Deposits of C3 glomerulopathies have ultrastructural hints to correlate with immunofluorescent findings

C3 glomerulopathy (C3G) is a rare type of glomerular disease characterized by predominant deposits of C3 complement. Although dominant C3 immunofluorescent (IF) staining has become well known as a diagnostic criterion, the findings of electron microscopy (EM) are not well specified. The goal of this study was to scrutinize the characteristic features of C3 deposits on EM and to correlate with C3 IF staining patterns.

We examined the EM images of a cohort of 24 cases of C3G (22 C3 dominant glomerulonephritis [C3GN] and 2 dense deposit disease [DDD]) to determine their characteristic features when compared to a cohort of patients with immune complex-mediated glomerulonephritis.

In our patients with C3G, the C3 deposits were present in all three glomerular compartments (mesangial, subendothelial, and subepithelial spaces) and they had the following features: (1) Smear pattern of C3 deposits along glomerular basement membranes (GBM) and subepithelial spaces; (2) C3 deposits were mostly lighter in gray colors as opposed to the dark black appearance of immune complex deposits (ICD); (3) C3 aggregates revealed smooth contours with a homogeneous fine granular appearance when compared to the humpy and bumpy appearance of ICD, and (4) C3 deposits rarely showed either retraction artifacts around the deposits or vacuolization within the GBM or mesangial areas.

In our cohort, C3 deposits exhibit reproducible EM features that are well correlated with clinical data and dominant C3 staining by IF and are different from ICD upon securitized review.