C5a and its receptors in human anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis.
BACKGROUND
The complement system is crucial for the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). In particular, C5a plays a central role. In this study, plasma and urinary levels of C5a as well as renal C5a receptors (CD88 and C5L2) expression were investigated in patients with AAV.


METHODS
Twenty-four patients with AAV in the active phase, 19 patients with AAV in the remission phase, and 20 patients with lupus nephritis (LN) were included. Plasma and urinary levels of C5a were measured with enzyme-linked immunosorbent assay (ELISA). The staining of CD88 and C5L2 in renal specimens was detected with immunohistochemistry.


RESULTS
The level of plasma C5a was significantly higher in patients with AAV in the active phase than that in patients in remission, that in patients with LN, and that in normal controls. The urinary C5a level was significantly higher in patients with AAV in the active phase than that in patients in remission and that in normal controls, but not significantly different between patients with active AAV and patients with LN. The mean optical density of CD88 staining in the tubulointerstitium was significantly lower in AAV patients than that in normal controls (0.0052 ± 0.0011 versus 0.029 ± 0.0042; P = 0.005). The mean optical density of C5L2 in glomeruli was significantly higher in AAV patients than that in normal controls (0.013 ± 0.0027 versus 0.0032 ± 0.0006; P < 0.001). The mean optical density of CD88 staining closely correlated with the initial eGFR (r = 0.835; P < 0.001) in AAV patients. Double-labeling immunofluorescence assay suggested that CD88 did not express on neutrophils, monocytes, or macrophages, but C5L2 expressed on neutrophils (or monocytes) and macrophages.


CONCLUSIONS
The elevated plasma and urinary C5a levels indicated complement activation in human AAV. The level of renal CD88 expression could reflect the disease severity of ANCA-associated glomerulonephritis. CD88 expression was downregulated, and C5L2 was upregulated in ANCA-associated glomerulonephritis.
Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China.
Jun
J
Yuan
Shen-Ju
SJ
Gou
Jing
J
Huang
Jian
J
Hao
Min
M
Chen
Ming-Hui
MH
Zhao
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology* / Q000378:metabolism*; D003167:Complement Activation / Q000502:physiology*; D015936:Complement C5a / Q000032:analysis* / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000032:analysis* / Q000096:biosynthesis; D055815:Young Adult
C488033:C5AR1 protein, human; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D015936:Complement C5a