1,721,088 research outputs found
150 Association between loss of immune checkpoint programmed cell death protein 1 and local synthesis of complement factor B in active ANCA-associated renal vasculitis
No full textMO279DETERMINANTS TO CONSIDER THERAPEUTIC PLASMA EXCHANGE FOR TREATMENT OF SEVERE ANCA-ASSOCIATED VASCULITIS: A RETROSPECTIVE STUDY FROM A SINGLE CENTER
No full text146 A transcriptome array-based approach to link SGLT-2 and tubulointerstitial synthesis of complement C5 in IgA nephropathy
No full text148 Intrarenal synthesis of complement C3 localized to distinct vascular compartments in ANCA-associated renal vasculitis
No full textMO303URINARY ALBUMIN-TO-CREATININE RATIO INDICATES NECROTIZING AND CRESCENTIC GLOMERULONEPHRITIS IN ANCA-ASSOCIATED VASCULITIS
No full text#2510 Urokinase plasminogen activator receptor upregulation in lupus nephritis associates with distinct interferon hub genes in stressed podocytes
No full textAbstract Background and Aims Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease characterized by immune system dysfunction, leading to inflammation and damage in various organs and tissues. Renal involvement known as lupus nephritis is one of the most severe complications occurring in 60% of patients with SLE, significantly impacting patient morbidity and mortality. Understanding the intricate relationship between SLE and renal manifestations is crucial for effective management and improved patient outcomes. Recently, the cell surface urokinase plasminogen activator receptor (uPAR) has emerged as a significant player in the pathogenesis of lupus nephritis. However, the molecular mechanisms through which uPAR influences lupus nephritis remain an active area of investigation. Therefore, we here pursued a transcriptome array-based approach to identify molecular patterns in association with uPAR in lupus nephritis. Method PLAUR mRNA expression levels (encoding uPAR, reporter ID: 210845_s_at, platform: Affymetrix Human Genome U133 Plus 2.0 Array, altCDF v10) were extracted from microdissected control kidneys (glomerular compartment: n = 14) and lupus nephritis (glomerular: n = 32, tubulointerstitial: n = 32). Pathway analysis was performed for gene enrichment associated with PLAUR mRNA expression with a correlation threshold of ≥0.5 by using reactome (https://reactome.org), pathways with a predefined entities value of P ≤ .001 were included. Data was validated in cultured podocytes stressed with Adriamycin, protein expression profiling was performed by mass spectrometry in combination with stable isotope labelling by amino acids in cell culture (SILAC). Results We here identified a predominant glomerular expression of uPAR in lupus nephritis that was increased as compared to healthy controls. While glomerular uPAR expression was predominantly associated with interferon signaling, none of type I or type II interferons were induced. Interestingly, we identified distinct interferon hub genes that were associated with uPAR in lupus nephritis and enriched in stressed podocytes (GBP2: P < .0001, IFI30: P = .0006, IFIT1: P < .0001, IFITM3: P = .0308). Finally, uPAR and associated interferon hub genes correlated with proteinuria in lupus nephritis. Conclusion The therapeutic implications of targeting uPAR in lupus nephritis are promising, and ongoing research endeavors are aimed at unraveling the complexities of uPAR as a potential diagnostic marker and therapeutic target for this challenging renal pathology. We here expand our current knowledge and link uPAR upregulation in lupus nephritis to distinct interferon hub genes in stressed podocytes
Correspondence on ‘What comes after the lockdown? Clustering of ANCA-associated vasculitis: single-centre observation of a spatiotemporal pattern’
No full textCase Report: ANCA-Associated Vasculitis Presenting With Rhabdomyolysis and Pauci-Immune Crescentic Glomerulonephritis After Pfizer-BioNTech COVID-19 mRNA Vaccination
