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Unveiling the Complement System's Impact on Antineutrophil Cytoplasmic Antibody (ANCA)–Associated Vasculitis (AAV)



Embark on a journey through the intricate landscape of AAV with LAURA LUCIENTES CONTINENTE and Elena Goicoechea de Jorge and their team as they unravel the role of the complement system's alternative pathway (AP) in AAV pathogenesis. 🌐📊


👉 Exploring the Genetic Landscape:

Common gene variants in CFH/CFHR1-5, CFB, C3, and MCP are scrutinized for their association with AAV susceptibility and kidney damage severity. The study, conducted on a Spanish AAV cohort and validated in ANCA-associated glomerulonephritis patients, unveils key genetic determinants.


👉 Plasma Profiles of Complement Components:

Dynamic assessments of plasma C3, C4, FH, FHR-1, FHR-2, FHR-5, FB, properdin, and sC5b-9 levels provide insights into the variations between active and remission AAV cohorts. Longitudinal observations highlight the correlation between heightened AP activation at diagnosis and adverse disease outcomes.


👉 Predictive Markers for Severity:

The study identifies high basal FHR-1 levels and lower FH/FHR-1 ratios as predictors of severe kidney-associated AAV. Autoantibodies against FH and C3 convertase further contribute to understanding disease complexity.


👉 Validation in Independent Cohort:

Validation in a separate cohort affirms the genetic and plasma components' role in determining AAV susceptibility, prognosis, and severity. The findings emphasize the delicate balance between FH and FHR-1, positioning FHR-1 as a promising AP-specific therapeutic target.


👩‍⚕️ Conclusions:

This comprehensive study sheds light on the genetic and plasma components governing AAV, offering valuable insights into susceptibility, prognosis, and severity. The delicate balance between FH and FHR-1 emerges as a critical factor, pointing towards FHR-1 as a potential therapeutic target in AAV. #ComplementSystem #AAVResearch #MedicalInsights 🌐🔍


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