Dominant C3 glomerulopathy: new roles for an old actor in renal pathology

• Published in: Journal of nephrology Vol. 31; no. 4; pp. 503 - 510
• Main Authors: Pirozzi, Nicola, Stoppacciaro, Antonella, Menè, Paolo
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.08.2018
• Subjects: Complement C3 - metabolism; Fluorescent Antibody Technique; Glomerular Mesangium - metabolism; Glomerular Mesangium - pathology; Glomerulonephritis - drug therapy; Glomerulonephritis - immunology; Glomerulonephritis - metabolism; Glomerulonephritis - pathology; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Nephrology; Prognosis; Review; Urology; Glomerulonephritis; C3; Immune deposits; Complement; Renal biopsy
• ISSN: 1121-8428; 1724-6059
• DOI: 10.1007/s40620-017-0458-y

Recently, a number of reports have described dominant C3 deposits in renal biopsies of patients with infection-related glomerulonephritis (GN). While acute post-infectious GN and membranoproliferative GN are commonly characterized by immune deposits containing C3 and/or C4, the absence of immunoglobulin (Ig) and/or immune complexes at light or electron microscopy is a rather unusual observation. Dominant C3 deposition is believed to result from the alternative pathway of complement activation via the C3bBb “tickover” convertase. The actual occurrence of C3 glomerulopathy could be underestimated, since infection-related GN often quickly subsides without the need for a renal biopsy. A more thorough understanding of the pathways that lead to complement assembly and deposition within the kidney is needed to support a new classification of complement-related lesions, including entities such as dense deposit disease, (atypical) hemolytic-uremic syndrome, dominant C1q, CFHR5, C4d, and C3 glomerulopathies. We will briefly review recent work in this area, focusing on GN with selective complement C3 deposits.