No full textAs the coronavirus disease 2019 (COVID-19) pandemic is ongoing and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging, there is an urgent need for COVID-19 vaccines to control disease outbreaks by herd immunity. Surveillance of rare safety issues related to these vaccines is progressing, since more granular data emerge with regard to adverse events of COVID-19 vaccines during post-marketing surveillance. Interestingly, four cases of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) presenting with pauci-immune crescentic glomerulonephritis (GN) after COVID-19 mRNA vaccination have already been reported. We here expand our current knowledge of this rare but important association and report a case of AAV presenting with massive rhabdomyolysis and pauci-immune crescentic GN after Pfizer-BioNTech COVID-19 mRNA vaccination. As huge vaccination programs are ongoing worldwide, post-marketing surveillance systems must continue to assess vaccine safety important for the detection of any events associated with COVID-19 vaccination. This is especially relevant in complex diseases where diagnosis is often challenging, as in our patient with AAV presenting with massive rhabdomyolysis and pauci-immune crescentic GN.As the coronavirus disease 2019 (COVID-19) pandemic is ongoing and new variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are emerging, there is an urgent need for COVID-19 vaccines to control disease outbreaks by herd immunity. Surveillance of rare safety issues related to these vaccines is progressing, since more granular data emerge with regard to adverse events of COVID-19 vaccines during post-marketing surveillance. Interestingly, four cases of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) presenting with pauci-immune crescentic glomerulonephritis (GN) after COVID-19 mRNA vaccination have already been reported. We here expand our current knowledge of this rare but important association and report a case of AAV presenting with massive rhabdomyolysis and pauci-immune crescentic GN after Pfizer-BioNTech COVID-19 mRNA vaccination. As huge vaccination programs are ongoing worldwide, post-marketing surveillance systems must continue to assess vaccine safety important for the detection of any events associated with COVID-19 vaccination. This is especially relevant in complex diseases where diagnosis is often challenging, as in our patient with AAV presenting with massive rhabdomyolysis and pauci-immune crescentic GN.Open-Access-Publikationsfonds 202
#2543 Complement receptor C5aR1 correlates with inflammatory responses driven by glomerular uPAR upregulation in renal vasculitides
No full textAbstract Background and Aims Avacopan is a novel promising treatment for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) targeting the complement system by blocking C5a receptor C5aR1. We here pursued a transcriptome array-based approach to dissect molecular signatures associated with C5aR1 in renal vasculitis. Method C5aR1 mRNA expression levels (reporter ID: 210845_s_at, platform: Affymetrix Human Genome U133 Plus 2.0 Array, altCDF v10) were extracted from microdissected samples of renal vasculitis (glomerular: n = 23, tubulointerstitial: n = 21). Pathway analysis was performed for gene enrichment associated with PLAUR mRNA expression with a correlation threshold of ≥0.5 by using reactome (http://reactome.org), pathways with a predefined entities value of p≤0.001 were included. Results We here identified a predominant glomerular expression of C5aR1 in renal vasculitis as compared to the tubulointerstitial compartment (p < 0.0001). Furthermore, glomerular C5aR1 induction correlated with impaired kidney function (eGFR: 0.0193). Gene set enrichment identified various inflammatory signatures including neutrophil degranulation and innate immunity, and particularly enrichment of urokinase plasminogen activator receptor (uPAR). uPAR itself also correlated with impairment of kidney function in renal vasculitis and particularly active glomerular lesions (cellular crescents and necrosis, p < 0.0001). Conclusion The therapeutic implications of targeting uPAR in renal vasculitis are promising, and ongoing research endeavors are aimed at unraveling the complexities of uPAR as a potential diagnostic marker and therapeutic target for this challenging renal pathology. We here expand our current knowledge and link C5aR1 to inflammatory responses driven by glomerular uPAR upregulation in renal vasculitis
MO205IMPACT OF THE COVID-19 PANDEMIC ON KIDNEY DISEASES REQUIRING RENAL BIOPSY: A SINGLE-CENTER OBSERVATIONAL STUDY
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