Membranoproliferative pattern of glomerular injury associated with complement component 9 deficiency due to Arg95Stop mutation.
BACKGROUND
Arg95Stop mutation of exon 4 in complement component 9 (C9) gene is common in individuals in Japan with C9 deficiency (C9D); however, understanding of the influences of C9D on human glomerulonephritis remains elusive.


METHODS
A total of 1288 patients with chronic kidney disease (CKD) were recruited from the hospitals in Niigata prefecture. They were screened for the Arg95Stop mutation of C9 gene by allele-specific PCR.


RESULTS
We identified two individuals with C9D among 1,288 CKD patients, a frequency comparable to that of the general Japanese population (0.16%). Case 1 involved a 44-year-old man presenting with nephrotic proteinuria. The hemolytic activity of CH50 was low, and the concentration of C9 was not detected. Sequencing of exon 4 of the C9 gene showed the Arg95Stop mutation. Renal biopsy revealed diffuse global mesangial proliferation with extensive duplication of glomerular capillary walls. Mesangial, subendothelial and subepithelial deposits were noticed with light and electron microscopy. Immunofluorescent study showed predominant mesangial IgA deposition. Case 2 involved a 62-year-old man presenting with proteinuria and hematuria. His CH50 level was decreased. Renal biopsy revealed diffuse global mesangial proliferation with extensive duplication of glomerular capillary walls. Immune deposits were also confirmed. The percentage of C9D among patients with mesangial proliferation and duplication of GBM in this study was 5.1%.


CONCLUSIONS
These results suggested that the lack of membrane attack complex because of an Arg95Stop mutation of the C9 gene predisposed patients to pathognomonic glomerulonephritis.
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi-dori, Niigata 951-8510, Japan.
Takayoshi
T
Miura
Shin
S
Goto
Seitaro
S
Iguchi
Hisaki
H
Shimada
Mitsuhiro
M
Ueno
Shin-ichi
S
Nishi
Ichiei
I
Narita
D000328:Adult; D001120:Arginine / Q000235:genetics*; D003186:Complement C9 / Q000172:deficiency* / Q000235:genetics*; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D005921:Glomerulonephritis / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007564:Japan; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation
D003186:Complement C9; D001120:Arginine