOR-CMV-mIL-10 plasmid showed suppression of histological signs of arthritis. CONCLUSIONS: Taken together, these data indicate that administration of an antiinflammatory plasmid-born gene by electrotransfer of naked DNA is effective in vivo in an arthritis model. | |
11949889 | Use of anti-platelet-endothelial cell adhesion molecule-1 antibody in the control of disea | 2002 Mar | Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is expressed on the membrane of leukocytes and vascular endothelial cells. PECAM-1 has been shown to play an important role in the process of leukocyte transmigration in various animal models of acute inflammation. We investigated the role of PECAM-1 in the progression of arthritis by systemically administering anti-murine PECAM-1 monoclonal antibody, 2H8, to DBA/1J mice with collagen-induced arthritis (CIA). Subcutaneous administration of dexamethasone (0.5 mg/kg per 2 days) significantly reduced hindpaw swelling and the clinical score of established CIA. Intraperitoneal administration of 2H8 (0.25 mg/mouse per 2 days) significantly inhibited hindpaw swelling in a time-dependent manner. 2H8 also significantly prevented further deterioration in the clinical score, but failed to reverse joint destruction discernible at the histological level. Both dexamethasone and 2H8 inhibited body weight decrease by preventing the further development of arthritis. Histopathological assessment revealed that 2H8, as well as dexamethasone, inhibited inflammatory cell transmigration into the synovium of the hind paw joint and ameliorated synovitis and cartilage erosion. These results suggest that PECAM-1 plays an important role in the progression of CIA and that an inhibitor of PECAM-1 might have therapeutic value for clinical treatment of rheumatoid arthritis. | |
18629129 | Gene selection in arthritis classification with large-scale microarray expression profiles | 2003 | The use of large-scale microarray expression profiling to identify predictors of disease class has become of major interest. Beyond their impact in the clinical setting (i.e. improving diagnosis and treatment), these markers are also likely to provide clues on the molecular mechanisms underlining the diseases. In this paper we describe a new method for the identification of multiple gene predictors of disease class. The method is applied to the classification of two forms of arthritis that have a similar clinical endpoint but different underlying molecular mechanisms: rheumatoid arthritis (RA) and osteoarthritis (OA). We aim at both the classification of samples and the location of genes characterizing the different classes. We achieve both goals simultaneously by combining a binary probit model for classification with Bayesian variable selection methods to identify important genes.We find very small sets of genes that lead to good classification results. Some of the selected genes are clearly correlated with known aspects of the biology of arthritis and, in some cases, reflect already known differences between RA and OA. | |
12734883 | Longterm protection of mice against collagen-induced arthritis after short-term LF 15-0195 | 2003 May | OBJECTIVES: LF 15-0195 is an immunosuppressive agent obtained by organic synthesis, currently under clinical development for the treatment of vasculitis. We define the effects of LF 15-0195 in the murine collagen-induced arthritis (CIA) model, an experimental model of human rheumatoid arthritis. METHODS: In our model, CIA was elicited in DBA/1 mice by immunization with bovine type II collagen (CII) in Freund's complete adjuvant, followed by a repeat injection 21 days later. Disease onset was observed 6 days after booster injection. In these experiments, mice were treated with 5 daily LF 15-0195 injections starting after the booster injection (days 21-25). The mice were observed for 40 days after the start of treatment, during which time arthritis was scored using clinical score and paw swelling assessment. Modulation of humoral immunity was documented by measuring the serum level of anti-CII IgG1 and IgG2a and cellular immunity by cytokines production by lymph node cells (LNC) and their proliferation in vitro. RESULTS: Short-term treatment of LF 15-0195 after booster injection prevented longterm development of CIA. LF 15-0195 inhibited B cell differentiation with a marked suppression of anti-CII IgG1 and IgG2a synthesis. Functional analyses of T lymphocytes showed that LF 15-0195 treatment reduces cytokine production by LNC after CII, anti-CD3, lipopolysaccharide stimulation. CONCLUSION: LF 15-0195 treatment during a short time period prevented development of arthritis, inhibited humoral-specific response longterm, induced a decrease in the number of LNC, and decreased cytokine production of T LNC after ex vivo stimulation. | |
12894136 | Evaluation and management of psoriatic arthritis: the role of biologic therapy. | 2003 Aug | Clinicians often view psoriatic arthritis (PsA) as a rather minor arthritic disorder because many are unaware of the substantial damage, disability, and reduced quality of life that patients with this disease can suffer. Compared with better-studied arthritic conditions, such as rheumatoid arthritis (RA) with well-known consequences of disease progression, PsA does not elicit the same urgency to treat early and aggressively. This is largely owing to the lack of predictive epidemiologic data regarding disease progression in PsA. However, numerous studies indicate that PsA and RA are comparable in terms of overall severity of joint involvement and disability over equivalent disease duration. Many of the drugs traditionally used for PsA therapy are also used to treat RA, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, methotrexate (MTX), sulfasalazine, cyclosporine, etretinate, auranofin, intramuscular gold, and azathioprine. All of these drugs have significant risk of toxicity over long-term use, and all provide variable efficacy. This makes it difficult for clinicians to make sound risk-benefit assessments regarding treatment or nontreatment of PsA, because the risks of disease progression cannot be weighed against the risks of therapy. The newer biologic antirheumatic drugs appear to combine greater efficacy of treatment with significantly less toxicity by targeting specific mediators involved in the pathogenesis of PsA. | |
