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C4d at Crossroads Between Post-Infectious Glomerulonephritis and C3 Glomerulopathy

Authors Bashir S, Hussain M, Afzal A, Hassan U, Hameed M, Mushtaq S

Received 8 October 2020

Accepted for publication 4 February 2021

Published 11 March 2021 Volume 2021:14 Pages 87—95


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Professor Pravin Singhal

Shaarif Bashir,1 Mudassar Hussain,1 Aurangzeb Afzal,2 Usman Hassan,1 Maryam Hameed,1 Sajid Mushtaq1

1Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, 54000, Pakistan; 2Department of Nephrology, Lahore General Hospital, Lahore, 54000, Pakistan

Correspondence: Shaarif Bashir
Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
Tel +923334245144
Email [email protected]

Background: Post-infectious glomerulonephritis (PIGN) (immune complex-mediated glomerulonephritis) and C3 glomerulopathy are sub-types of glomerulonephritis (GN) with hypercellularity. Both have overlapping clinical and morphologic features on a kidney biopsy, however, the treatment and prognosis of these diseases are quite different making their distinction of utmost importance. Immune complex-mediated glomerulonephritis arises from glomerular deposition of immune-complexes (Igs) and C3 as a result of activation of classical (CP) and lectin pathways (LP). C4d is produced as a result of activation of the CP/LP. On the other hand, C3 glomerulopathy results from activation of alternative pathway of complement.
Aim: To distinguish between PIGN and C3 glomerulopathy with the help of C4d IHC stain.
Materials and Methods: We studied 28 biopsies reported as GN with hypercellularity from January 2015 to January 2020. Clinical information, histological features and immunofluorescence patterns were analyzed. C4d IHC was performed on all the biopsies. Six known cases of immune complex-mediated GN were selected to act as a positive control for C4d staining.
Results: Amongst 28 cases originally reported as GN with hypercellularity, 18 were labeled as post-infectious GN and 10 as C3 glomerulopathy based on clinical information and serological findings. 13 of 18 (72.2%) cases of PIGN had mild to moderate (1– 2+) C4d staining, 2 (11.1%) had strong (3+) staining and 3 (16.7%) cases were negative for C4d staining. In the 10 biopsies of C3 glomerulopathy, mild (1+) C4d staining was noted only in 3 (30%) biopsies. C4d had moderate to strong (2– 3+) staining in the control group.
Conclusion: C4d IHC stain can be helpful in distinguishing PIGN from C3 glomerulopathy.

Keywords: proliferative, post-infectious, C3 glomerulopathy, C4d

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