Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 18063842 | TNF signaling: early events and phosphorylation. | 2007 Sep | Tumor necrosis factor-alpha (TNF) is a major mediator of apoptosis as well as immunity and inflammation. Inappropriate production of TNF or sustained activation of TNF signaling has been implicated in the pathogenesis of a wide spectrum of human diseases, including cancer, osteoporosis, sepsis, diabetes, and autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. TNF binds to two specific receptors, TNF-receptor type I (TNF-R1, CD120a, p55/60) and TNF-receptor type II (TNF-R2, CD120b, p75/80). Signaling through TNF-R1 is extremely complex, leading to both cell death and survival signals. Many findings suggest an important role of phosphorylation of the TNF-R1 by number of protein kinases. Role of TNF-R2 phosphorylation on its signaling properties is understood less than TNF-R1. Other cellular substrates as TRADD adaptor protein, TRAF protein family and RIP kinases are reviewed in relation to TNF receptor-mediated apoptosis or survival pathways and regulation of their actions by phosphorylation. | |
| 17926524 | [Risk factors and comorbidities for NSAID associated ulcer]. | 2007 Oct | Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to increase the risk of upper gastrointestinal tract bleeding. To reduce the morbidity associated with NSAID, it will be necessary to establish specific estimates individual drugs and different risk profile. Advanced age has been identified as one of the primary risk factors for adverse GI events in NSAID users. This may be due to the increased use of these drugs by the elderly population or to pathophysiological mechanisms such as age-related changes in drug pharmacokinetics or reductions in gastroduodenal defensive mechanisms. Many studies have also identified the following risk factor: sexuality; history of previous GI problems; higher NSAID doses; concomitant anticoagulant use. Corticosteroids, bisphosphonates and selective serotonin reuptake inhibitors increase the risk of upper gastrointestinal bleeding. The combined use of these drug and NSAID strongly increases the risk of gastrointestinal bleeding. Adverse GI events in NSAID users can be affected by the following comorbidities: rheumatoid arthritis; liver cirrhosis; renal failure; diabetes; arteriosclerosis. | |
| 17627791 | Obesity in psoriasis: the metabolic, clinical and therapeutic implications. Report of an i | 2007 Oct | Experts on psoriasis convened with authorities from other medical specialties to discuss the recently described association between psoriasis, obesity and subsequent cardiovascular comorbidity. Similar to other diseases of increased systemic inflammation, psoriasis has been linked to a heightened risk of myocardial infarction, especially in the more severely affected, younger patients. However, unlike in other inflammatory diseases - such as rheumatoid arthritis - more severely affected patients with psoriasis are much more likely to be obese. Importantly, the pathophysiology of both psoriasis and obesity shows many shared cytokines that are known to contribute to features of the metabolic syndrome, such as hypertension, dyslipidaemia and insulin resistance. The strong association between psoriasis and obesity potentially makes psoriasis an important healthcare issue that requires an update in its standard of care. This meeting reviewed the evidence-based literature and addressed how, moving forward, dermatologists and other specialists may redefine the magnitude of health risk associated with more severe psoriasis and its comorbidities, while clarifying both the epidemiology and pathophysiology of the association with obesity. | |
| 17347487 | cAMP signaling in leukocyte transendothelial migration. | 2007 May | The migration of leukocytes across the vascular endothelium is crucial for immunosurveillance as well as for inflammatory responses. Uncontrolled leukocyte transendothelial migration results in pathologies such as asthma, rheumatoid arthritis, and atherosclerosis. The molecular mechanisms that regulate leukocyte transendothelial migration involve signaling downstream of intracellular messengers such as cAMP, calcium, phosphoinositol lipids, or reactive oxygen species. Among these, cAMP is particularly intriguing because it is generated in both leukocytes and endothelial cells and regulates leukocyte chemotaxis as well as endothelial barrier function. In addition, physiological stimuli that induce cAMP production generate both pro- and antiinflammatory signals, underscoring the complexity of cAMP-driven signaling. This review discusses our current knowledge of the control of leukocyte transendothelial migration by two main cAMP effectors: protein kinase A and the Rap exchange factor Epac (Exchange protein directly activated by cAMP). | |
