Association of FHR5 With Disease Severity in ANCA-Associated Vasculitis

Area of Science:

• Nephrology
• Immunology
• Complement System

Background:

• Alternative complement pathway activation is key in ANCA-associated vasculitis (AAV) pathogenesis.
• Complement factor H (FH) plays a crucial role in AAV.
• FH-related protein 5 (FHR5) antagonizes FH activity.

Purpose of the Study:

• To investigate the association between FHR5 and disease severity in AAV.
• To determine the relationship between FHR5 and renal outcomes in AAV patients.

Main Methods:

• Retrospective cohort study of 154 active AAV patients and 55 in remission.
• Plasma FHR5 levels measured by ELISA.
• Renal FHR5 deposition assessed by immunohistochemistry (IHC).

Main Results:

• Higher plasma FHR5 in active AAV than remission/controls, correlating with inflammation and renal damage.
• Glomerular FHR5 deposition found in 69% of kidney biopsies.
• Moderate/strong FHR5 deposition linked to worse renal function, injury, and treatment response.

Conclusions:

• Elevated plasma and glomerular FHR5 are associated with active AAV and severe kidney damage.
• Glomerular FHR5 deposition is an independent risk factor for end-stage kidney disease (ESKD) in AAV.