Complement factors as biomarkers in ANCA-associated vasculitis in remission

Area of Science:

• Immunology
• Nephrology
• Rheumatology

Background:

• Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) involves autoimmune inflammation affecting blood vessels, frequently impacting kidneys.
• Complement activation plays a role in AAV pathogenesis and persists even during remission, with its implications unclear.

Purpose of the Study:

• To investigate the significance of persistent complement activation in patients with AAV in remission.
• To determine if complement activation levels correlate with disease flares or organ involvement in AAV.

Main Methods:

• Analyzed 147 plasma samples from 65 AAV patients in remission.
• Measured complement activation biomarkers: C4d, C3bBbP, and soluble terminal complement complex (sTCC) using ELISA.
• Employed an improved assay for C4d detection, targeting a neoepitope exposed during activation.

Main Results:

• No significant difference in complement activation was found between patients who did or did not experience flares.
• Higher sTCC levels correlated with kidney involvement at diagnosis and creatinine levels during remission.
• Microscopic polyangiitis (MPA) patients showed higher sTCC levels than granulomatosis with polyangiitis (GPA) patients; C-reactive protein correlated with sTCC.

Conclusions:

• Persistent complement activation in AAV remission reflects underlying disease severity and organ damage.
• Complement activation levels in remission do not predict future disease flares in AAV.