title: C3 glomerulopathy and current dilemmas.
abstract: C3 glomerulopathy (C3G) is a recently identified disease entity caused by dysregulation of the alternative complement pathway, and dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are its components. Because laboratory detection of complement dysregulation is still uncommon in practice, "dominant C3 deposition by two orders greater than that of immunoglobulins in the glomeruli by immunofluorescence", as stated in the consensus report, defines C3G. However, this morphological definition possibly includes the cases with glomerular diseases of different mechanisms such as post-infectious glomerulonephritis. In addition, the differential diagnosis between DDD and C3GN is often difficult because the distinction between these two diseases is based solely on electron microscopic features. Recent molecular and genetic advances provide information to characterize C3G. Some C3G cases are found with genetic abnormalities in complement regulatory factors, but majority of cases seem to be associated with acquired factors that dysregulate the alternative complement pathway. Because clinical courses and prognoses among glomerular diseases with dominant C3 deposition differ, further understanding the background mechanism, particularly complement dysregulation in C3G, is needed. This may resolve current dilemmas in practice and shed light on novel targeted therapies to remedy the dysregulated alternative complement pathway in C3G.
authors.affiliation: Kidney and Vascular Pathology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ito
authors.affiliation: Department of Diagnostic Pathology, Nippon Medical School Hospital, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Ohashi
authors.affiliation: Kidney and Vascular Pathology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305-8577, Japan. nagatam@md.tsukuba.ac.jp.
authors.forename: Michio
authors.identifier: http://orcid.org/0000-0002-7360-5524
authors.initials: M
authors.lastname: Nagata
mesh_terms: D000818:Animals; D001706:Biopsy; D003176:Complement C3 / Q000276:immunology*; D051056:Complement Inactivating Agents / Q000627:therapeutic use; D003170:Complement Pathway, Alternative / Q000187:drug effects; D003937:Diagnosis, Differential; D015432:Glomerulonephritis, Membranoproliferative / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007678:Kidney Glomerulus / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D010951:Plasma Exchange; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D003176:Complement C3; D051056:Complement Inactivating Agents; D007166:Immunosuppressive Agents
keywords: Alternative complement pathway; C3 glomerulonephritis; C3 glomerulopathy; Dense deposit disease; Dominant C3 deposition; Membranoproliferative glomerulonephritis