Glomeruli of Dense Deposit Disease contain components of the alternative and terminal complement pathway

Sanjeev Sethi; Jeffrey D Gamez; Julie A Vrana; Jason D Theis; H Robert  Bergen; Peter F Zipfel; Ahmet Dogan; Richard J.H Smith

doi:10.1038/ki.2008.657

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Glomeruli of Dense Deposit Disease contain components of the alternative and terminal complement pathway

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Glomeruli of Dense Deposit Disease contain components of the alternative and terminal complement pathway

Sanjeev Sethi, Jeffrey D Gamez, Julie A Vrana, Jason D Theis, H Robert Bergen, Peter F Zipfel, Ahmet Dogan and Richard J.H Smith

Kidney international, Vol.75(9), pp.952-960

05/01/2009

DOI: 10.1038/ki.2008.657

PMCID: PMC2738640

PMID: 19177158

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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.

Dense Deposit Disease

kidney

Factor H–related protein I

alternative and terminal complement pathways

Details

Title: Subtitle: Glomeruli of Dense Deposit Disease contain components of the alternative and terminal complement pathway
Creators: Sanjeev Sethi - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Jeffrey D Gamez - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Julie A Vrana - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Jason D Theis - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
H Robert Bergen - Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA
Peter F Zipfel - Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany
Ahmet Dogan - Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
Richard J.H Smith - Department of Internal Medicine, Division of Nephrology and Department of Otolaryngology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Kidney international, Vol.75(9), pp.952-960
DOI: 10.1038/ki.2008.657
PMID: 19177158
PMCID: PMC2738640
NLM abbreviation: Kidney Int
ISSN: 0085-2538
eISSN: 1523-1755
Publisher: Elsevier Inc
Language: English
Date published: 05/01/2009
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984006311902771

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