C3 Glomerulopathy: A Review with Emphasis on Ultrastructural Features.

Abstract

C3 glomerulopathy (C3G) is a rare disease resulting from dysregulation of the alternative complement pathway, resulting in the deposition of complement component 3 (C3) in the kidney. It encompasses two major subgroups: dense deposit disease and C3 glomerulonephritis (C3GN). Although the alternative complement pathway is typically a very tightly controlled system, dysregulation can be a result of genetic mutations in the fluid phase or membrane-bound inhibitors or accelerators. In addition, de novo/acquired autoantibodies against any of the regulatory proteins can alter complement activation either by negating an inhibitor or activating an accelerator. Triggering events can be complex; however, the final pathway is characterized by the uncontrolled deposition of C3 in glomeruli and the formation of the membrane attack complex. Light microscopic findings can be quite heterogeneous with a membranoproliferative pattern most commonly encountered. Diagnostic confirmation of C3G is based on a characteristic pattern of glomerular immunofluorescence staining, with C3-dominant deposits that are at least 2 orders of intensity greater than staining for any immunoglobulin (Ig) or C1q. Electron microscopy is necessary for diagnosing DDD in particular, but can also help to distinguish C3GN from other glomerular disease mimickers.