Ficolin-1 is upregulated in leukocytes and glomeruli from microscopic polyangiitis patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41744 | GEO | 2013/08/18
SECONDARY ACCESSION(S): PRJNA178101
REPOSITORIES: GEO
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Project description:To search for new markers of active lesions that might help better understand the molecular basis of MPA and aid in its diagnosis, DNA microarray analysis was performed with peripheral blood mononuclear cells (PBMCs). A total of 12 sets of two color arrays were performed and each individual array included a target sample and a control sample.
2013-08-18 | E-GEOD-41744 | biostudies-arrayexpress
Project description:ANCA associated vasculitis(AAV) is a systemic vasculitis of small vessels, characterzied by injury of vascular endothelial cells induced by abnormally activated neutrophils. Microscopic polyangiitis (MPA) is a member of AAV with a high risk of kidney involvement. Blood lipid disorder promotes endothelial injury. We aim to investigate the correlation between blood lipid levels and renal prognosis in MPA patients. Firstly, we retrospectively included 110 patients diagnosed with MPA and the primary endpoint was the occurrence of ESRD. The association between blood lipids and renal outcome was evaluated with logistic regression analysis and survival analysis. During a median follow-up period of 23 months, 44 out of 110 patients (40%) developed ESRD. High serum triglycerides (TG) and VLDL at diagnosis were associated with ESRD development after adjusting for several confounding factors. MPA patients with TG >1.45 mmol/L or VLDL > 0.66mmol/L had significantly higher risk of ESRD development than those with TG ≤1.45 mmol/L or VLDL ≤0.66 mmol/L. Secondly, we explored the underlying mechanism of poor renal prognosis in patients with high TG levels using data independent acquisition (DIA) quantitative proteomics. DIA quantitative proteomics analysis suggested that patients in high TG group had up-regulated profibrotic pathway, inflammatory signaling pathways and complement and coagulation cascades compared with those in low TG group. In conclusion, high baseline TG or VLDL is associated with an increased risk of ESRD development in MPA patients. The potential mechanisms may be the upregulation of pro-fibrotic and inflammatory signaling pathways, and the activation of complement and coagulation cascades.
2025-01-06 | PXD045969 | Pride
Project description:To search for new markers of active lesions that might help better understand the molecular basis of MN and IgAN and aid in their diagnosis, DNA microarray analysis was performed with peripheral blood mononuclear cells (PBMCs)
2016-04-22 | GSE73953 | GEO
Project description:Clinical trials and observational studies have established cyclophosphamide (CY) or rituximab plus glucocorticoid (GC) as standard remission induction therapies in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, because these regimens are associated with serious adverse drug reactions, the development of drugs with novel mechanisms of actions are needed. Progress in basic and clinical research has identified novel candidate targeting molecules, including B-cell activating factor (BAF), C5a receptor, and interleukin-6. The combination of rituximab and BAF blockade in patients with MPA and GPA is under investigation in an effort to strike a better benefit-risk balance. Phase II clinical trials of avacopan (CCX168), an orally administered C5a receptor antagonist, have suggested a reduction in the dosage of concomitant GC or the replacement of GC in patients with MPA and GPA. The results from a currently ongoing phase III trial are awaited. Anecdotal case reports and an open-label pilot study have indicated the effectiveness of tocilizumab in patients with MPA and GPA. A randomized clinical trial comparing tocilizumab and intravenous CY in combination with GC is currently in progress. Molecular targeted therapy is expected to transform the treatment strategy for MPA and GPA to allow GC-free or at least less GC-dependent forms of therapy.
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Project description:The antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitides (AAVs), which include fever of unknown origin (FUO), are rare diseases characterized by necrotizing inflammation of small blood vessels and the presence of ANCAs. Microscopic polyangiitis (MPA) is a subtype of the AAVs. Although the prevalence of AAVs has generally increased over the last 20 years, there have been rare reports from the dental and oral surgery field. In this article, we present a case of MPA suspected to be infective endocarditis (IE) following tooth extraction.
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Project description:Genome-Scale draft model for Human Peripheral Blood Mononuclear Cells (PBMCs). A GEM for PBMCs was developed by applying the INIT
algorithm on Human Metabolic Reconstruction (HMR 2.0) as a template model. GEMs were contextualised/ constrained for different conditions using expression datasets. The gene/transcript expression data obtained from PBMCs of Type 1 Diabetes progressors, non-progressors, and healthy controls were employed to score each reaction of HMR 2.0. For further detail please refer to Electronic Supplementary Information of Sen et.al, Metabolic alterations in immune cells associate with progression to type 1 diabetes, Diabetologia, 15/01/2020, (https://doi.org/10.1007/s00125-020-05107-6).
