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2015 ; 26
(11
): 2852-9
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C4d as a Diagnostic Tool in Proliferative GN
#MMPMID25991041
Sethi S
; Nasr SH
; De Vriese AS
; Fervenza FC
J Am Soc Nephrol
2015[Nov]; 26
(11
): 2852-9
PMID25991041
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Proliferative GN is classified as immune complex-mediated or complement-mediated
(C3 glomerulopathy). Immune complex-mediated GN results from glomerular
deposition of immune-complexes/Ig and C3; the C3 is derived from activation of
the classical and/or lectin pathways of complement. C3 glomerulopathy results
from deposition of C3 and other complement fragments with minimal or no
deposition of immune complexes/Ig; the C3 is derived from activation of the
alternative pathway of complement. C4d is a byproduct of activation of the
classic and lectin pathways. Although widely used as a marker for
antibody-mediated rejection, the significance of C4d in C3 glomerulopathy is
undetermined. We studied glomerular C4d staining in 18 biopsy specimens of
immune-complex GN, 30 biopsy specimens of C3 GN, and 13 biopsy specimens of
postinfectious GN. All specimens of immune complex-mediated GN, except two
specimens of IgA nephropathy and one specimen of sclerosing membranoproliferative
GN, showed bright (2-3+) C4d staining. The staining pattern of C4d mirrored the
staining patterns of Ig and C3. Conversely, C4d staining was completely negative
in 24 (80%) of 30 specimens of C3 glomerulopathy, and only trace/1+ C4d staining
was detected in six (20%) specimens. With regard to postinfectious GN, C4d
staining was negative in six (46%) of 13 specimens, suggesting an abnormality in
the alternative pathway, and it was positive in seven (54%) specimens. To
summarize, C4d serves as a positive marker for immune complex-mediated GN but is
absent or minimally detected in C3 glomerulopathy.
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