Renal Expression of Annexin A1 Is Associated With the Severity of Renal Injury in Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis

Abstract

BackgroundIncreasing studies demonstrated the importance of activation of neutrophils in the pathogenesis of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Previous studies showed that annexin A1 (ANXA1) inhibited the recruitment, transendothelial migration and respiratory burst of neutrophils and induced apoptosis of neutrophils. The current study aimed to investigate the plasma and renal levels of ANXA1 as well as their association with the disease severity in AAV patients.MethodsThirty-one AAV patients in active stage and 35 AAV patients in remission stage were recruited. The expression of ANXA1 in renal specimens was assessed by immunohistochemistry. The co-localization of ANXA1 with renal intrinsic and infiltrating cells was detected by double immunofluorescence. The plasma levels of ANXA1 were determined by ELISA. The association of plasma and renal levels of ANXA1 with clinicopathological parameters was further analyzed.ResultsPlasma levels of ANXA1 were significantly higher in active AAV patients than those in AAV patients in remission as well as healthy controls. The renal expression of ANXA1 was significantly higher in active AAV patients than in healthy controls and disease controls. Double immunofluorescence assay showed that ANXA1 was expressed in glomerular endothelial cells, mesangial cells, podocytes, proximal tubular epithelial cells, neutrophils, monocytes/macrophages and T cells in AAV patients. The mean optical density of ANXA1 in glomeruli was correlated with serum creatinine levels (r = −0.491, P = 0.005) and eGFR (r = 0.492, P = 0.005) at renal biopsy and the proportion of crescents (r = −0.423, P = 0.018) in renal specimens of AAV patients. The expression of ANXA1 in glomeruli of AAV patients achieving complete renal recovery was significantly higher than those achieving partial renal recovery.ConclusionIn AAV patients, the renal expression of ANXA1 was associated with the severity of renal injury.