12668251 | Spinal adenosine agonist reduces c-fos and astrocyte activation in dorsal horn of rats wit | 2003 Apr 10 | Adjuvant-induced arthritis (AIA) is a useful animal model of rheumatoid arthritis (RA). We have previously shown that stimulation of spinal adenosine A1 receptors decreases peripheral signs of AIA. In this study we show that when the final dose of adenosine A1 agonist is given 1 h prior to sacrifice the number of c-Fos positive cells evoked by the AIA in both the superficial and deep dorsal horns decreases by about 50%. In saline-treated AIA animals the increase in c-Fos expression seen in laminae I-IV was accompanied by an increase in glial fibrillary acidic protein immunoreactivity, indicative of astrocyte activation. Astrocyte activation was only partially attenuated by adenosine A1 receptor agonist treatment. | |
12418440 | Arthritis in the intensive care unit. | 2002 Oct | Acute arthritis in critically ill patients may be caused by local or systemic infection, by a flare of chronic joint disease such as rheumatoid or crystal-associated arthritis, or by less common entities such as hemarthrosis. Diagnosis requires analysis of synovial fluid, and appropriate treatment is based on its findings. Prompt diagnosis and treatment are usually necessary to prevent the significant morbidity associated with these conditions. | |
12587951 | Stress-induced lidocaine modification in serum and tissues. | 2002 Oct | The aim of this study is to examine the influence of acute (trauma) and chronic (cold swimming and adjuvant rheumatoid arthritis) stress on lidocaine concentrations in plasma. Forty male Wistar rats were used. The animals were divided into four groups. Group A served as control. Group B underwent mandible osteotomy. Group C was submitted to swimming stress in cold water 4 degrees C for ten minutes daily for 15 minutes, while group D underwent experimental arthritis with Freud's adjuvant. All groups received lidocaine i.m (2.5 mg/kg). Blood samples were collected and FFA (free fatty acid), unbound-lidocaine, albumin and a1-acid glycoprotein concentrations were estimated. Furthermore, the adrenals, heart and liver were isolated. The adrenals' relative weight (adrenal weight/body weight) was assessed, while lidocaine concentrations in the heart and the liver incubation medium were measured by intertechnic a-counter. Lidocaine and FFA levels in serum as well as the adrenal weights demonstrated a significant elevation in stress-groups as compared to the control group. Furthermore, in the stress-groups, lidocaine concentrations in heart tissue were significantly increased, whereas in the liver they were significantly reduced as compared to the control group. Our results indicate that stress can alter lidocaine levels in plasma and tissues, suggesting that stress should be considered an important factor when determining the dosage of lidocaine in clinical application. | |
12749755 | Role of novel biological therapies in psoriatic arthritis: effects on joints and skin. | 2003 | Psoriatic arthritis (PsA) is a partly debilitating disease that may affect small and large joints and the spine. Patients with PsA are divided into different subgroups according to joint involvement and their disease may be classified as part of the spectrum of spondyloarthritides or seronegative rheumatoid arthritis. Traditional treatment comprises nonsteroidal anti-inflammatory drugs, systemic and intra-articular corticosteroids and disease-modifying antirheumatic drugs such as sulfasalazine, methotrexate and cyclosporin. On the basis of the very recent studies performed in the US and Germany, patients with severe disease can be treated with anti-tumour necrosis factor (TNF) therapy. Biologicals such as etanercept and infliximab have been used successfully to treat PsA. While etanercept is a 75kD TNF receptor fusion protein that binds to TNFalpha and TNFbeta, infliximab is a chimeric monoclonal antibody that binds to TNFalpha both in its soluble form in the serum and on the cell membrane. Adalimumab is a fully humanised antibody recognising TNFalpha that has not been tested in PsA to date. Another biological agent, alefacept, is directed against the adhesion molecule lymphocyte function-associated antigen (LFA)-2, which is known to interfere with T-cell activation. Alefacept has been shown to be efficacious in a limited number of patients with PsA. Taken together, there has been definite recent progress in the treatment of PsA. Severely affected patients may especially have substantial benefit from therapy with biologicals directed against TNFalpha and other targets. | |
15554372 | [Extraskeletal manifestations of seronegative spondyloarthropathies]. | 2004 | Spondyloarthropathies constitute a cluster of interrelated and overlapping chronic inflammatory rheumatic diseases of unknown etiology that include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis and undifferentiated spondyloarthritis. These diseases are not associated with rheumatoid factor, they occur in genetically predisposed individuals and show a strong association with HLA-B27. The primary pathologic sites include the entheses, the sacroiliac joints and the axial skeleton with or without some nonarticular structures, such as the skin, eye, aortic valve, heart and kidney. |