| 17127203 | Infection and musculoskeletal conditions: Bacterial and opportunistic infections during an | 2006 Dec | Tumour necrosis factor alpha (TNF-alpha) plays a crucial role in host defence against bacterial infections. Summarizing the results, the findings of immunological and clinical research suggest a higher infection risk in rheumatoid arthritis and ankylosing spondylitis patients receiving anti-TNF treatment. This is especially true for granulomatous infections in patients treated with the monoclonal TNF-alpha antibodies infliximab or adalimumab. Furthermore, patients treated with TNF inhibitors have a higher susceptibility to infections because of their higher active and more severe disease. Therefore, patients receiving anti-TNF treatment should be closely monitored for serious infections. A rapid and sufficient treatment of infections that are not mild and transient is recommended. There are atypical signs and symptoms as well as atypical pathogen that should be considered. Patients should be educated about how to avoid infectious complications. | |
| 17110316 | Malignancies and soluble tumor antigens in rheumatic diseases. | 2006 Nov | Paraneoplastic symptoms, caused by a malignancy, but not directly related to invasion by the tumor or its metastases are the result of a wide variety of tumor-derived biologic mediators like hormones, peptides, antibodies, cytotoxic lymphocytes, autocrine and paracrine mediators. Recognition of paraneoplastic syndromes is important, as it may lead to an early diagnosis of cancer. There is some evidence that systemic inflammatory diseases, such as rheumatoid arthritis (RA), lupus, scleroderma or dermatomyositis may increase the risk for the development of malignancies, predominantly lymphoproliferative disorders. However, reports are somewhat controversial. Immunosuppressive and cytotoxic drugs used in antirheumatic therapy, such as methotrexate, cyclophosphamide, azathioprine or anti-TNF biologicals may also lead to the development of such tumors. Tumor-associated antigens may be produced by inflammatory cells and their production may be increased in RA and other autoimmune diseases. | |
| 17056036 | An estrogen receptor-beta agonist is active in models of inflammatory and chemical-induced | 2006 Dec 28 | ERB-041 (2-(3-Fluoro-4-hydroxyphenyl)-7-vinyl-1,3 benzoxazol-5-ol) is a selective estrogen receptor-beta agonist with activity in rodent models of rheumatoid arthritis and endometriosis. Clinical trials for these diseases are underway: however, the role of estrogen receptor-beta in modulating pain associated with inflammation remains unknown. These studies demonstrate that acutely administered ERB-041 is anti-hyperalgesic in preclinical models of chemical-induced and acute inflammatory pain, thus suggesting that ERB-041 may be useful for modulating pain associated with some types of inflammation. | |
| 17018000 | Structural requirements of heparin and related molecules to exert a multitude of anti-infl | 2006 Sep | Chronic inflammatory diseases are common and still remain a therapeutic challenge for both efficacy and safety reasons. Hence, novel therapeutics addressing these issues would for example improve treatment of severe diseases such as psoriasis, rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis. Inappropriate leukocyte homing to the affected compartments is a common feature of these diseases. Heparin and related polysaccharides have been shown to interfere with leukocyte homing through a variety of effects distinct from their anticoagulant properties. In this review, data on heparin as an anti-inflammatory agent are presented. In addition, structure-activity requirements for the anti-inflammatory properties of heparin are discussed, which should aid the drug development based on structurally modified heparin or other sulfated carbohydrates for treatment of inflammatory diseases. | |
| 17009017 | Accelerated apoptosis in SLE neutrophils cultured with anti-dsDNA antibody isolated from S | 2006 Dec | Increased numbers of apoptotic neutrophils are found in SLE, related to disease activity and levels of anti-dsDNA antibody. The mechanism of increased apoptosis is not clear, but anti-dsDNA antibody has been shown to induce apoptosis in neutrophils from normal subjects and in certain cell lines. In this study, polyclonal anti-dsDNA antibody was isolated from the serum of a patient with active SLE, and was shown to substantially accelerate apoptosis in neutrophils from SLE patients as compared with neutrophils from healthy control or rheumatoid arthritis subjects. | |
