Complement regulatory proteins in kidneys of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis

Abstract

The complement system activation is involved in the development of antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The study aimed to investigate the expression of complement regulatory proteins (CRPs) CD46, CD55 and CD59 in kidneys of 51 AVV patients. The expression of CD46, CD55 and CD59 in kidneys was detected by immunohistochemistry and double immunofluorescence staining. The immunohistochemical examination revealed that expression of the three CRPs could be detected in the glomeruli and tubules of both AAV patients and normal controls. The expression levels of the three CRPs in glomeruli of patients with AAV were significantly lower than those of normal controls. The scores of CD46 and CD55 expression in the tubules of AAV patients were significantly lower than those of normal controls, while there was no significant difference between the scores of CD59 expression in tubules of AAV patients and those of normal controls. Among AAV patients, the expression level of CD46 in glomeruli correlated inversely with the proportion of normal glomeruli, while it correlated with tubular atrophy in renal interstitium (r 5 -0Á305, P 5 0Á026; r 5 0Á330, P 5 0Á023, respectively). The expression levels of CD55 and CD59 in glomeruli correlated with the proportion of total crescents (r 5 0Á384, P 5 0Á006; r 5 0Á351, P 5 0Á011, respectively). Double immunofluorescence staining indicated that all three CRPs were expressed on endothelial cells, podocytes and mesangial cells in glomeruli. The expression levels of the three CRPs were dysregulated in kidneys of patients with AAV. The expression levels of CD46, CD55 and CD59 were associated with the severity of renal injury of AAV patients.

Human kidney clonal proliferation disclose lineage-restricted precursor characteristics

“…Interestingly, Elevation of CD genes related to immune response and exosomal communication was noted in EL clones. The former included CD46 associated with compliment pathway retardation 50 and CD274, linked with inhibition of T cell function, all three were shown to decrease kidney allograft rejection 51,52 . CD9, an exosome-complex gene was also elevated in EL clones.…”

Hypocomplementemia is associated with worse renal survival in ANCA-positive granulomatosis with polyangiitis and microscopic polyangiitis

“…The functional activities of factor H are also diminished in AAV patients through a decreased binding affinity for C3b; a decrease in decay-accelerating activity and cofactor activity for the factor I-mediated cleavage of C3b; and less efficient binding to monomeric C-reactive protein and endothelial cells [ 16 ]. In contrast, the expression levels of the membrane-bound complement regulatory proteins CD46, CD55, and CD59 are significantly lower in renal biopsy specimens of AAV patients compared to controls [ 17 ]. Taken together, the rationale for complement-targeted therapy shows promising results in GPA and MPA with positive ANCA.…”

Role of tubulointerstitial injury in ANCA-associated vasculitis is underestimated

“…Potentially promising biomarkers of tubular epithelium injury that were studied in patients with chronic kidney disease include α 1 -microglobulin, β 2 -microglobulin, liver-type fatty acid-binding protein, N-acetyl-beta-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, retinol-binding protein and urinary decoy receptor 2. Furthermore, the degree of tubular atrophy correlated with the expression of complement regulatory protein CD46 and alternative complement pathway marker Bb 12 13…”