Association of FHR5 With Disease Severity in ANCA-Associated Vasculitis

Alternative complement activation is pivotal in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) pathogenesis. Growing evidence highlights an important role of complement factor H (FH) in AAV. FH-related protein 5 (FHR5) functions as a competitive antagonist of FH. This study aimed to investigate the association of FHR5 with disease severity and renal outcomes in patients with AAV.

In this retrospective cohort study, plasma FHR5 levels were measured using enzyme-linked immunosorbent assay in 154 patients with AAV at active stage and 55 patients in remission. Renal FHR5 deposition was assessed using immunohistochemistry (IHC) in 71 of the 154 patients. The association of plasma FHR5 levels and renal FHR5 deposition with clinicopathological parameters was analyzed.

Plasma levels of FHR5 were significantly higher in patients with active AAV than in those in remission and healthy controls, and correlated with increased inflammatory parameters and more severe renal damage. Positive FHR5 staining was observed in the glomeruli of 49 (69%) renal specimens. Patients with moderate or strong glomerular FHR5 deposition (grade > 1+) demonstrated significantly worse baseline renal function, more severe histopathological kidney injury, and poorer treatment response than those with negative or few deposition of FHR5 (grade ≤ 1+). Multivariable Cox regression analysis indicated that moderate or strong glomerular FHR5 deposition was independently associated with an increased risk of end-stage kidney disease (ESKD).

Both plasma levels and glomerular deposition of FHR5 were elevated in patients with AAV and associated with more active disease and more severe renal damage. Glomerular FHR5 deposition was an independent risk factor for ESKD in AAV.