| 16956369 | Therapeutic targeting of molecules involved in leukocyte-endothelial cell interactions. | 2006 Oct | Inflammation is traditionally viewed as a physiological reaction to tissue injury. Leukocytes contribute to the inflammatory response by the secretion of cytotoxic and pro-inflammatory compounds, by phagocytotic activity and by targeted attack of foreign antigens. Leukocyte accumulation in tissues is important for the initial response to injury. However, the overzealous accumulation of leukocytes in tissues also contributes to a wide variety of diseases, such as atherosclerosis, chronic inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, vasculitis, systemic inflammatory response syndrome, juvenile diabetes and psoriasis. Many therapeutic interventions target immune cells after they have already migrated to the site of inflammation. This review addresses different therapeutic strategies, used to reduce or prevent leukocyte-endothelial cell interactions and communication, in order to limit the progression of inflammatory diseases. | |
| 16819203 | Folate-linked lipid-based nanoparticles deliver a NFkappaB decoy into activated murine mac | 2006 Jul | Activated macrophages are the key effector cells in rheumatoid arthritis (RA) and secrete multiple mediators of inflammation including proinflammatory cytokines. We investigated delivery of a nuclear factor kappa B (NFkappaB) decoy by folate-linked lipid-based nanoparticles (NP-F) into murine macrophages. The expression of folate receptor (FR) in RAW264.7 cells activated by lipopolysaccaride was confirmed by strong expression of FR mRNA, and association of FITC-labeled folate-BSA conjugate. When transfected via NP-F, the NFkappaB decoy was strongly detected in the cytoplasm, and an inhibitory effect on the translocation of NFkappaB into the nucleus was observed at 0.03 microM of the decoy, suggesting that NP-F effectively delivered the NFkappaB decoy into the cytoplasm. This information is of value for the design of NFkappaB decoy carrier systems targeting FR in activated macrophages in gene therapy for autoimmune diseases such as RA. | |
| 16332285 | Immunomodulatory effect of various anti-parasitics: a review. | 2006 Mar | This paper reviews the immunomodulatory effects (immunosuppression or immunoactivation) of various anthelmintics including levamisole, fenvalerate, dieldrin, carbofuran, aminocarb, thiabendazole, fenbendazole, oxfendazole and ivermectin. The induced modulation of immune function may occur via direct and/or indirect mechanisms. The immunomodulatory effects of these anti-parasitics have been studied in a variety of bacterial (e.g. brucellosis, salmonellosis, paratuberculosis, mastitis), viral (e.g. infectious bovine rhinotracheitis, Herpes, foot and mouth disease), parasitic (e.g. onchocerciasis, coccidiosis, ascariasis, schistosomiasis) and neoplastic diseases. Some antiparasitics have also been used to boost immunity in a number of human diseases including leprosy, Hodgkin's disease, rheumatoid arthritis, and in adjuvanted therapy of colorectal cancer. The ability to stimulate the immune response of animals offers a new means of disease intervention. Future research on immunomodulatory effects of anti-parasitics, for humans and domestic farm animals, will provide additional methods of treating immunosuppressed subjects. The immunopotentiating or immunosuppressing activity of anti-parasitics will dictate whether co-administration of vaccines and anthelmintics or administration of vaccines during the window of immunoactivation is justified or not. | |
| 16213771 | Is restless legs syndrome underrecognized? Current management. | 2006 Jul | Restless legs syndrome (RLS) is a poorly understood sensory-motor neurological disorder whose prevalence in Caucasian populations ranges from 10% to 15%. The patient reports unpleasant sensations in the lower limbs with dysesthesia resulting in an urge to move the legs. The symptoms occur during periods of inactivity, increasing in the evening and at night. Moving the legs provides relief. In 80% of cases, polysomnography shows periodic leg movements during sleep. Patients with idiopathic RLS often report similar symptoms in family members. Secondary RLS may be due to medications, diabetes mellitus, renal failure, iron deficiency, neurological disorders, or rheumatoid arthritis. In secondary RLS, the management rests on treatment of the cause. Symptomatic treatment is warranted in patients with moderate-to-severe symptoms that adversely affect the quality of life. Dopaminergic agents are tried first. When they fail or induce adverse effects, weak opioids, benzodiazepines, anticonvulsants or, if needed, strong opioids, may be used. | |
| 27157077 | Nonprosthesis Orthopedic Applications of (18)F Fluoro-2-Deoxy-d-Glucose PET in the Detecti | 2006 Apr | This article describes the impact of [(18)F]2-fluoro-2-deoxy-d-glucose (FDG) PET in the diagnosis of non-prosthesis-related orthopedic infections and inflammation. FDG-PET has an excellent sensitivity in the detection of osteomyelitis (OM). Early data indicate that FDG-PET may be more specific than MRI in diagnosing OM. The role of the combination of FDG and PET-CT in the diagnosis of OM is likely to be determined as this combination is used on a routine basis. Early data from studies in rheumatoid arthritis indicate that FDG-PET is highly accurate in early diagnosis and that it provides results comparable to the most advanced conventional techniques. | |
