Glomerular C4d Staining Does Not Exclude a C3 Glomerulopathy.

Area of Science:

• Nephrology
• Immunology
• Complement System

Background:

• C4d, a complement pathway product, aids in evaluating C3 glomerulopathy.
• Absence of C4d suggests an alternative pathway abnormality.
• Glomerular C4d staining offers a diagnostic alternative where genetic testing is unavailable.

Purpose of the Study:

• To assess the utility of glomerular C4d staining in diagnosing C3 glomerulopathy.
• To correlate C4d staining intensity with immunofluorescence and ultrastructural findings.
• To investigate the significance of discordant C4d staining patterns.

Main Methods:

• Immunohistochemistry for C4d was performed on 41 C3 glomerulopathy cases (2011-2017).
• C4d staining was scored (0-3+) and correlated with immunofluorescence and ultrastructural data.
• Paraffin immunofluorescence was used to detect immunoglobulins in cases with discordant C4d staining.

Main Results:

• C4d staining was negative/trace in 22% of dense deposit disease (DDD) and 64% of C3 glomerulonephritis (C3GN) cases.
• Lower intensity C4d (1-2+) generally correlated with Ig/C1q deposits.
• Intense, discordant C4d (3+) occurred in 50% of DDD and 20% of C3GN cases, with some revealing polyclonal Igs.

Conclusions:

• Glomerular C4d presence does not exclude C3 glomerulopathy diagnosis.
• Low-intensity C4d suggests classical/lectin pathway activation with concordant deposits.
• High-intensity, discordant C4d may indicate associated lectin pathway abnormalities, a focus for future research.