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WG Patients (wg + patient)
Selected AbstractsAssociation study of Wegener granulomatosis and the functionally relevant A645G polymorphism in the bactericidal/permeability increasing protein (BPI) geneINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2005P. Jagiello Summary In antineutrophil cytoplasmatic antibody (ANCA)-associated vasculitides (AAV), bactericidal/permeability increasing protein (BPI) ANCAs are detected. Recent observations suggest that BPI-ANCAs can potentially contribute to a proinflammatory setting in the absence of proteinase 3 (PRTN3) ANCAs during the development of a pulmonary relapse by impeding the elimination of Gram-negative bacteria (GNB). However, it is as yet not clear whether the genetic background contributes to the generation of BPI-ANCAs in Wegener granulomatosis (WG) or if BPI polymorphisms are associated with WG. In this study we genotyped the functionally relevant single nucleotide polymorphism (SNP) A645 (Glu216Lys) of the BPI gene in 201 WG patients and 608 healthy controls. To investigate whether further SNPs might be associated with WG, we also examined an intragenic microsatellite marker. No significant differences were found between patients and controls. Thus BPI polymorphisms do not appear to contribute to genetic predisposition to WG. Moreover, our data do not suggest a genetic background for the generation of BPI-ANCAs in WG. [source] Transcription of proteinase 3 and related myelopoiesis genes in peripheral blood mononuclear cells of patients with active Wegener's granulomatosisARTHRITIS & RHEUMATISM, Issue 6 2010Chris Cheadle Objective Wegener's granulomatosis (WG) is a systemic inflammatory disease that is associated with substantial morbidity. The aim of this study was to understand the biology underlying WG and to discover markers of disease activity that would be useful for prognosis and treatment guidance. Methods Gene expression profiling was performed using total RNA from peripheral blood mononuclear cells (PBMCs) and granulocyte fractions from 41 patients with WG and 23 healthy control subjects. Gene set enrichment analysis (GSEA) was performed to search for candidate WG-associated molecular pathways and disease activity biomarkers. Principal components analysis was used to visualize relationships between subgroups of WG patients and controls. Longitudinal changes in proteinase 3 (PR3) gene expression were evaluated using reverse transcription,polymerase chain reaction, and clinical outcomes, including remission status and disease activity, were determined using the Birmingham Vasculitis Activity Score for WG (BVAS-WG). Results Eighty-six genes in WG PBMCs and 40 in WG polymorphonuclear neutrophils (PMNs) were significantly up-regulated relative to controls. Genes up-regulated in WG PBMCs were involved in myeloid differentiation, and these included the WG autoantigen PR3. The coordinated regulation of myeloid differentiation genes was confirmed by GSEA. The median expression values of the 86 up-regulated genes in WG PBMCs were associated with disease activity (P = 1.3 × 10,4), and WG patients with low-level expression of the WG signature genes showed expression profiles that were only modestly different from that in healthy controls (P = 0.07). PR3 transcription was significantly up-regulated in WG PBMCs (P = 1.3 × 10,5, false discovery rate [FDR] 0.002), but not in WG PMNs (P = 0.03, FDR 0.28), and a preliminary longitudinal analysis showed that the fold change in PR3 RNA levels in WG PBMCs corresponded to changes in the BVAS-WG score over time. Conclusion Transcription of PR3 and related myeloid differentiation genes in PBMCs may represent novel markers of disease activity in WG. [source] Classification, presentation, and initial treatment of Wegener's granulomatosis in childhoodARTHRITIS & RHEUMATISM, Issue 11 2009David A. Cabral Objective To compare the criteria for Wegener's granulomatosis (WG) of the American College of Rheumatology (ACR) with those of the European League Against Rheumatism/Pediatric Rheumatology European Society (EULAR/PRES) in a cohort of children with WG and other antineutrophil cytoplasmic antibody (ANCA),associated vasculitides (AAVs), and to describe the interval to diagnosis, presenting features, and initial treatment for WG. Methods Eligible patients had been diagnosed by site rheumatologists (termed the "MD diagnosis") since 2004. This diagnosis was used as a reference standard for sensitivity and specificity testing of the 2 WG classification criteria. Descriptive analyses were confined to ACR-classified WG patients. Results MD diagnoses of 117 patients (82 of whom were female) were WG (n = 76), microscopic polyangiitis (n = 17), ANCA-positive pauci-immune glomerulonephritis (n = 5), Churg-Strauss syndrome (n = 2), and unclassified vasculitis (n = 17). The sensitivities of the ACR and EULAR/PRES classification criteria for WG among the spectrum of AAVs were 68.4% and 73.6%, respectively, and the specificities were 68.3% and 73.2%, respectively. Two more