Format

Send to:

Choose Destination
See comment in PubMed Commons below
Am J Kidney Dis. 2010 Nov;56(5):977-82. doi: 10.1053/j.ajkd.2010.06.021. Epub 2010 Sep 15.

Dense deposit disease associated with monoclonal gammopathy of undetermined significance.

Author information

  • 1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA. sethi.sanjeev@mayo.edu

Abstract

Dense deposit disease (DDD) is a rare glomerular disease that typically affects children, young adults, and much less commonly, older patients. The pathophysiologic process underlying DDD is uncontrolled activation of the alternative pathway (AP) of complement cascade, most frequently secondary to an autoantibody to C3 convertase called C3 nephritic factor, although mutations in factor H and autoantibodies to this protein can impair its function and also cause DDD. Since 1995, we have diagnosed DDD in 14 patients aged 49 years or older; 10 of these patients (71.4%) carry a concomitant diagnosis of monoclonal gammopathy of undetermined significance (MGUS). In 1 of these 10 patients, the index case described here, we evaluated the AP and showed low serum AP protein levels consistent with complement activity, heterozygosity for the H402 allele of factor H, and low levels of factor H autoantibodies, which can affect the ability of factor H to regulate AP activity. In aggregate, these findings suggest that in some adults with MGUS, DDD may develop as a result of autoantibodies to factor H (or other complement proteins) that on a permissive genetic background (the H402 allele of factor H) lead to dysregulation of the AP with subsequent glomerular damage. Thus, DDD in some older patients may be a distinct clinicopathologic entity that represents an uncommon complication of MGUS.

Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

PMID:
20832153
[PubMed - indexed for MEDLINE]
PMCID:
PMC3970198
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk