title: C4d as a Diagnostic Tool in Proliferative GN.
abstract: 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.
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology and Sethi.sanjeev@mayo.edu.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology and.
authors.forename: Samih H
authors.initials: SH
authors.lastname: Nasr
authors.affiliation: Division of Nephrology, AZ Sint-Jan Brugge, Brugge, Belgium.
authors.forename: An S
authors.initials: AS
authors.lastname: De Vriese
authors.affiliation: Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota; and.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
mesh_terms: D000936:Antigen-Antibody Complex; D001706:Biopsy; D003176:Complement C3 / Q000737:chemistry; D015935:Complement C4b / Q000737:chemistry*; D005921:Glomerulonephritis / Q000097:blood* / Q000175:diagnosis; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000175:diagnosis; D015432:Glomerulonephritis, Membranoproliferative / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry; D007668:Kidney / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D008856:Microscopy, Fluorescence; D010446:Peptide Fragments / Q000737:chemistry*
chemical_list: D000936:Antigen-Antibody Complex; D003176:Complement C3; D007136:Immunoglobulins; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d
keywords: glomerulonephritis; immunology and pathology; kidney biopsy; membranoproliferative glomerulonephritis (MPGN); renal pathology