Differential deposition of C4d and MBL in glomeruli of patients with ANCA-negative pauci-immune crescentic glomerulonephritis.
OBJECTIVE
Our previous study suggested involvement of alternative pathway activation of complement in ANCA-positive pauci-immune crescentic glomerulonephritis (CrGN). This study was to investigate the evidence of complement activation in renal biopsy specimens of patients with ANCA-negative pauci-immune CrGN.


METHODS
Renal biopsy specimens from 12 patients with ANCA-negative pauci-immune CrGN were used to detect the staining of membrane attack complex (MAC), C3d, C4d, mannose-binding lectin (MBL), factor B by immunohistochemistry, and/or immunofluorescence. Renal tissue from eight patients with minimal change disease (MCD) and renal tissue obtained from a normal kidney and the normal parts of a nephrectomized kidney due to renal carcinoma was used as disease and normal controls, respectively.


RESULTS
MAC and C3d could be detected in the active renal lesions of cellular crescents in each of the 12 ANCA-negative CrGN patients but not or scarcely detected in patients with MCD and in normal renal tissue. The deposition of other complement components in the 12 patients was heterogeneous. Although none of them had C1q staining, eight of the 12 were C4d positive and six out of the eight were MBL positive. The remaining four only had evidence of the alternative pathway activation by positive staining of C3d, factor B, and MAC. The staining intensity of C4d and MBL was much higher in dialysis-dependent patients than that in dialysis-independent patients.


CONCLUSIONS
Complement activation was involved in renal damage of human ANCA-negative pauci-immune CrGN but with heterogeneous activation pathways. Positive staining of C4d and MBL might be associated with poor renal outcome.
Xing
Guang-qun
GQ
Renal Division, Department of Medicine, Institute of Nephrology, Key Laboratory of Renal Disease, Ministry of Health of China, Peking University First Hospital, Peking University, Beijing, China.
Chen
Min
M
Liu
Gang
G
Zheng
Xin
X
E
Jie
J
Zhao
Ming-hui
MH
D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D002478:Cells, Cultured; D003176:Complement C3 / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism*; D011415:Complement Factor B / Q000378:metabolism; D003170:Complement Pathway, Alternative; D005260:Female; D005921:Glomerulonephritis; D006801:Humans; D007668:Kidney / Q000473:pathology; D008297:Male; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000378:metabolism*; D050527:Mesangial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D010446:Peptide Fragments / Q000378:metabolism*
D019268:Antibodies, Antineutrophil Cytoplasmic; D003176:Complement C3; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; D050606:Mannose-Binding Protein-Associated Serine Proteases; D011415:Complement Factor B