C4d at Crossroads Between Post-Infectious Glomerulonephritis and C3 Glomerulopathy

Area of Science:

• Nephrology
• Immunopathology
• Complement System

Background:

• Post-infectious glomerulonephritis (PIGN) and C3 glomerulopathy are distinct glomerulonephritis subtypes characterized by glomerular hypercellularity.
• Both conditions share overlapping clinical and histological features, complicating diagnosis and impacting treatment strategies and patient prognosis.
• PIGN involves immune complex deposition from classical/lectin complement pathway activation, producing C4d, while C3 glomerulopathy stems from alternative complement pathway dysregulation.

Purpose of the Study:

• To evaluate the utility of C4d immunohistochemistry (IHC) staining in differentiating between PIGN and C3 glomerulopathy.
• To establish diagnostic criteria for distinguishing these two hypercellular glomerulonephritis subtypes using C4d IHC.

Main Methods:

• Analysis of 28 kidney biopsies diagnosed with glomerulonephritis (GN) with hypercellularity between January 2015 and January 2020.
• Review of clinical, histological, and immunofluorescence data for all cases.
• Performance of C4d IHC staining on all biopsies, with known immune complex-mediated GN cases serving as positive controls.

Main Results:

• Of 28 cases, 18 were classified as PIGN and 10 as C3 glomerulopathy based on clinical and serological findings.
• C4d staining was observed in 72.2% of PIGN cases (mild-moderate) and 11.1% (strong), while only 30% of C3 glomerulopathy cases showed mild C4d staining.
• Control cases exhibited moderate to strong C4d staining, consistent with immune complex deposition.

Conclusions:

• C4d IHC staining demonstrates significant potential in distinguishing PIGN from C3 glomerulopathy.
• This diagnostic tool can aid in accurate classification, leading to more targeted therapeutic interventions for patients with glomerulonephritis.