The functional activities of complement factor H are impaired in patients with ANCA-positive vasculitis.

ABSTRACT

Increasing evidences have demonstrated that the activation of the alternative complement pathway is crucial for the pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Our recent study found that circulating levels of complement factor H (FH), a key regulator of the alternative pathway, were associated with disease activity. In the current study, functional activities of FH were assessed to further explore the potential role of FH in the pathogenesis of AAV. We found that the two patients with ANCA-negative pauci-immune necrotizing crescentic glomerulonephritis exhibited relatively normal functional activities of FH. However, patients with ANCA-positive vasculitis exhibited deficient functional activities of FH, in terms of interaction with and the regulation of C3b, binding to mCRP and endothelial cells, and the protection of host cells against complement attack. Our findings indicate that functional activities of FH are deficient in patients with ANCA-positive vasculitis, potentially contributing to the disease development.