| 16899499 | Individual fracture risk and the cost-effectiveness of bisphosphonates in patients using o | 2007 Mar | OBJECTIVES: There are few data on the cost-effectiveness of bisphosphonates with oral glucocorticoids (GCs). An individual patient-based pharmaco-economic model was developed. METHODS: Data were obtained from a cohort of oral GC users aged 40+ (n = 190 000) in the UK General Practice Research Database. Individualized fracture and mortality risks were calculated specific for age, sex, daily and cumulative GC dose, indication and other clinical risk factors. UK costs of medication and direct costs of fracture were obtained from National Institute for Clinical Excellence and used to estimate costs per quality-adjusted life-year (QALY) gained and fracture prevented for bisphosphonates in patients treated for 5 yrs with GCs. RESULTS: With the use of 5 mg GCs daily, the cost per one QALY gained with bisphosphonates was 41k UK pounds (95% confidence intervals 22-72k) in women aged <60 [men 40k pounds (29-54k)], 17k pounds (13-24k) in women aged 60-79 [men 43k pounds (31-60k)], 5k pounds(3-6k) in women aged 80+ [men 35k pounds (25-46k)]. With 15 mg GC, these figures were 17k pounds (14-21k), 13k pounds (10-16k) and 15k pounds (9-26k) in women and 22k pounds (17-26k), 34 pounds (23-53k) and 33k pounds (27-42k) in men, respectively. When stratifying by overall fracture risk and life expectancy at the start of GC therapy, cost per QALY increased with decreasing life expectancy. Patients with rheumatoid arthritis had comparatively better cost-effectiveness, given higher fracture risk and better life expectancy. CONCLUSIONS: The cost-effectiveness of bisphosphonates varied substantially. Bisphosphonates can be considered cost-effective in patients with higher fracture risks, such as elderly patients (with a life expectancy over 5 yrs), and younger patients with a fracture history, low body mass index, rheumatoid arthritis or using high GC doses. | |
| 18797871 | Diagnostic performance of minor salivary gland biopsy, serological and clinical data in Sj | 2009 Feb | The aim of this study was to investigate the performance of minor salivary gland biopsy (MSGB), serological and clinical data in diagnosis of primary Sjögren's syndrome (pSS). Retrospective review of 216 patients who underwent minor labial salivary gland biopsy in last 5 years was performed. Results of the patients with diagnosis of pSS were compared with the patients failing to fill the classification criteria of pSS. Two groups did not differ significantly in terms of clinical symptoms and signs except presence of Raynaud's phenomenon. Specificity and positive likelihood ratio of clinical signs in diagnosis of pSS were quiet low. A total of 78.7% of pSS patients had a focus score >or=1 (Chiscolm's score III/IV) while all of the non-SS patients had a focus score <1 (P < 0.001). MSGB has the best predictive value with highest sensitivity and specificity for pSS diagnosis. Serological markers have higher predictive values compared to clinical symptoms and signs. Presence of Raynaud's phenomenon, lymphopenia and/or hypergammaglobulinemia strengthens the probability of pSS in a patient with sicca symptoms. | |
| 18580434 | Potential for differential diagnosis of autoimmune pancreatitis and pancreatic cancer usin | 2008 Jul | OBJECTIVES: Pancreatic ductal epithelia contain an abundance of carbonic anhydrase (CA), and the presence of antibodies to this enzyme has been described in autoimmune disorders. We previously found a small amount of an immunoglobulin G-like material in purchased CAII reagents, which led to pseudopositive reactions. METHODS: We determined the optimum measurement conditions for detecting anti-CAII antibody using an enzyme-linked immunosorbent assay and sera from 140 patients with pancreatic diseases. RESULTS: Compared with the prevalence of anti-CAII antibody in healthy subjects, a significantly higher seroprevalence of the antibody was detected in patients with autoimmune pancreatitis (AIP) (88.9%, P < 0.02), Sjögren syndrome (67.6%, P < 0.01), and alcoholic chronic pancreatitis (45.8%, P < 0.01). No positive results were obtained among patients with pancreatic cancer. Moreover, the antibody value obtained in the pancreatic cancer patients was actually lower than that obtained in healthy subjects. CONCLUSIONS: The anti-CAII antibody is probably not a specific marker of AIP because it was present at a higher frequency in the sera of patients with other pancreatic diseases. Nevertheless, the anti-CAII antibody may be a useful tool for the differential diagnosis of AIP and pancreatic cancer. | |
| 17530708 | Female mice are more susceptible to developing inflammatory disorders due to impaired tran | 2007 Jun | OBJECTIVE: Transforming growth factor beta (TGFbeta) plays a key role in the onset and resolution of autoimmune diseases and chronic inflammation. The aim of this study was to delineate the precise function of TGFbeta signaling in salivary gland inflammation. METHODS: We impaired TGFbeta signaling in mouse salivary glands by conditionally inactivating expression of TGFbeta receptor type I (TGFbetaRI), either by using mouse mammary tumor virus-Cre mice or by delivering adenoviral vector containing Cre to mouse salivary glands via retrograde infusion of the cannulated main excretory ducts of submandibular glands. RESULTS: TGFbetaRI-conditional knockout (TGFbetaRI-coko) mice were born normal; however, female TGFbetaRI-coko mice developed severe multifocal inflammation in salivary and mammary glands and in the heart. The inflammatory disorder affected normal growth and resulted in the death of the mice at ages 4-5 weeks. Interestingly, male TGFbetaRI-coko mice did not exhibit any signs of inflammation. The female TGFbetaRI-coko mice also showed an increase in Th1 proinflammatory cytokines in salivary glands and exhibited an up-regulation of peripheral T cells. In addition, these mice showed an atypical distribution of aquaporin 5 in their salivary glands, suggesting likely secretory impairment. Administration of an adenoviral vector encoding Cre recombinase into the salivary glands resulted in inflammatory foci only in the glands of female TGFbetaRI-loxP-flanked (floxed) mice (TGFbetaRI-f/f mice), but not in those of male and female wild-type mice or male TGFbetaRI-f/f mice. CONCLUSION: These results suggest that female mice are uniquely more susceptible to developing inflammatory disorders due to impaired TGFbeta signaling in their salivary glands. | |
| 17999070 | [Indications and options of new immune modulatory therapies for Sjögren's syndrome]. | 2007 Dec | Sjögren's syndrome is a systemic inflammatory rheumatic disorder of unknown origin with so far inadequate therapy options. Management of Sjögren's syndrome is still primarily palliative using local symptomatic measures, and if appropriate glucocorticoids, NSAIDs and immunosuppressive drugs. New clues to the pathogenesis of this disorder pave the way for new therapeutic strategies. In particular targeting B-cells offers promising results and emphasizes the role of B-cells in the pathogenesis of this complex disorder. Rituximab was introduced into the standard treatment of different forms of low-grade and high-grade B-cell non-Hodgkins lymphomas, and is also an option for some lymphomas associated with Sjögren's syndrome. Whether interference with T-cell function is also a safe and effective strategy in Sjögren's syndrome, has to be shown in controlled clinical trials. However, there is no clear evidence to suggest that treatment with TNF-alpha blockers is efficacious in Sjögren's syndrome. Standardization of disease activity and outcome measurements are critical for further clinical trials for Sjögren's syndrome. | |
| 17075845 | Overexpression of phosphorylated STAT-1alpha in the labial salivary glands of patients wit | 2006 Nov | OBJECTIVE: To clarify the molecular mechanisms of Sjögren's syndrome (SS), we analyzed the functional role of the STAT-1 gene, one of the interferon-gamma (IFNgamma)-inducible genes, in labial salivary glands (LSGs) from SS patients. METHODS: The expression of STAT-1 messenger RNA (mRNA) was examined by real-time polymerase chain reaction (PCR) analysis, and the phosphorylation of STAT-1 protein (Tyr(701) and Ser(727) pSTAT-1) was investigated by Western blot and immunohistochemical analyses. The expression of IFNgamma-inducible 10-kd protein (IP-10), IFN regulatory factor 1 (IRF-1), and Fas was also examined by real-time PCR and immunohistochemical analyses. RESULTS: STAT-1alpha and STAT-1beta mRNA were highly expressed in LSGs from SS patients. The level of STAT-1alpha protein in SS LSGs was higher than that in 3 control LSGs, whereas STAT-1beta protein was not clearly detected by Western blot analysis. Moreover, Tyr(701) and Ser(727) pSTAT-1alpha proteins were specifically detected in SS LSGs. Immunohistochemical analysis showed localization of Tyr(701) pSTAT-1 in infiltrating lymphocytes and the adjacent ductal epithelium from SS patients. Ser(727) pSTAT-1 was localized only in the ductal epithelium of SS LSGs. The STAT-1-inducible genes IP-10 and IRF-1 and the Fas genes were highly expressed in SS LSGs and were colocalized with Ser(727) pSTAT-1-positive, but not Tyr(701) pSTAT-1-positive, cells. CONCLUSION: We found evidence of the up-regulation of STAT-1alpha mRNA and protein in LSGs from SS patients, as well as the presence of pSTAT-1alpha in ductal epithelium from SS patients. Our findings suggest that STAT-1alpha, especially Ser(727) pSTAT-1, may function as a key molecule in the pathogenesis of SS. |