共查询到20条相似文献,搜索用时 31 毫秒
1.
Objective
The objective of this study was to detect the prevalence of anti-3-hydroxyl-3- methylglutaryl coenzyme A reductase (anti-HMGCR) antibodies in Chinese patients with idiopathic inflammatory myopathies (IIMs), and to analyze the clinical features of the antibody-positive IIM patients.Methods
The presence of anti-HMGCR antibodies was detected in 405 patients with IIMs, 90 healthy controls, and 221 patients with other rheumatic diseases by using an ELISA kit. Clinical data from anti-HMGCR antibody-positive and -negative patients were compared. Long-term follow-up of the anti-HMGCR antibody-positive patients was conducted to evaluate the role of anti-HMGCR antibody in IIM disease prognosis.Results
Of the 405 IIM patients, 22 (5.4%) were found to carry the anti-HMGCR antibody. These IIM patients were predominantly female (73%), and only 3 anti-HMGCR antibody-positive patients with IIM were exposure to statins. Most patients experienced progressive onset, and presented with muscular weakness. Dysphagia was observed in half of the patients (p < 0.01), and 15% of these patients experienced the complication of interstitial lung disease (ILD) (p > 0.05). Mean creatine kinase (CK) levels were higher in antibody-positive patients than in antibody-negative patients (p < 0.05). Muscle biopsies were available from 12 anti-HMGCR antibody-positive patients, eight who experienced myofiber necrosis and showed very little or no evidence of inflammatory cell infiltrates in their muscle biopsies. Of these eleven patients who were followed-up 2.5- to 29-month, 73% experienced improvement after treatment. A cross-sectional study showed that anti-HMGCR antibody levels were significantly associated with CK levels (r = 0.486, p = 0.026) as well as with Myositis Disease Activity Assessment (MYOACT) scores (r = -0.67, p = 0.003) during the initial visit. However, changes in serum anti-HMGCR antibody levels did not correlate with changes in CK levels, Manual Muscle Testing 8 (MMT-8) scores or MYOACT scores in long-term follow-up.Conclusion
The major clinical features of anti-HMGCR antibody-positive Chinese IIM patients were muscle weakness and dysphagia, which were seen in patients with and without statin exposure. This subtype of patients were responsive to immunosuppressive treatment and received good prognoses after treatment, but serum levels of the anti-HMGCR antibody do not correlate with disease activity. 相似文献2.
Background
Inclusion body myositis (IBM) is a poorly understood and refractory autoimmune muscle disease. Though widely believed to have no significant humoral autoimmunity, we sought to identify novel autoantibodies with high specificity for this disease.Methodology/Principal Findings
Plasma autoantibodies from 65 people, including 25 with IBM, were analyzed by immunoblots against normal human muscle. Thirteen of 25 (52%) IBM patient samples recognized an approximately 43 kDa muscle protein. No other disease (N = 25) or healthy volunteer (N = 15) samples recognized this protein.Conclusions
Circulating antibodies against a 43-kDa muscle autoantigen may lead to the discovery of a novel biomarker for IBM. Its high specificity for IBM among patients with autoimmune myopathies furthermore suggests a relationship to disease pathogenesis. 相似文献3.
Andrew J. Solomon William Hills Zunqiu Chen James Rosenbaum Dennis Bourdette Ruth Whitham 《PloS one》2013,8(6)
Background
Rheumatologic diseases may cause neurologic disorders that mimic multiple sclerosis (MS). A panel of serum autoantibodies is often obtained as part of the evaluation of patients suspected of having MS.Objectives
To determine, in light of recently revised diagnostic criteria for MS, neuromyelitis optica, and Sjogren’s Syndrome, if testing for autoantibodies in patients with a confirmed diagnosis of MS would reveal a frequency or demonstrate a clinical utility divergent from previous reports or lead to identification of undiagnosed cases of Sjogren’s Syndrome.Methods
Convenience sample cross-sectional study of MS patients recruited from the OHSU Multiple Sclerosis Center.Results
Autoantibodies were detected in 38% (35/91) of patients with MS and were not significantly associated with disease characteristics or severity. While four patients had SSA antibodies, none met diagnostic criteria for Sjogren’s Syndrome.Conclusions
Rheumatologic autoantibodies are frequently found in MS patients and are not associated with disease severity or systemic rheumatologic disease. Our demonstration of the low specificity of these autoantibodies suggests that the diagnostic utility and cost-effectiveness of testing is not supported when there is strong clinical suspicion of MS and low clinical suspicion of rheumatologic disease. 相似文献4.
Xinyu Xu Yun Shi Yun Cai Qingqing Zhang Fan Yang Heng Chen Yong Gu Mei Zhang Liping. Yu Tao Yang 《PloS one》2013,8(11)
Objectives
Follicular helper T (Tfh) cells exert an important role in autoimmune diseases. Whether it might be involved in type 1 diabetes (T1D) is unknown. Our aim was to investigate the role of Tfh cells in patients with T1D and the effect of anti-CD20 monoclonal antibody (rituximab) on Tfh cells from T1D patients.Patients and Methods
Fifty-four patients with T1D and 37 healthy controls were enrolled in the current study. 20 of those patients were treated with rituximab. The frequencies of circulating CD4+CXCR5+ICOS+T cells were analyzed by flow cytometry. The serum autoantibodies were detected by radioligand assay. The levels of IL-21, IL-6 and BCL-6 were assessed using ELISA and/or real-time PCR.Results
Increased frequencies of circulating Tfh cells together with enhanced expression of IL-21 were detected in patients. The correlation between the frequencies of circulating Tfh cells and the serum autoantibodies or C-peptide level was comfirmed. After rituximab therapy, follow-up analysis demonstrated that the frequencies of circulating Tfh cell and serum IA2A were decreased. The levels of IL-21, IL-6 and Bcl-6 mRNA were decreased after treatment. Furthermore, beta cell function in 10 of 20 patients was improved.Conclusions
These data indicate Tfh cells may participate in the T1D-relatede immune responses and B cells might play a role in the development of Tfh responses in the disease progression. 相似文献5.
Introduction
Several reports have found the onset or activity of inflammatory myopathies to show spatial clustering and seasonal association. We recently detected autoantibodies against melanoma differentiation-associated gene 5 (MDA-5) in more than 20% of patients with dermatomyositis. Anti-MDA-5 antibodies were associated with the presence of rapidly progressive interstitial lung disease in clinically amyopathic dermatomyositis (CADM). The present study aims to assess the growing prevalence of CADM and the geographical incidence of anti-MDA-5-positive patients.Methods
We reviewed medical charts and examined the presence of anti-MDA-5 antibodies in 95 patients, including 36 CADM patients. Sera were obtained from 1994 through 2011. Statistical analyses were performed to assess whether CADM development and the presence of anti-MDA-5 antibodies were associated with various parameters, including age at disease onset, season of onset, annual positivity, and population of resident city.Results
Tertiles based on the year when the sera were collected showed increasing tendencies of CADM and anti-MDA-5-positive patients among all of the dermatomyositis patients. From 1994 to 2010, the relative prevalence of CADM and anti-MDA-5 antibody-positive patients significantly increased. Interestingly, the presence of anti-MDA-5 antibodies in 26 patients was inversely associated with the population of their city of residence.Conclusions
This is the first study to examine the distribution of anti-MDA-5-positive dermatomyositis phenotypes in Japan. Regional differences in the incidences of these phenotypes would suggest that environmental factors contribute to the production of antibodies against MDA-5, which triggers innate antiviral responses. 相似文献6.
Fragoso-Loyo H Cabiedes J Orozco-Narváez A Dávila-Maldonado L Atisha-Fregoso Y Diamond B Llorente L Sánchez-Guerrero J 《PloS one》2008,3(10):e3347
Background
Despite the uncertainty in the diagnosis of neuropsychiatric involvement in systemic lupus erythematosus (SLE), attempts have been made to record the association of certain antibodies in serum with neuropsychiatric (NP) manifestations. We aimed to assess the behaviour and the association of serum and cerebrospinal fluid (CSF) autoantibodies with NP manifestations in SLE patients (NPSLE).Methodology/Principal Findings
Forty-seven SLE patients, hospitalized because of NP manifestations were included. They were evaluated at hospitalization and six months later, and serum and CSF samples were obtained at each evaluation. As controls, serum samples were taken from 49 non-NPSLE patients at hospitalization and six months later; serum and CSF samples were also obtained from 6 SLE patients with septic meningitis, 16 surgical SLE patients and 25 patients without autoimmune diseases. Antinuclear, anti-dsDNA, anti-ribosomal P, Anti-N-Methyl-D-Aspartate receptor (NMDAR), anti-cardiolipin, and anti-β2 glycoprotein-I antibodies were measured. In serum, anti-ribosomal P, anti-NMDAR, and other antibodies did not differentiate among SLE groups, and the levels of all antibodies were similar among the SLE groups. Six-months later, this scenario remained unchanged and the decrease in the levels of some autoantibodies reflected a decline in disease activity, rather than a change in NPSLE. In CSF, only the presence and the levels of anti-NMDAR antibodies showed a characteristic distribution in central NPSLE and septic meningitis patients. Six months later the prevalence of most antibodies in CSF did not change, however the levels of anti-dsDNA, anti-ribosomal P, and anti-NMDAR decreased.Conclusion
In NPSLE, autoantibodies in serum do not reflect their behaviour in CSF. All autoantibodies were elevated in septic meningitis reflecting the global penetration of serum antibodies into the CSF in this condition. Anti-NMDAR antibodies in CSF identified patients with central NPSLE; their continued presence in CSF 6 months after neurologic symptoms raise questions regarding the conditions under which they are pathogenic. 相似文献7.
Mária Filková Hana Hulejová Klára Kuncová Lenka Ple?tilová Lucie Andrés Cerezo He?man Mann Martin Klein Josef Záme?ník Steffen Gay Ji?í Vencovsky Ladislav ?enolt 《Arthritis research & therapy》2012,14(3):R111-9
Introduction
The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity.Methods
Serum resistin levels were determined in 42 patients with inflammatory myopathies and 27 healthy controls. The association among resistin levels, inflammation, global disease activity and muscle strength was examined. The expression of resistin in muscle tissues from patients with inflammatory myopathies and healthy controls was evaluated. Gene expression and protein release from resistin-stimulated muscle and mononuclear cells were assessed.Results
In patients with inflammatory myopathies, the serum levels of resistin were significantly higher than those observed in controls (8.53 ± 6.84 vs. 4.54 ± 1.08 ng/ml, P < 0.0001) and correlated with C-reactive protein (CRP) levels (r = 0.328, P = 0.044) and myositis disease activity assessment visual analogue scales (MYOACT) (r = 0.382, P = 0.026). Stronger association was observed between the levels of serum resistin and CRP levels (r = 0.717, P = 0.037) as well as MYOACT (r = 0.798, P = 0.007), and there was a trend towards correlation between serum resistin and myoglobin levels (r = 0.650, P = 0.067) in anti-Jo-1 positive patients. Furthermore, in patients with dermatomyositis, serum resistin levels significantly correlated with MYOACT (r = 0.667, P = 0.001), creatine kinase (r = 0.739, P = 0.001) and myoglobin levels (r = 0.791, P = 0.0003) and showed a trend towards correlation with CRP levels (r = 0.447, P = 0.067). Resistin expression in muscle tissue was significantly higher in patients with inflammatory myopathies compared to controls, and resistin induced the expression of interleukins (IL)-1β and IL-6 and monocyte chemoattractant protein (MCP)-1 in mononuclear cells but not in myocytes.Conclusions
The results of this study indicate that higher levels of serum resistin are associated with inflammation, higher global disease activity index and muscle injury in patients with myositis-specific anti-Jo-1 antibody and patients with dermatomyositis. Furthermore, up-regulation of resistin in muscle tissue and resistin-induced synthesis of pro-inflammatory cytokines in mononuclear cells suggest a potential role for resistin in the pathogenesis of inflammatory myopathies. 相似文献8.
Marzia Dolcino Claudio Lunardi Andrea Ottria Elisa Tinazzi Giuseppe Patuzzo Antonio Puccetti 《PloS one》2014,9(12)
Background
Psoriatic arthritis (PsA) is a chronic inflammatory disease of unknown origin, characterized by erosions and new bone formation. Diagnosis of PsA is mainly clinical and there are no biomarkers available. Moreover in PsA autoantibodies have not been described so far. Indeed an autoimmune origin has been suggested but never proven. Aim of the study was to investigate the possible presence of autoantibodies typically associated with PsA.Methods
We used pooled IgG immunoglobulins derived from 30 patients with PsA to screen a random peptide library in order to identify disease relevant autoantigen peptides.Results
Among the selected peptides, one was recognised by nearly all the patients’ sera. The identified peptide (PsA peptide: TNRRGRGSPGAL) shows sequence similarities with skin autoantigens, such as fibrillin 3, a constituent of actin microfibrils, desmocollin 3, a constituent of the desmosomes and keratin 78, a component of epithelial cytoskeleton. Interestingly the PsA peptide shares homology with the nebulin-related anchoring protein (N-RAP), a protein localized in the enthesis (point of insertion of a tendon or ligament to the bone), which represents the first affected site during early PsA. Antibodies affinity purified against the PsA peptide recognize fibrillin, desmocollin, keratin and N-RAP. Moreover antibodies directed against the PsA peptide are detectable in 85% of PsA patients. Such antibodies are not present in healthy donors and are present in 13/100 patients with seroposive rheumatoid arthritis (RA). In seronegative RA these antibodies are detectable only in 3/100 patients.Conclusions
Our results indicate that PsA is characterized by the presence of serum autoantibodies crossreacting with an epitope shared by skin and joint antigens. 相似文献9.
Caroline Charpin Fanny Arnoux Marielle Martin Eric Toussirot Nathalie Lambert Nathalie Balandraud Daniel Wendling Elisabeth Diot Jean Roudier Isabelle Auger 《Arthritis research & therapy》2013,15(4):R78
Introduction
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease causing articular cartilage and bone destruction. Since irreversible joint destruction can be prevented by intervention at the early stages of disease, early diagnosis of RA is important. In this study, we identified new autoantibodies in the sera of patients with early (less than one year) RA.Methods
We screened the sera of 20 RA patients with disease duration less than one year, 19 RA patients with disease duration more than five years and 23 controls on 8,268 human protein arrays. We confirmed the validity of protein array detection by ELISA assays. We then performed epitope mapping with overlapping 15-mers to analyze RA sera reactivity.Results
WIBG (within BGCN homolog (Drosophila)), GABARAPL2 (GABA(A) receptor associated protein like 2) and ZNF706 (zinc finger protein 706) proteins are preferentially recognized by autoantibodies from early RA patients. Of interest, autoantibodies to WIBG are very specific for early RA. Indeed, 33% of early RA patients'' sera recognize WIBG versus 5% of RA patients with disease duration more than 5 years and 2% of controls. We identified three linear peptides on WIBG GABARAPL2 and ZNF706 that are preferentially recognized by sera of early RA patients.Conclusions
We identified new autoantibodies associated with RA with disease duration less than one year. These autoantibodies could be used as diagnosis markers in RA patients. 相似文献10.
Wolfgang Hueber Beren H Tomooka Franak Batliwalla Wentian Li Paul A Monach Robert J Tibshirani Ronald F Van Vollenhoven Jon Lampa Kazuyoshi Saito Yoshiya Tanaka Mark C Genovese Lars Klareskog Peter K Gregersen William H Robinson 《Arthritis research & therapy》2009,11(3):R76
Introduction
Anti-TNF therapies have revolutionized the treatment of rheumatoid arthritis (RA), a common systemic autoimmune disease involving destruction of the synovial joints. However, in the practice of rheumatology approximately one-third of patients demonstrate no clinical improvement in response to treatment with anti-TNF therapies, while another third demonstrate a partial response, and one-third an excellent and sustained response. Since no clinical or laboratory tests are available to predict response to anti-TNF therapies, great need exists for predictive biomarkers.Methods
Here we present a multi-step proteomics approach using arthritis antigen arrays, a multiplex cytokine assay, and conventional ELISA, with the objective to identify a biomarker signature in three ethnically diverse cohorts of RA patients treated with the anti-TNF therapy etanercept.Results
We identified a 24-biomarker signature that enabled prediction of a positive clinical response to etanercept in all three cohorts (positive predictive values 58 to 72%; negative predictive values 63 to 78%).Conclusions
We identified a multi-parameter protein biomarker that enables pretreatment classification and prediction of etanercept responders, and tested this biomarker using three independent cohorts of RA patients. Although further validation in prospective and larger cohorts is needed, our observations demonstrate that multiplex characterization of autoantibodies and cytokines provides clinical utility for predicting response to the anti-TNF therapy etanercept in RA patients. 相似文献11.
Julia Sieber Capucine Daridon Sarah J Fleischer Vanessa Fleischer Falk Hiepe Tobias Alexander Guido Heine Gerd R Burmester Simon Fillatreau Thomas D?rner 《Arthritis research & therapy》2014,16(6)
Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disease associated with a break in self-tolerance reflected by a production of antinuclear autoantibodies. Since autoantibody production can be activated via nucleic acid Toll-like receptor 9 (TLR9), the respective pathway has been implicated in the development of SLE and pathogenic B cell responses. However, the response of B cells from SLE patients to TLR9 stimulation remains incompletely characterized.Methods
In the current study, the response of B cells from SLE patients and healthy donors upon TLR9 stimulation was analyzed in terms of proliferation and cytokine production and correlated with the lupus disease activity and anti-dsDNA titers.Results
B cells from SLE patients showed a reduced response to TLR9 agonist compared to B cells from healthy donors in terms of proliferation and activation. B cells from SLE patients with higher disease activity produced less interleukin (IL)-6, IL-10, vascular endothelial growth factor, and IL-1ra than B cells from healthy donors. Further analyses revealed an inverse correlation of cytokines produced by TLR9-stimulated B cells with lupus disease activity and anti-dsDNA titer, respectively.Conclusion
The capacity of B cells from lupus patients to produce cytokines upon TLR9 engagement becomes less efficient with increasing disease activity, suggesting that they either enter an exhausted state or become tolerant to TLR stimulation for cytokine production when disease worsens.Electronic supplementary material
The online version of this article (doi:10.1186/s13075-014-0477-1) contains supplementary material, which is available to authorized users. 相似文献12.
Abdur Rahman Khan Muhammad Riaz Aref A. Bin Abdulhak Mohamad A. Al-Tannir Musa A. Garbati Patricia J. Erwin Larry M. Baddour Imad M. Tleyjeh 《PloS one》2013,8(1)
Background
Emerging epidemiological evidence suggests that statins may reduce the risk of community-acquired pneumonia (CAP) and its complications.Purpose
Performed a systematic review to address the role of statins in the prevention or treatment of CAP.Data Source
Ovid MEDLINE, Cochrane, EMBASE, ISI Web of Science, and Scopus from inception through December 2011 were searched for randomized clinical trials, cohort and case-control studies.Study Selection
Two authors independently reviewed studies that examined the role of statins in CAP.Data Extraction
Data about study characteristics, adjusted effect-estimates and quality characteristics was extracted.Data Synthesis
Eighteen studies corresponding to 21 effect-estimates (eight and 13 of which addressed the preventive and therapeutic roles of statins, respectively) were included. All studies were of good methodological quality. Random-effects meta-analyses of adjusted effect-estimates were used. Statins were associated with a lower risk of CAP, 0.84 (95% CI, 0.74–0.95), I2 = 90.5% and a lower short-term mortality in patients with CAP, 0.68 (95% CI, 0.59–0.78), I2 = 75.7%. Meta-regression did not identify sources of heterogeneity. A funnel plot suggested publication bias in the treatment group, which was adjusted by a novel regression method with a resultant effect-estimate of 0.85 (95% CI, 0.77–0.93). Sensitivity analyses using the rule-out approach showed that it is unlikely that the results were due to an unmeasured confounder.Conclusions
Our meta-analysis reveals a beneficial role of statins for the risk of development and mortality associated with CAP. However, the results constitute very low quality evidence as per the GRADE framework due to observational study design, heterogeneity and publication bias. 相似文献13.
Albert Wu Chester Good John R. Downs Michael J. Fine Mary Jo V. Pugh Antonio Anzueto Eric M. Mortensen 《PloS one》2014,9(1)
Introduction
Little research has examined whether cardiovascular medications, other than statins, are associated with improved outcomes after pneumonia. Our aim was to examine the association between the use of beta-blockers, statins, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) with pneumonia-related outcomes.Materials and Methods
We conducted a retrospective population-based study on male patients ≥65 years of age hospitalized with pneumonia and who did not have pre-existing cardiac disease. Our primary analyses were multilevel regression models that examined the association between cardiovascular medication classes and either mortality or cardiovascular events.Results
Our cohort included 21,985 patients: 22% died within 90 days of admission, and 22% had a cardiac event within 90 days. The cardiovascular medications studied that were associated with decreased 90-day mortality included: statins (OR 0.70, 95% CI 0.63–0.77), ACE inhibitors (OR 0.82, 95% CI 0.74–0.91), and ARBs (OR 0.58, 95% CI 0.44–0.77). However, none of the medications were significantly associated with decreased cardiovascular events.Discussion
While statins, ACE inhibitors, and ARBs, were associated with decreased mortality, there was no significant association with decreased CV events. These results indicate that this decreased mortality is unlikely due to their potential cardioprotective effects. 相似文献14.
Isabelle Schepens Fabienne Jaunin Nadja Begre Ursula L?derach Katrin Marcus Takashi Hashimoto Bertrand Favre Luca Borradori 《PloS one》2010,5(8)
Background
Paraneoplastic pemphigus (PNP) is a devastating autoimmune blistering disease, involving mucocutaneous and internal organs, and associated with underlying neoplasms. PNP is characterized by the production of autoantibodies targeting proteins of the plakin and cadherin families involved in maintenance of cell architecture and tissue cohesion. Nevertheless, the identity of an antigen of Mr 170,000 (p170), thought to be critical in PNP pathogenesis, has remained unknown.Methodology/Principal Findings
Using an immunoprecipitation and mass spectrometry based approach, we identified p170 as alpha-2-macroglobuline-like-1, a broad range protease inhibitor expressed in stratified epithelia and other tissues damaged in the PNP disease course. We demonstrate that 10 PNP sera recognize alpha-2-macroglobuline-like-1 (A2ML1), while none of the control sera obtained from patients with bullous pemphigoid, pemphigus vulgaris, pemphigus foliaceus and normal subjects does.Conclusions/Significance
Our study unravels a broad range protease inhibitor as a new class of target antigens in a paraneoplastic autoimmune multiorgan syndrome and opens a new challenging investigation avenue for a better understanding of PNP pathogenesis. 相似文献15.
Andrea Wuestenberg Janine Kah Katrin Singethan Hüseyin Sirma Amelie Dorothea Keller Sergio René Perez Rosal J?rg Schrader Christine Loscher Tassilo Volz Ralf Bartenschlager Volker Lohmann Ulrike Protzer Maura Dandri Ansgar W. Lohse Gisa Tiegs Gabriele Sass 《PloS one》2014,9(5)
Background & Aims
HMG-CoA-reductase-inhibitors (statins) have been shown to interfere with HCV replication in vitro. We investigated the mechanism, requirements and contribution of heme oxygenase-1(HO-1)-induction by statins to interference with HCV replication.Methods
HO-1-induction by fluva-, simva-, rosuva-, atorva- or pravastatin was correlated to HCV replication, using non-infectious replicon systems as well as the infectious cell culture system. The mechanism of HO-1-induction by statins as well as its relevance for interference with HCV replication was investigated using transient or permanent knockdown cell lines. Polyacrylamide(PAA) gels of different density degrees or the Rho-kinase-inhibitor Hydroxyfasudil were used in order to mimic matrix conditions corresponding to normal versus fibrotic liver tissue.Results
All statins used, except pravastatin, decreased HCV replication and induced HO-1 expression, as well as interferon response in vitro. HO-1-induction was mediated by reduction of Bach1 expression and induction of the Nuclear factor (erythroid-derived 2)-like 2 (NRF2) cofactor Krueppel-like factor 2 (KLF2). Knockdown of KLF2 or HO-1 abrogated effects of statins on HCV replication. HO-1-induction and anti-viral effects of statins were more pronounced under cell culture conditions mimicking advanced stages of liver disease.Conclusions
Statin-mediated effects on HCV replication seem to require HO-1-induction, which is more pronounced in a microenvironment resembling fibrotic liver tissue. This implicates that certain statins might be especially useful to support HCV therapy of patients at advanced stages of liver disease. 相似文献16.
Background
To investigate the regulation of K17 expression by the pro-inflammatory cytokine IL-22 in keratinocytes and its important role in our previously hypothesized “K17/T cell/cytokine autoimmune loop” in psoriasis.Materials and Methods
K17 expression was examined in the IL-22-treated keratinocytes by real-time quantitative PCR, ELISA, Western blot and Immunofluorescence. In addition, the signaling pathways involved in K17 regulation were investigated with related inhibitors and siRNAs. In addition, K17 expression was examined in the epidermis of IL-22-injected mouse skin.Results
IL-22-induced K17 expression was confirmed in keratinocytes and the epidermis of IL-22-injected mouse skin at both mRNA and protein levels, which is an important complement to the autoimmune loop. We further investigated the regulatory mechanisms and found that both STAT3 and ERK1/2 were involved in the up-regulation of K17 expression induced by IL-22.Conclusion
IL-22 up-regulates K17 expression in keratinocytes in a dose-dependent manner through STAT3- and ERK1/2-dependent mechanisms. These findings indicated that IL-22 was also involved in the K17/T cell/cytokine autoimmune loop and may play an important role in the progression of psoriasis. 相似文献17.
Macchia A Laffaye N Comignani PD Cornejo Pucci E Igarzabal C Scazziota AS Herrera L Mariani JA Bragagnolo JC Catalano H Tognoni G Nicolucci A 《PloS one》2012,7(3):e32894
Background
The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG) among patients with type II diabetes mellitus and no previous cardiovascular events.Methodology/Principal Findings
Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks), assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018). On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716). The effects of treatments on measurements of TG using other agonists were consistent.Conclusions/Significance
While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG.Trial Registration
ClinicalTrials.gov NCT00793754相似文献18.
Anne Becker Nicole Ludwig Andreas Keller Bj?rn Tackenberg Christian Eienbr?ker Wolfgang H. Oertel Klaus Fassbender Eckart Meese Klemens Ruprecht 《PloS one》2013,8(3)
Background
Myasthenia gravis is a disorder of neuromuscular transmission associated with autoantibodies against the nicotinic acetylcholine receptor. We have previously developed a customized protein macroarray comprising 1827 potential human autoantigens, which permitted to discriminate sera of patients with different cancers from sera of healthy controls, but has not yet been evaluated in antibody-mediated autoimmune diseases.Objective
To determine whether autoantibody signatures obtained by protein macroarray separate sera of patients with myasthenia gravis from healthy controls.Methods
Sera of patients with acetylcholine receptor antibody-positive myasthenia gravis (n = 25) and healthy controls (n = 32) were analyzed by protein macroarrays comprising 1827 peptide clones.Results
Autoantibody signatures did not separate patients with myasthenia gravis from controls with sufficient sensitivity, specificity, and accuracy. Intensity values of one antigen (poly A binding protein cytoplasmic 1, p = 0.0045) were higher in patients with myasthenia gravis, but the relevance of this and two further antigens, 40S ribosomal protein S13 (20.8% vs. 0%, p = 0.011) and proteasome subunit alpha type 1 (25% vs. 3.1%, p = 0.035), which were detected more frequently by myasthenia gravis than by control sera, currently remains uncertain.Conclusion
Seroreactivity profiles of patients with myasthenia gravis detected by a customized protein macroarray did not allow discrimination from healthy controls, compatible with the notion that the autoantibody response in myasthenia gravis is highly focussed against the acetylcholine receptor. 相似文献19.
Laura Pasin Giovanni Landoni Maria Lourdes Castro Luca Cabrini Alessandro Belletti Paolo Feltracco Gabriele Finco Andrea Carozzo Roberto Chiesa Alberto Zangrillo 《PloS one》2013,8(12)
Objective
Statins are among the most prescribed drugs worldwide and their recently discovered anti-inflammatory effect seems to have an important role in inhibiting proinflammatory cytokine production, chemokines expression and counteracting the harmful effects of sepsis on the coagulation system. We decided to perform a meta-analysis of all randomized controlled trials ever published on statin therapy in septic patients to evaluate their effect on survival and length of hospital stay.Data sources and study selection
Articles were assessed by four trained investigators, with divergences resolved by consensus. BioMedCentral, PubMed, Embase and the Cochrane Central Register of clinical trials were searched for pertinent studies. Inclusion criteria were random allocation to treatment and comparison of statins versus any comparator in septic patients.Data extraction and synthesis
Data from 650 patients in 5 randomized controlled studies were analyzed. No difference in mortality between patients receiving statins versus control (44/322 [14%] in the statins group vs 50/328 [15%] in the control arm, RR = 0.90 [95% CI 0.65 to 1.26], p = 0.6) was observed. No differences in hospital stay (p = 0.7) were found.Conclusions
Published data show that statin therapy has no effect on mortality in the overall population of adult septic patients. Scientific evidence on statins role in septic patients is still limited and larger randomized trials should be performed on this topic. 相似文献20.
Masayuki Hanaoka Mark R Nicolls Andrew P Fontenot Donatas Kraskauskas Douglas G Mack Adelheid Kratzer Jonas Salys Vita Kraskauskiene Nana Burns Norbert F Voelkel Laimute Taraseviciene-Stewart 《Respiratory research》2010,11(1):179