children were identified as having WG by the EULAR/PRES criteria than by the ACR criteria. For the 65 ACR-classified WG patients, the median age at diagnosis was 14.2 years (range 4,17 years), and the median interval from symptom onset to diagnosis was 2.7 months (range 0,49 months). The most frequent presenting features by organ system were constitutional (89.2%), pulmonary (80.0%), ear, nose, and throat (80.0%), and renal (75.4%). Fifty-four patients (83.1%) commenced treatment with the combination of corticosteroids and cyclophosphamide, with widely varying regimens; the remainder received methotrexate alone (n = 1), corticosteroids alone (n = 4), or a combination (n = 6). Conclusion The EULAR/PRES criteria minimally improved diagnostic sensitivity and specificity for WG among a narrow spectrum of children with AAVs. Diagnostic delays may result from poor characterization of childhood WG. Initial therapy varied considerably among participating centers. [source] Increased morbidity from ischemic heart disease in patients with Wegener's granulomatosisARTHRITIS & RHEUMATISM, Issue 4 2009Mikkel Faurschou Objective Experimental studies indicate that patients with Wegener's granulomatosis (WG) experience accelerated atherosclerosis. The purpose of this study was to investigate whether the occurrence of overt ischemic heart disease (IHD) is increased in WG. Methods A total of 293 WG patients were included in the study. Information on all hospitalizations for IHD in Denmark from 1977 to 2006 was obtained from the Danish National Hospital Register. The WG patients were compared with the Danish background population with respect to rates of hospitalization for clinical manifestations of IHD after the date of vasculitis diagnosis by calculating standardized ratios of observed to expected (O:E) events. Results Sixty-three first IHD events were registered in the WG group during the 2,482 patient-years of followup, corresponding to a significantly increased O:E ratio for IHD of 1.9 (95% confidence interval [95% CI] 1.4,2.4). A significantly increased risk was found for acute myocardial infarction (MI) (O:E ratio 2.5 [95% CI 1.6,3.7]), but not for angina pectoris (O:E ratio 1.3 [95% CI 0.7,2.1]). In analyses stratified according to the time between the diagnosis of vasculitis and the cardiovascular event, increased O:E ratios were found for IHD and acute MI occurring <5.0 years after WG diagnosis (2.1 [95% CI 1.4,3.0] for IHD and 3.6 [95% CI 2.0,5.9] for acute MI) and for IHD occurring ,10.0 years after WG diagnosis (2.2 [95% CI 1.3,3.4]). Significantly increased O:E ratios for IHD and acute MI were found in patients who were ,50.0 years of age at the time of diagnosis of WG, in male patients, and in patients who received high cumulative doses of cyclophosphamide. Conclusion Compared with the background population, WG patients seem to experience an increased number of both early and late cardiovascular events due to IHD. [source] Functional defect of circulating regulatory CD4+ T cells in patients with Wegener's granulomatosis in remissionARTHRITIS & RHEUMATISM, Issue 6 2007Wayel H. Abdulahad Objective Accumulating data support the role of regulatory T cells, a subset of CD4+ T cells that expresses CD25high and the transcription factor forkhead box P3 (FoxP3), in controlling and preventing autoimmunity. In Wegener's granulomatosis (WG), an autoimmune vasculitis, up-regulation of CD25 on circulating CD4+ T cells has been observed, even in patients in remission. The objective of this study was to test whether the frequency and/or function of Treg cells from WG patients in remission are disturbed. Methods Peripheral blood mononuclear cells were freshly isolated from 52 WG patients in remission and from 27 age- and sex-matched healthy control subjects. The proportion of circulating Treg cells was assessed by flow cytometry using CD4, CD25, FoxP3, and CD45RO markers. Anergy and suppressive function of CD25high,CD4+ T cells were determined using polyclonal stimulants and coculture assay in 10 WG patients in remission and in 10 age- and sex-matched healthy controls. Results In WG patients, a significant increase was observed in the percentage of circulating CD25high,CD4+ and CD25low,CD4+ T cells, whereas CD25,,CD4+ T cells were decreased, as compared with healthy controls. Among circulating CD4+ T cells, an expanded percentage of Treg cells (CD25high,FoxP3+) with memory phenotype was present in WG patients. However, when the suppressive function of CD25high,CD4+ T cells was tested, CD25high,CD4+ T cells from WG patients showed diminished or absent suppression of responder T cell proliferation. The impaired suppression was not due to responder cell resistance (as shown by crisscross experiments with T cells from healthy controls) or altered survival of Treg cells. Conclusion These data indicate that WG patients in remission have an expanded proportion of Treg cells that are functionally defective. This observation may be relevant to the development and relapsing course of this autoimmune vasculitis. [source] | ||||||||||