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: Sanjeev Sethi, Samih H Nasr, An S De Vriese, Fernando C Fervenza
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 26 Issue 11 Pg. 2852-9 (Nov 2015) ISSN: 1533-3450 [Electronic] United States
• PMID: 25991041 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 by the American Society of Nephrology.

Chemical References

• Antigen-Antibody Complex
• Complement C3
• Immunoglobulins
• Peptide Fragments
• Complement C4b
• complement C4d

Topics

• Antigen-Antibody Complex
• Biopsy
• Complement C3 (chemistry)
• Complement C4b (chemistry)
• Glomerulonephritis (blood, diagnosis)
• Glomerulonephritis, IGA (blood, diagnosis)
• Glomerulonephritis, Membranoproliferative (blood, diagnosis)
• Humans
• Immunoglobulins (chemistry)
• Kidney (pathology)
• Kidney Glomerulus (immunology, pathology)
• Microscopy, Fluorescence
• Peptide Fragments (chemistry)