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Dense deposit disease associated with monoclonal gammopathy of undetermined significance
Journal article   Open access   Peer reviewed

Dense deposit disease associated with monoclonal gammopathy of undetermined significance

Sanjeev Sethi, William R Sukov, Yuzhou Zhang, Fernando C Fervenza, Donna J Lager, Dylan V Miller, Lynn D Cornell, Srivilliputtur G Santhana Krishnan and Richard J H Smith
American journal of kidney diseases, Vol.56(5), pp.977-982
11/2010
DOI: 10.1053/j.ajkd.2010.06.021
PMCID: PMC3970198
PMID: 20832153
url
https://www.ncbi.nlm.nih.gov/pmc/articles/3970198View
Open Access

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.
 Paraproteinemias - immunology Complement Factor H - immunology Diagnosis, Differential Paraproteinemias - diagnosis Humans Middle Aged Paraproteinemias - complications Kidney Glomerulus - ultrastructure Autoantibodies - immunology Glomerulonephritis, Membranoproliferative - immunology Complement Factor H - metabolism Biopsy Female Glomerulonephritis, Membranoproliferative - diagnosis Glomerulonephritis, Membranoproliferative - etiology Microscopy, Fluorescence

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