2020-03-11 | MODEL1905270001 | BioModels
Project description:ObjectiveThe present study was undertaken to conduct a phase IV, open-label, prospective study to characterize the long-term safety of rituximab in a 4-year observational registry of adult patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) within the US.MethodsPatients initiating treatment with rituximab were evaluated every 6 months for up to 4 years. Outcomes included the incidence of serious adverse events (SAEs), infusion-related reactions (IRRs), and SAEs of specific interest, including serious infections, serious cardiac events, serious vascular events, and malignancies.ResultsOverall, 97 patients (72 with GPA and 25 with MPA) received rituximab through a median of 8 (range 1-28) infusions and were followed up for a median of 3.94 years (range 0.05-4.32 years). The estimated incidence rates (95% confidence interval [95% CI]) of serious infections, serious cardiac events, and serious vascular events were 7.11 (4.55-10.58), 5.03 (2.93-8.06), and 2.37 (1.02-4.67) per 100 patient-years (PYs), respectively. No IRRs or SAEs occurred within 24 hours of an infusion of rituximab. None of the 9 deaths reported (crude mortality rate 2.67 [95% CI 1.22-5.06] per 100 PYs) were considered to be related to use of rituximab.ConclusionThe safety profile of long-term treatment with rituximab in patients with GPA or MPA was consistent with that of rituximab administered for shorter durations and with rituximab's known safety profile in other autoimmune diseases for which it has received regulatory approval. These findings provide clinicians with long-term, practice-level safety data for rituximab in the treatment of GPA or MPA.
| S-EPMC8457173 | biostudies-literature
Project description:The epidemiology of ANCA-associated vasculitis is substantially different between Caucasians and Japanese, which may be related to differences in genetic backgrounds. In this review, I discussed our findings on the genetics of microscopic polyangiitis (MPA) in Japanese. Analysis of HLA genes revealed a significant increase in the HLA-DRB1*09:01-DQB1*03:03 haplotype MPA. This is one of the most frequent haplotypes in Japanese, but is nearly absent in Caucasians, and has been shown to be associated with multiple autoimmune diseases. Analysis of KIR genes revealed significant decreases in the carrier frequency of an activating receptor KIR2DS3 in MPA. When KIRs were analyzed in combination with HLA ligands, the proportion of individuals carrying KIR3DL1 and HLA-Bw4 but not KIR3DS1, the most inhibitory of all KIR3DS1/3DL1/HLA-B combinations, was significantly increased in MPA. These results suggested that decreased activation of NK and/or T cells may cause a predisposition to MPA. LILRA2 is an activating receptor involved in granulocyte and macrophage activation. LILRA2 SNP rs2241524 G >A, which disrupts the intron 6 splice acceptor site, was significantly associated with MPA. The risk allele produces an LILRA2 isoform lacking three amino acids in the linker region. These findings, when confirmed by larger-scale studies, will shed light on the molecular mechanisms of MPA. (*English Translation of J Jpn Coll Angiol 2009; 49: 31-37.).
| S-EPMC3595849 | biostudies-literature
Project description:Granulomatosis with polyangiitis and microscopic polyangiitis are anti-neutrophil cytoplasmic antibody-associated vasculitides (AAVs) that are prone to cycles of remission and relapse. The introduction of cytotoxic therapy has changed the prognosis for these diseases from typically fatal to manageable chronic illnesses with a relapsing course. Despite improvements in outcomes, recurrence of disease and drug-related toxicity continue to produce significant morbidity and mortality. Better understanding of the pathogenesis of AAV and the mechanism of action of cyclophosphamide has led to investigation of therapies that target B cells. Two randomized controlled trials have shown that rituximab is not inferior to cyclophosphamide for induction of remission in severe AAV, with no significant difference in the incidence of overall adverse events in rituximab- versus cyclophosphamide-treated patients. Data from ongoing clinical trials will determine the role of rituximab in the maintenance of remission.
| S-EPMC4322237 | biostudies-other
Project description:ObjectivesPrevious studies have shown that adipokines may serve as potential biomarkers reflecting disease activity in various autoimmune diseases. Here, we investigated the relationship between four adipokines and clinical/laboratory findings in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).MethodsSera from 63 patients with MPA and GPA who were registered in a prospective cohort were used to detect serum levels of adiponectin, chemerin, resistin, and vaspin using commercial enzyme-linked immunosorbent assay kits. Associations between adipokines and clinical and laboratory data was assessed using Pearson's correlation analysis.ResultsThe median age was 65.0 years, 24 patients were male, and 42 patients were diagnosed with MPA. The median levels of adiponectin, chemerin, resistin, and vaspin in patient sera were 13.9 ng/mL, 9.2 ng/mL, 23.7 ng/mL, and 0.1 ng/mL, respectively. A significant correlation between chemerin level and five-factor score (FFS) was found (r = 0.320, p = 0.011), and resistin was correlated with both Birmingham vasculitis activity score and FFS (r = 0.256, p = 0.043 and r = 0.320, p = 0.011). Regarding laboratory data, adiponectin level was associated with creatinine, and chemerin level was associated with creatinine, albumin, and erythrocyte sedimentation rate (ESR). On the other hand, resistin was found to be associated with white blood cell count, creatinine, ESR, and C-reactive protein. Age did not have a significant impact on the levels of adipokines.ConclusionsThe expression of adipokines in the sera of patients with MPA and GPA differs depending on clinical and laboratory features, and serum resistin may be suggested as a potential biomarker reflecting disease activity.
| S-EPMC8270208 | biostudies-literature