title: Glomeruli of Dense Deposit Disease contain components of the alternative and terminal complement pathway.
abstract: Dense Deposit Disease (DDD), or membranoproliferative glomerulonephritis type II, is a rare renal disease characterized by dense deposits in the mesangium and along the glomerular basement membranes that can be seen by electron microscopy. Although these deposits contain complement factor C3, as determined by immunofluorescence microscopy, their precise composition remains unknown. To address this question, we used mass spectrometry to identify the proteins in laser microdissected glomeruli isolated from paraffin-embedded tissue of eight confirmed cases of DDD. Compared to glomeruli from five control patients, we found that all of the glomeruli from patients with DDD contain components of the alternative pathway and terminal complement complex. Factor C9 was uniformly present as well as the two fluid-phase regulators of terminal complement complex clusterin and vitronectin. In contrast, in nine patients with immune complex-mediated membranoproliferative glomerulonephritis, glomerular samples contained mainly immunoglobulins and complement factors C3 and C4. Our study shows that in addition to fluid-phase dysregulation of the alternative pathway, soluble components of the terminal complement complex contribute to glomerular lesions found in DDD.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA. sethi.sanjeev@mayo.edu
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sethi
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Gamez
authors.forename: Julie A
authors.initials: JA
authors.lastname: Vrana
authors.forename: Jason D
authors.initials: JD
authors.lastname: Theis
authors.forename: H Robert
authors.initials: HR
authors.lastname: Bergen
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D000936:Antigen-Antibody Complex; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D051152:Clusterin / Q000032:analysis; D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D003186:Complement C9 / Q000032:analysis; D003170:Complement Pathway, Alternative; D005920:Glomerular Mesangium / Q000737:chemistry* / Q000473:pathology; D015432:Glomerulonephritis, Membranoproliferative / Q000473:pathology*; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D013058:Mass Spectrometry; D008875:Middle Aged; D019096:Vitronectin / Q000032:analysis; D055815:Young Adult
chemical_list: D000936:Antigen-Antibody Complex; D051152:Clusterin; D003176:Complement C3; D003181:Complement C4; D003186:Complement C9; D007136:Immunoglobulins; D019096:Vitronectin